Optimal antithrombotic strategy in patients with atrial fibrillation beyond 1 year after drug-eluting stent implantation: Design and rationale of the randomized ADAPT AF-DES trial.

BACKGROUND: Both anticoagulation and antiplatelet therapies are recommended after percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF). Although contemporary guidelines recommend discontinuation of antiplatelet therapy 1 year after drug-eluting stent (DES) implantation due to excessive bleeding risk, supporting randomized trials are still lacking. METHODS: The ADAPT AF-DES trial is a multicenter, prospective, open-label, randomized, non-inferiority trial, enrolling 960 patients with AF with a CHA2DS2-VASc score > 1, who underwent PCI with DES implantation at least 12 months before enrollment. Eligible patients are randomly assigned to receive either non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy or NOAC plus clopidogrel combination therapy. The primary outcome is net adverse clinical event (NACE) at 1 year after randomization, defined as a composite of all-cause death, myocardial infarction, stent thrombosis, stroke, systemic embolism, and major or clinically relevant non-major bleeding, as defined by the International Society on Thrombosis and Hemostasis criteria. We hypothesize that NOAC monotherapy would be non-inferior to NOAC plus clopidogrel combination therapy for NACE in patients with AF beyond 12 months after DES implantation. CONCLUSIONS: The ADAPT AF-DES trial will evaluate the efficacy and safety of NOAC monotherapy versus NOAC plus clopidogrel combination therapy in patients with AF beyond 12 months after PCI with DES implantation. The ADAPT AF-DES trial will provide robust evidence for an optimal antithrombotic strategy in patients with AF after DES implantation. CLINICAL TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov. Unique identifier: NCT04250116.

How well do workplace-based assessments support summative entrustment decisions? A multi-institutional generalisability study.

BACKGROUND: Assessment of the Core Entrustable Professional Activities for Entering Residency requires direct observation through workplace-based assessments (WBAs). Single-institution studies have demonstrated mixed findings regarding the reliability of WBAs developed to measure student progression towards entrustment. Factors such as faculty development, rater engagement and scale selection have been suggested to improve reliability. The purpose of this investigation was to conduct a multi-institutional generalisability study to determine the influence of specific factors on reliability of WBAs. METHODS: The authors analysed WBA data obtained for clerkship-level students across seven institutions from 2018 to 2020. Institutions implemented a variety of strategies including selection of designated assessors, altered scales and different EPAs. Data were aggregated by these factors. Generalisability theory was then used to examine the internal structure validity evidence of the data. An unbalanced cross-classified random-effects model was used to decompose variance components. A phi coefficient of >0.7 was used as threshold for acceptable reliability. RESULTS: Data from 53 565 WBAs were analysed, and a total of 77 generalisability studies were performed. Most data came from EPAs 1 (n = 17 118, 32%) 2 (n = 10 237, 19.1%), and 6 (n = 6000, 18.5%). Low variance attributed to the learner (<10%) was found for most (59/77, 76%) analyses, resulting in a relatively large number of observations required for reasonable reliability (range = 3 to >560, median = 60). Factors such as DA, scale or EPA were not consistently associated with improved reliability. CONCLUSION: The results from this study describe relatively low reliability in the WBAs obtained across seven sites. Generalisability for these instruments may be less dependent on factors such as faculty development, rater engagement or scale selection. When used for formative feedback, data from these instruments may be useful. However, such instruments do not consistently provide reasonable reliability to justify their use in high-stakes summative entrustment decisions.

Effects of hydrogen permeation on the mechanical characteristics of electroless nickel-plated free-cutting steel for application to the hydrogen valves of hydrogen fuel cell electric vehicles.

Electroless nickel plating is a suitable technology for the hydrogen industry because electroless nickel can be mass-produced at a low cost. Investigating in a complex environment where hydrogen permeation and friction/wear work simultaneously is necessary to apply it to hydrogen valves for hydrogen fuel cell vehicles. In this research, the effects of hydrogen permeation on the mechanical characteristics of electroless nickel-plated free-cutting steel (SUM 24L) were investigated. Due to the inherent characteristics of electroless nickel plating, the damage (cracks and delamination of grain) and micro-particles by hydrogen permeation were clearly observed at the grain boundaries and triple junctions. In particular, the cracks grew from grain boundary toward the intergranualr. This is because the grain boundaries and triple junctions are hydrogen permeation pathways and increasing area of the hydrogen partial pressure. As a result, its surface roughness increased by a maximum of two times, and its hardness and adhesion strength decreased by hydrogen permeation. In particular, hydrogen permeation increased the friction coefficient of the electroless nickel-plated layer, and the damage caused by adhesive wear was significantly greater, increasing the wear depth by up to 5.7 times. This is believed to be due to the decreasing in wear resistance of the electroless nickel plating layer damaged by hydrogen permeation. Nevertheless, the Vickers hardness and the friction coefficient of the electroless nickel plating layer were improved by about 3 and 5.6 times, respectively, compared with those of the free-cutting steel. In particular, the electroless nickel-plated specimens with hydrogen embrittlement exhibited significantly better mechanical characteristics and wear resistance than the free-cutting steel.

Efficacy of Multimodal Analgesia with Transversus Abdominis Plane Block in Comparison with Intrathecal Morphine and Intravenous Patient-Controlled Analgesia after Robot-Assisted Laparoscopic Partial Nephrectomy.

Background: Robot-assisted laparoscopic partial nephrectomy (RAPN) for renal tumor treatment provides ergonomic advantages to surgeons and improves surgical outcomes. However, moderate-to-severe pain is unavoidable even after minimally invasive surgery. Despite the growing interest in multimodal analgesia, few studies have directly compared its efficacy with intrathecal morphine, a traditional opioid-based analgesic. Methods: We retrospectively investigated the efficacy of multimodal analgesia compared with that of intrathecal analgesia and intravenous patient-controlled analgesia (IV-PCA) in patients who underwent transperitoneal RAPN at our institute between 2020 and 2022. Among the 334 patients who met the inclusion criteria, intrathecal analgesia using morphine 200 µg was performed in 131 patients, and multimodal analgesia, including transversus abdominis plane block and intraoperative infusion of paracetamol 1 g and nefopam 20 mg, was administered to 105 patients. The remaining 98 patients received postoperative IV-PCA alone. Results: As the primary outcome, the area under the curve of pain scores over 24 h was significantly lower in the intrathecal analgesia and multimodal analgesia groups than in the IV-PCA group (89 [62-108] vs. 86 [65-115] vs. 108 [87-126] h, p < 0.001). Cumulative opioid requirements were also significantly lower in the intrathecal analgesia and multimodal analgesia groups at 24 h after surgery (p < 0.001). However, postoperative nausea and vomiting were significantly increased in the intrathecal analgesia group (27.5% vs. 13.3% vs. 13.3%, p = 0.005). Conclusions: Multimodal analgesia with a transversus abdominis plane block is an efficient analgesic method with fewer adverse effects compared to other analgesic methods. Our findings suggest the efficacy and safety of a multimodal approach for opioid-sparing analgesia after RAPN in the current opioid epidemic.

Long-term outcomes of percutaneous transluminal renal artery intervention: a retrospective study at a single center.

BACKGROUND: The indications, benefits, and outcomes of percutaneous transluminal renal artery intervention (PTRI) remain controversial. The study purpose was to evaluate the long-term outcomes of PTRI in clinical practice. METHODS: A retrospective review of 217 subjects (254 renal arteries; mean age, 59.8 years) who underwent PTRI based on medical database. RESULTS: The most common cause of renal artery stenosis was atherosclerosis in 217 (85.4%), followed by Takayasu arteritis (TA) in 23 (9.1%), fibromuscular dysplasia in five (2.0%) and others in nine (3.5%). Mean follow-up duration was 5.7 ± 3.7 years. The first restenosis rate was 7.5% (n = 19; highest in TA: n = 9, 47.4%) and second restenosis occurred in six arteries (five TAs, one fibromuscular dysplasia). Follow-up blood pressure improved from 142.0/83.5 to 122.8/73.5 mmHg (P < 0.001). There was no change within 5 years' follow-up in estimated glomerular filtration rate (P = 0.44), whereas TA changed from 69.8 ± 20.5 to 84.2 ± 17.9 mL/min/1.73 m² (P = 0.008). Progressive renal dysfunction was related to diabetes mellitus, chronic kidney disease, and peripheral artery obstructive disease on multivariate analysis with hazard ratios (95% confidence intervals) of 2.24 (1.21-4.17), 2.54 (1.33-4.84), and 3.93 (1.97-7.82), respectively. CONCLUSIONS: PTRI was associated with a blood pressure reduction. Despite a higher rate of restenosis, patients with TA showed significant improvement in estimated glomerular filtration rate. Diabetes mellitus, chronic kidney disease, and peripheral artery obstructive disease were related with progressive renal dysfunction after PTRI.

Feasibility study for the development of multilayered solar cells for proton linear energy transfer depth profile measurement.

BACKGROUND: Previous study proposed a method to measure linear energy transfer (LET) at specific points using the quenching magnitude of thin film solar cells. This study was conducted to propose a more advanced method for measuring the LET distribution. PURPOSE: This study focuses on evaluating the feasibility of estimating the proton LET distribution in proton therapy. The feasibility of measuring the proton LET and dose distribution simultaneously using a single-channel configuration comprising two solar cells with distinct quenching constants is investigated with the objective of paving the way for enhanced proton therapy dosimetry. METHODS: Two solar cells with different quenching constants were used to estimate the proton LET distribution. Detector characteristics (e.g., dose linearity and dose-rate dependency) of the solar cells were evaluated to assess their suitability for dosimetry applications. First, using a reference beam condition, the quenching constants of the two solar cells were determined according to the modified Birks equation. The signal ratios of the two solar cells were then evaluated according to proton LET in relation to the estimated quenching constants. The proton LET distributions of six test beams were obtained by measuring the signal ratios of the two solar cells at each depth, and the ratios were evaluated by comparing them with those calculated by Monte Carlo simulation. RESULTS: The detector characterization of the two solar cells including dose linearity and dose-rate dependence affirmed their suitability for use in dosimetry applications. The maximum difference between the LET measured using the two solar cells and that calculated by Monte Carlo simulation was 2.34 keV/µm. In the case of the dose distribution measured using the method proposed in this study, the maximum difference between range measured using the proposed method and that measured using a multilayered ionization chamber was 0.7 mm. The expected accuracy of simultaneous LET and dose distribution measurement using the method proposed in this study were estimated to be 3.82%. The signal ratios of the two solar cells, which are related to quenching constants, demonstrated the feasibility of measuring LET and dose distribution simultaneously. CONCLUSION: The feasibility of measuring proton LET and dose distribution simultaneously using two solar cells with different quenching constants was demonstrated. Although the method proposed in this study was evaluated using a single channel by varying the measuring depth, the results suggest that the proton LET and dose distribution can be simultaneously measured if the detector is configured in a multichannel form. We believe that the results presented in this study provide the envisioned transition to a multichannel configuration, with the promise of substantially advancing proton therapy's accuracy and efficacy in cancer treatment.

Cannabidiol Alleviates Chronic Prostatitis and Chronic Pelvic Pain Syndrome via CB2 Receptor Activation and TRPV1 Desensitization.

PURPOSE: This study elucidates the mechanism of the physiological effect of cannabidiol (CBD) by assessing its impact on lipopolysaccharide (LPS)-induced inflammation in RWPE-1 cells and prostatitis-induced by 17ß-estradiol and dihydrotestosterone in a rat model, focusing on its therapeutic potential for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). MATERIALS AND METHODS: RWPE-1 cells were stratified in vitro into three groups: (1) controls, (2) cells with LPS-induced inflammation, and (3) cells with LPS-induced inflammation and treated with CBD. Enzyme-linked immunosorbent assays and western blots were performed on cellular components and supernatants after administration of CBD. Five groups of six Sprague-Dawley male rats were assigned: (1) control, (2) CP/CPPS, (3) CP/CPPS and treated with 50 mg/kg CBD, (4) CP/CPPS and treated with 100 mg/kg CBD, and (5) CP/CPPS and treated with 150 mg/kg CBD. Prostatitis was induced through administration of 17ß-estradiol and dihydrotestosterone. After four weeks of CBD treatment, a pain index was evaluated, and prostate tissue was collected for subsequent histologic examination and western blot analysis. RESULTS: CBD demonstrated efficacy in vivo for CP/CPPS and in vitro for inflammation. It inhibited the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway by activating the CB2 receptor, reducing expression of interleukin-6, tumor necrosis factor-alpha, and cyclooxygenase-2 (COX2) (p<0.01). CBD exhibited analgesic effects by activating and desensitizing the TRPV1 receptor. CONCLUSIONS: CBD inhibits the TLR4/NF-κB pathway by activating the CB2 receptor, desensitizes the TRPV1 receptor, and decreases the release of COX2. This results in relief of inflammation and pain in patients with CP/CPPS, indicating CBD as a potential treatment for CP/CPPS.

Developing a national surveillance system for stroke and acute myocardial infarction using claims data in the Republic of Korea: a retrospective study.

BACKGROUND: Limited information is available concerning the epidemiology of stroke and acute myocardial infarction (AMI) in the Republic of Korea. This study aimed to develop a national surveillance system to monitor the incidence of stroke and AMI using national claims data. METHODS: We developed and validated identification algorithms for stroke and AMI using claims data. This validation involved a 2-stage stratified sampling method with a review of medical records for sampled cases. The weighted positive predictive value (PPV) and negative predictive value (NPV) were calculated based on the sampling structure and the corresponding sampling rates. Incident cases and the incidence rates of stroke and AMI in the Republic of Korea were estimated by applying the algorithms and weighted PPV and NPV to the 2018 National Health Insurance Service claims data. RESULTS: In total, 2,200 cases (1,086 stroke cases and 1,114 AMI cases) were sampled from the 2018 claims database. The sensitivity and specificity of the algorithms were 94.3% and 88.6% for stroke and 97.9% and 90.1% for AMI, respectively. The estimated number of cases, including recurrent events, was 150,837 for stroke and 40,529 for AMI in 2018. The age- and sex-standardized incidence rate for stroke and AMI was 180.2 and 46.1 cases per 100,000 person-years, respectively, in 2018. CONCLUSION: This study demonstrates the feasibility of developing a national surveillance system based on claims data and identification algorithms for stroke and AMI to monitor their incidence rates.

Cervi Parvum Cornu complex for men with lower urinary tract symptoms: a multicenter, randomized, double-blind, placebo-controlled trial.

Background: To evaluate the efficacy and safety of Cervi Parvum Cornu, Angelicae Gigantis Radix and Glycyrrhizae Radix complex (CAG) in men with moderate lower urinary tract symptoms (LUTS). Materials and methods: From November 2020 to January 2022, participants with International Prostate Symptom Score (IPSS) of 12-19 in two centers were recruited and randomize into three groups: a CAG 500 mg/day group (CAG 500), a CAG 1000 mg/day group (CAG 1000), and a placebo group (PG). They were treated for 12 weeks. The primary endpoint was change of IPSS at the end of study from baseline. Secondary end points included change of prostate specific antigen (PSA), testosterone, dihydrotestosterone (DHT), maximum urinary flow rate (Q max), post-void residual volume (PVR), International Index of Erectile Function (IIEF), and drug safety. Results: A total of 103 patients were able to finish the study according to the study protocol. Total IPSS and sub-scores (residual urine sensation, frequency, weak stream, hesistancy, nocturia, and quality of life) in CAG 500 and CAG 1000 were significantly improved at the 12th week compared to those of the PG. Changes of serum PSA, DHT, and testosterone levels at the 12th week from baseline did not show significant differences among the three groups. Q max and PVR changes did not show significant differences among the three groups either. Total IIEF and sub-scores (erectile function, orgasmic function, sexual desire, intercourse satisfaction) in CAG 1000 were significantly improved at 12th week compared to those in PG. No significant adverse events were found. Conclusions: CAG is well tolerated in patients with moderate LUTS. Treatment with CAG for 12 weeks has a therapeutic effect on moderate LUTS.