Preferred Option Research Articles

(280) Innovative Team Approach to Sexual Health Counseling; Partnership of Urology, Infectious Disease and Pelvic Floor Therapy to Increase Access to Care

Abstract Introduction Despite the prevalence and availability of HIV (Pre-exposure Prophylaxis i.e., PrEP), the number of new AIDS diagnoses continues to outpace treatment and prevention. Stigma, discrimination, lack of access continue to remain significant barriers in the prevention of new HIV infections, especially amongst vulnerable groups (i.e. LGBTQ, women, and minorities). We present a novel strategy to address a comprehensive approach to sexual health medicine through the partnership of Urology, Infectious Disease, and Pelvic Floor therapy. Objective Men who have sex with men (M2M) who either currently use or have an interests in use of pre-exposure prophylaxis (PrEP) continue to face barriers with respect to access to care, stigma, and or availability of effective partnerships to address and offer culturally competent care. The objective of this study is to assess attitudes and barriers to conventional and novel PrEP offerings as well as to present an innovative team approach between Urology, Infectious Disease (ID) Medicine and Pelvic Floor Therapy to offer a comprehensive multidisciplinary approach to treatment and care. Methods We enrolled 6 candidates (M2M) into our PrEP clinic which offers the Apretude (Cabotegivir 600 mg/3mL) injections. We conducted interviews, focused groups, and provided questionnaires to detail their experiences, beliefs, attitudes, barriers, and considerations for therapy. Results First, the preliminary results and findings of our study has shown that the needs, considerations, and beliefs of M2M is more varied, nuanced, and divergent with need to characterize, understand, and offer more specific culturally competent care in Sexual Health Medicine with respect to PrEP. Second, M2M designation does not exclude men from having sex with the opposite gender. These man preferred injectable PrEP option. Third, the partnership of Urology, Infectious Disease and Pelvic Floor Therapy reduced barriers, increased access to care, and decreased stigma as M2M felt more comfortable in the Urological setting. Conclusions M2M patients stated hesitancy, increased stigma and “shame” in going to ID for sexual health. Additionally, for M2M who have sexual partners of the opposite sex this would further increase stigma. Urology practices are accustomed to having discussions surrounding men’s sexual health with reduced stigma. The combination of Infectious Disease has presented an innovative partnership to discuss, prevent, and treat sexuallly transmited infections amongst M2M. Disclosure No.

INCIDENCE OF CONVERSION TO OPEN APPENDECTOMY FROM LAPAROSCOPIC APPENDECTOMY IN PREGNANT FEMALES

Acute appendicitis is a common non-obstetric indication for surgery in pregnant women, and the choice between laparoscopic and open appendectomy remains a subject of debate. While the benefits of laparoscopic appendectomy over open surgery are well-established in the non-pregnant population, consensus is lacking in the pregnant cohort. This study aims to contribute insights into the optimal surgical approach for acute appendicitis in pregnant women. The study, conducted from January 2020 to December 2022 at Nishtar Hospital, Multan, focused on 45 pregnant women presenting with abdominal pain and diagnosed with acute appendicitis. Two patients were discharged after magnetic resonance imaging (MRI) revealed a normal appendix. Of the remaining 43 cases, 27 were in the first trimester, 8 in the second trimester, and 8 in the third trimester. All patients underwent successful laparoscopic appendectomy without any conversion to open surgery. The laparoscopic procedure duration ranged from 50 to 80 minutes, with an average postoperative hospital stay of 1.5-3 days. Postoperative wound infection occurred in three patients (6.66%), and two patients (4.44%) experienced preterm labor. Fetal outcomes, assessed through Apgar grading, size, and weight, showed no notable abnormalities after birth. Laparoscopic appendectomy, regardless of gestational age, proves generally safe and suitable for pregnant women with acute appendicitis. The procedure has minimal complications, making it a viable and preferred option during pregnancy. These findings advocate for the continued consideration of laparoscopic appendectomy as a standard approach for managing acute appendicitis in pregnant patients.

Anterior vs Posterior Surgery for Patients With Degenerative Cervical Myelopathy: An Observational Study From the Canadian Spine Outcomes and Research Network.

The advantages and disadvantages of anterior vs posterior surgical approaches for patients with progressive degenerative cervical myelopathy (DCM) remain uncertain. Our primary objective was to evaluate patient-reported disability at 1 year after surgery. Our secondary objectives were to evaluate differences in patient profiles selected for each approach in routine clinical practice and to compare neurological function, neck and arm pain, health-related quality of life, adverse events, and rates of reoperations. We analyzed data from patients with DCM who were enrolled in an ongoing multicenter prospective observational cohort study. We controlled for differences in baseline characteristics and numbers of spinal levels treated using multivariable logistic regression. Adverse events were collected according to the Spinal Adverse Events Severity protocol. Among 559 patients, 261 (47%) underwent anterior surgery while 298 (53%) underwent posterior surgery. Patients treated posteriorly had significantly worse DCM severity and a greater number of vertebral levels involved. After adjusting for confounders, there was no significant difference between approaches for odds of achieving the minimum clinically important difference for the Neck Disability Index (odds ratio 1.23, 95% CI 0.82 to 1.86, P = .31). There was also no significant difference for change in modified Japanese Orthopedic Association scores, and differences in neck and arm pain and health-related quality of life did not exceed minimum clinically important differences. Patients treated anteriorly experienced greater rates of dysphagia, whereas patients treated posteriorly experienced greater rates of wound complications, neurological complications, and reoperations. Patients selected for posterior surgery had worse DCM and a greater number of vertebral levels involved. Despite this, anterior and posterior surgeries were associated with similar improvements in disability, neurological function, pain, and quality of life. Anterior surgery had a more favorable profile of adverse events, which suggests it might be a preferred option when feasible.

An unusual complication after transcatheter aortic valve implantation: a case report

Abstract Background Ventricular septal defect (VSD) is an unusual complication of transcatheter aortic valve implantation (TAVI). The risk factors are not well understood but may include oversizing, calcification amount and location, left-ventricular chamber morphology, and valve-in-valve (ViV) procedures. Percutaneous treatment is challenging but is usually the preferred option. Case summary An 80-year-old woman with two previous surgical aortic valve replacements was admitted to our Cardiology Department for decompensated heart failure. New bioprosthesis degeneration (19 mm Mitroflow™, Sorin Group, Canada) was observed with severe intraprosthetic aortic regurgitation. After evaluation, the heart team chose to perform ViV TAVI. Because of the high risk of coronary obstruction, chimney stenting of both coronary arteries was performed. A 23 mm self-expandable Navitor™ valve (Abbott, IL, USA) was implanted, but the Mitroflow™ valve had to be cracked to minimize the persistent high gradient. During valve fracture, the non-compliant balloon broke and a small iatrogenic VSD appeared. However, the patient remained stable, so conservative management was selected. During follow-up, she developed severe haemolytic anaemia and heart failure; therefore, percutaneous closure of the iatrogenic VSD was performed twice, which was a difficult challenge. Discussion A viable alternative to redo surgery is ViV TAVI. Risks include higher rates of prosthesis–patient mismatch and coronary obstruction. Occasionally, bioprosthetic valve fracture is required, particularly in small bioprostheses, to achieve low gradients. Anecdotally, fracture has led to annular rupture and VSD. Most VSDs are small and without clinical or haemodynamic repercussions; however, in symptomatic cases, percutaneous closure is a viable alternative to surgery.

TransCatheter aortic valve implantation and fractional flow reserve-guided percutaneous coronary intervention versus conventional surgical aortic valve replacement and coronary bypass grafting for treatment of patients with aortic valve stenosis and multivessel or advanced coronary disease: The transcatheter valve and vessels trial (TCW trial): Design and rationale

Background: Patients with severe aortic stenosis (AS) frequently present with concomitant obstructive coronary artery disease (CAD). In those, current guidelines recommend combined coronary artery bypass grafting (CABG) and surgical aortic valve replacement (SAVR) as the preferred treatment option, although this surgical approach is associated with a high rate of clinical events. Combined transcatheter aortic valve implantation (TAVI) and percutaneous coronary intervention (PCI) with or without FFR have evolved as a valid alternative for cardiac surgery in patients with AS and multivessel or advanced CAD. To date, no dedicated trial has prospectively evaluated the outcomes of a percutaneous versus surgical treatment for patients with both severe AS and CAD. Aims: To investigate whether fractional-flow reserve (FFR)-guided PCI and TAVI is non-inferior to combined CABG and SAVR for the treatment of severe AS and multivessel or advanced CAD. Methods: The Transcatheter Valve and Vessels (TCW) trial (clinicaltrial.gov: NCT03424941) is a prospective, randomized, controlled, open label, international trial. Patients ≥ 70 years with severe AS and multivessel (≥ 2 vessels) or advanced CAD, deemed feasible by the heart team for both; a full percutaneous or surgical treatment, will be randomised in a 1:1 fashion to either FFR-guided PCI followed by TAVI (intervention arm) vs. CABG and SAVR (control arm). The primary endpoint is a patient-oriented composite of all-cause mortality, myocardial infarction, disabling stroke, unscheduled clinically-driven target vessel revascularization, valve re-intervention, and life threatening or disabling bleeding at one year. The TCW trial is powered for non-inferiority, and if met, superiority will be tested. Assuming a primary endpoint rate of 30% in the CABG-SAVR arm, with a significance level α of 5%, a non-inferiority limit delta of 15% and a loss to follow-up of 2%, a total of 328 patients are needed to obtain a power of 90%. The primary endpoint analysis is performed on an intention-to-treat basis. Summary: The TCW Trial is the first prospective randomized trial that will study if a less invasive percutaneous treatment for severe AS and concomitant advanced CAD (i.e., FFR-guided PCI - TAVI) is non-inferior to the guidelines recommended approach (CABG-SAVR).

Estimation of Circular Statistics in the Presence of Measurement Bias.

Circular statistics and Rayleigh tests are important tools for analyzing cyclic events. However, current methods are not robust to significant measurement bias, especially incomplete or otherwise non-uniform sampling. One example is studying 24-cyclicity but having data not recorded uniformly over the full 24-hour cycle. Our objective is to present a robust method to estimate circular statistics and their statistical significance in the presence of incomplete or otherwise non-uniform sampling. Our method is to solve the underlying Fredholm Integral Equation for the more general problem, estimating probability distributions in the context of imperfect measurements, with our circular statistics in the presence of incomplete/non-uniform sampling being one special case. The method is based on linear parameterizations of the underlying distributions. We simulated the estimation error of our approach for several toy examples as well as for a real-world example: analyzing the 24-hour cyclicity of an electrographic biomarker of epileptic tissue controlled for states of vigilance. We also evaluated the accuracy of the Rayleigh test statistic versus the direct simulation of statistical significance. Our method shows a very low estimation error. In the real-world example, the corrected moments had a root mean square error of [Formula: see text]. In contrast, the Rayleigh test statistic overestimated the statistical significance and was thus not reliable. The presented methods thus provide a robust solution to computing circular moments even with incomplete or otherwise non-uniform sampling. Since Rayleigh test statistics cannot be used in this circumstance, direct estimation of significance is the preferable option for estimating statistical significance.

Comparative effectiveness of biologics in patients with rheumatoid arthritis stratified by body mass index: a cohort study in a Swiss registry

ObjectivesObesity is associated with lower treatment response in patients with rheumatoid arthritis (RA). In patients with obesity, abatacept was suggested as a preferable option to tumour necrosis factor-alpha inhibitors. We...

Probing corrosion protective mechanism of an amide derivative additive on anode for enhanced alkaline Al-air battery performance

Screening green corrosion inhibitors to prevent Al anode corrosion is essential for the development of high-performance Al-air batteries. This paper explores the potential of amide derivative, thiobenzamide (TBA), as the corrosion inhibitor for Al anode, and provides a universal and preferred option for improving Al-air batteries. An array of techniques were employed to probe the inhibition effect of TBA for Al-air battery in 4 M NaOH electrolyte. It is encouraging that TBA as a mixed-type corrosion inhibitor reached the inhibition efficiency of 67.8 % at an optimum addition of 0.07 M, and the specific capacity of Al-air battery dramatically increased from 461.9 mAh·g−1 (for the uninhibited system) to 1532.6 mAh·g−1 (for the TBA added system). The results of X-ray photoelectron spectroscopy (XPS) combined with ab initio molecular dynamics (AIMD) confirm that TBA can be adsorbed on the surface of Al to form a protective film, thus preventing the hydrogen evolution self-corrosion of Al anode. Herein the adsorption behavior occurred mainly through the Al–S–Al and N–Al bonding interaction between S/N atoms in TBA and Al atoms on Al surface based on the investigation of coordination numbers. The computational modeling analysis has revealed an electrolyte regulation way to improve the performance of Al-air batteries in alkaline medium.

What Do We Know and How Much Do We Know About the Intricate Relationship Between Price Discounts and Financial Performance of Online Sellers in India

Purpose: Retailing has become the backbone of economies worldwide, and is the employer of the majority. Today retailing has become a necessity for consumers for the seamless digital shopping experience it is providing today. This review focuses on technological advancements, changing consumer preferences, and economic shifts that have shaped the growth of retailing from offline to online. Design/Methodology/Approach: The interpretivism approach is used to reach the research objective and derive conclusions without bias through content analysis. Finding/Result: Online retailing has undoubtedly become the consumer's first preference for shopping because of the various benefits and privileges offered to them by these platforms. It is not only the mere success in sales but also the e-retailing that has significantly focused on customer satisfaction by offering diversified products at an affordable range making them the most preferred option for the shopping experience by the customers. There is relatively scant evidence to support general assertions concerning the price discounts (cause) offered by online sellers/external brands (unit of analysis) on an online marketplace (E-retailers/Online retailers) and their financial performance (effect). Originality/Value: Various researchers have studied in the view of the success or growth pattern of offline and online retail. This research has tried to find out the research gap and make it an objective for further research. Paper Type: Content analysis

Reperfusion in Patients With ST-Segment-Elevation Myocardial Infarction With Cardiogenic Shock and Prolonged Interhospital Transport Times.

In patients with ST-segment-elevation myocardial infarction complicated by cardiogenic shock, primary percutaneous coronary intervention (pPCI) is the preferred revascularization option. Little is known about the efficacy and safety of a pharmacoinvasive approach for patients with cardiogenic shock presenting to a non-PCI hospital with prolonged interhospital transport times. In a retrospective analysis of geographically extensive ST-segment-elevation myocardial infarction network (2006-2021), 426 patients with cardiogenic shock and ST-segment-elevation myocardial infarction presented to a non-PCI-capable hospital and underwent reperfusion therapy (53.8% pharmacoinvasive and 46.2% pPCI). The primary clinical outcome was a composite of in-hospital mortality, renal failure requiring dialysis, cardiac arrest, or mechanical circulatory support, and the primary safety outcome was major bleeding defined as an intracranial hemorrhage or bleeding that required transfusion was compared in an inverse probability weighted model. The electrocardiographic reperfusion outcome of interest was the worst residual ST-segment-elevation. Patients with pharmacoinvasive treatment had longer median interhospital transport (3 hours versus 1 hour) and shorter median symptom-onset-to-reperfusion (125 minute-to-needle versus 419 minute-to-balloon) times. ST-segment resolution ≥50% on the postfibrinolysis ECG was 56.6%. Postcatheterization, worst lead residual ST-segment-elevation <1 mm (57.3% versus 46.3%; P=0.01) was higher in the pharmacoinvasive compared with the pPCI cohort, but no differences were observed in the worst lead ST-segment-elevation resolution ≥50% (77.4% versus 81.8%; P=0.57). The primary clinical end point was lower in the pharmacoinvasive cohort (35.2% versus 57.0%; inverse probability weighted odds ratio, 0.44 [95% CI, 0.26-0.72]; P<0.01) compared with patients who received pPCI. An interaction between interhospital transfer time and reperfusion strategy with all-cause mortality was observed, favoring a pharmacoinvasive approach with transfer times >60 minutes. The incidence of the primary safety outcome was 10.1% in the pharmacoinvasive arm versus 18.7% in pPCI (adjusted odds ratio, 0.41 [95% CI, 0.14-1.09]; P=0.08). In patients with ST-segment-elevation myocardial infarction presenting with cardiogenic shock and prolonged interhospital transport times, a pharmacoinvasive approach was associated with improved electrocardiographic reperfusion and a lower rate of death, dialysis, or mechanical circulatory support without an increase in major bleeding.

Evolutionary game analysis of carbon emission reduction of Internet enterprises under multiple constraints.

With the rapid development of information technology, internet enterprises have sprung up, bringing about huge power consumption due to constantly expanding enterprise scale, which in turn leads to significant carbon emissions. Additionally, the large influence of internet enterprises on the public and other businesses makes it particularly necessary to pay attention to their carbon emission reduction efforts. To explore the evolution path and patterns of carbon emission reduction among internet enterprises under the carbon neutrality goal, this paper constructs an evolutionary game model for internet enterprises to enter the carbon emissions trading market based on Externality and Sustainable Development Theories, while considering constraints from the carbon market, financial institutions and the public. The model utilizes Python 3.8.2 software for numerical simulations, aiming to push internet enterprises towards low-carbon development. The research findings indicate that: (1) Carbon emission reduction behavior of internet enterprises exhibits significant externality, and when constraints are weak or incentives are not evident, the motivation for enterprises to reduce carbon emissions is insufficient. (2) The carbon market can effectively promote carbon emission reduction among internet enterprises, and the strategy of entering the carbon market becomes the preferred option for these enterprises gradually. (3) Multiple constraints, including emission reduction costs, penalty for non-compliance, government subsidies, financing costs, opportunity losses, and reputation losses, can force internet enterprises towards low-carbon development.

Trans-lateral ventricular approach for surgical treatment of high-located P2–P3 junction posterior cerebral artery aneurysms: from anatomical research to clinical application

BackgroundPosterior cerebral artery (PCA) aneurysms, though rare, pose treatment challenges. Endovascular therapy is the preferred option, but microsurgery becomes necessary in certain cases. Various microsurgical approaches have been suggested for PCA aneurysms, particularly those at the P2–P3 junction. This study highlights the trans-lateral ventricular approach (TVA) for addressing these complex aneurysms. This study aims to assess the feasibility and safety of the trans-lateral ventricular approach (TVA) for treating high-located complex PCA aneurysms at the P2–P3 junction. The study evaluates both clinical outcomes and anatomical considerations.MethodsTwo cases of PCA aneurysms at the P2–P3 junction were treated using TVA in 2019. Navigation-guided entry via the interparietal sulcus was planned. Ventriculostomy was performed from the cortex to the lateral ventricle’s atrium. Medial atrial floor dissection exposed PCA’s P2–P3 segments. Neuronavigation and ultrasound-aided guidance was used. Anatomical studies on fixed and contrast-perfused specimens refined the approach.ResultsBoth cases saw successful aneurysm clipping. The unruptured aneurysm patient was discharged in 6 days. The poor-grade SAH patient required extended ICU care, moving to rehabilitation with mRS = 4. The unruptured complex aneurysm case exhibited no deficits, returning to work in 3 months. Anatomical dissections validated TVA for high-located P2–P3 junction PCA aneurysms.ConclusionWhile endovascular therapy remains primary, this study demonstrates the viability of navigation-guided TVA for select high-located P2–P3 junction PCA aneurysms. Successes and challenges underscore the importance of patient selection and anatomical awareness.

Comparison of percutaneous nephrolithotomy and flexible ureterorenoscopy in the treatment of single upper ureteral calculi measuring 1 to 2 centimeters: a retrospective study

PurposeTo compare the efficacy and safety of micropercutaneous nephrolithotomy (MPCNL) and flexible ureteroscopy (FURS) in the treatment of single upper ureteral calculi measuring 1 to 2 centimeters.MethodsThis study is a retrospective analysis that combines a review of medical records with an outcomes management database. A total of 163 patients who underwent MPCNL and 137 patients who had FURS were identified between January 2017 and December 2021. Demographic data, operation time, hospitalization time, stone-free rate, and complication rate were collected and analyzed.ResultsPreoperative general data of sex, age, BMI, serum creatinine, time of stone existence, stone hardness, stone diameter, preoperative hydronephrosis, and preoperative infection of the MPCNL group have no statistically significant difference with that of the FURS group. All MPCNL or FURS operations in both groups were successfully completed without any instances of reoperation or conversion to another surgical procedure. Patients who underwent MPCNL had a considerably reduced operation time (49.6 vs. 72.4 min; P<0.001), but a higher duration of hospitalization (9.1 vs. 3.9 days; P<0.001) compared to those who underwent FURS. The stone-free rate in the MPCNL group was superior to that of the FURS group, with a percentage of 90.8% compared to 71.5% (P<0.001). There was no statistically significant disparity in the rate of complications between the two groups (13.5% vs. 15.3%; P = 0.741).ConclusionBoth MPCNL and FURS are viable and secure surgical choices for individuals with solitary upper ureteral calculi measuring 1 to 2 cm. The FURS procedure resulted in a shorter duration of hospitalization compared to MPCNL. However, it had a comparatively lower rate of successfully removing the stones and required a longer duration for the operation.There were no substantial disparities observed in the complication rate between the two groups.FURS is the preferable option for treating uncomplicated upper ureteral calculi, whereas MPCNL is the preferable option for treating complicated upper ureteral calculi.Prior to making treatment options, it is crucial to take into account the expertise of surgeons, the quality of the equipment, and the preferences of the patient.Trial registrationNo.

Unraveling the efficacy network: A network meta-analysis of adjuvant external beam radiation therapy methods after hepatectomy.

Primary liver cancer is a malignant tumor with a high recurrence rate that significantly affects patient prognosis. Postoperative adjuvant external radiation therapy (RT) has been shown to effectively prevent recurrence after liver cancer resection. However, there are multiple RT techniques available, and the differential effects of these techniques in preventing postoperative liver cancer recurrence require further investigation. To assess the advantages and disadvantages of various adjuvant external RT methods after liver resection based on overall survival (OS) and disease-free survival (DFS) and to determine the optimal strategy. This study involved network meta-analyses and followed the PRISMA guidelines. The data of qualified studies published before July 10, 2023, were collected from PubMed, Embase, the Web of Science, and the Cochrane Library. We included relevant studies on postoperative external beam RT after liver resection that had OS and DFS as the primary endpoints. The magnitudes of the effects were determined using risk ratios with 95% confidential intervals. The results were analyzed using R software and STATA software. A total of 12 studies, including 1265 patients with hepatocellular carcinoma (HCC) after liver resection, were included in this study. There was no significant heterogeneity in the direct paired comparisons, and there were no significant differences in the inclusion or exclusion criteria, intervention measures, or outcome indicators, meeting the assumptions of heterogeneity and transitivity. OS analysis revealed that patients who underwent stereotactic body radiotherapy (SBRT) after resection had longer OS than those who underwent intensity modulated radiotherapy (IMRT) or 3-dimensional conformal RT (3D-CRT). DFS analysis revealed that patients who underwent 3D-CRT after resection had the longest DFS. Patients who underwent IMRT after resection had longer OS than those who underwent 3D-CRT and longer DFS than those who underwent SBRT. HCC patients who undergo liver cancer resection must consider distinct advantages and disadvantages when choosing between SBRT and 3D-CRT. IMRT, a RT technique that is associated with longer OS than 3D-CRT and longer DFS than SBRT, may be a preferred option.

A cost-effectiveness analysis of the combination of serplulimab with chemotherapy for advanced esophageal squamous cell carcinoma: insights from the ASTRUM-007 trial

BackgroundCombined serplulimab and chemotherapy demonstrated improved clinical survival outcomes in patients with advanced esophageal squamous cell carcinoma (ESCC) and PD-L1 combined positive scores (CPS) ≥ 1. The present study aimed to evaluate the economic viability of integrating serplulimab in combination with chemotherapy as a potential therapeutic approach for treating ESCC in China.MethodsA Markov model was constructed to evaluate the economic and health-related implications of combining serplulimab with chemotherapy. With the incremental cost-effectiveness ratio (ICER), costs and results in terms of health were estimated. For assessing parameter uncertainty, one-way and probabilistic sensitivity studies were carried out.ResultsThe combination of serplulimab and chemotherapy yielded incremental costs and QALYs of $3,163 and 0.14, $2,418 and 0.10, and $3,849 and 0.15, respectively, for the overall population as well as patients with PD-L1 CPS1-10 and PD-L1 CPS ≥ 10. This corresponds to ICER values per QALY of $23,657, $23,982, and $25,134. At the prespecified WTP limit, the probabilities of serplulimab with chemotherapy being the preferred intervention option were 74.4%, 61.3%, and 78.1% for the entire patient population, those with PD-L1 1 ≤ CPS < 10, and those with PD-L1 CPS ≥ 10, respectively. The stability of the presented model was confirmed through sensitivity studies.ConclusionsIn conclusion, the combination of Serplulimab and chemotherapy showed excellent cost-effectiveness compared to chemotherapy alone in treating PD-L1-positive patients with ESCC in China.

COST-EFFECTIVENESS ANALYSIS OF MIRIKIZUMAB VERSUS USTEKINUMAB IN ADVANCED THERAPY EXPERIENCED PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS IN THE US

Abstract BACKGROUND Mirikizumab, an interleukin (IL)-23p19 inhibitor, demonstrated efficacy compared to placebo in clinical trials in adult patients with moderately to severely active ulcerative colitis (UC). Mirikizumab is expected to receive approval from the United States (US) Food and Drug Administration in 2023. Ustekinumab, an IL12/23 antagonist, is the preferred option in advanced therapy (AT; biologics, novel targeted systemics) experienced patients. OBJECTIVES To evaluate the cost effectiveness of mirikizumab compared to ustekinumab in the US among patients diagnosed with moderately to severely active UC who have been previously treated with AT. METHODS A Markov model was developed in MS Excel, comprising an AT layer, a second line (2L) AT layer, a conventional treatment (CT) layer, and a surgery layer. Following initial induction (2-week cycle length), responders transition to maintenance, while non-responders transition to induction in 2L, consisting of a weighted mix of ATs used in clinical practice according to market shares, or CT. During the maintenance phase (12-week cycle length), the AT layers include remission and non-remission response health states; patients who lose response transition to the 2L, CT or surgery layer, comprising surgery and post-surgery health states. Death is possible from all health states, as per US 2020 national life tables. Probabilities for remission, non-remission response at the end of induction, and transition probabilities during maintenance were derived from a network meta-analysis and published literature, as were health state utilities. The analysis from a US payer's perspective over a lifetime horizon considered only direct medical costs in 2023 US dollars (USD). Costs and outcomes were discounted at 3%. Sensitivity analyses were performed; scenario analyses explored the impact of re-induction, dose escalation, and including societal costs. RESULTS Mirikizumab resulted in lower total costs (USD 1,232,582) and more quality-adjusted life-years (QALYs) (10.352) when compared to ustekinumab at standard doses (USD 1,279,620; 10.247 QALYs). Key drivers of cost savings (USD -47,038) and higher QALYs (0.105) for mirikizumab were assumptions on loss of response, the efficacy of mirikizumab at induction and the price of mirikizumab. The probability that mirikizumab is cost-effective at a willingness to pay threshold of USD 100,000 per QALY gained was 74.9%. Adopting an escalated dose for ustekinumab and re-induction for mirikizumab considerably increased savings. CONCLUSIONS The analyses provided insights into the cost-effectiveness of mirikizumab compared to ustekinumab in the US for patients with moderately to severely active UC previously treated with AT. Results demonstrated that adopting mirikizumab can be considered cost-effective compared to ustekinumab, contributing to decision-making in healthcare management.

P779 Long term efficacy of azathioprine monotherapy in patients with Inflammatory Bowel Disease

Abstract Background ECCO guidelines recommend monotherapy with azathioprine (AZA) as maintenance therapy of patients with inflammatory bowel disease (IBD) mainly in steroid-dependent disease. However, in the era of the new advanced treatments AZA is not considered as a preferable option, mainly because of the referred side effects and its use is limited in combination with biologic agents. Methods This is a retrospective observational study using data from the longitudinal, prospective IBD registry of University Hospital of Heraklion, Greece. Our aim was to study IBD patients who started on monotherapy with AZA, the profile of adverse effects they developed, the treatment persistence in monotherapy, as well as the possible related factors of treatment success [including age, gender, smoking status, body mass index, disease type, disease phenotype for Crohn’s disease (CD), history of IBD related surgery and the presence of extraintestinal manifestations]. Results Of 168 IBD patients treated with AZA, 89 (53%) were under AZA monotherapy [38 (43%) female, 67 (74%) CD, median age (IQR) 47 (32-56) years, mean (±SD) disease duration 17 (±8.4) years, median (IQR) time receiving AZA 72 (7-120) months]. Thirty (34%) patients continue their treatment till now (23 CD, 7 ulcerative colitis-UC), with a median time (IQR) of 108 (81-132) months. Of these, 18 (60%) (15 with CD and 3 with UC) present endoscopic remission and 11 (36%) (8 with CD, 3 with UC) mild endoscopic activity (based on SES-CD Score for CD and Mayo endoscopic score for UC). Of the 59 who discontinued, 33 (37%) experienced adverse events, 5 (5.5%) developed malignancy, 5 (5.5%) did not respond at baseline, 6 (6.5%) had loss of response (at a median of 91 months), 3 (3%) discontinued due to advanced age, 3 (3%) discontinued their medication on their own and 2 because of treatment de-escalation due to deep remission. Using logistic regression analysis, patients who responded to AZA monotherapy were patients without a history of IBD surgery or any extraintestinal manifestation, P=0.001 and 0.004, respectively. In the multivariate analysis, these associations remained statistically significant (P=0.01 and 0.006 respectively). Conclusion About one third of patients with IBD under AZA monotherapy experience long term response and about two thirds of them prolonged disease remission. Patients without either a history of IBD surgery or extraintestinal manifestations seem to respond better to AZA monotherapy.

P1050 A cost-utility analysis of ferric derisomaltose versus ferric carboxymaltose in patients with inflammatory bowel disease and iron deficiency anaemia in Finland

Abstract Background Anaemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD), with iron deficiency being the most common cause. Iron deficiency anaemia (IDA) can be treated with oral iron, but where oral administration is contraindicated, not tolerated, or proves to be ineffective, intravenous (IV) iron is the preferred treatment option, facilitating rapid iron replenishment. Ferric derisomaltose (FDI) and ferric carboxymaltose (FCM) are two high-dose, rapid-infusion, IV iron formulations that have recently been compared in three head-to-head randomized controlled trials (RCTs), with FCM administration resulting in significantly higher hypophosphataemia incidence versus FDI, and phosphate monitoring after repeat FCM infusions is now recommended in the FCM product information (PI). Between 2000 and 2020, Finland has seen the average incidence of IBD increase by 2.4% annually, accompanied by a commensurate increase in sequelae such as IDA. The objective of the present study was therefore to evaluate the cost-utility of FDI versus FCM in patients with IBD and IDA in Finland. Methods A published patient-level simulation model was used to evaluate the cost-utility of FDI versus FCM in Finland. The model captured quality of life differences based on SF-36 data from the PHOSPHARE-IBD RCT and differences in the number of FDI and FCM infusions required. A Finnish societal perspective was adopted and the analysis was conducted over a five-year time horizon. Unit costs were obtained from publicly available Finnish sources. Costs were reported in 2022 Euros and a discount rate of 3% per annum was applied to future costs and effects. Results Over the five-year time horizon, patients received 3.95 courses of iron treatment on average, requiring 1.63 fewer infusions of FDI than FCM (5.57 versus 7.20). This resulted in iron procurement and administration cost savings of EUR 471 with FDI versus FCM (EUR 2,286 versus EUR 2,757). Differences in health-related quality of life and the number of IV iron infusions resulted in an increase of 0.076 quality-adjusted life years with FDI versus FCM. Further cost savings of EUR 273 over five years were also realised with FDI versus FCM, driven by reduced need for phosphate testing (saving EUR 90) and reduced travel and productivity loss (saving EUR 183). Total cost savings were EUR 745 (Figure) and FDI was therefore the dominant intervention. Conclusion Relative to FCM, FDI resulted in improvements in quality-adjusted life expectancy in Finnish patients with IBD and IDA. FDI also resulted in cost savings, arising from reduced infusion frequency, phosphate monitoring, patient travel, and productivity loss. FDI therefore represents the dominant choice of IV iron in Finnish patients with IBD and IDA.

Chemical Framework to Design Linear-like Relaxors toward Capacitive Energy Storage.

ABO3-type perovskite relaxor ferroelectrics (RFEs) have emerged as the preferred option for dielectric capacitive energy storage. However, the compositional design of RFEs with high energy density and efficiency poses significant challenges owing to the vast compositional space and the absence of general rules. Here, we present an atomic-level chemical framework that captures inherent characteristics in terms of radius and ferroelectric activity of ions. By categorizing A/B-site ions as host framework, rattling, ferroelectrically active, and blocking ions and assembling these four types of ions with specific criteria, linear-like relaxors with weak locally correlated and highly extendable unit-cell polarization vectors can be constructed. As example, we demonstrate two new compositions of Bi0.5K0.5TiO3-based and BaTiO3-based relaxors, showing extremely high recoverable energy densities of 17.3 and 12.1 J cm-3, respectively, both with a high efficiency of about 90%. Further, the role of different types of ions in forming heterogeneous polar structures is identified through element-specific local structure analysis using neutron total scattering combined with reverse Monte Carlo modeling. Our work not only opens up new avenues toward rational compositional design of high energy storage performance lead-free RFEs but also sheds light on atomic-level manipulation of functional properties in compositionally complex ferroelectrics.

Neutrosophic data envelopment analysis based on parametric ranking method

The use of fuzzy numbers and their extensions, especially neutrosophic fuzzy numbers, is inevitable to express the value of the parameters of optimization problems derived from the real world. In this regard, the comparison and ranking of neutrosophic fuzzy numbers as one of the main research topics that can provide a suitable decision to solve optimization problems is of interest to researchers. In this study, we introduce a parametric approach to rank single value trapezoidal neutrosophic numbers which are based on decision–maker aspiration level for degree of the truth membership function and selecting appropriate levels for non-indeterminacy and non-falsity–membership functions. A prominent feature of this method is its high flexibility, which is due to the consideration of acceptable levels for evaluation by the decision maker. Therefore, in most decision issues, it can be used to determine the preferred option. Also, some theorems and reasonable properties are given to demonstrate the effectiveness of our proposed parametric approach. Furthermore, in an example of data envelopment analysis model with neutrosophic information the validity and applicability of the suggested method are examined.