Standard Option Research Articles

Literacy Deep Reinforcement Learning-Based Federated Digital Twin Scheduling for the Software-Defined Factory

As user requirements become increasingly complex, the demand for product personalization is growing, but traditional hardware-centric production relies on fixed procedures that lack the flexibility to support diverse requirements. Although bespoke manufacturing has been introduced, it provides users with only a few standardized options, limiting its ability to meet a wide range of needs. To address this issue, a new manufacturing concept called the software-defined factory has emerged. It is an autonomous manufacturing system that provides reconfigurable manufacturing services to produce tailored products. Reinforcement learning has been suggested for flexible scheduling to satisfy user requirements. However, fixed rule-based methods struggle to accommodate conflicting needs. This study proposes a novel federated digital twin scheduling that combines large language models and deep reinforcement learning algorithms to meet diverse user requirements in the software-defined factory. The large language model-based literacy module analyzes requirements in natural language and assigns weights to digital twin attributes to achieve highly relevant KPIs, which are used to guide scheduling decisions. The deep reinforcement learning-based scheduling module optimizes scheduling by selecting the job and machine with the maximum reward. Different types of user requirements, such as reducing manufacturing costs and improving productivity, are input and evaluated by comparing the flow-shop scheduling with job-shop scheduling based on reinforcement learning. Experimental results indicate that in requirement case 1 (the manufacturing cost), the proposed method outperforms flow-shop scheduling by up to 14.9% and job-shop scheduling by 5.6%. For requirement case 2 (productivity), it exceeds the flow-shop method by up to 13.4% and the job-shop baseline by 7.2%. The results confirm that the literacy DRL scheduling proposed in this paper can handle the individual characteristics of requirements.

Targeting online sales through last‐mile delivery platform integration

AbstractWe analyze channel integration between a last‐mile delivery platform and a general merchandise retailer in two distinct stages: (1) platform delivery access (PDA), where the retailer continues to offer standard delivery through its own website but directs customers to the platform's website for new same‐day delivery; and (2) integrated delivery access (IDA), where customers can continue to use same‐day delivery service at the delivery platform website but can purchase products in a single order with both same‐day and standard delivery options at the retailer's website. We perform a quasi‐experiment using consumer spending data from retailer, target, and delivery platform, Shipt. We find that PDA provides positive impacts to the delivery platform through increased sales. IDA, on the other hand, increases the retailer's online channel sales but does not impact the delivery platform's sales. Moreover, we find that the positive effects of PDA on the delivery platform's sales are stronger in markets where online grocery penetration is lower, indicating that the effects were likely driven by increased purchases for groceries. Finally, the positive effect of IDA on the retailer's online channel sales is stronger in markets where the retailer has a greater loyal customer base and online grocery penetration is lower.

A Comparative study of anterior cruciate ligament repair effectiveness in proximal ACL tears

Background. Anterior cruciate ligament (ACL) reconstruction is a gold standard surgical option for ACL tears. Another go-to method is primary ACL repair. The latter has its own limitations such as small range of indications – proximal tears only, which constitute a significant portion of ACL injuries. Although the primary repair has been known for a long time and is still developing, recent publications show conflicting outcomes. Aim of study was to compare functional outcomes of patients with ACL reconstruction and primary repair. Methods. During 2020-2023 we conducted randomized prospective multicenter control comparative study which included 170 patients with ACL tear types A, B, E according to Gächter classification, with injuries no older than 3 months. Patients were divided into two groups: 1st group – primary repair of ACL, 2nd group – ACL reconstruction. Knee function was assessed before surgery and 3, 6, 12, 24 months after the treatment using the IKDC 2000 and Lyshlom Knee Score. Results. Type E ACL injury prevailed in the sample. The most common associated injury in both cohorts was medial meniscus tear (39,3±0,05% and 45,3±0,05%). 15,5±0,04% patients with primary repair had chondrolabral defects, reconstruction group – 10,5±0,03%. 46,03±0,06% of 2nd and 25,35±0,05% of 1st group (p0,05) received pain relief therapy in the form of opioid analgesics. The proportion of patients requiring reoperation for ACL injury in 1st group was 3,5%, in 2nd group – 1,2%. Both groups had a statistically significant increase in functional outcomes at 3, 6, 12 months (p0,05). The difference of knee function between groups was not statistically significant (p0,05). Conclusion. Primary ACL repair still retains a large number of limitations: it cannot and should not replace ACL reconstruction, but should be used with strict adherence to the indications and surgical technique to show comparable functional outcomes.

Magnitude, Matter, and Kant’s Principle of Mechanism

Abstract For Kant, inquiry into nature requires seeking to explain all material wholes merely mechanically, in terms of their parts. There is no consensus on how he justifies this Principle of Mechanism. I argue that Kant seeks to derive this claim about part and wholes neither from his laws of mechanics, nor from the mere discursivity of our understanding (two standard options in the literature), but instead from a priori principles laid out in the first Critique, which govern parts, wholes, and magnitudes. These principles are also fundamental to Kant’s account of mathematics. Therefore, Kant’s Principle of Mechanism and his philosophy of mathematics have common foundations.

Lessons Learned from Offering Video Visits as an Alternative to Phone Visits: A Case Study from a Safety-Net Obstetrics Clinics.

Before the Covid-19 pandemic, human-centered design work in San Francisco found video visits promising for Medicaid-insured pregnant individuals. They were deemed likely better than phone at addressing concerns about remoteness. We describe our experience with introducing video visits within a safety net clinic that had rapidly adopted phone visits as the standard telemedicine option early in the pandemic. By utilizing Kotter's change framework, providing an equity-focused vision, and supporting the implementation with a skilled, on-the-ground project manager, temporary uptake of offering video visits was achieved. However, competing priorities, staffing structure, and institutional culture were barriers to creating sustained change once grant funding ended, even after improvement of digital infrastructure. Efforts to increase video visit uptake in systems where telephone visits are the norm-as is in many safety net systems-may have limited success without leadership-driven prioritization and culture change at all levels.

Does the experience of the endoscopic vein harvester matter to the quality of the vein conduit: A critical thematic literature review.

Coronary artery bypass graft surgery remains the golden standard surgical option for multiple vessel disease. Harvesting the long saphenous vein using endoscopic vein harvesting requires advanced surgical skills dexterity, but the lack of a national standardised training programme allows for variance in the learning curve and the quality of the vein during the learning cycle is unknown. A search of bibliographic databases: CINHAL Plus, Embase, Pubmed and the Cochrane register for randomised controlled trials identified 11 articles eligible for review. The themes emerging were learning curve-associated injuries to the long saphenous vein, intimal wall remodelling of the long saphenous vein and incidence of graft patency rates. Harvesting practitioners with less than 100 cases of experience inflict more conduit injuries leading to endothelial remodelling and narrowed vein grafts at the six-month point resulting in lumen loss. Practitioners with more than 100 cases demonstrated reduced learning curve-related injuries on the conduit. Adopting a formalised structured training programme such as the Manchester Endoscopic Learning Tool has shown to reduce endothelial injury to the long saphenous vein minimising early vein graft failure during the learning cycle.

Pricing of timer volatility-barrier options under Heston’s stochastic volatility model

Timer options are financial instruments that enable investors to exercise their rights on a random maturity date the realized variance reaches the level of variance budget. These options provide a stable investment opportunity for investors under the unpredictable and complex financial markets, such as global financial crisis or COVID-19 pandemic, which can induce the drastic changes of the volatility for the underlying asset. Meanwhile, in the financial markets, investors who invest in standard timer options may face the problems caused by the postponement of the exercising time for too low volatility, compared to standard vanilla options. In this regard, to overcome such disadvantages, we propose timer volatility-barrier options, which are activated and expired when the volatility arrives at a relatively low barrier level, with the original properties of the standard timer options. In this paper, by making use of the method of images, we derive an analytical formulas for the timer volatility-barrier options so that the volatility process can be driven by Heston stochastic volatility model, and verify the pricing accuracy of the timer options by comparing our solutions with those obtained from Monte Carlo simulations. Finally, we conduct numerical studies on the timer volatility-barrier options to examine the pricing sensitivities with respect to the various model parameters, and implement the discussion for pricing formula of double volatility barrier type of the timer options.

The Smirnov Property for Weighted Lebesgue Spaces

We establish lower norm bounds for multivariate functions within weighted Lebesgue spaces, characterised by a summation of functions whose components solve a system of nonlinear integral equations. This problem originates in portfolio selection theory, where these equations allow one to identify mean-variance optimal portfolios, composed of standard European options on several underlying assets. We elaborate on the Smirnov property—an integrability condition for the weights that guarantees the uniqueness of solutions to the system. Sufficient conditions on weights to satisfy this property are provided, and counterexamples are constructed, where either the Smirnov property does not hold or the uniqueness of solutions fails.

Case Report: Spontaneous cornual Pregnancy at 7 Weeks: A Gynecological challenge

Introduction and Importance Cornual pregnancy (CP) is a rare and dangerous type of ectopic pregnancy, occurring in 2% to 4% of cases. Due to its atypical location in the uterine horn, it poses a high risk for severe complications, such as rupture of the uterus, and life-threatening bleeding, particularly when diagnosis is delayed. Case Presentation We report the case of a 35-year-old female patient presenting with severe pelvic pain and vaginal bleeding, with 12 weeks of amenorrhea. Clinical evaluation revealed elevated β-HCG levels and transvaginal ultrasound showed a 7-week unruptured right cornual pregnancy. Surgical management involved a mini-laparotomy, which confirmed the diagnosis and a cornuostomy along with a right salpingectomy was performed. The patient’s postoperative course was uneventful, and follow-up confirmed complete recovery. Clinical Discussion Cornual pregnancies, though rare, carry a significant risk of serious complications and maternal death due to delayed diagnosis. Risk factors encompass a history of miscarriage, elective abortion, sexually transmitted infections, and smoking, all contributing to abnormal implantation. Early diagnosis is challenging but crucial, with ultrasound being key for detection. Management depends on gestational age, patient stability, and future reproductive plans, with methotrexate or surgical intervention being standard options. Conclusion Cornual pregnancy, despite its rarity, demands prompt and accurate diagnosis to prevent catastrophic outcomes. This case underscores the need for individualized treatment strategies and highlights the importance of early intervention. Ongoing research is vital to improving diagnostic approaches and therapeutic outcomes.

Tabular review of contemporary fenestrated-branched endovascular aortic repair experiences for treatment of thoracoabdominal aortic aneurysms.

Repair of thoracoabdominal aortic aneurysms (TAAAs) represents a technical challenge regardless of which technique is used. Open surgical repair (OSR) is the time-tested option against which novel techniques must be compared and it is still considered the gold standard option for younger, fit patients with heritable aortic diseases. Endovascular repair offers a less-invasive alternative in patients with suitable anatomy. This article aims to present a tabular review of the contemporary published data on endovascular repair of TAAAs using fenestrated-branched techniques. The published literature for single-center and multicenter studies evaluating the outcomes of FB-EVAR for TAAAs was searched using MEDLINE and Embase databases. Studies published between January 1st 2010 and July 11th 2024, in the English language which provided data on FB-EVAR of TAAAs with more than fifty reported cases were included. The average patient age at time of repair was 71 years old with majority of males (65.5%). Most patients presented with a Crawford Extent II TAAAs (21.6%), followed by Extent III (21.2%). Early mortality was 4.9% for the entire cohort. The most prevalent adverse event was acute kidney injury (9.4%), followed by spinal cord injury (8.0%). FB-EVAR of TAAAs continues to evolve. Pooled analysis of early mortality and morbidity is lower in this tabular review than historical outcomes of open TAAA repair.

Algorithme thérapeutique des CBNPC sans mutation addictive

The development of immunotherapy in first-line therapy with anti-PD-1 and anti-PD-L1 has changed the first line treatment algorithm of advanced NSCLC. The anti-PD-(L)1 pembrolizumab, atezolizumab and cemiplimab clearly improve the overall survival in NSCLC with high PD-L1 expression (≥ 50 % of tumour cells), comparatively to cytotoxic chemotherapy. Combinations of anti-PD(L)-1 to platinum-based chemotherapy are superior to chemotherapy alone, regardless of PD-L1 level of expression. They represent the 1st line gold-standard when PD-L1 is expressed in less than 50 % of tumour cells and might reduce the risk of early disease progression in comparison with pembrolizumab when PD-L1 ≥ 50 %. The room for anti-CTLA-4 + anti-PD(L)-1 combinations which are not available in France remains to be established. Second-line treatment is currently based on chemotherapy, with a platinum-based doublet for patients treated in first line by pembrolizumab alone, and standard second-line chemotherapy options for patients treated by chemotherapy-immunotherapy combinations, i.e. docetaxel regardless of histology or pemetrexed for non-squamous cell carcinoma when not used in first line. Addition of an antiangiogenic agent to docetaxel only achieved a modest improvement of overall survival but neither nintedanib, nor docetaxel is available in France. Combination of paclitaxel and bevacizumab is also an option. Immunotherapy still benefits only a minority of patients whose identification is imperfect, underscoring the need for new strategies based on ne< combination amplifying the anti-tumour immune response as well as understanding the mechanisms of resistance to treatment in order to improve these results.1877-1203/© 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.

The Therapeutic Potential of Transdermal Gabapentin in the Symptomatic Management of Chronic Neuropathy

Standard pharmacotherapeutic options in the management of neuropathic pain are often poorly tolerated due to various contraindications, drug interactions, and troublesome adverse events. The investigation and pharmaceutical development of localized anti-neuropathic options is increasing among researchers and manufacturers, but results have not yet determined the role in therapy of transdermal/locally acting analgesics, anti-neuropathics, and anti-inflammatories. Compounding Pharmacies and FDA 503b Outsourcing Facilities aid in this critical endeavor through endogenous compounding and manufacturing (respectively) of transdermal analgesic formulations. This review summarizes the currently available clinical data supporting the implementation of transdermal gabapentin preparations in the management of chronic neuropathic symptoms. Transdermally applied analgesic, anti-inflammatory, and anti-neuropathic preparations are crucial in the development of pain management modalities which reduce the risk of numerous well-known complications, including drug-drug interactions, conflicting patient comorbidities, and CNS depressant effects. The adjunctive treatment of neuropathy with a transdermal analgesic/antispasmodic preparation remains under-investigated, and the role of these preparations in the management of chronic neuropathic pain remains unclear.

NRG1 Fusions in NSCLC: Being eNRGy Conscious.

Fusions in neuregulin 1 (NRG1) are rare oncogenic drivers that occur across a number of tumor types, including non-small cell lung cancer (NSCLC). NRG1 has an EGF-like domain that serves as a ligand for HER3 receptors, inducing heterodimerization, usually with HER2, and subsequent activation of oncogenic downstream signaling pathways. Emerging evidence suggests that NSCLC harboring NRG1 fusions do not respond as well to standard therapeutic options including chemotherapy and immunotherapy, and prognosis is poor. Novel treatment approaches targeting the HER2/HER3 pathway are under investigation. Here, we discuss the biology and detection of NRG1 fusions in NSCLC and promising targeted treatment strategies for tumors harboring the mutation.

Selective Implementation of Belatacept (Bela) Every Other Month as a Standard Care Option with the Use of Donor-Derived Cell-Free DNA (dd-cfDNA) Testing

Selective Implementation of Belatacept (Bela) Every Other Month as a Standard Care Option with the Use of Donor-Derived Cell-Free DNA (dd-cfDNA) Testing

TAS-102 (trifluridine/tipiracil) plus bevacizumab versus TAS-102 alone as salvage treatment options for metastatic colorectal cancer in routine clinical practice.

Both regimens of TAS-102 (trifluridine/tipiracil) with and without bevacizumab are considered standard options for salvage treatment in patients with refractory metastatic colorectal cancer. This analysis included patients with metastatic colorectal cancer who received either TAS-102 plus bevacizumab or TAS-102 alone between July 2022 and November 2023 at Samsung Medical Center. We evaluated the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety profile of both regimens. In total, 139 patients were included in this analysis. Median age was 60.8 years, and median number of previous lines of therapy was four (range: 2.45-6.55). More than half of the subjects (56.8%) had RAS mutations and 92.9% received previous anti-VEGF therapy. 83 (59.7%) patients received the combination of TAS-102 and bevacizumab and 56 (40.3%) received TAS-102 alone. The number of patients with prior regorafenib treatment was 14 in the TAS-102 with bevacizumab group and 5 in the TAS-102 alone group. The disease control rate was 51.8% in the combination group and 32.1% in the TAS-102 alone group. The median PFS was 3.3 months (95% CI, 2.7-6.6) in the combination group and 2.5 months (95% CI, 2.0-3.8) in the TAS-102 alone group (HR, 0.56; 95% CI, 0.38-0.82; p=0.003). The median OS in these two groups was 10.8 months (95% CI, 8.4-NA) and 6.0 months (95% CI, 4.8-9.8), respectively (HR, 0.62; 95% CI, 0.40-0.97, p=0.033). In the exploratory analysis of TAS-102 + Bev group, patients with the KRAS G12 mutation had inferior OS compared to those without the mutation (HR, 2.01, 95% CI, 1.04-3.90, p=0.035). Commonly observed adverse events were hematologic-related, including neutropenia, anemia, and thrombocytopenia, as well as nausea. While any grade neutropenia was observed at similar frequencies in the two groups (57.8% and 57.1%), grade 3 or higher neutropenia was more frequent in the combination group than the TAS-102 alone group (31.3% vs. 17.9%). Among patients who received subsequent anticancer therapy after treatment failure, 74.1% received regorafenib. The combination of TAS-102 and bevacizumab resulted in a better survival outcome than TAS-102 monotherapy, consistent with previous studies. This analysis supports the use of the combination of TAS-102 and bevacizumab as the best therapeutic option for patients with refractory metastatic colorectal cancer in clinical practice.

Experiences and perceptions of patients with cancer receiving home-based chemotherapy: a qualitative systematic review protocol

BackgroundHome-based chemotherapy (HBC) has emerged as a standard option for treating various types of cancer, primarily to decrease the waiting time for treatment. As HBC gains more recognition, ongoing research is delving into the experiences of patients with cancer who receive chemotherapy in a home setting or chemotherapy closer to home. Understanding these experiences is vital for the use of chemotherapy delivery outside the traditional hospital environments. This review aims to synthesize and critically appraise qualitative studies that investigate the experience and perspectives of patients with cancer who received parenteral chemotherapy administration in home settings. Findings will be used to develop evidence-based policies to support home-based care models.MethodsThis review will follow JBI methods for systematic reviews of qualitative evidence. The databases for searching will include MEDLINE (PubMed), CINAHL (EBSCOhost), PsycINFO (EBSCOhost), ProQuest Health and Medical Collection, two Chinese databases, CNKI and Wanfang, and one Thai database, ThaiJO. Studies published in English, Chinese, and Thai will be considered for inclusion. Two reviewers will independently undertake study selection, data extraction, and critical appraisal of the methodological quality of studies. The synthesized findings will be assessed using the ConQual approach.DiscussionThe synthesis of qualitative studies on this topic will provide insights into the nuanced and varied experiences of patients receiving chemotherapy within the comfort of their homes. The review will also provide evidence-based recommendations to policymakers and healthcare administrators, to support the implementation of HBC for patients.Systematic review registrationSystematic review registration: PROSPERO CRD42024500476.

Liver transplantation plus chemotherapy versus chemotherapy alone in patients with permanently unresectable colorectal liver metastases (TransMet): results from a multicentre, open-label, prospective, randomised controlled trial

Despite the increasing efficacy of chemotherapy, permanently unresectable colorectal liver metastases are associated with poor long-term survival. We aimed to assess whether liver transplantation plus chemotherapy could improve overall survival. TransMet was a multicentre, open-label, prospective, randomised controlled trial done in 20 tertiary centres in Europe. Patients aged 18-65 years, with Eastern Cooperative Oncology Group performance score 0-1, permanently unresectable colorectal liver metastases from resected BRAF-non-mutated colorectal cancer responsive to systemic chemotherapy (≥3 months, ≤3 lines), and no extrahepatic disease, were eligible for enrolment. Patients were randomised (1:1) to liver transplantation plus chemotherapy or chemotherapy alone, using block randomisation. The liver transplantation plus chemotherapy group underwent liver transplantation for 2 months or less after the last chemotherapy cycle. At randomisation, the liver transplantation plus chemotherapy group received a median of 21·0 chemotherapy cycles (IQR 18·0-29·0) versus 17·0 cycles (12·0-24·0) in the chemotherapy alone group, in up to three lines of chemotherapy. During first-line chemotherapy, 64 (68%) of 94 patients had received doublet chemotherapy and 30 (32%) of 94 patients had received triplet regimens; 76 (80%) of 94 patients had targeted therapy. Transplanted patients received tailored immunosuppression (methylprednisolone 10 mg/kg intravenously on day 0; tacrolimus 0·1 mg/kg via gastric tube on day 0, 6-10 ng/mL days 1-14; mycophenolate mofetil 10 mg/kg intravenously day 0 to <2 months and switch to everolimus 5-8 ng/mL), and postoperative chemotherapy, and the chemotherapy group had continued chemotherapy. The primary endpoint was 5-year overall survival analysed in the intention to treat and per-protocol population. Safety events were assessed in the as-treated population. The study is registered with ClinicalTrials.gov (NCT02597348), and accrual is complete. Between Feb 18, 2016, and July 5, 2021, 94 patients were randomly assigned and included in the intention-to-treat population, with 47 in the liver transplantation plus chemotherapy group and 47 in the chemotherapy alone group. 11 patients in the liver transplantation plus chemotherapy group and nine patients in the chemotherapy alone group did not receive the assigned treatment; 36 patients and 38 patients in each group, respectively, were included in the per-protocol analysis. Patients had a median age of 54·0 years (IQR 47·0-59·0), and 55 (59%) of 94 patients were male and 39 (41%) were female. Median follow-up was 59·3 months (IQR 42·4-60·2). In the intention-to-treat population, 5-year overall survival was 56·6% (95% CI 43·2-74·1) for liver transplantation plus chemotherapy and 12·6% (5·2-30·1) for chemotherapy alone (HR 0·37 [95% CI 0·21-0·65]; p=0·0003) and 73·3% (95% CI 59·6-90·0) and 9·3% (3·2-26·8), respectively, for the per-protocol population. Serious adverse events occurred in 32 (80%) of 40 patients who underwent liver transplantation (from either group), and 69 serious adverse events were observed in 45 (83%) of 54 patients treated with chemotherapy alone. Three patients in the liver transplantation plus chemotherapy group were retransplanted, one of whom died postoperatively of multi-organ failure. In selected patients with permanently unresectable colorectal liver metastases, liver transplantation plus chemotherapy with organ allocation priority significantly improved survival versus chemotherapy alone. These results support the validation of liver transplantation as a new standard option for patients with permanently unresectable liver-only metastases. French National Cancer Institute and Assistance Publique-Hôpitaux de Paris.

Is Oncoplastic Surgery Safe in High-Risk Breast Cancer Phenotypes?

Oncoplastic surgery (OPS) has increased in popularity over the recent years. It is a form of breast conservation surgery allowing for larger partial mastectomy (PM) resections followed by either volume displacement or volume replacement reconstruction techniques. However, there is a lack of evidence on the effectiveness and safety of OPS with radiotherapy (OPS + RT) in high-risk breast cancer phenotypes, such as triple negative breast cancer (TNBC) and HER2 positive (HER2+) patients. Our aim was to compare the breast cancer-specific survival (BCSS) and postoperative surgical complications in OPS + RT compared to PM alone with radiation (PM + RT) and total mastectomy (MTX) without radiotherapy (MTX-RT). Patient data were analyzed from the Surveillance, Epidemiology, and End Results (SEER) cancer registries from January 1, 2012 to December 31, 2020. Patients were stratified according to the type of surgery. Cox regression analysis was performed to assess prognostic factors of BCSS. A total of 24 621 patients with high-risk breast cancer phenotypes were identified, 180 underwent OPS + RT; 13 402, PM + RT; and 11 039 MTX-RT. OPS + RT was more frequently performed in younger (mean age of 65.53 years, SD: 9.29, p < 0.001), non-Hispanic White (90.5% vs. 77.7% vs. 76.3%) and single women (17.9% vs. 12.1% vs. 13.3%). MTX-RT was usually performed in patients with high histological grade, TNBC, and higher stages. Overall complication rates were higher in the MTX-RT, compared to OPS + RT and PM + RT, 2%, 1.1%, and 0.7%, respectively, p < 0.001. Rates of hematoma and surgical site infections were higher in the MTX-RT group. With a median follow-up of 46 months, OPS + RT had better BCSS rates at 5 years compared to PM + RT and MTX-RT (97.1% vs. 94.7% vs. 89.8%, p < 0.001). MTX-RT was found to be an independent prognostic factor of worse BCSS compared to OPS + RT (hazard ratio [HR] = 2.584; 95% confidence interval [CI]: 1.005-7.171), while PM + RT had no difference compared to OPS + RT (HR = 1.670, 95% CI: 0.624-4.469). OPS is a safe breast surgical option in patients with HER2+ and TNBC. Patients with high-risk phenotypes who underwent OPS + RT and have similar BCSS and complication rates compared to standard breast surgical options. As such, OPS should be considered as an option whenever breast conservation surgery is being discussed.

Clinical and economic analysis of the use of dapagliflozin in patients with chronic heart failure with reduced left ventricular ejection fraction in various subgroups of standard therapy in the Russian Federation

To evaluate the clinical and economic effectiveness of dapagliflozin in patients with chronic heart failure (CHF) with reduced left ventricular ejection fraction (HFrEF) in the Russian Federation in various subgroups of standard therapy for CHF. A clinical and economic analysis of the use of the drug dapagliflozin in addition to standard therapy was carried out in comparison with standard therapy in various subgroups of standard therapy for HFrEF using a modeling method. Cost calculations were carried out in a mathematical model adapted to the healthcare conditions of the Russian Federation by using Russian cost indicators and characteristics of the patient population. The present study demonstrates that the addition of dapagliflozin is beneficial in terms of clinical and cost-effectiveness, regardless of the initial regimen (angiotensin receptor-neprilysin inhibitors [ARNI] or angiotensin-converting enzyme inhibitors [ACEi]/angiotensin II receptor blockers [ARB]) of standard drug therapy for HFrEF and in all cases leads to an increase in life expectancy, a decrease in the number of hospitalizations and emergency visits due to CHF, as well as cardiovascular mortality. The obtained values of added value per additional year of life in all cases are significantly lower than the willingness-to-pay threshold, which indicates the clinical and economic effectiveness of the strategy of prescribing dapagliflozin as part of standard therapy for patients with HFrEF. In the case of adding dapagliflozin the values of the additional cost of an added year of life in the 3 considered standard therapy options (ARNI or ACEi/ARB, only ACEi/ARB and only ARNI) were 291,256, 279,571 and 338,374 rubles respectively. Thus, the scenario of using dapagliflozin with standard therapy, which included only ACEi/ARB, is characterized by the lowest additional cost and has the best clinical and economic characteristics. At the same time the scenario of use with standard therapy, which included only ARNI, is characterized by the highest value of the additional value of the added year of life.

The Fletcher-Cox Pathway: A Unique View on Clinical Trial Education

PurposeThere currently are no established formal mentorship and training program for radiation oncology (RO) trainees to learn trial design, creation, writing, or implementation. There only exists informal training on analyzing clinical trials in RO residency programs. The integration of a longitudinal formal training and mentorship program for clinical trialists - consisting of clinical trial education, design, mentorship, and implementation during the RO residency education will give residents not only formal teaching in the subject, but strong tools and requisite mentorship in hopes to help them succeed as future academic physicians and leaders in the field of radiation oncology. Methods and MaterialsWe developed a clinical trial training pathway in 2018 at XXX, proposing it as a pilot program. The “Fletcher-Cox Pathway” was accepted with a highly positive response by trainees. and is is now offered as a standard option to RO trainees at our institution. ResultsWith the guidance of their principal investigator (PI), residents participating in this pathway design and submit a clinical trial for institutional review board (IRB) review. In 2019, after implementation of the pilot program, 4 of the incoming 7 residents joined the pathway. The program continues, and the current cohort of trainees have received training in clinical trials design andworked with dedicated mentor(s) regarding clinical trial ideas; their studies are currently accruing patients. ConclusionsThis pilot program has been viewed by trainees and mentors as successful; it highlights how a structured approach meets a clear need within RO training. We envision the creation of a national platform to increase access, whereby programs adopt this clinical trialist educational pathway, which ultimately leads to the development of a robust clinical trial community with communal resources. We hope that this not only improves and provides educational initiatives to all trainees but also initiates further collaboration.