Effectiveness Endpoint Research Articles

Atrial fibrillation symptom reduction and improved quality of life following the hybrid convergent procedure: a CONVERGE trial subanalysis.

CONVERGE was a prospective, multicenter, randomized controlled trial that evaluated the safety of Hybrid Atrial Fibrillation Convergent (HC) and compared its effectiveness to endocardial catheter ablation (CA) for the treatment of persistent atrial fibrillation (PersAF) and longstanding PersAF (LSPAF). In 2020, we reported that CONVERGE met its primary safety and effectiveness endpoints. The primary objective of the present study is to report CONVERGE trial results for quality of life (QOL) and Class I/III anti-arrhythmic drug (AAD) utilization following HC. Eligible patients had drug-refractory symptomatic PersAF or LSPAF and a left atrium diameter ≤6.0 cm. Enrolled patients were randomized 2:1 to receive HC or CA. Atrial Fibrillation Severity Scale (AFSS) and the 36-Item Short Form Health Survey (SF-36) were assessed at baseline and 12 months; statistical comparison was performed using paired t-tests. AAD utilization at baseline through 12 and 18 months post-procedure was evaluated; statistical comparison was performed using McNemar's tests. A total of 153 patients were treated with either HC (n=102) or CA (n=51). Of the 102 HC patients, 38 had LSPAF. AFSS and SF-36 Mental and Physical Component scores were significantly improved at 12 months versus baseline with HC overall and for the subset of LSPAF patients treated with either HC or CA. The proportion of HC patients (n=102) who used Class I /III AADs at 12 and 18 months was significantly less (33.3% and 36.3%, respectively) than baseline (84.3%; P<0.001). In LSPAF patients who underwent HC (n=38), AADs use was 29.0% through 18 months follow-up versus 71.1% at baseline (P<0.001). HC reduced AF symptoms, significantly improved QOL, and reduced AAD use in patients with PersAF and LSPAF. NCT01984346.

Clinical Results of a Trifocal Toric Intraocular Lens Using the Holladay Total Surgically Induced Astigmatism Formula for Correcting Low Corneal Astigmatism in Japanese Patients.

To evaluate the effectiveness and safety of the AcrySof IQ PanOptix toric intraocular lens (IOL) with cylinder power of 1.0 D (TFNT20) in a Japanese population with low corneal astigmatism and compare with historical control data for nontoric IOLs. Tokyo Dental College Suidobashi Hospital, Tokyo, Japan. Prospective, single-center study. Patients ≥20 years old received TFNT20 IOL in at least 1 eye based on Alcon Toric calculator (Holladay Total surgically induced astigmatism). Effectiveness endpoints included the percentage of eyes with refractive cylinder ≤0.25 D at 30-60 days after surgery, which was compared with a historical control threshold rate of 29.2% for nontoric IOLs and refractive cylinder ≤0.50 D. Monocular uncorrected distance visual acuity (UDVA; 5 m), uncorrected intermediate visual acuity (UIVA; 60 cm), uncorrected near visual acuity (UNVA; 40 cm), and adverse events were evaluated. Of 41 eyes implanted with TFNT20 IOLs, 37 eyes (90%) achieved refractive cylinder ≤0.25 D at 30-60 days after surgery, demonstrating the superiority of TFNT20 compared with historical data (P<0.0001). Refractive cylinder of ≤0.50 D was achieved by 41 eyes (100%). At 30-60 days, mean ± SD monocular CDVA was -0.15 ± 0.07 logMAR, UDVA was -0.09 ± 0.09 logMAR, UIVA was -0.00 ± 0.07 logMAR, and UNVA was 0.03 ± 0.07 logMAR. Six eyes (15%) had elevated postoperative intraocular pressure, which returned to normal and was not device-related. TFNT20 IOLs successfully reduced postoperative refractive cylinder and provided good distance, intermediate, and near uncorrected VAs in Japanese patients with low corneal astigmatism.

A Prospective, Multicenter, Real-World Registry of Coronary Lithotripsy in Calcified Coronary Arteries: The REPLICA-EPIC18 Study

BackgroundIntravascular lithotripsy (IVL) has demonstrated effectiveness in the treatment of calcified lesions in selected patients with stable coronary disease. ObjectivesThe authors sought to assess the performance of coronary IVL in calcified coronary lesions in a real-life, all comers, setting. MethodsThe REPLICA-EPIC18 study prospectively enrolled consecutive patients treated with IVL in 26 centers in Spain. An independent core laboratory performed the angiographic analysis and event adjudication. The primary effectiveness endpoint assessed procedural success (successful IVL delivery, final diameter stenosis <20%, and absence of in-hospital major adverse cardiovascular events [MACE]). The primary safety endpoint measured freedom from MACE at 30 days. A predefined substudy compared outcomes between acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) patients. ResultsA total of 426 patients (456 lesions) were included, 63% of the patients presenting with ACS. IVL delivery was successful in 99% of cases. Before IVL, 49% of lesions were considered undilatable. The primary effectiveness endpoint was achieved in 66% of patients, with similar rates among CCS patients (68%) and ACS patients (65%). Likewise, there were no significant differences in angiographic success after IVL between CCS and ACS patients. The rate of MACE at 30 days (primary safety endpoint) was 3% (1% in CCS and 5% in ACS patients [P = 0.073]). ConclusionsCoronary IVL proved to be a feasible and safe procedure in a “real-life” setting, effectively facilitating stent implantation in severely calcified lesions. Patients with ACS on admission showed similar angiographic success rates but showed a trend toward higher 30-day MACE compared with patients with CCS. (REPLICA-EPIC18 study [Registry of Coronary Lithotripsy in Spain]; NCT04298307)

Prospective, Randomized Controlled Trial of Cataract Surgery vs Combined Cataract Surgery With Insertion of iStent Inject

PurposeTo evaluate the efficacy and safety of combined cataract surgery with insertion of an ab interno trabecular microbypass device (iStent Inject, Glaukos Corporation) compared to cataract surgery alone in patients with mild-to-moderate glaucoma. DesignProspective, randomized, assessor-masked controlled trial at a single centre. ParticipantsEyes with visually-significant cataract and mild-to-moderate glaucoma with preoperative intraocular pressure (IOP) of 12 – 30 mmHg on 0 to 3 ocular hypotensive medications. MethodsParticipants eyes were randomised (2017-2020) 1:1 to combined cataract surgery with iStent Inject (treatment group, n= 56) or cataract surgery alone (control group, n=48), and followed up for two years. Main Outcome MeasuresThe co-primary effectiveness endpoints were the number of ocular hypotensive medications and IOP at 24-months post-surgery. The secondary effectiveness endpoints were ocular comfort as measured by the Ocular Surface Disease Index (OSDI) and vision-related quality of life as measured by the Glaucoma Activity Limitation Questionnaire (GAL-9) at 24-months. Safety measures included postoperative visual acuity, any unplanned return to the operating theatre, adverse events, and complications. ResultsParticipants (67.3% male) were aged 53-85 years and treatment groups were similar in terms of mean medicated IOP (treatment group 17.7 mmHg ± 4.0; control group 17.1 mmHg ± 3.1), and number of ocular hypotensive medications (treatment group 1.69 ± 1.05; control group 1.80 ± 1.22) at baseline. At 24 months, the number of ocular hypotensive medications were 0.7 ± 0.9 in the treatment groups compared to 1.5 ± 1.9 in the control group, with an adjusted difference of 0.6 fewer medications per eye in the treatment group (95% CI 0.2 to 1.1, p=0.008). 57% of eyes in the treatment group were on no glaucoma medications compared to 36% in the control group. There was no significant difference in IOP between the two groups beyond the 4-weeks. There were no differences in patient-reported outcomes between the two groups. The visual outcomes and safety profiles were similar between the two groups. ConclusionsCombined cataract surgery with iStent Inject achieved a clinically- and statistically-significantly greater reduction in ocular hypotensive medication usage at 24-months compared to cataract surgery alone, with no significant difference in IOP.

DETOUR2 trial outcomes demonstrate clinical utility of percutaneous transmural bypass for the treatment of long segment, complex femoropopliteal disease

ObjectivePercutaneous transmural arterial bypass (PTAB) using the DETOUR system aims to create a percutaneous, endovascular femoropopliteal bypass for the treatment of long segment, complex superficial femoral and proximal popliteal artery disease. The goal of the DETOUR2 study is to investigate the safety and effectiveness of the therapy in comparison with pre-established performance goals. MethodsThe DETOUR2 investigational device exemption study is a prospective, single-arm, multicenter, international trial of symptomatic peripheral arterial disease patients (Rutherford classes 3-5) undergoing the DETOUR procedure for long segment (>20 cm) superficial femoral artery disease. Prespecified end points included primary safety (composite of major adverse events) at 30 days, and effectiveness (primary patency defined as freedom from restenosis or clinically driven target lesion revascularization) at 1 year. ResultsWe enrolled 202 patients at 32 sites with 200 treated with the DETOUR system. The mean lesion length was 32.7 cm, of which 96% were chronic total occlusions (CTO) and 70% were severely calcified. Technical success was achieved in 100% of treated patients. The primary safety end point was met with a 30-day freedom from major adverse event rate of 93.0%. The 1-year primary effectiveness end point was met with 72.1% primary patency at 12 months. Primary-assisted and secondary patency were 77.7% and 89.0%, respectively, at 12 months. The 12 month deep venous thrombosis incidence was 4.1% with no pulmonary emboli reported. Venous quality-of-life scores showed no significant changes from baseline. There was a Rutherford improvement of at least one class through 12 months in 97.2% of patients. The mean ankle-brachial index also improved from 0.61 to 0.95 during this period. There were marked improvements in quality-of-life and functional status measures. ConclusionsThe DETOUR2 study met both the primary safety and effectiveness end points, demonstrating clinical usefulness of this novel therapeutic strategy in long femoropopliteal lesions.

Characteristics and outcome of patients with left atrial appendage closure in China: a single-center experience

BackgroundClinical characteristics and long-term data on the safety and efficacy of LAAC in preventing cerebrovascular accident and thromboembolism among Chinese patients with non-valvular AF (NVAF) remain limited.MethodsData of consecutive NVAF patients who underwent LAAC at Beijing Anzhen Hospital, Capital Medical University, from June 1, 2014, to December 31, 2021, were collected and analyzed retrospectively. The primary effectiveness endpoint was the composite endpoint of stroke/transient ischemic attack, systemic embolism, and death from cardiovascular causes. The primary safety endpoint is the severe bleeding defined by the LAAC Munich consensus.ResultsOf the 222 patients enrolled, the mean age was 66.90 ± 9.62 years, with a majority being male (77.03%). Many patients are non-paroxysmal AF (71.19%) with a median duration of AF of 4.00 years. The mean CHA2DS2-VASc score was 3.78 ± 1.49, and the mean HAS-BLED score was 1.68 ± 0.86. Thromboembolic events (76.58%) were the most common indication for LAAC. The device, technical, and procedural success rates were 98.65%, 98.65%, and 93.69%, respectively. The anticoagulation continuation rate was 56.36%, 31.25%, and 22.60% at 3-, 6- and 12 months post-procedure, respectively. Throughout a mean 2.81 years of follow-up, the incidence of the primary efficacy endpoint was 4.27 per 100 patient-years, predominantly attributable to stroke/TIA (3.12 per 100 PYs). Five patients experienced major bleeding during the follow-up period. Post-procedure imaging revealed minimal complications, with only one substantial peri-device leak. Device-related thrombus occurred in 2.33% of patients, resolving with anticoagulation.ConclusionThe study demonstrates that LAAC is a safe and effective alternative option for Chinese patients with AF, with a high success rate, few complications as well as fewer long-term adverse outcome events.

543 - Early repigmentation of stable vitiligo through point-of-care melanocyte transfer using non-cultured autologous skin cell suspension

Abstract Introduction Vitiligo is an acquired depigmenting skin condition characterized by the loss of skin pigmentation, impacting 0.5% to 2% of the global population.1–3 Vitiligo presents as distinct depigmented patches resulting from autoimmune melanocyte destruction. Individuals with visual vitiligo lesions often experience negative body image, diminished self-confidence, discomfort, and overall lower quality of life (QoL).4 While there are medical treatment options available, these can be associated with poor efficacy and low medication compliance.4 Residual lesions after treatment may require surgical intervention which allows for melanocyte transplantation from an area that is pigmented to one that is lacking functional melanocytes. Through a point-of-care device, a non-cultured autologous skin cell suspension (ACSC) can be prepared using a small skin sample; the ASCS contains healthy melanocytes and is immediately applied onto skin treated with ablative laser to aid in the repigmentation of affected areas. Objective The objective of this study was to evaluate the one-time application of ASCS, with a 1:20 donor to treatment site expansion ratio, for the safe and effective repigmentation of stable vitiligo lesions. Methods A randomized, within-subject controlled, central observer-blinded study was conducted to compare the clinical performance of laser ablation, ASCS, and NB-UVB to NB-UVB alone for repigmentation of stable vitiligo lesions in adults. Subjects received NB-UVB phototherapy on both ASCS-treated and controlled lesions as per recommended by the Vitiligo Working Group. Repigmentation of ASCS-treated and control lesions were categorized by a Central Review Committee (CRC) of blinded dermatologists as one of the following: 0%-25%, 26%-50%, 51%-79%, or 80-100%. The primary effectiveness endpoint was defined as the proportion of lesions achieving ≥80% repigmentation for ASCS-treated versus control areas at Week 24. Early regimentation was assessed at Weeks 4 and 12 as a post hoc analysis. Results A significantly higher proportion of the ASCS-treated areas (36.0%, n = 9) compared to control-treated areas (0.0%) attained ≥80% repigmentation at Week 24 (P = 0.012). At Week 4, 30.4% (n = 7/23) of ASCS-treated areas had ≥26% repigmentation compared to 4.3% (n = 1/23) in the control areas. At Week 12, 56.5% (n = 13/23) of ASCS-treated areas had ≥26% repigmentation compared to 21.7% (n = 5/23) in the control areas. At Week 24, 64% (n = 16/25) of ASCS-treated areas had ≥26% repigmentation compared to 28% (n = 7/25) in the control areas. Conclusion A one-time treatment of ASCS, with the addition of NB-UVB, can result in excellent repigmentation results by 24 weeks, with most subjects seeing ≥26% repigmentation as early as 4 to 12 weeks.

A Prospective Clinical Study to EvaluAte the AbiliTy of the CloudCath System to Detect Peritonitis During In-Home Peritoneal Dialysis (CATCH)

Peritonitis is the leading complication of peritoneal dialysis (PD). Patients are instructed to seek care promptly for signs (cloudy effluent) or symptoms (abdominal pain), and earlier treatment improves outcomes. The CloudCath Peritoneal Dialysis Drain Set Monitoring (CloudCath) system monitors turbidity in dialysis effluent and sends notifications of changes signaling possible peritonitis. We conducted this single-arm, open-label, multicenter study of CloudCath system use during PD. We deactivated system notifications to participants and investigators, who followed standard-of-care for peritonitis signs and symptoms. Effectiveness endpoints measured time between CloudCath system notifications and peritonitis events using International Society of Peritoneal Dialysis (ISPD) criteria. Two hundred forty-three participants used the CloudCath system for 178.8 patient-years. Of 71 potential peritonitis events, 51 events (0.29 per patient-year) met ISPD white blood cell (WBC) count criteria. The system triggered notifications for 41 of 51 events (80.4%), with a median lead time of 2.6 days (10%-90% range, -1.0 to 15.7; P< 0.0001). Excluding 6 peritonitis events that occurred when the system was not in use, the system triggered notifications for 41 of 45 events (91.1%), with a median lead time of 3.0 days (10%-90% range, -0.5 to 18.8; P< 0.0001). Of the 0.78 notifications per patient-year, the majority were peritonitis events or nonperitonitis events such as exit site and tunnel infections or catheter/cycler issues. The CloudCath system detected peritonitis events during PD several days earlier than the current standard-of-care and has the capacity to send notifications that could expedite peritonitis diagnosis and treatment.

Early Repigmentation of Stable Vitiligo through Point-of-Care Melanocyte Transfer Using Non-Cultured Autologous Skin Cell Suspension

Introduction: Vitiligo is an acquired depigmenting skin condition characterized by the loss of skin pigmentation, impacting 0.5% to 2% of the global population.1,2 Vitiligo presents as distinct depigmented patches resulting from autoimmune melanocyte destruction. Individuals with visual vitiligo lesions often experience negative body image, diminished self-confidence, discomfort, and overall lower quality of life (QoL).3 While there are medical treatment options available, these can be associated with poor efficacy and low medication compliance.4 Residual lesions after treatment may require surgical intervention which allows for melanocyte transplantation from an area that is pigmented to one that is lacking functional melanocytes. Through a point-of-care device, a non-cultured autologous skin cell suspension (ACSC) can be prepared using a small skin sample; the ASCS contains healthy melanocytes and is immediately applied onto skin treated with ablative laser to aid in the repigmentation of affected areas. The objective of this study was to evaluate the one-time application of ASCS, with a 1:20 donor to treatment site expansion ratio, for the safe and effective repigmentation of stable vitiligo lesions. Methods: A randomized, within-subject controlled, central observer-blinded study was conducted to compare the clinical performance of laser ablation, ASCS, and NB-UVB to NB-UVB alone for repigmentation of stable vitiligo lesions in adults. Subjects received NB-UVB phototherapy on both ASCS-treated and controlled lesions as per recommended by the Vitiligo Working Group. Repigmentation of ASCS-treated and control lesions were categorized by a Central Review Committee (CRC) of blinded dermatologists as one of the following: 0%-25%, 26%-50%, 51%-79%, or 80-100%. The primary effectiveness endpoint was defined as the proportion of lesions achieving ≥80% repigmentation for ASCS-treated versus control areas at Week 24. Early regimentation was assessed at Weeks 4 and 12 as a post hoc analysis. Results: A significantly higher proportion of the ASCS-treated areas (36.0%, n = 9) compared to control-treated areas (0.0%) attained ≥80% repigmentation at Week 24 (P = 0.012). At Week 4, 30.4% (n = 7/23) of ASCS-treated areas had ≥26% repigmentation compared to 4.3% (n = 1/23) in the control areas. At Week 12, 56.5% (n = 13/23) of ASCS-treated areas had ≥26% repigmentation compared to 21.7% (n = 5/23) in the control areas. At Week 24, 64% (n = 16/25) of ASCS-treated areas had ≥26% repigmentation compared to 28% (n = 7/25) in the control areas. Conclusion: A one-time treatment of ASCS, with the addition of NB-UVB, can result in excellent repigmentation results by 24 weeks, with most subjects seeing ≥26% repigmentation as early as 4 to 12 weeks.

Real-world Effectiveness and Safety of Risankizumab in Patients with Moderate to Severe Multirefractory Crohn's Disease: A Belgian Multicentric Cohort Study.

As real-world data on risankizumab in patients with moderate to severe Crohn's disease (CD) are scarce, we evaluated its effectiveness and safety in multirefractory Belgian patients. Data from consecutive adult CD patients who started risankizumab before April 2023 were retrospectively collected at 6 Belgian centers. Clinical remission and response were defined using the 2-component patient-reported outcome. Endoscopic response was defined as a decrease in baseline Simple Endoscopic Score with ≥50%. Both effectiveness end points were evaluated at week 24 and/or 52, while surgery-free survival and safety were assessed throughout follow-up. A total of 69 patients (56.5% female, median age 37.2 years, 85.5% exposed to ≥4 different advanced therapies and 98.6% to ustekinumab, 14 with an ostomy) were included. At week 24, 61.8% (34 of 55) and 18.2% (10 of 55) of patients without an ostomy achieved steroid-free clinical response and remission, respectively. At week 52, these numbers were 58.2% (32 of 55) and 27.3% (15 of 55), respectively. Endoscopic data were available in 32 patients, of whom 50.0% (16 of 32) reached endoscopic response within the first 52 weeks. Results in patients with an ostomy were similar (steroid-free clinical response and remission, 42.9% and 14.3%, respectively). During a median follow-up of 68.3 weeks, 18.8% (13 of 69) of patients discontinued risankizumab, and 20.3% (14 of 69) of patients underwent CD-related intestinal resections. The estimated surgery-free survival at week 52 was 75.2%. No new safety issues were observed. In this real-world cohort of multirefractory CD patients, risankizumab was effective in inducing both clinical remission and endoscopic response. Risankizumab was well tolerated with no safety issues.

Rapid, on-site and yes-or-no detection of Salmonella typhimurium in foods using Argonaute-enabled assay

Early detection and control of foodborne diseases are crucial for ensuring food safety and consumer health. Therefore, there is a need for faster and more sensitive detection methods. We developed a rapid, portable and visible lateral flow biosensor (LFB) for foodborne pathogenic bacteria detection powered by a Pyrococcus furiosus Argonaute nuclease (PfAgo), named as PfAgo-LFB. LAMP (Loop-mediated isothermal amplification) was used to amplify the target nucleic acid. By using PfAgo as the “lighting up” technology, we can overcome the limitations of false-positive results and lack of effective endpoint monitoring in LAMP, greatly enhancing its applicability. It turned out that PfAgo-LFB was able to provide yes-or-no (positive or negative) results with a limit of detection (LOD) as low as 1 CFU/mL for S. typhimurium and the detection range was between 100 to 108 CFU/mL. It was able to secure a sample-to-answer test for contaminated food samples in less than 45 min and demonstrated satisfactory selectivity. In summary, we designed a PfAgo-LFB that rendered a novel, rapid, accurate, easy-to-deploy, on-site and yes or no detection of S. typhimurium, which could be generalized for building a “one-for-all” biosensing platform.

НОВІ ПІДХОДИ ДО ПРИЗНАЧЕННЯ СПЕЦИФІЧНОЇ ТЕРАПІЇ ХВОРИМ НА САРКОЇДОЗ ЛЕГЕНЬ

Sarcoidosis is a systemic disease with unknown cause, characterized by a presence of epitheliod-cell non-necrotizing granulomas in different organs. In most cases the disease manifests with an involvement of intrathoracic and pulmonary lymphatic nodes. Sometimes it affects eyes, skin, heart, liver, spleen, kidney and central nervous system. Sarcoid granulomas are considered a protective mechanism aimed at elimination of yet unidentified antigens and limitation of an inflammatory focus. Hence the presence of granuloma in lung parenchyma is not the indication for treatment of its own, since sarcoid granuloma on the contrast to infectious granuloma (e.g. in tuberculosis) is not the source of pathological process widespread. In recent years the criteria for evaluation of treatment outcomes have been revised, mainly the term “clinical remission”, which meant lung computed tomography symptoms resolution. The quality of life, which includes the level of patient’s work capability and social status restoration, is now considered a primary endpoint of treatment effectiveness (ERS clinical practice guidelines on treatment of sarcoidosis, 2021). Two tools for quality-of-life assessment in patients with pulmonary sarcoidosis have been reviewed in current article: Fatigue Assessment Scale (FAS) and King's Sarcoidosis Questionnaire (KSQ). New statements of 2021 ERS clinical practice guidelines, which underline the importance of quality-of-life evaluation for the patients with pulmonary sarcoidosis, and the literature data presented in current report, substantiate the use of FAS і KSQ scores and its change during treatment as an instrument for making a decision regarding either initiation or discontinuation of specific therapy. Key words: pulmonary sarcoidosis, indications for specific therapy, methods of quality of life evaluation, FAS, KSQ.

Efficacy and safety of glecaprevir and pibrentasvir in Saudi patients with chronic hepatitis C virus infection at a major tertiary hospital.

To evaluate the effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) in chronic hepatitis C (HCV) patients, and to assess the prescribers' adherence to Food and Drug Administration recommendations on treatment duration. A retrospective cohort study was carried out on chronic HCV patients of ≥18 years, with or without cirrhosis, naive or experienced, and with normal kidney function or chronic kidney disease (including dialysis patients) at Prince Sultan Military Medical City in Riyadh, Saudi Arabia, between February 2020 and March 2021. The primary effectiveness end-point was the number and percentage of patients who achieved a sustained virologic response (SVR12), virologic failure, and non-response. Safety was determined considering both serious and non-serious adverse events. A total of 92 patients were enrolled in this study. Among patients, 52 (56.5%) were female, 84 (91.3%) were naive, and 45 (48.9 %) had HCV genotype 4. The SVR12 was achieved in 91 (98.9%, 95% CI: [94-99.8]) patients. Only one patient (1.1%, 95% CI: [0.2-5.9]) developed virologic non-response and there were missing data on virologic failure. Overall, non-serious adverse events were observed in 26 (28.5%) patients, and none of them had serious adverse events that led to treatment discontinuation. Approximately 75% of the patients received an inappropriate treatment duration (12 weeks vs. the recommended 8 weeks) and most (n=40, 58%; p<0.022) of the exceedingly long treatments were prescribed by registrars. The GLE/PIB was highly effective and safe in chronic HCV Saudi patients.

Reactivation Risk of Latent Tuberculosis or Inactive Hepatitis B Virus Infection and Effectiveness of Ustekinumab in Chinese Plaque Psoriasis Patients: A 28-Week Retrospective, Observational Study.

This study observed the effectiveness of ustekinumab and reactivation risk of concurrent latent tuberculosis infection (LTBI) and inactive hepatitis B virus (HBV) infection in Chinese mainland psoriasis patients on ustekinumab treatment. This retrospective, multicenter, observational study was conducted in three centers in China. Adult patients with moderate to severe plaque psoriasis were treated with ustekinumab for 28 weeks. The effectiveness endpoint included 75% and 90% improvement in Psoriasis Area Severity Index (PASI75/90) response rate, percentage of PASI improvement, change of absolute PASI score and body surface area involvement (BSA) score, absolute PASI ≤1/3 and Physicians' Global Assessment (PGA)=0/1, as well as Dermatology life quality index (DLQI)=0/1 response rate at week 4, 16 and 28. Screening of tuberculosis and hepatitis were performed at baseline and week 28. A total of 82 patients were enrolled between March 2021 and May 2023 and the number of patients combined with LTBI and inactive HBV infection was 20 and 21 respectively. The PASI75 and PASI90 response rate at week 28 was 95.1% and 81.7% respectively. The mean PASI score decreased from 14.93 ± 12.07 at baseline to 0.78 ± 1.86 at week 28, and the mean BSA score decreased from 21% ± 18% at baseline to 1% ± 2% at week 28 (both P<0.001 compared with baseline). DLQI 0/1 response rate at week 28 was 73.2%. No reactivation of LTBI and inactive HBV infection and also no new-onset tuberculosis and hepatitis B occurred in patients without LTBI and inactive HBV infection at baseline. Ustekinumab demonstrated great effectiveness in Chinese plaque psoriasis patients and good safety in psoriasis concurrent with LTBI and inactive HBV infection under the real-world setting.

Safety and Effectiveness of Passeo-18 Lux Drug-Coated Balloon Catheter in Infrainguinal Endovascular Revascularization in the Korean Population: A Multicenter Post-Market Surveillance Study.

To evaluate the safety and clinical outcomes of the Passeo-18 Lux drug-coated balloon (DCB) in endovascular revascularization procedures under real-world conditions in a Korean population with atherosclerotic disease of the infrainguinal arteries, including below-the-knee (BTK) arteries. Eight institutions in the Republic of Korea participated in this prospective, multicenter, single-arm, post-market surveillance study. Two hundred patients with Rutherford class 2-5 peripheral arterial disease and infrainguinal lesions suitable for endovascular treatment were competitively enrolled. Data were collected at baseline, the time of intervention, discharge, and 1-, 6-, 12-, and 24-month follow-up visits. The primary safety endpoint was freedom from major adverse events (MAE) within 6 months (except when limiting the time frame for procedure- or device-related mortality to within 30 days), and the primary effectiveness endpoint was freedom from clinically driven target lesion revascularization (CD-TLR) within 12 months after the procedure. A total of 197 patients with 332 target lesions were analyzed. Two-thirds of the patients had diabetes mellitus, and 41.6% had chronic limb-threatening ischemia. The median target lesion length was 100 mm (interquartile range: 56-133 mm). Of the target lesions, 35.2% were occlusions, and 14.8% were located in the BTK arteries. Rate of freedom from MAE was 97.9% at 6 months, and the rate of freedom from CD-TLR was 95.0% and 92.2% at 12 and 24 months, respectively. Subgroup analysis of 43 patients and 49 target lesions involving the BTK arteries showed rate of freedom from MAE of 92.8% at 6 months and rates of freedom from CD-TLR of 88.8% and 84.4% at 12 and 24 months, respectively. The results of the present study, including the BTK subgroup analysis, showed outcomes comparable to those of other DCB studies, confirming the safety and effectiveness of Passeo-18 Lux DCB in the Korean population.

Risk assessment of nutrients: There must be a threshold for their effects

Nutrients serve physiological functions in a dose-dependent manner and that needs to be recognized in risk assessment. An example of the consequences of not properly considering this can be seen in a recent assessment by the European Food Safety Authority (EFSA). EFSA concluded in 2022 that the intake of added and free sugars should be “as low as possible in the context of a nutritionally adequate diet”. That conclusion of EFSA is based on the effects on two surrogate endpoints for an adverse effect found in randomized controlled trials with high sugars intake levels: fasting glucose and fasting triglycerides. The lowest intake levels in these trials were around 10 energy% and at this intake level there were no adverse effects on the two outcomes. This indicates that the adverse effects of sugars have an observable threshold value for these two endpoints. The most appropriate interpretation from the vast amount of data is that currently no definitive conclusion can be drawn on the tolerable upper intake level for dietary sugars. Therefore, EFSA's own guidance would lead to the conclusion that the available data do not allow the setting of an upper limit for added sugars and hence, that more robust data are required to identify the threshold value for intake of sugars.

Intravascular Lithotripsy for Vessel Preparation in Calcified Coronary Arteries Prior to Stent Placement - Japanese Disrupt CAD IV Study 2-Year Results.

Background: Intravascular lithotripsy (IVL) delivers acoustic pressure waves to modify calcification to enhance vessel compliance and optimize stent deployment. The Disrupt CAD IV study enrolled patients with severe coronary artery calcification. The primary safety (30-day major adverse coronary events [MACE], 6.3%) and effectiveness (procedural success, 93.8%) endpoints were achieved. The present analysis evaluated the 2-year outcomes of the study. Methods and Results: Disrupt CAD IV (NCT04151628) was a prospective, single-arm, multicenter study designed for regulatory approval of the Shockwave Coronary C2 IVL system in Japan. Angiographic outcomes were analyzed by an independent core laboratory and adverse events were adjudicated by a Clinical Events Committee. Kaplan-Meier analysis was performed for MACE (composite of cardiac death, MI or target-vessel revascularization [TVR]), target lesion failure (TLF: composite of cardiac death, TV-MI, and target lesion revascularization [TLR]), and stent thrombosis (ST). At 2 years, 62 subjects had completed follow-up. MACE occurred in 12.6% (cardiac death 0.0%, MI 6.3%, TVR 7.9%) and TLF occurred in 7.8% of patients, with both rates driven by non-Q-wave MI events (6.3%). TLR was 3.2%; no ST occurred through 2 years. Conclusions: Treatment with IVL in patients with severely calcified coronary lesions was associated with low rates of MACE, TLR, and ST at 2 years, demonstrating continued durable safety and effectiveness of coronary IVL in a Japanese population.

Safety andeffectiveness ofpeficitinib 100 mg/day inpatients achieving clinical remission from a long-term open-label extension study inJapan, Korea, andTaiwan (RAJ2).

This post hoc analysis of the RAJ2 study assessed long-term safety and effectiveness of peficitinib 100 mg/day for treatment of rheumatoid arthritis. Eligible patients previously completed two Phase 3 (RAJ3 and RAJ4) studies of peficitinib in Asia. All patients received peficitinib 100 mg/day at RAJ2 Week (W)0; dose change to 50 mg/day or 150 mg/day was permitted. Safety endpoints included treatment-emergent adverse events and laboratory test results. Effectiveness endpoints included peficitinib exposure pattern, achievement of Clinical Disease Activity Index (CDAI) remission by peficitinib exposure pattern at W0 and W48, and association of demographics/characteristics with CDAI remission at W0 and W48. Overall, no new safety findings were reported at W48, and renal function was unaffected. Of patients included in effectiveness analyses at W48, 70.9% (451/636) had maintained peficitinib 100 mg/day since W0. Of patients who achieved CDAI remission at W0 and maintained peficitinib 100 mg/day to W48, 50.3% (79/157) maintained CDAI remission to W48. Low disease activity and a lower number of prior disease-modifying antirheumatic drugs were significantly associated with CDAI remission at W48. Long-term peficitinib treatment at a dose of 100 mg/day was generally well tolerated and, following induction therapy, maintained effectiveness through to W48.

RWD16 Identifying Oncology Effectiveness Endpoints Using Administrative Secondary Databases: An Example Utilising Hospital Episode Statistics in England

RWD16 Identifying Oncology Effectiveness Endpoints Using Administrative Secondary Databases: An Example Utilising Hospital Episode Statistics in England

Prospective, multicenter clinical trial comparing the M6-C compressible cervical disc with anterior cervical discectomy and fusion for the treatment of single-level degenerative cervical radiculopathy: 5-year results of an FDA investigational device exemption study

BACKGROUND CONTEXTVarious total disc replacement (TDR) designs have been compared to anterior cervical discectomy and fusion (ACDF) with favorable short and long-term outcomes in FDA-approved investigational device exemption (IDE) trials. The unique design of M6-C, with a compressible viscoelastic nuclear core and an annular structure, has previously demonstrated favorable clinical outcomes through 24 months. PURPOSETo evaluate the long-term safety and effectiveness of the M6-C compressible artificial cervical disc and compare to ACDF at 5 years. STUDY DESIGNProspective, multicenter, concurrently and historically controlled, FDA-approved IDE clinical trial. PATIENT SAMPLESubjects with one-level symptomatic degenerative cervical radiculopathy were enrolled and received M6-C (n=160) or ACDF (n=189) treatment as part of the IDE study. Safety outcomes were evaluated at 5 years for all subjects. The primary effectiveness endpoint was available at 5 years for 113 M6-C subjects and 106 ACDF controls. OUTCOME MEASURESThe primary endpoint of this analysis was composite clinical success (CCS) at 60 months. Secondary endpoints were function and pain (neck disability index, VAS), physical quality of life (SF-36, SF-12), safety, neurologic, and radiographic assessments. METHODSPropensity score subclassification was used to control for selection bias and match baseline covariates of the control group to the M6-C subjects. Sixty-month CCS rates were estimated for each treatment group using a generalized linear model controlling for propensity score. RESULTSAt 5 years postoperatively, the M6-C treatment resulted in 82.3% CCS while the ACDF group showed 67.0% CCS (superiority p=.013). Secondary endpoints indicated that significantly more M6-C subjects achieved VAS neck and arm pain improvements and showed maintained or improved physical functioning on quality-of-life measures compared to baseline assessments. The M6-C group-maintained flexion-extension motion, with significantly greater increases from baseline disc height and disc angle than observed in the control group. The rates of M6-C subsequent surgical interventions (SSI; 3.1%) and definitely device- or procedure-related serious adverse events (SAE failure; 3.1%) were similar to ACDF rates (SSI=5.3%, SAE failure=4.8%; p>.05 for both). CONCLUSIONSSubjects treated with the M6-C artificial disc demonstrated superior 5-year achievement of clinical success when compared to ACDF controls. In addition, significantly more subjects in the M6-C group showed improved pain and physical functioning scores than observed in ACDF subjects, with no difference in reoperation rates or safety outcomes.