Effectiveness and Safety of Direct Oral Anticoagulants Versus Warfarin in Patients with Atrial Fibrillation and Cancer: A Target Trial Emulation from SEER-Medicare Database.

BACKGROUND: Direct oral anticoagulants (DOACs) are preferred over warfarin in patients with atrial fibrillation (AFib). However, their safety and effectiveness in patients with AFib and cancer are inconclusive. METHODS: We conducted a retrospective cohort study by emulating a target trial. Patients with a record of cancer (breast, prostate, or lung), newly diagnosed with AFib initiated DOACs or warfarin within 3 months after AFib diagnosis from the 2012-2019 Surveillance, Epidemiology, and End Results (SEER)-Medicare database were included. We compared the risk of ischemic stroke, major bleeding, and secondary outcomes (venous thromboembolism, intracranial bleeding, gastrointestinal bleeding, and non-critical site bleeding) between patients who initiated DOACs and warfarin. Inverse probability treatment weights and inverse probability censoring weights were used to adjust imbalanced patient and disease characteristics and loss to follow-up between the two groups. Weighted pooled logistic regression were used to estimate treatment effect with hazard ratios (HRs) with 95% confidence interval (95% CIs). RESULTS: The incidence rates of stroke and major bleeding between DOAC and warfarin initiators were 9.97 vs. 9.91 and 7.74 vs. 9.24 cases per 1000 person-years, respectively. In adjusted intention-to-treat analysis, patients initiated DOACs had no statistically significant difference in risk of ischemic stroke (HR = 0.87, 95% CI 0.52-1.44) and major bleeding (HR = 1.14, 95% CI 0.77-1.68) compared to those initiated warfarin. In adjusted per-protocol analysis, there was no statistical difference in risk of ischemic stroke (HR = 1.81, 95% CI 0.75-4.36) and lower risk for major bleeding, but the 95% CI was wide (HR = 0.35, 95% CI 0.12-0.99) among DOAC initiators compared to warfarin initiators. The benefits in secondary outcomes were in favor of DOACs. The findings remained consistent across subgroups and sensitivity analyses. CONCLUSION: DOACs are safe and effective alternatives to warfarin in the management of patients with AFib and cancer.

Comparison of the Protective Effects of Casein Hydrolysate Containing Tyr-Pro-Val-Glu-Pro-Phe and Casein on the Behaviors and Peripheral and Brain Functions in Mice with Chronic-Stress-Induced Anxiety and Insomnia.

Chronic stress is a major inducer of anxiety and insomnia. Milk casein has been studied for its stress-relieving effects. We previously prepared a casein hydrolysate (CP) rich in the sleep-enhancing peptide YPVEPF, and this study aims to systemically investigate the different protective effects of CP and casein on dysfunction and anxiety/insomnia behavior and its underlying mechanisms in chronically stressed mice. Behavioral results showed that CP ameliorated stress-induced insomnia and anxiety more effectively than milk casein, and this difference in amelioration was highly correlated with an increase in GABA, 5-HT, GABAA, 5-HT1A receptors, and BDNF and a decrease in IL-6 and NMDA receptors in stressed mice. Furthermore, CP restored these dysfunctions in the brain and colon by activating the HPA response, modulating the ERK/CREB-BDNF-TrκB signaling pathway, and alleviating inflammation. The abundant YPVEPF (1.20 ± 0.04%) and Tyr-based/Trp-containing peptides of CP may be the key reasons for its different effects compared to casein. Thus, this work revealed the main active structures of CP and provided a novel dietary intervention strategy for the prevention and treatment of chronic-stress-induced dysfunction and anxiety/insomnia behaviors.

The association between polypharmacy and health-related quality of life among older adults with prostate cancer.

INTRODUCTION: Older adults with prostate cancer (PC) are at risk of polypharmacy, which further complicates disease management and health-related quality of life (HRQoL). This study evaluated the association between polypharmacy and HRQoL among Medicare beneficiaries with PC. MATERIALS AND METHODS: This observational, retrospective study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) Medicare Health Outcomes Survey (MHOS) data resource. Beneficiaries aged ≥65 and enrolled in Medicare Advantage Organizations were included if they had a PC diagnosis and continuously enrolled in Part D for 12 months prior to the completion of MHOS. Polypharmacy was determined based on the unique number of concurrent Part D prescriptions during 12 months before survey: no polypharmacy (NP, n = 0-4), polypharmacy (PP, n = 5-9), and excessive polypharmacy (EPP, n ≥ 10). HRQoL was assessed using the Physical and Mental Component Summary T-scores (PCS and MCS, respectively) in MHOS. ANOVA and Pearson's Chi-Square tests were performed to assess variances between polypharmacy and continuous/categorical variables. Multivariate linear regression models with generalized estimating equations were used to assess the association between polypharmacy and HRQoL. The severely impaired HRQoL cohort was identified based on normalized z-scores of PCS and MCS. Odds ratios were calculated to prioritize drug-drug and class-class pairs associated with patients with severely impaired HRQoL. RESULTS: Data from 16,573 beneficiaries (24,126 records) showed that 44.4% had PP and 10.1% had EPP. Beneficiaries with PP and EPP had significantly lower mean PCS and MCS scores compared to those without polypharmacy (p < 0.001). After adjusting for covariates, beneficiaries with EPP had clinically significantly lower PCS (adjusted marginal difference: -8.47 [-9.00, -7.94]) and MCS (adjusted marginal difference: -4.32 [-4.89, -3.75]) compared to the NP group. Top-ranked drug-drug pairs like tiotropium bromide and oxycodone/acetaminophen exhibited significant associations with HRQoL decline. Analysis of class-class pairs highlighted (1) corticosteroid hormone receptor agonists and opioid agonists and (2) benzodiazepines and adrenergic beta2-agonists as having significant associations with HRQoL decline. DISCUSSION: Polypharmacy exhibits a significant association with HRQoL declines among older adults with PC.

Safety of marketed biosimilar monoclonal antibody cancer treatments in the US: a disproportionality analysis using the food and drug administration adverse event reporting system (FAERS) database.

BACKGROUND: By 31 December 2022, the United States Food and Drug Administration (FDA) has approved 12 biosimilar monoclonal antibody cancer treatments. This study detected disproportionate adverse event (AE) reporting signals and compared safety profile of individual biosimilars to their originator biologics and between each pair of biosimilars. RESEARCH DESIGN AND METHODS: The FDA Adverse Event Reporting System data (6/1/2018-12/31/2022) were used to identify AE reports for rituximab, bevacizumab, trastuzumab, and their marketed biosimilars. Reporting odds ratios and empirical Bayesian geometric mean were computed to detect reporting disproportionality in serious, death, and specific AEs between studied biologics/biosimilars and all other drugs. RESULTS: Significant AE reporting signals were identified: 1) death for biological rituximab, pruritus for biosimilar rituximab-pvvr, and infusion-related reactions for biological rituximab and biosimilar rituximab-pvvr (significantly higher ROR for rituximab-pvvr than biological rituximab, p < .0001); 2) death for biological bevacizumab and biosimilar bevacizumab-bvzr (significantly higher ROR for bevacizumab-bvzr than biological bevacizumab, p < .0001), hypertension, platelet count decreased (PCD), and proteinuria for biological bevacizumab and biosimilar bevacizumab-awwb (significantly higher ROR of PCD for bevacizumab-awwb than originator bevacizumab, p = .001); and 3) rash for biosimilar trastuzumab-anns. CONCLUSIONS: Findings call for large, longitudinal studies to examine causality of certain AEs with rituximab-pvvr and bevacizumab biosimilars.

New Prospects Arising from Dynamically Crosslinked Polymers: Reprogramming Their Properties.

Dynamically crosslinked polymers (DCPs) have gained significant attention owing to their applications in fabricating (re)processable, recyclable, and self-healable thermosets, which hold great promise in addressing ecological issues, such as plastic pollution and resource scarcity. However, the current research predominantly focuses on redefining and/or manipulating their geometries while replicating their bulk properties. Given the inherent design flexibility of dynamic covalent networks, DCPs also exhibit a remarkable potential for various novel applications through postsynthesis reprogramming their properties. In this review, the recent advancements in strategies that enable DCPs to transform their bulk properties after synthesis are presented. The underlying mechanisms and associated material properties are overviewed mainly through three distinct strategies, namely latent catalysts, material-growth, and topology isomerizable networks. Furthermore, the mutual relationship and impact of these strategies when integrated within one material system are also discussed. Finally, the application prospects and relevant issues necessitating further investigation, along with the potential solutions are analyzed.

Benefit and risk of oral anticoagulant initiation strategies in patients with atrial fibrillation and cancer: a target trial emulation using the SEER-Medicare database.

Oral anticoagulants (OACs) are recommended for patients with atrial fibrillation (AFib) having CHA2DS2-VASc score ≥ 2. However, the benefits of OAC initiation in patients with AFib and cancer at different levels of CHA2DS2-VASc is unknown. We included patients with new AFib diagnosis and a record of cancer (breast, prostate, or lung) from the 2012-2019 Surveillance, Epidemiology, and End Results (SEER)-Medicare database (n = 39,915). Risks of stroke and bleeding were compared between 5 treatment strategies: (1) initiated OAC when CHA2DS2-VASc ≥ 1 (n = 6008), (2) CHA2DS2-VASc ≥ 2 (n = 8694), (3) CHA2DS2-VASc ≥ 4 (n = 20,286), (4) CHA2DS2-VASc ≥ 6 (n = 30,944), and (5) never initiated OAC (reference group, n = 33,907). Confounders were adjusted using inverse probability weighting through cloning-censoring-weighting approach. Weighted pooled logistic regressions were used to estimate treatment effect [hazard ratios (HRs) and 95% confidence interval (95% CIs)]. We found that only patients who initiated OACs at CHA2DS2-VASc ≥ 6 had lower risk of stroke compared without OAC initiation (HR 0.64, 95% CI 0.54-0.75). All 4 active treatment strategies had reduced risk of bleeding compared to non-initiators, with OAC initiation at CHA2DS2-VASc ≥ 6 being the most beneficial strategy (HR = 0.49, 95% CI 0.44-0.55). In patients with lung cancer or regional/metastatic cancer, OAC initiation at any CHA2DS2-VASc level increased risk of stroke and did not reduce risk of bleeding (except for Regimen 4). In conclusion, among cancer patients with new AFib diagnosis, OAC initiation at higher risk of stroke (CHA2DS2-VASc score ≥ 6) is more beneficial in preventing ischemic stroke and bleeding. Patients with advanced cancer or low life-expectancy may initiate OACs when CHA2DS2-VASc score ≥ 6.

Development and Validation of Machine Learning Algorithms to Predict 1-Year Ischemic Stroke and Bleeding Events in Patients with Atrial Fibrillation and Cancer.

In this study, we leveraged machine learning (ML) approach to develop and validate new assessment tools for predicting stroke and bleeding among patients with atrial fibrillation (AFib) and cancer. We conducted a retrospective cohort study including patients who were newly diagnosed with AFib with a record of cancer from the 2012-2018 Surveillance, Epidemiology, and End Results (SEER)-Medicare database. The ML algorithms were developed and validated separately for each outcome by fitting elastic net, random forest (RF), extreme gradient boosting (XGBoost), support vector machine (SVM), and neural network models with tenfold cross-validation (train:test = 7:3). We obtained area under the curve (AUC), sensitivity, specificity, and F2 score as performance metrics. Model calibration was assessed using Brier score. In sensitivity analysis, we resampled data using Synthetic Minority Oversampling Technique (SMOTE). Among 18,388 patients with AFib and cancer, 523 (2.84%) had ischemic stroke and 221 (1.20%) had major bleeding within one year after AFib diagnosis. In prediction of ischemic stroke, RF significantly outperformed other ML models [AUC (0.916, 95% CI 0.887-0.945), sensitivity 0.868, specificity 0.801, F2 score 0.375, Brier score = 0.035]. However, the performance of ML algorithms in prediction of major bleeding was low with highest AUC achieved by RF (0.623, 95% CI 0.554-0.692). RF models performed better than CHA2DS2-VASc and HAS-BLED scores. SMOTE did not improve the performance of the ML algorithms. Our study demonstrated a promising application of ML in stroke prediction among patients with AFib and cancer. This tool may be leveraged in assisting clinicians to identify patients at high risk of stroke and optimize treatment decisions.

Potential Mechanisms of Casein Hexapeptide YPVEPF on Stress-Induced Anxiety and Insomnia Mice and Its Molecular Effects and Key Active Structure.

The hexapeptide YPVEPF with strong sleep-enhancing effects could be detected in rat brain after a single oral administration as we previously proved. In this study, the mechanism and molecular effects of YPVEPF in the targeted stress-induced anxiety mice were first investigated, and its key active structure was further explored. The results showed that YPVEPF could significantly prolong sleep duration and improve the anxiety indexes, including prolonging the time spent in the open arms and in the center. Meanwhile, YPVEPF showed strong sleep-enhancing effects by significantly increasing the level of the GABA/Glu ratio, 5-HT, and dopamine in brain and serum and regulating the anabolism of multiple targets, but the effects could be blocked by bicuculline and WAY100135. Moreover, the molecular simulation results showed that YPVEPF could stably bind to the vital GABAA and 5-HT1A receptors due to the vital structure of Tyr-Pro-Xaa-Xaa-Pro-, and the electrostatic and van der Waals energy played dominant roles in stabilizing the conformation. Therefore, YPVEPF displayed sleep-enhancing and anxiolytic effects by regulating the GABA-Glu metabolic pathway and serotoninergic system depending on distinctive self-folding structures with Tyr and two Pro repeats.

A survey on awareness, knowledge and preferences toward genetic testing among the United States general public.

Aim: To understand awareness, knowledge and preferences regarding genetic testing among the USA general public. Methods: A cross-sectional online survey using a Qualtrics Panel. Results: Among 1600 respondents, 545 (34%) were White, 411 (26%) Black, 412 (26%) Hispanic or Latin(x) and 232 (15%) Asian. Most had heard of ancestry testing (87%) and genetic health risk testing (69%), but a third thought inherited genes were only a little or not at all responsible for obesity (36%) and mental health (33%). The majority preferred pre-emptive pharmacogenetic testing (n = 74%) compared with reactive testing. Statistically significant differences between racial/ethnic groups and rural-urban respondents were observed. Conclusion: Most preferred pre-emptive pharmacogenetic testing; however, about one-quarter preferred reactive testing. Preferences should be discussed during patient-clinician interactions.

What is this study about? This study presents a large online survey among the USA general public to understand their awareness, knowledge and preferences about genetic testing and how this may vary by racial/ethnic group and rural/urban status.What were the results? Most survey respondents had heard of ancestry testing (87%) and genetic health risk testing (69%). However, over a third of respondents thought that inherited genes may be only a little or not at all responsible for obesity (36%) and mental health (33%). When asked about preferences for pre-emptive compared with reactive pharmacogenetic testing, the majority preferred pre-emptive testing (n = 74%). Statistically significant differences between racial/ethnic groups as well as rural-urban respondents were seen.What do the results mean? The US general public may have a different understanding of genetic testing for different diseases, and have different preferences when it comes to the timing of testing. Appropriate educational content targeting the link between genetics and specific diseases should be prepared, and preferences for pre-emptive or reactive testing should be discussed during visits with healthcare providers.

Transcutaneous fluorescence spectroscopy: development and characterization of a compact, portable, and fiber-optic sensor.

Significance: The integrity of the intestinal barrier is gaining recognition as a significant contributor to various pathophysiological conditions, including inflammatory bowel disease, celiac disease, environmental enteric dysfunction (EED), and malnutrition. EED, for example, manifests as complex structural and functional changes in the small intestine leading to increased intestinal permeability, inflammation, and reduced absorption of nutrients. Despite the importance of gut function, current techniques to assess intestinal permeability (such as endoscopic biopsies or dual sugar assays) are either highly invasive, unreliable, and/or difficult to perform in certain patient populations (e.g., infants). Aim: We present a portable, optical sensor based on transcutaneous fluorescence spectroscopy to assess gut function (in particular, intestinal permeability) in a fast and noninvasive manner. Approach: Participants receive an oral dose of a fluorescent contrast agent, and a wearable fiber-optic probe detects the permeation of the contrast agent from the gut into the blood stream by measuring the fluorescence intensity noninvasively at the fingertip. We characterized the performance of our compact optical sensor by comparing it against an existing benchtop spectroscopic system. In addition, we report results from a human study in healthy volunteers investigating the impact of skin tone and contrast agent dose on transcutaneous fluorescence signals. Results: The first study with eight healthy participants showed good correlation between our compact sensor and the existing benchtop spectroscopic system [correlation coefficient (r)>0.919, p<0.001]. Further experiments in 14 healthy participants revealed an approximately linear relationship between the ingested contrast agent dose and the collected signal intensity. Finally, a parallel study on the impact of different skin tones showed no significant differences in signal levels between participants with different skin tones (p>0.05). Conclusions: In this paper, we demonstrate the potential of our compact transcutaneous fluorescence sensor for noninvasive monitoring of intestinal health.

Did the 2021 federal change in the practice guidelines for the administration of buprenorphine for treating opioid use disorder increase buprenorphine prescription dispensing in Medicaid population?

BACKGROUND AND OBJECTIVES: In April 2021, the Department of Health and Human Services released new federal practice guidelines and allowed physicians who wish to treat ≤30 patients with opioid use disorder (OUD) to forego the X-waiver training requirement. METHODS: This observational study compared annual number, dose, and spending of buprenorphine OUD treatments dispensed in the Medicaid population in 2021 versus 2020 using the CMS State Drug Utilization Data (n = 50 states plus D.C.). RESULTS: Compared to 2020, there was a slight decrease (-3.1%) in the annual number of buprenorphine prescriptions dispensed but an increase in total doses (+3.2%) and payment (10.6%) for buprenorphine prescriptions in 2021. DISCUSSION AND CONCLUSIONS: Decrease in number of buprenorphine prescriptions in Medicaid population was observed in 2021. SCIENTIFIC SIGNIFICANCE: Our findings support the hypothesis generation in which the removal of X-waiver training alone is not adequate to increase prescribing and access to OUD treatment buprenorphine.

Factors associated with adherence to medications for lowering breast cancer risk between female Medicare beneficiaries in Alabama and nationwide.

PURPOSE: The U.S. Preventive Services Task Force recommends use of selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) for breast cancer (BC) prevention. We examined factors associated with adherence to SERMs/AI treatments among female Medicare beneficiaries in Alabama and those nationwide. METHODS: This retrospective new user cohort study analyzed the 2013-2016 Medicare administrative claims data files (100% Alabama and random 5% national samples). Female Medicare beneficiaries without invasive BC and osteoporosis, continuously enrolled in Medicare Parts A, B, and D for at least 18 months (with a 6-month washout and a 12-month follow-up period) in 2013-2016. Among beneficiaries who initiated (6-month washout) any of the SERMs/AIs (tamoxifen, raloxifene, anastrozole, and exemestane), we examined their 1-year treatment adherence using proportion of days covered (PDC) and operationalized as both continuous (0-1) and dichotomized (≥ 80% as adherent and < 80% as non-adherent) outcomes. Multivariable logistic models were used to identify factors associated with adherence (PDC ≥ 80%) among Alabama and national samples, respectively. RESULTS: A total of 885 women in Alabama and 1,213 women in national sample initiated these SERMs/AI treatments. Among those with ≥ 2 prescriptions (n = 479 in Alabama and n = 870 in national sample), Mean PDC was 0.74 [standard deviation (SD) = 0.30] among Alabamian women, similar to those in the national sample [0.71 (SD = 0.31), p = 0.09]. Use of mammography prior to treatment initiation was associated with higher likelihood of adherence to treatments in both samples. CONCLUSION: Our findings highlight the importance of access to preventive services such as mammography to better adherence to BC preventive treatments among female Medicare beneficiaries.

Nucleic Acid Amplification-Free Digital Detection Method for SARS-CoV-2 RNA Based on Droplet Microfluidics and CRISPR-Cas13a.

Most of the methods currently developed for RNA detection based on CRISPR were combined with nucleic acid amplification. As a result, such methods inevitably led to certain disadvantages such as multiple operations, expensive reagents, and amplification bias. To solve the above problems, we developed a highly sensitive and specific nucleic acid amplification-free digital detection method for SARS-CoV-2 RNA based on droplet microfluidics and CRISPR-Cas13a. In this assay, thousands of monodisperse droplets with a size of 30 µm were generated within 2 min by a negative pressure-driven microfluidic chip. By confining a single target RNA recognition event to an independent droplet, the collateral cleavage products of activated Cas13a could be accumulated in one droplet. By combining the droplet microfluidics and CRISPR-Cas13a, SARS-CoV-2 RNA could be easily detected within 30 min with a detection limit of 470 aM. The performance of this assay was verified by specificity experiments and spiking and recovery experiments with human saliva. Compared with many developed methods for SARS-CoV-2 RNA detection, our method is time- and reagent-saving and easy to operate. Taken together, this digital detection method based on droplet microfluidics and CRISPR-Cas13a provides a promising approach for RNA detection in clinical diagnostics.

Use of second-generation antidiabetic medication among a nationally representative sample.

OBJECTIVES: Existing studies have shown the benefits of second-generation antidiabetic medications in patients with type 2 diabetes (T2D). However, the medications' real-world utilization was not well understood. Our study assessed patient factors associated with the use of second-generation antidiabetic medications in a nationally representative sample of patients with T2D. STUDY DESIGN: This retrospective, cross-sectional analysis used the 2005 to 2018 National Health and Nutrition Examination Survey (NHANES) data. METHODS: Survey participants 18 years and older who had a diagnosis of T2D and had used antidiabetic medications in the past 30 days were included. The primary outcome was the prescription of any second-generation antidiabetic medication. Weighted stepwise multivariable logistic regression models were used to assess the associations between the use of second-generation antidiabetic medications and patients' characteristics. RESULTS: Among 4493 patients with T2D, 533 (weighted %, 13.67%) reported using at least 1 second-generation antidiabetic drug. In multivariable analyses, patients with incomes at least 400% of the federal poverty level (adjusted odds ratio [AOR], 2.30; 95% CI, 1.58-3.34), with higher hemoglobin A1c levels (AOR, 1.10; 95% CI, 1.02-1.18), and taking more medications (AOR, 1.14; 95% CI, 1.09-1.20) were more likely to use second-generation antidiabetic drugs compared with their counterparts. CONCLUSIONS: The uptake of second-generation antidiabetic medications was 14% among patients with T2D in the United States. Prescription benefit design that targets lower out-of-pocket payments for these newer drugs may improve patient access and clinical outcomes for patients with T2D.

Granulocyte-macrophage colony-stimulating factor promotes endometrial repair after injury by regulating macrophages in mice.

Intrauterine adhesion (IUA) caused by endometrial injury is a common cause of female infertility and is challenging to treat. Macrophages play a critical role in tissue repair and cyclical endometrial regeneration. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has significant reparative and anti-fibrotic effects in various tissues. However, there is limited research on the role of GM-CSF in the repair of endometrial injury and the involvement of macrophages in GM-CSF-mediated endometrial repair. In this study, using a mouse model of endometrial scratching injury, we found that GM-CSF treatment accelerated the repair of endometrial injury and improved fertility. At the molecular level, we observed that GM-CSF can downregulate the transcript levels of tumor necrosis factor (TNF) in mouse bone marrow-derived macrophages (BMDMs) stimulated by lipopolysaccharide (LPS) and upregulate the expression of Arginase-1 (Arg-1) and mannose receptor C-type 1 (MRC1). Importantly, during the early and middle stages of injury, GM-CSF increased the proportion of M1-like, M2-like, and M1/M2 mixed macrophages, while in the late stage of injury, GM-CSF facilitated a decline in the number of M2-like macrophages. These findings suggest that GM-CSF may promote endometrial repair by recruiting macrophages and modulating the LPS-induced M1-like macrophages into a less inflammatory phenotype. These insights have the potential to contribute to the development of novel therapeutic approaches for the treatment of intrauterine adhesion and related infertility.

Heat-stone massage for patients with chronic musculoskeletal pain: a protocol for multicenter randomized controlled trial.

Introduction: Chronic musculoskeletal pain bothers the quality of life for approximately 1.71 billion people worldwide. Although pharmacological therapies play an important role in controlling chronic pain, overuse of opioids, persistent or recurrent symptoms, and pain-related disability burden still need to be addressed. Heat-stone massage is using the heated stone to stimulate muscles and ligaments followed by massage for relax, which can potentially treat the chronic musculoskeletal pain. To determine the efficacy and safety of heat-stone massage for patients with chronic musculoskeletal pain is needed. Methods and analysis: This multicenter, 2-arm, randomized, positive drug-controlled trial will include a total of 120 patients with chronic musculoskeletal pain. The intervention group will receive a 2 week heat-stone massage, 3 times per week, whereas the control group will receive the flurbiprofen plaster twice per day for 2 weeks. The primary end point is the change in Global Pain Scale from baseline to the end of the 2 week intervention. The secondary outcomes include the pain severity (Numerical Rating Scale), pain acceptance (Chronic Pain Acceptance Questionnaire), self-management (Health Education Impact Questionnaire), self-efficacy (Pain Self-Efficacy Questionnaire), anxiety and depression (Hospital Anxiety and Depression Scale), quality of life (Short Form-36). The intention-to-treat dataset will be used for analysis. Discussion: The pain management remains the research topic that patients always pay close attention to. This will be the first randomized clinical trial to evaluate whether heat-stone massage, a non-pharmacological therapy, is effective in the chronic musculoskeletal pain management. The results will provide evidence for new option of daily practice. Clinical trial registration: World Health Organization Chinese Clinical Trial Registry [ChiCTR2200065654; https://www.chictr.org.cn/showproj.html?proj=185403]; International Traditional Medicine Clinical Trial Registry [ITMCTR2022000104; http://itmctr.ccebtcm.org.cn/en-US/Home/ProjectView?pid=51776b6f-77b8-4811-9b5a-a0fec10f2cee].

Screening for clinically relevant drug-drug interactions between direct oral anticoagulants and antineoplastic agents: a pharmacovigilance approach.

BACKGROUND: Use of direct oral anticoagulants (DOACs) in patients with cancer remains suboptimal due to the concern regarding potential drug-drug interactions (DDIs) with antineoplastic treatments. However, the clinical relevance of these DDIs is unknown. METHODS: We conducted a pharmacovigilance study of adverse event (AE) reports from the US Food and Drug Administration Adverse Event Reporting System from 1/1/2004 to 12/31/2021. AE reports containing DOACs and antineoplastic agents with CYP3A4/P-gp inhibitory or inducing activity suggested by published pharmacokinetic studies were included (n = 36,066). The outcomes of interest were bleeding or stroke, identified by MedDRA dictionary version 25.0. We used disproportionality analyses (DPA), logistic regression models (LR), and Multi-item Gamma-Poisson Shrinker (MGPS) (Empirical Bayes Geometric Means (EBGM) and 90% credible intervals (90% CIs)) algorithms to identify the safety signal of DDIs. RESULTS: The highest bleeding reporting rates for each drug class were the combination of DOACs with neratinib (39.08%, n = 34), tamoxifen (21.22%, n = 104), irinotecan (20.54%, n = 83), and cyclosporine (19.17%, n = 227). The highest rate of stroke was found for prednisolone (2.43%, n = 113). In the primary analysis, no signal of DDIs by the antineoplastic therapeutic class was detected by MGPS, DPA, and LR approaches. By individual antineoplastic drug, DOACs-neratinib was the only signal detected [EBGM (EB05-EB95) = 2.71 (2.03-3.54)]. CONCLUSION: No signal of DDIs between DOACs and antineoplastic agents was detected, except for DOAC-neratinib. Most DDIs between DOACs and antineoplastic agents may not be clinically relevant. The DDIs between DOACs and neratinib should be further examined in future research.

A systematic review of digital health technologies for the care of older adults during COVID-19 pandemic.

Objective: During the Coronavirus Disease 2019 (COVID-19) pandemic, digital health technologies (DHTs) became increasingly important, especially for older adults. The objective of this systematic review was to synthesize evidence on the rapid implementation and use of DHTs among older adults during the COVID-19 pandemic. Methods: A structured, electronic search was conducted on 9 November 2021, and updated on 5 January 2023, among five databases to select DHT interventional studies conducted among older adults during the pandemic. The bias of studies was assessed using Version 2 of the Cochrane Risk-of-Bias Tool for randomized trials (RoB 2) and Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I). Results: Among 20 articles included in the review, 14 (70%) focused on older adults with chronic diseases or symptoms, such as dementia or cognitive impairment, type 2 diabetes, and obesity. DHTs included traditional telehealth interventions via telephone, video, and social media, as well as emerging technologies such as Humanoid Robot and Laser acupuncture teletherapy. Using RoB 2 and ROBINS-I, four studies (20%) were evaluated as high or serious overall risk of bias. DHTs have shown to be effective, feasible, acceptable, and satisfactory for older adults during the COVID-19 pandemic compared to usual care. In addition, some studies also highlighted challenges with technology, hearing difficulties, and communication barriers within the vulnerable population. Conclusions: During the COVID-19 pandemic, DHTs had the potential to improve various health outcomes and showed benefits for older adults' access to health care services.

The investigation of constraints in implementing robust AI colorectal polyp detection for sustainable healthcare system.

Colorectal cancer (CRC) is one of the significant threats to public health and the sustainable healthcare system during urbanization. As the primary method of screening, colonoscopy can effectively detect polyps before they evolve into cancerous growths. However, the current visual inspection by endoscopists is insufficient in providing consistently reliable polyp detection for colonoscopy videos and images in CRC screening. Artificial Intelligent (AI) based object detection is considered as a potent solution to overcome visual inspection limitations and mitigate human errors in colonoscopy. This study implemented a YOLOv5 object detection model to investigate the performance of mainstream one-stage approaches in colorectal polyp detection. Meanwhile, a variety of training datasets and model structure configurations are employed to identify the determinative factors in practical applications. The designed experiments show that the model yields acceptable results assisted by transfer learning, and highlight that the primary constraint in implementing deep learning polyp detection comes from the scarcity of training data. The model performance was improved by 15.6% in terms of average precision (AP) when the original training dataset was expanded. Furthermore, the experimental results were analysed from a clinical perspective to identify potential causes of false positives. Besides, the quality management framework is proposed for future dataset preparation and model development in AI-driven polyp detection tasks for smart healthcare solutions.