Incidence Rate Of Adverse Events Research Articles

Abstract 4122650: 1-year comparison of quadruple therapy sequencing strategies for heart failure with reduced ejection fraction using an individual-based state-transition microsimulation model

Introduction: Guidelines recommend quadruple therapy (angiotensin receptor blocker-neprilysin inhibitor [ARNI]), beta-blocker, mineralocorticoid receptor antagonist (MRA), and sodium-glucose co-transporter 2 inhibitor [SGLT2I]) as the cornerstone of heart failure (HF) with reduced ejection fraction (HFrEF) management. Yet, guidelines do not propose a specific order of initiation and titration (or “sequencing strategy”) of these agents, due to the absence of trial evidence. Aims: To model the 1-year efficacy and harms of proposed HFrEF quadruple therapy sequencing strategies using a microsimulation model. Methods: We conducted an individual-based state-transition microsimulation modeling study to compare the 1-year cumulative incidence of death, total HF hospitalization, and adverse events with 6 different HFrEF medication sequencing strategies (emulating 2 different traditional strategies, 2 two-drug combinations, a "cluster" strategy, and four-drug "simultaneous" strategy), each with two versions (weekly or biweekly medication adjustments), applied to treatment-naïve outpatients with HFrEF. We modeled death as an incidence at 1 year, and total HF hospitalization (first and recurrent events) and adverse events (bradycardia, hyperkalemia, hypotension, and renal impairment) as incidence rates per 100 patient-years. Results: At 1 year, an estimated 15.5% died without treatment compared to 6.9% with the traditional sequence adjusted biweekly, and 5.2-6.3% with other sequencing strategies. Similarly, the HF hospitalization rate decreased from 32.8 per 100 patient-years with no treatment to 11.1 per 100 patient-years traditional sequencing adjusted biweekly, and 6.9-9 per 100 patient-years with other strategies. The incidence rates of medication-related adverse events per 100 patient-years were: hypotension (5.8-6.9), renal impairment (4.6-6.0), bradycardia (2.9-3.2), and hyperkalemia (approximately 0.5). Conclusions: For treatment-naïve outpatients with HFrEF, pharmacotherapy sequencing strategies that started 2 to 4 medications on the first visit reduced the risk of death and hospitalization at 1 year compared to a traditional sequencing strategy. Weekly medication adjustments did not outperform biweekly adjustments when >=2 medications were started on the initial visit. These findings can inform clinicians and policymakers in developing HFrEF medication optimization programs with sequencing strategy protocols that fit the local practical context.

Evaluating the safety of procedural sedation in emergency department settings among the pediatric population: a systematic review and meta-analysis of randomized controlled trials.

Our meta-analysis aimed to evaluate the safety of procedural sedation and analgesia in pediatric emergency department (ED) settings by investigating the incidence of cardiac, respiratory, gastrointestinal, and neurological adverse events associated with different sedation medications. In accordance with PRISMA guidelines, a comprehensive database search for randomized controlled trials was performed across ten databases from January 2005 to June 2024. Our inclusion criteria included randomized controlled trials involving children under 18years old undergoing pediatric sedation and analgesia in the ED. Data on medication types, dosages, administration routes, and adverse events were extracted and analyzed. Primary endpoints included cardiac, respiratory, gastrointestinal, and neurological adverse events. Seventeen studies met the inclusion criteria, a total of 2,302 procedural sedations. The most common adverse events were vomiting, agitation, and hypoxia, which occurred in 104.9 [95% CI = 76.9-132.9], 37.5 [95% CI = 20.6-54.4], 38.3 [95% CI = 23.9-52.6] of each 1000 sedations, respectively. Other adverse events included apnea, hypotension, and the need for bag-valve mask ventilation, which occurred in 8.6 [95% CI: 3.5-13.6], 9.3 [95% CI: -1.4 to 20.1], and 13.5 [95% CI: 3.2-23.8] of each 1,000 sedations, respectively. Severe adverse events were rare, with no reported instances of intubation and only one case of laryngospasm. Subgroup analyses revealed varying incidence rates of adverse events across different sedation protocols, with ketamine and its combinations showing higher rates of specific respiratory complications. Procedural sedation in pediatric EDs is generally safe, with a low incidence of adverse events, such as vomiting, agitation, and hypoxia. Life-threatening respiratory adverse events are extremely rare. Our findings thus support the careful selection and monitoring of sedation protocols to minimize risks.

Cancer and treatment specific incidence rates of immune-related adverse events induced by immune checkpoint inhibitors: a systematic review.

Immune-related adverse events (irAE) induced by immune checkpoint inhibitors (ICI) are a treatment-limiting barrier. There are few large-scale studies that estimate irAE prevalence. This paper presents a systematic review that reports the prevalence of irAE by cancer type and ICI. A systematic review was undertaken in MEDLINE OVID, EMBASE and Web of Science databases from 2017-2021. A total of 293 studies were identified for analysis and, of these, event rate was calculated for 272 studies, which involved 58,291 patients with irAE among 305,879 total patients on ICI. Event rate was calculated by irAE and ICI type. Mean event rate for general irAE occurrence across any grade was 40.0% (37.3-42.7%) and high grade was 19.7% (15.8-23.7%). Mean event rates for six specific types of irAE are reported. Mean event rate for ICI monotherapy was 29.7% (27.7-33.2%), 45.7% (29.6-61.7%) for ICI combination therapy, and 30.3% (27.3-35.0%) for both ICI monotherapy and combination therapy. This systematic review characterises irAE prevalence across current research that examines irAE risk factors across cancers and ICI. The findings confirms that irAE occurrence is very common in the real-world setting, both high grade and irAE across any grade.

Plaque-Psoriasis: Langzeitdaten bestätigen positives Sicherheitsprofil von Deucravacitinib

Background: Two phase 3 trials, POETYK PSO-1 and PSO-2, previously established the efficacy and overall safety of deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, in plaque psoriasis. Objectives: To further assess the safety of deucravacitinib over 52 weeks in the pooled population from these two trials. Methods: Pooled safety data were evaluated from PSO-1 and PSO-2 in which patients with moderate-to-severe plaque psoriasis were randomized 1:2:1 to receive oral placebo, deucravacitinib or apremilast. Results: A total of 1683 patients were included in the pooled analysis. Adverse event (AE) incidence rates were similar in each treatment group, serious AEs were low and balanced across groups, and discontinuation rates were lower with deucravacitinib versus placebo or apremilast. No new safety signals emerged with longer deucravacitinib treatment. Exposure-adjusted incidence rates of AEs of interest with placebo, deucravacitinib and apremilast, respectively, were as follows: serious infections (0.8/100 person-years [PY], 1.7/100 PY, and 1.8/100 PY), major adverse cardiovascular events (1.2/100 PY, 0.3/100 PY, and 0.9/100 PY), venous thromboembolic events (0, 0.2/100 PY, and 0), malignancies (0, 1.0/100 PY and 0.9/100 PY), herpes zoster (0.4/100 PY, 0.8/100 PY, and 0), acne (0.4/100 PY, 2.9/100 PY, and 0) and folliculitis (0, 2.8/100 PY, and 0.9/100 PY). No clinically meaningful changes from baseline in mean levels, or shifts from baseline to CTCAE grade ≥3 abnormalities, were reported in laboratory parameters with deucravacitinib.

Adverse events associated with herbal medicine products reported in the Korea Adverse Event Reporting System from 2012 to 2021.

Systematic collection of diverse adverse events during herbal medicine administration is crucial. The Korea Adverse Event Reporting System (KAERS) compiles spontaneously reported adverse event data for medicinal products including herbal medicines. This study focused on extracting and analyzing adverse event data specifically related to herbal medicine products from the KAERS database. Individual case safety reports (ICSRs) encompassing 84 types of herbal medicine products, identified by item codes from 2012 to 2021, were extracted from the KAERS database. Descriptive statistics were employed to analyze the characteristics of the extracted reports, and adverse event information was systematically categorized and analyzed based on the MedDRA System Organ Class and preferred term classification. In total, 1,054 ICSRs were extracted, with some documenting multiple adverse events in a single ICSR, resulting in 1,629 extracted adverse events. When categorized by the MedDRA System Organ Class, gastrointestinal disorders were the most prevalent (28.7%), followed by skin and subcutaneous tissue disorders (20.1%). Based on the preferred terms, the most frequently reported adverse events were diarrhea (5.8%), urticaria (5.3%), pruritus (4.7%), rash (4.4%), and abdominal discomfort (4.2%). The most frequently reported herbal medicines were Bangpungtongseong-san (297 cases), Kyeongok-go (144 cases), and Eunkyo-san (108 cases). Spontaneously reported adverse events associated with herbal medicine products were systematically documented using the KAERS database. This study, which focused on voluntarily reported adverse reactions, underscores the need for additional research to estimate the incidence rate of adverse events and assess causality.

Application effect of task-oriented multi-dimensional nursing intervention in patients with coronary atherosclerotic heart disease and concurrent hypertension

Background: The purpose of this study was to explore the application effect of task-oriented multi-dimensional nursing interventionin patients with coronary atherosclerotic heart disease (CAD) and concurrent hypertension. Methodology: The clinical data of 196 patients with CAD and concurrent hypertension in our hospital between January 2019 and January 2022 were retrospectively analysed. The patients receiving task-oriented multi-dimensional nursing were set as study group (n=98), while those given routine nursing as control group (n=98). The two groups were compared in the Hamilton Anxiety Scale (HAMA) scores, left ventricular end-diastolic diameter (LVEDD), 36-Item Short Form Health Survey (SF-36) scores, left ventricular ejection fraction (LVEF), Hamilton Depression Scale (HAMD) scores, systolic blood pressure (SBP), treatment compliance and incidence rates of adverse events. Results: After intervention, study group showed lower HAMA and HAMD scores, SBP and LVEDD, but higher SF-36 scores and LVEF than control group (P<0.05). The treatment compliance rate was higher in control group than that in study group (92.86% vs. 80.61%), while an opposite result was detected in the total incidence rate 5.10% vs. 13.27%, P<0.05). Conclusion: Multidimensional nursing benefits CAD patients with hypertension, improving emotions, compliance, and quality of life, reducing adverse events, and promoting recovery. Recommended for clinical use. Keywords: Coronary atherosclerotic heart disease; task-oriented theory; multi-dimensional nursing care; clinical nursing.

Safety and efficacy assessment of the Inno-Xmart venous stent system in managing symptomatic iliofemoral venous obstruction: a 12-month outcome analysis.

This study aims to evaluate the safety and efficacy of the dedicated Inno-Xmart braided venous stent system (Suzhou Innomed Medical Device Co., Ltd., Jiangsu, China) in treating symptomatic iliofemoral venous obstruction. This clinical study followed a prospective, multicentre, single-arm design with the application of an objective performance goal. Patients diagnosed with symptomatic iliofemoral venous obstruction who met the eligibility criteria of this study were enrolled and treated with the Inno-Xmart venous stent system. The safety endpoints included the assessment of stent fracture, satisfaction of delivery system and 12-month incidence rate of major adverse events (MAEs). The primary efficacy endpoint focused on evaluating the 12-month primary patency rate through venography as determined by core laboratory. Secondary efficacy endpoints included surgical success rate, 6-month primary patency rate and the changes in quality of life from baseline to 6- and 12-month follow-up intervals. Between September 18, 2019, and April 26, 2021, 193 patients were successfully enrolled across 18 research institutions. The surgical success rate was 95.3% (184/193), the 12-month MAE rate was 5.1% (9/178) with no stent fractures or migrations. The 12-month primary patency rate for the participants was 96.1%, significantly surpassing the literature-derived objective performance of 80% (95% confidence interval [CI], 92.1-98.4; P < 0.0001). In addition, the mean venous clinical severity score (VCSS) and Chronic Venous Disease Quality of Life Questionnaire (CIVIQ) scores at the 6- and 12-month follow-ups were significantly lower than the preoperative scores (P < 0.001). The innovative, dedicated braided venous stent designed to address symptomatic iliofemoral venous obstruction demonstrates a high technical success rate, low complication rates, and impressive mid-term (12-month) patency. It effectively enhanced the quality of life for patients and holds promising prospects for a wide range of applications. The clinical study was officially registered in the "Chinese Clinical Trial Registry" (Registration number: ChiCTR2000040216, date of registration: November 25th, 2020).

Geographical Differences in the Safety and Efficacy of Tofacitinib Versus TNFi: APost Hoc Analysis of ORAL Surveillance.

In ORAL Surveillance, incidence rates (IRs) of major adverse cardiovascular events (MACE) and malignancies (excluding non-melanoma skin cancer [NMSC]) in cardiovascular (CV)-risk-enriched patients with rheumatoid arthritis (RA) were numerically greater with tofacitinib in North America versus the rest of the world, due to underlying risk factors. Here, we evaluated the safety and efficacy of tofacitinib versus tumor necrosis factor inhibitors (TNFi) among patients with RA across geographical regions. Patients with RA in ORAL Surveillance (NCT02092467), who were aged ≥ 50years with ≥ 1additional CV risk factor, received tofacitinib 5 or 10mg twice daily or TNFi; 45.9% were from either Poland or North America. This post hoc analysis stratified patients by region (Poland, North America, Other countries). Efficacy endpoints included Clinical Disease Activity Index, Disease Activity Score in 28 joints, with C-reactive protein (DAS28-4[CRP]), and Health Assessment Questionnaire-Disability Index (HAQ-DI). IRs and hazard ratios for adverse events were reported. Of 4362 patients (Poland, N = 759; North America, N = 1243; Other countries, N = 2360), more patients from North America versus Poland/Other countries had CV risk factors such as body mass index ≥ 30kg/m2 and history of diabetes/hypertension; however, more patients from Poland versus other regions were ever smokers and more patients from Poland/North America versus Other countries had history of coronary artery disease. MACE IRs were similar in North America and Poland, and numerically higher versus Other countries. IRs for malignancies (excluding NMSC) were numerically higher in NorthAmerica versus Poland/Other countries with tofacitinib. Serious infections IRs werenumerically higher in North America versus Poland across treatments. Venousthromboembolism/all-cause mortality IRs were generally comparable across regions. DAS28-4(CRP)/HAQ-DI improvements were generally lowest in North America. Differences in safety outcomes were driven by the presence of baseline risk factors; North America and Poland demonstrated a higher proportion of patients with some baseline CV risk factors/comorbidities versus Other countries. NCT02092467 (ClinicalTrials.gov).

First real-world study on the effectiveness and tolerability of rimegepant for acute migraine therapy in Chinese patients

BackgroundRimegepant, a small molecule calcitonin gene-related peptide (CGRP) receptor antagonist, is indicated for acute and preventive migraine treatment in the United States and other countries. However, there is a lack of prospective real-world evidence for the use of rimegepant in Chinese migraine patients.MethodsThis was a single-arm, prospective, real-world study. While taking rimegepant to treat migraine attacks as needed, eligible participants were asked to record their pain intensity, functional ability, and accompanying symptoms for a single attack at predose and 0.5, 1, 2, 24, and 48 h postdose via a digital platform. Adverse events (AEs) during the rimegepant treatment period were recorded and analysed. The percentages of participants who experienced moderate to severe pain at predose and 0.5, 1, 2, 24, and 48 h postdose were assessed. Additionally, the percentages of participants who reported better/good outcomes in terms of pain intensity, functional ability, and accompanying symptoms at 0.5, 1, 2, 24, and 48 h postdose were analysed. In addition, the total cohort (full population, FP) was stratified into a prior nonresponder (PNR) group to observe the effectiveness and safety of rimegepant for relatively refractory migraine and a rimegepant and eptinezumab (RE) group to observe the effectiveness and safety of the combination of these drugs.ResultsBy November 24th, 2023, 133 participants (FP, n = 133; PNR group, n = 40; RE group, n = 28) were enrolled, and 99 participants (FP, n = 99; PNR group, n = 30; RE group, n = 23) were included in the analysis. Rimegepant was effective in treating migraine in the FP and both subgroups, with a significant decreasing trend in the percentages of participants experiencing moderate to severe pain postdose (p < 0.05) and a marked increase in the percentages of participants who reported better/good outcomes in terms of pain intensity, functional ability, and accompanying symptoms at 0.5, 1, 2, 24, and 48 h postdose compared with predose. AEs were reported by 6% of participants in the FP, and all AEs were mild.ConclusionsIn the real world, rimegepant is effective in the acute treatment of migraine patients in China. The low incidence rate of AEs highlighted the favourable tolerability profile of rimegepant.Trial registrationClinicaltrials.gov NCT05709106. Retrospectively registered on 2023-02-01.Graphical

Assessment of prolonged safety and tolerability of erenumab in migraine patients in a long-term open-label study (APOLLON)

BackgroundEfficacy and safety of human monoclonal antibody erenumab used for migraine prophylaxis have been shown in clinical studies. APOLLON is an open-label, multi-center, single arm study, which permits dose adjustments of erenumab and includes an option for a drug holiday. The findings contribute to the accumulating long-term evidence regarding erenumab’s tolerability and safety profile in individuals experiencing episodic and chronic migraines.MethodsThe study population consisted of adult patients with episodic or chronic migraine, who had successfully completed the HER-MES study (NCT03828539). Patients were treated with erenumab for 128 weeks at a flexible dose of either 70 mg or 140 mg. Treatment discontinuation attempts were allowed as voluntary single treatment interruption (‘drug holiday’) of up to 24 weeks.Results701 patients were enrolled in APOLLON. The exposure associated incidence rate (EAIR) of adverse events (AEs) (N = 601) per 100 subject years was 101.71 (95% CI [92.28; 111.14]) meaning a patient could expect having about one adverse event per each year of treatment. EAIR was higher in females (n = 524, EAIR: 104.40, 95% CI [93.93; 114.86]) than in males (n = 77, EAIR: 86.55, 95% CI [65.39; 107.71]) and increased with initial monthly migraine days (MMD) and prior prophylactic treatment failures. A total of 155 patients discontinued erenumab treatment during open-label treatment phase. Of these, 29 were due to AEs (4.1% of total cohort) and out of these 65.5% (N = 19) were considered treatment-related. Safety parameters were in line with HER-MES data and did not reveal new safety signals. Drug holidays were realized by 108 patients (15.4%), of which 64.8% (N = 70) returned to treatment. The mean number of monthly headache days (MHDs), MMDs, and days with acute headache medication significantly increased during drug holiday. After resumption of erenumab treatment, a rapid reduction of the migraine parameters was observed.ConclusionsAPOLLON provides long-term safety and tolerability data confirming the beneficial safety profile of erenumab over a period of 128 weeks. In addition, reversibility of migraine deterioration during drug holiday was shown and most patients returned to their treatment with similar response rates compared to initial treatment.Trial registrationClinicalTrials.gov ID: NCT04084314 (https://clinicaltrials.gov/study/NCT04084314), First submitted: 2019-09-06.

Complications of Oral Corticosteroid Use in Otolaryngology.

Oral corticosteroids (OCS) are frequently prescribed by otolaryngologists. However, there are limited quantitative data on OCS-related adverse events (AEs) in otolaryngology. We sought to quantify OCS-related AEs in otolaryngology. All outpatient otolaryngology encounters in our healthcare system (2018-2023) at which an OCS was prescribed were identified via the electronic medical record. The diagnoses indicating OCS were categorized as sinonasal, otologic, pharyngo-laryngeal, and other. The medical record was subsequently examined to assess for OCS AEs during the 21-day period following the prescription. OCS AEs were grouped into (1) gastrointestinal, (2) metabolic, (3) bone/muscle, (4) ophthalmologic, and/or (5) psychiatric complications. The frequency and types of OCS related AEs were determined. A total of 20 746 otolaryngology encounters with OCS prescribed were examined. Seventy OCS courses had 1 or more AEs, implying a number needed to harm of 296.4 (240.2-386.8). There were 83 total OCS-related AEs, yielding an AE incidence rate of 4.0:1000 (95% CI, 3.0-5.0:1000) OCS prescriptions. The mean age of subjects with AEs (61.5 years) was significantly higher than those without (50.3 years; P < .001). Forty-seven (56.6%) of the complications were metabolic, with hyperglycemia and hypokalemia the most common, followed by gastrointestinal (26.5%), ophthalmologic (3.6%), psychiatric (2.4%), and musculoskeletal (2.4%). AEs related to OCS prescribed by otolaryngologists occur at a rate of once per 296 courses of treatment and older populations may be at increased risk for AEs. Otolaryngologists should balance AE rates against anticipated benefits of steroid therapy. 3.

Robust safety monitoring and signal detection using alternatives to the standard poisson distribution

ABSTRACT Proper and timely characterization of the safety profile of a pharmaceutical product under development is imperative for assessing the overall benefit-risk relationship of the product and for making key development decisions. For ongoing clinical development, a comprehensive and robust safety monitoring and safety signal detection program which is based upon quantitative statistical reasoning is critical. Methods presented here can be applied to safety signal detection and periodic safety monitoring. Various statistical properties, distributions, and models, all utilizing a Bayesian framework are considered and further examined in order to identify robust methods applicable to a broad set of scenarios and situations. Methods developed for incidence counts (including those with under-dispersed distributions) with variable time-at-risk and with underlying constant or non-constant hazard rates, are proposed and compared to traditional methods designed to assess adverse event incidence rates or binomial incidence proportions (which assume an underlying constant hazard rate and subsequent Poisson distribution for modeling event counts).

Efficacy and Safety of Durvalumab/Tremelimumab in Unresectable Hepatocellular Carcinoma as Immune Checkpoint Inhibitor Rechallenge Following Atezolizumab/Bevacizumab Treatment.

While guidelines recommend immune checkpoint inhibitor (ICI) rechallenge as second-line therapy for unresectable hepatocellular carcinoma (HCC), data supporting this remain limited, particularly regarding a standard regimen for first- and second-line treatments. Tremelimumab/durvalumab was recently approved but data on ICI rechallenge are lacking. The purpose of this study was to evaluate the early efficacy and safety of tremelimumab/durvalumab for HCC as an ICI rechallenge following initial ICI therapy with atezolizumab/bevacizumab. This multicenter retrospective study included patients with HCC who underwent treatment with tremelimumab/durvalumab, with relevant available clinical information. We evaluated the safety and efficacy of tremelimumab/durvalumab as ICI rechallenge following initial treatment with atezolizumab/bevacizumab. We analyzed the outcomes in patients who underwent tremelimumab/durvalumab as an ICI rechallenge and those who received tremelimumab/durvalumab as their initial ICI therapy RESULT: A total of 45 patients treated with tremelimumab/durvalumab were included, with 55.6% (25/45) undergoing ICI rechallenge. The objective-response and disease-control rates in patients who underwent ICI rechallenge were 14.3% (3/21) and 47.6% (10/21), respectively, similar to those in patients initially treated with tremelimumab/durvalumab. All patients (n = 3) who experienced the best response to progressive disease (PD) with initial atezolizumab/bevacizumab experienced PD during ICI rechallenge. The incidence rates of adverse events were similar between patient groups treated with tremelimumab/durvalumab as ICI rechallenge and initial ICI. Among patients experiencing immune-related adverse events (irAEs) with atezolizumab/bevacizumab, 75% (3/4) encountered similar irAEs during ICI rechallenge. Early safety and efficacy profiles of durvalumab/tremelimumab as ICI rechallenge are satisfactory.

431P Exposure-adjusted incidence rates (EAIRs) of adverse events (AEs) from the TROPION-Breast01 study of datopotamab deruxtecan (Dato-DXd) vs investigator’s choice of chemotherapy (ICC) in patients (pts) with pretreated, inoperable/metastatic HR+/HER2– breast cancer (BC)

431P Exposure-adjusted incidence rates (EAIRs) of adverse events (AEs) from the TROPION-Breast01 study of datopotamab deruxtecan (Dato-DXd) vs investigator’s choice of chemotherapy (ICC) in patients (pts) with pretreated, inoperable/metastatic HR+/HER2– breast cancer (BC)

Safety and Efficacy of Bimekizumab in Patients with Psoriatic Arthritis: 2-Year Results from Two Phase 3 Studies.

Psoriatic arthritis (PsA) is a chronic inflammatory disease requiring long-term treatment. Bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated tolerability and sustained clinical efficacy for up to 1year for patients with PsA. Here, we report the longer-‍term safety and efficacy of bimekizumab up to 2years. BE OPTIMAL (biologic disease-modifying antirheumatic drug [bDMARD]-naïve) and BE COMPLETE (prior inadequate response/intolerance to tumor necrosis factor inhibitors [TNFi-IR]) assessed subcutaneous bimekizumab 160mg every 4weeks in patients with PsA. BE OPTIMAL included a reference arm (adalimumab 40mg every 2weeks); patients switched to bimekizumab at week 52 with no washout between treatments. BE OPTIMAL week 52 and BE COMPLETE week 16 completers were eligible for the BE VITAL open-label extension. Efficacy outcomes are reported to week 104/100 (BE OPTIMAL/BE COMPLETE). A total of 710/852 (83.3%) bDMARD-naïve and 322/400 (80.5%) TNFi-IR patients completed week 104/100. Up to 104weeks, patients treated with bimekizumab in BE OPTIMAL and BE COMPLETE had treatment-emergent adverse event incidence rates (exposure-adjusted incidence rate/100 patient-years) of 179.9 (95% CI 166.9, 193.7) and 100.3 (89.2, ‍112.4), respectively. The proportion of patients achieving efficacy outcomes (≥ 50% improvement from baseline in American College of Rheumatology [ACR] response criteria, 100% improvement from baseline in Psorisis Area and Severity Index [PASI], minimal disease activity [MDA]) was sustained in all patients from week 52 to week 104/100. Bimekizumab was well tolerated for up to 2years of treatment and no new safety signals were observed. Sustained clinical efficacy was observed up to 2years in bDMARD-naïve and TNFi-IR patients with active PsA. Patients switching from adalimumab to bimekizumab demonstrated further improvement in skin and nail symptoms, and sustained efficacy in joint symptoms. BE OPTIMAL (NCT03895203), BE COMPLETE (NCT03896581), BE VITAL (NCT04009499).

Effect of RDN on long-term blood pressure in refractory hypertensive patients with different cardiovascular risk stratification

Objective: To investigate the long-term therapeutic effects and safety of renal denervation (RDN) on hypertensive patients with different cardiovascular risks, as well as its impact on adverse events, cardiovascular death and all-cause mortality. Methods: This was a single-center, single-arm, real-world retrospective study. Patients with refractory hypertension who underwent RDN at Tianjin First Central Hospital from July 6, 2011 to December 23, 2015 were enrolled and divided into either a high or intermediate-low risk group based on baseline cardiovascular risk. The treatment responsiveness of hypertensive patients with different cardiovascular stratification to RDN was assessed by comparing the results of office blood pressure, home blood pressure, and 24-h ambulatory blood pressure monitoring at 1, 5, and 11 years after RDN. Long-term safety of RDN was assessed by creatinine, and estimated glomerular filtration rate (eGFR) at 1 and 11 years after RDN. In addition, the total defined daily dose (DDD) of antihypertensive medications and the incidence of long-term adverse events, cardiovascular deaths, and all-cause deaths after RDN were followed up 11 years after RDN in person or by telephone. Results: A total of 62 patients with refractory hypertension, aged (50.2±15.0) years, of whom 35 (56.5%) were male, were included. There were 35 cases in high-risk group and 27 cases in low and medium risk group. The decrease in clinic systolic blood pressure (high risk vs. low-medium risk: (-38.0±15.1) mmHg vs. (-25.0±16.6) mmHg(1 mmHg=0.133kPa),P=0.002), home self-measured systolic blood pressure ((-28.4±12.7) mmHg vs. (-19.7±13.1) mmHg,P=0.011) and clinic systolic blood pressure 11 years after RDN ((-43.0±18.4) mmHg vs. (-27.8±17.9) mmHg,P=0.003) in the high-risk group was significantly higher than that in the low-medium risk group. The differences in heart rate and the decrease in total DDD number of antihypertensive drugs between the two groups were not statistically significant (all P>0.05). Creatinine and eGFR levels in the two groups at 1 and 11 years after RDN were not statistically significant when compared with the baseline values (all P>0.05). The cumulative cardiovascular mortality rate was 1.6% (1/62) and 8.1% (5/62), and the cumulative all-cause mortality rate was 3.2% (2/62) and 11.3% (7/62) at 5 and 11 years after RDN, respectively. The differences in the incidence rate of adverse events, cardiovascular mortality, and all-cause mortality rate between the two groups were not statistically significant (all P>0.05). Conclusions: RDN has long-term antihypertensive effect and good safety. Hypertensive patients who belong to the high-risk stratification of cardiovascular risk may respond better to RDN treatment.

Efficacy and Safety of Orally Administered East Asian Herbal Medicine Combined with Narrowband Ultraviolet B against Psoriasis: A Bayesian Network Meta-Analysis and Network Analysis.

Psoriasis is a chronic, immune-mediated inflammatory skin disease with many complications and a poor prognosis that imposes a significant burden on individuals and society. Narrowband ultraviolet B (NB-UVB) represents a cost-effective non-drug therapeutic intervention for psoriasis. East Asian herbal medicine (EAHM) is currently being investigated for its potential as a safe and effective psoriasis treatment. Consequently, it has the potential to be employed as a combination therapy with NB-UVB. The objective was to ascertain the efficacy and safety of the EAHM with NB-UVB combination therapy and to identify important drugs for further research. In this study, randomized controlled trials (RCTs) were retrieved from ten databases in Korea, China, and Japan. All statistical analyses were conducted using R software version 4.3.0. The primary outcomes were the Psoriasis Area and Severity Index (PASI) and the incidence rate of adverse events (AEs), while the secondary outcomes were hematologic markers and the Dermatology Life Quality Index (DLQI), which reflect the immune-mediated inflammatory pathology of psoriasis. The analysis of 40 RCTs, including 3521 participants, demonstrated that EAHM with NB-UVB combination therapy exhibited a statistically significant superiority over NB-UVB monotherapy with respect to primary and secondary outcomes. The Bayesian network meta-analysis revealed that Investigator Presciption 3 and Ziyin Liangxue Decoction exhibited a consistent relative advantage with respect to each PASI-based efficacy metric. The network analysis estimated the potential influence ranking for all individual herbs according to PageRank centrality. The findings of this study suggest that EAHMs co-administered with NB-UVB may provide additional efficacy and safety-related benefits for patients with psoriasis. However, the quality of evidence is still low, and further high-quality trials are needed to reach more definitive conclusions.

Prevention of venous thrombosis through intraoperative intermittent pneumatic compression (IPC): a best practice implementation project

IntroductionVenous thromboembolism (VTE), including deep venous thrombosis and pulmonary embolism, is a common and potentially fatal post-surgery complication. Research has shown that 50% of VTE causes are intraoperative, with the risk of occurrence highest during and immediately post-surgery. Therefore, strategies for early assessment and prevention should be established.ObjectiveTo identify optimal equipment selection, compression protocols, and strategies for complication prevention and management during intraoperative intermittent pneumatic compression (IPC), this study aims to synthesize the best available evidence. The objective is to inform accurate risk assessment and facilitate early mechanical prophylaxis against venous thrombosis.MethodsThe Practical Application to Clinical Evidence model proposed by the Joanna Briggs Institute was utilized. Indicators were identified using the available best evidence from January 2023 to October 2023, and a baseline review was conducted. Negative factors were identified based on clinical evidence-based practice. The implementation rates of different indicators before (n = 372) and after (n = 405) evidence-based practice, the incidence rates of intraoperative IPC-related adverse events and VTE, and the risk of venous thrombosis before (n = 50) and after (n = 50) practice were identified and compared. Furthermore, medical staff’s knowledge of best practices for intraoperative IPC was assessed through pre- and post-intervention surveys involving 109 operating room personnel.ResultsAll review indicators significantly improved (P < 0.01) after the evidence-based practice, and 9 reached 100%. Two intraoperative venous thrombosis events occurred before the evidence-based practice, with an incidence rate of 0.53%; no intraoperative venous thrombosis event occurred after the evidence-based practice, with no significant difference (X2 = 2.171, P = 0.141 > 0.05). However, there were significant differences in intraoperative venous blood hemodynamics before and after the practice (P < 0.05). Moreover, 9 IPC-related adverse events, including 4 cases of skin pressure, 3 cases of skin allergy, and 2 cases of lower limb circulation disorders, were reported before the evidence-based practice, with an incidence rate of 2.4%. Notably, no intraoperative IPC-associated adverse events occurred after the evidence-based practice(X2 = 9.913, P < 0.01). Meanwhile, the score of comprehension of the standard utilization of IPC for preventing venous thrombosis by medical staff in the operating room was 93.34 ± 3.64 after the evidence-based practice, which was higher than that (67.55 ± 5.45) before the evidence-based practice. Overall, the clinical practice was significantly improved the evidence-based practice.ConclusionsApplying intraoperative IPC utilization standards based on the best evidence in clinical practice effectively reduces the intraoperative IPC-associated adverse event rate and the risks of intraoperative venous thrombosis. It also improves the execution rates and compliance with mechanical prevention standards in the operating room by medical staff. Future research should prioritize the development and refinement of best clinical practices for intraoperative venous thrombosis prevention, with a particular emphasis on the integration of mechanical prophylaxis strategies.

Individualized sublingual immunotherapy with dynamic maintenance dose ascending for house dust mite-induced allergic rhinitis

BackgroundPrecision dosing in sublingual immunotherapy (SLIT) has become a hotspot gradually, yet no standardized dose adjustment pattern for house dust mite (HDM)-SLIT. This study aims to investigate the clinical feasibility of the dynamic maintenance dose ascending regimen for individualized SLIT. MethodsA total of 258 allergic rhinitis (AR) patients treated with HDM-SLIT were included in this retrospective study. Patients were divided into the regular dose (RD) group (n = 101) and the high dose (HD) group (n = 157) according to different maintenance dosages of SLIT. In the RD group, patients received the fixed dose recommended by the manufacturer. In the HD group, patients received a maximum tolerance dose determined by dynamic dose ascending. The clinical efficacy was evaluated by combined symptom and medication score (CSMS) and visual analogue scale score (VAS) at the baseline, 0.5-year, 1-year, and 2-year. The safety was evaluated by adverse events (AEs). ResultsSignificant reductions of CSMS and VAS at 0.5-year, 1-year, and 2-year were observed in both the RD group and the HD group compared to the baseline (P < 0.05). In addition, greater improvements in these clinical parameters from 0.5- to 2-year were found in the HD group compared to the RD group (P < 0.05). For subgroup analysis in the HD group, no significant differences in CSMS and VAS were observed among subgroups of patients <14 years old and patients ≥14 years old (P > 0.05). No serious AEs in the two groups and no significant differences were observed between the AE incidence rate of the RD group and HD group during the incremental and maintenance phases. ConclusionsThe 2-year HDM-SLIT with dynamic maintenance dose ascending regimen offers an “optimal” treatment for AR patients while maintaining safety. This study introduced a pattern for individualized dose adjustment in clinical practice, offering potential benefits for AR patients.

Changes in the treatment landscape of metastatic hormone-sensitive prostate cancer: A multicenter study.

118 Background: A multicenter database was utilized to examine the current treatment landscape and clinical outcomes among patients with metastatic hormone-sensitive prostate cancer (mHSPC) following approval of upfront androgen receptor signaling inhibitors (ARSIs). Methods: We retrospectively analyzed patients with mHSPC who commenced treatment between February 2018 and June 2023. The Kaplan–Meier method was used to assess oncological outcomes, including time to castration-resistant prostate cancer (CRPC), progression-free survival 2 (PFS2, duration from initial treatment to tumor progression during second-line treatment), cancer-specific survival (CSS), and overall survival (OS). Cox regression analyses were performed to determine the impact of treatment choices on oncological outcomes. In addition, the incidence rate of adverse events was assessed. Results: In total, 829 patients were analyzed; 42.5% received ARSIs with androgen deprivation therapy (ADT), 44.0% received combined androgen blockade (CAB), and 13.5% received ADT alone. Analysis of annual treatment choice trends revealed an increasing preference for ARSIs with ADT. Kaplan–Meier curves and multivariate Cox regression analyses indicated higher rates of CRPC and shorter PFS2 in patients treated with CAB versus ARSIs with ADT. By contrast, CSS and OS were not significantly different between the ARSI with ADT group and the CAB group. Grade 3–4 adverse events occurred in 1.9% of patients receiving CAB and 6.0% of those receiving ARSIs with ADT. Conclusions: For patients with mHSPC, initial treatment with ARSIs in combination with ADT resulted in a longer time to CRPC and longer PFS2 compared to CAB. Although CAB and ADT alone were associated with fewer adverse events, ARSIs with ADT should be considered a first-line treatment option given its superior oncological outcomes.