Differences In Event Rates Research Articles

Fastidious adherence to 0/1-hour high-sensitivity troponin T testing reduces emergency department length of stay in patients presenting with suspected acute coronary syndromes

Abstract Background High-sensitivity cardiac troponins (hs-cTn) are key clinical biomarkers in patients presenting with suspected acute coronary syndromes (ACS) to Emergency Departments (EDs). They have facilitated rapid 0h/1h troponin testing protocols, leading to safe, effective, and efficient triage of patients. However, early distinction of myocardial infarction (MI), which has a reported frequency of less than 10% in most cohorts, from the apparently stable hs-cTn elevations of chronic myocardial injury (CMI) remains a challenge. Often CMI patients require confirmation by further testing and observation, prolonging patient length of stay. Further, reliably obtaining serial hs-cTn samples at 60-minutes in a busy ED setting may be difficult. A potential explanation for only 5-6% of Australian sites adopting 0h/1h hs-cTn testing. Methods and Results We undertook a case-control study between March and August 2023 among patients with suspected ACS presenting to Liverpool Hospital ED (Sydney, Australia). 185 patients (cases) underwent hs-cTnT sampling at 30- and 60-minutes (± 5 minutes) after baseline. Diagnosis of MI was made in 8.6%, 35.7% were placed into a further observation group and MI ruled-out in 55.7%. The latter two groups were matched to 169 patients (controls) who received ‘usual’ care, which was a 0h/1h hs-cTnT testing protocol. The case and control arms were matched by age, gender, time from symptom onset and main presenting symptom. Control patients had a median sampling interval of 118 [85 to 174] minutes, rather 60 minutes as the protocol directs. When comparing the paired differences between the case and control arms, there was a mean reduction in length of stay of 104 (95% CI: 41 to 186, P = 0.01) and 47 (95% CI: 11 to 84, P = 0.01) minutes, for the observation and rule-out MI groups respectively. The figure shows the distribution of lengths of stay by group. Among the rule-out group, Wilcoxon signed rank test indicated the control arm had a longer median length of stay of 6.3 [5.1 to 8.4] hours, compared to 5.0 [4.5 to 7.1] hours in the case arm (P=0.005). Similarly, in the further observation group, control patients also had a longer median length of stay of 9.2 [6.9 to 10.4] hours compared to case patients of 8.1 [5.1 to 10.3] hours (P = 0.009). At 30-days, ED representation rates were 10.7% in controls and 8.3% in cases, rehospitalisation 3.6% in controls and 5.3% in cases, cardiac death 0% in both arms and non-cardiac death 1% in both arms. There were no differences in event rates between each arm (P > 0.05). Conclusion Accurate 0h/1h hs-cTnT testing reduces patient length of stay in ED and offers more personalised prediction of MI risk. The importance of adherence to protocol-directed sampling times is clear, where further studies are required regarding routine implementation in a busy ED setting.Exact 60 min TnT and LOSOutcomes at 30 days

Bioadaptor implant versus contemporary drug-eluting stent in percutaneous coronary interventions in Sweden (INFINITY-SWEDEHEART): a single-blind, non-inferiority, registry-based, randomised controlled trial

Persistent non-plateauing adverse event rates in patients who underwent percutaneous coronary intervention (PCI) remain a challenge. A bioadaptor is a novel implant that addresses this issue by restoring the haemodynamic modulation of the artery, allowing cyclic pulsatility, vasomotion, and adaptative remodelling, by unlocking and providing dynamic support to the artery. We aimed to assess outcomes with the device versus a contemporary drug-eluting stent (DES) in a representative PCI population. INFINITY-SWEDEHEART is a single-blind, non-inferiority, registry-based, randomised controlled study conducted in 20 hospitals in Sweden. Patients aged 18-85 years, with chronic or acute coronary syndrome ischaemic heart disease, with an indication for PCI, with up to three de novo lesions suitable for implantation with one single device per lesion, and successful pre-dilatation were identified via the Swedish Coronary Angiography and Angioplasty Registry and eligible for enrolment. Participants were randomly assigned (1:1), using block randomisation with random variation in block size and stratified by site, to either the DynamX bioadaptor (Elixir Medical, Milpitas, CA, USA) or a zotarolimus-eluting DES (Resolute Onyx and Onyx Trustar, Medtronic, Minneapolis, MN, USA). The primary endpoint was the device-oriented clinical endpoint of target lesion failure at 12 months (a composite of cardiovascular death, target vessel myocardial infarction, and ischaemia-driven target lesion revascularisation), assessed in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment, regardless of treatment received) who had either experienced an event up to 12 months or completed the trial up to 12 months. Non-inferiority was established if the upper limit of the two-sided 95% CI for the absolute risk difference was less than 4·2%. Powered secondary endpoints were landmark analyses from 6 months onwards for target lesion failure, target vessel failure (composite of cardiovascular death, target vessel myocardial infarction, and ischaemia-driven target vessel revascularisation), and target lesion failure for patients with acute coronary syndrome assessed in the ITT population). This study is registered with ClinicalTrials.gov, NCT04562805, and follow-up to 5 years is ongoing. Between Sept 30, 2020, and July 11, 2023, 2399 patients were randomly assigned to receive the bioadaptor (n=1201) or DES (n=1198; ITT population). Median age was 69·5 years (IQR 61·2-75·6), 575 (24·0%) of 2399 patients were female, and 1824 (76·0%) were male (data on race and ethnicity were not collected), and 1838 (76·6%) patients presented with acute coronary syndrome. The primary endpoint of 12-month target lesion failure occurred in 28 (2·4%) of 1189 assessable patients in the bioadaptor group versus 33 (2·8%) of 1192 assessable patients in the DES group, with a risk difference of -0·41% (95% CI -1·94 to 1·11; pnon-inferiority<0·0001). In the prespecified landmark analysis from 6 months to 12 months, the Kaplan-Meier estimates of target lesion failure were 0·3% (with events in three of 1170 patients) in the bioadaptor group versus 1·7% (with events in 16 of 1176 patients) in the DES group (hazard ratio 0·19 [95% CI 0·06 to 0·65]; p=0·0079), of target vessel failure were 0·8% (events in eight of 1167) versus 2·5% (events in 23 of 1174; 0·35 [0·16 to 0·79]; p=0·011), and of target lesion failure in patients with acute coronary syndrome were 0·3% (events in two of 906) versus 1·8% (events in 12 of 895; 0·17 [0·04 to 0·74]; p=0·018). The rate of definite or probable device thrombosis, which was recorded as a safety outcome, was low and did not differ between groups (eight [0·7%] of 1201 in the bioadaptor group vs six [0·5%] of 1198 in the DES group; difference in event rates of 0·16% [95% CI -0·50 to 0·83]). Among patients with coronary artery disease, including those with acute coronary syndrome, treatment with the bioadaptor was non-inferior to contemporary DES, showing potential to mitigate non-plateauing device-related events and improving outcomes in patients undergoing PCI. The additional planned follow-up will help to reinforce the clinical significance of the 1-year findings. Elixir Medical.

81 mRNA COVID-19 vaccine safety among children and adolescents from the Canadian National Vaccine Safety Network

Abstract Background The Canadian National Vaccine Safety Network (CANVAS) expanded its active safety surveillance for COVID-19 vaccines among children and adolescents during the COVID-19 pandemic. Objectives This analysis aimed to determine whether the first or second dose of mRNA COVID-19 vaccination is associated with health events in children and adolescents. Design/Methods Adolescents 15-19 years of age or parents/guardians of children 5-14 years of age were recruited from seven Canadian provinces/territories and followed for the occurrence of health events seven days after doses 1 and 2 or for a seven-day period for unvaccinated participants. The primary outcome was a health event that prevented daily activities, resulted in school absenteeism, and/or required a medical consultation, including emergency department visits or hospitalization. Aged-stratified multivariable logistic regression examined health events associated with mRNA COVID-19 vaccines (BNT162b2, mRNA1273, and mixed [different products for doses 1 and 2]) for children aged 5 to 11 years and adolescents aged 12 to 19 years. Results Between January 2021 and February 2023, a total of 249,418 (Children BNT162b2: 205,744, mRNA-1273: 36, and Adolescent BNT162b2: 39,628, mRNA-1273: 4,010) completed the first dose survey and 128,599 (Children BNT162b2: 109,625, mRNA-1273: 3, mixed: 235, and Adolescent BNT162b2: 17,202, mRNA-1273: 1,155, mixed: 474) had completed the second dose survey. A total of 668 unvaccinated participants (Children 431 and Adolescent 237) completed the control survey. In the week following dose 1, health event rates among vaccinated children and adolescents were &amp;lt;4% and lower than in unvaccinated counterparts (6.9%), and neither BNT162b2 nor mRNA-1273 were associated with health events in either age group. Following dose 2, among vaccinated adolescents health events rates (BNT162b2 4.6%, mRNA-1273 8.5%, mixed 10.4%) were higher than unvaccinated adolescents (3.4%), but were self-limiting and resolved within 7 days. Among children, there was no difference in health event rates between vaccinated and unvaccinated groups. Conclusion For children, mRNA COVID-19 vaccines were not associated with health events preventing daily activities, resulting in school absenteeism and/or requiring medical consultation. Similar to vaccinated adults our findings found vaccinated adolescents reported higher rates of health events after dose 2 mRNA COVID-19 vaccines, but these were self-limiting and resolved quickly. Our findings can be used to inform adolescents and their parents of what to expect following COVID-19 vaccination.

Efficacy and Safety of Left Atrial Appendage Occlusion during Cardiac Surgery to Prevent Stroke: A Systematic Review and Meta-analysis

Introduction: Stroke remains a major cause of morbidity and mortality after cardiac surgery. One factor associated with stroke occurrence is postoperative AF (pAF), which predisposes to the formation of atrial thrombus. As most thrombi form in the left atrial appendage (LAA), there is significant interest in LAA as a potential therapeutic target. While guidelines recommend direct oral anticoagulants (DOACs) as the preferred therapy for stroke prevention in patients with AF and a CHA2DS2-VASc score of ≥2, they cannot be administered to all patients who are poor candidates for long-term oral anticoagulation because of the high risk of bleeding, drug compliance and drug tolerance. There are limited data on the efficacy and safety of LAA occlusion (LAAO) during cardiac surgery for stroke prevention. Methods: A comprehensive and relevant search of randomised controlled trials, cohort and case–control studies was conducted. Outcome measures for ischaemic stroke events, all-cause mortality and pAF were extracted and analysed using a random-effects model. Results: Twelve studies were included and 18,982 subjects were analysed. There were 231 ischaemic stroke events in 9,473 patients who received LAAO compared with 371 ischaemic stroke events in 9,509 patients who did not receive LAAO. Concomitant LAAO showed a significant difference in ischaemic event rate (risk ratio [RR] 0.65; [95% CI: 0.55–0.77]; p&lt;0.00001, I2=0%) and all-cause mortality (RR 0.74; 95% CI [0.57–0.97]; p=0.03; I2=68%). For pAF, there was no difference between the two groups (RR 1.08; 95% CI [0.95–1.22]; p=0.24; I2=72). Conclusion: Concomitant LAAO was more effective in preventing ischaemic stroke events and all-cause mortality, with an overall moderate certainty of evidence. However, pAF rates were similar between LAAO and non-LAAO groups.

5185 A Meta-Analysis Evaluating the Efficacy of Liraglutide in Reducing Cardiovascular Complications Among Patients With Type 2 Diabetes

Abstract Disclosure: M.P. Del Rosario: None. C. Ong-Ramos: None. Background: The objective of this study was to determine the efficacy of Liraglutide in reducing cardiovascular complications Methodology: Literature searches of electronic databases (PubMed and ScienceDirect) were performed to identify relevant studies. Relevant journals included were electronically searched for randomized controlled trials (RCTs) regarding the use of Liraglutide versus placebo in reducing the rate of cardiovascular complications. Data extraction and quality assessment were done from independent reviewers. Statistical analysis of the study was accomplished using Cochrane Systematic Review Software Review Manager. A p-value of less than 0.05 for the observed effect size was considered statistically significant. Results: A total of 2 RCTs with 16, 977 patients were included in this meta-analysis. The results showed that in the Liraglutide group there is a lower rate of the following: Major Adverse Cardiovascular Events (MACE) (risk ratio of 0.86 [0.78, 0.95]), cardiovascular events (risk ratio 0.75 [0.63, 0.89]), and all-cause mortality (risk ratio 0.81 [0.70, 0.93]), but is not statistically significant when compared to the placebo group in terms of non-fatal myocardial infarction and and non-fatal stroke. There is no significant difference in rates of severe adverse events in general (p &amp;gt; 0.05). However, Liraglutide caused significant reduction in rates of severe hypoglycemia as an independent secondary outcome (p &amp;lt; 0.05). Conclusions: Compared with placebo, Liraglutide provided significant reduction in MACE, cardiovascular events, all-cause mortality and severe hypoglycemia as an adverse event. Presentation: 6/3/2024

Efficacy and Safety of Hepatic Arterial Infusion Chemotherapy(HAIC) Combined with PD-1 Inhibitors for Advanced Hepatocellular Carcinoma with Macrovascular Invasion: A Multicenter Propensity Score Matching Analysis.

To investigate the efficacy and safety of HAIC combined with programmed cell death protein-1 (PD1) inhibitors in MVI-positive advanced hepatocellular carcinoma(HCC). From September 2017 to May 2019, we retrospectively collected the clinical data from three medical centers in China pertaining to patients diagnosed with BCLC C stage HCC with MVI and receiving treatment with a combination of HAIC and PD-1 inhibitors treatment or HAIC alone, and we compared the efficacy of HAIC combined with PD-1 inhibitors and HAIC monotherapy. Propensity score matching(PSM) was utilized to adjust for baseline differences between groups. Survival outcomes and tumor response rate were used to assess survival benefits, while the incidence of adverse events was used to evaluate safety. After screening for eligibility, 489 patients diagnosed with HCC and concomitant MVI were enrolled. Of these, 173 patients received treatment combining HAIC with PD-1 inhibitors, while 316 patients underwent HAIC monotherapy. After PSM adjustment, the combination therapy group demonstrate superior survival outcomes. Median overall survival(OS) and progression free survival(PFS) were 31.8 months and 10.8 months, respectively, significantly higher than those in the monotherapy group (OS: 10.0 months; PFS: 6.1 months; both P<0.0001). Moreover, ORR and DCR remained significantly elevated in the combination therapy group (ORR: 44.3% vs 20.4%, P<0.0001; DCR: 89.8% vs 82.0%, P=0.041). Safety profiles indicated no significant differences in adverse event rates between the two treatment groups, encompassing both overall and grade-specific assessments. Compared to HAIC alone, the combination of HAIC with PD-1 inhibitors represents a more promising and effective approach for patients with HCC complicated by macrovascular invasion.

There is no correlation between differences in adverse events and differences in patient-reported outcome measures in orthopaedic trauma randomized controlled trials: A systematic review

IntroductionA recovery without adverse events is a top priority of orthopaedic trauma patients, however many randomized controlled trials (RCTs) are only powered to detect a difference in patient-reported outcome measures (PROMs). While it may be assumed that differences in major adverse event rates between treatment groups will result in differences in PROMs, this has not been established. The purpose of this study was to perform a systematic review of RCTs to evaluate if differences in these outcomes were correlated. MethodsA systematic search was conducted of online databases to identify RCTs in orthopaedic trauma fracture management that reported both major adverse events and PROMs. Adverse events included secondary surgeries or complications that could negatively affect long-term outcomes (nonunion, chronic regional pain syndrome, etc.). The correlation between a difference (p < 0.05) in adverse events and a difference in PROMs was assessed. ResultsThe systematic review yielded 30 RCTs involving 6,769 patients. The primary outcome was a continuous PROM in 70.0 % (21/30). A difference in major adverse events was reported in 23.3 % (7/30) and a difference in PROMs was reported in 6.7 % (2/30). Studies reporting a difference in adverse events, compared to those that did not, were not more likely to report a difference in PROMs (14.3 % (1/7) vs. 4.3 % (1/23); p = 0.42). ConclusionsThere was no correlation between differences in adverse event rates and differences in PROMs in orthopaedic trauma RCTs. Investigators should consider powering studies to detect differences in the major adverse events that both patients and surgeons wish to avoid. Level of evidenceLevel I

Efficacy and Safety of Pioglitazone/Metformin Fixed-Dose Combination Versus Uptitrated Metformin in Patients with Type 2 Diabetes without Adequate Glycemic Control: A Randomized Clinical Trial.

We aim to evaluate the efficacy and safety of pioglitazone/metformin fixed-dose combination (FDC) versus uptitrated metformin in patients with type 2 diabetes mellitus (T2DM) without adequate glycemic control. A total of 304 patients were recruited from 15 hospitals in China and randomly assigned (1:1) to the test group (pioglitazone/metformin FDC, 15/500mg) or the control group (uptitrated metformin, 2000-2500mg/day). The primary endpoint was the proportion of patients with glycated hemoglobin A1c (HbA1c) ≤ 6.5% and ≤ 7.0% at week 16. The secondary outcomes included the change from baseline in glucose, serum lipids, and liver function. Full analysis set (FAS) and per-protocol set (PPS) were used for analyses. In the test group, 103 (69.59%) patients reached HbA1c ≤ 7.0% (FAS, P = 0.009), with 68 (45.95%) patients achieved HbA1c ≤ 6.5 (FAS, P = 0.043). More reduction in HbA1c, homeostatic model assessment for insulin resistance, and diastolic pressure was found. Bodyweight, body mass index, and high-density lipoprotein cholesterol increased markedly. The changes of triglycerides, alanine transaminase, aspartate aminotransferase, and high-sensitivity C-reactive protein decreased noticeably. There were no significant differences in rates of adverse events between the two groups. Pioglitazone/metformin FDC was superior to uptitrated metformin among patients with T2DM without adequate glycemic control. This trial is registered with the Chinese Clinical Trial Registry (ChiCTR1900028606).

Comparing Endoscopic Treatment Modalities for Gastric Antral Vascular Ectasia: Efficacy, Safety, and Outcomes in a Network Meta-analysis.

Gastric antral vascular ectasia (GAVE) is characterized by vascular ectasias accounting for 4% of nonvariceal upper gastrointestinal bleeds, which can range from occult bleeds to severe acute upper gastrointestinal bleeding. In turn, GAVE can lead to severe morbidity and recurrent hospitalization. Current endoscopic treatments for GAVE include argon plasma coagulation (APC), endoscopic band ligation (EBL), and radiofrequency ablation. With this significant burden in mind, a systematic review and network meta-analysis were conducted to compare the efficacy and safety of various modalities in the treatment of GAVE. All studies that involved adults and children with endoscopic characteristics of GAVE undergoing treatment with APC, EBL, radiofrequency ablation, or a combination of 2 treatment modalities were included. There was no statistical difference in the rate of adverse events and the number of red blood cell transfusions across all 3 groups (APC, EBL, and APC + EBL). However, statistical differences were noted for outcomes of bleeding recurrence, length of hospitalization, and change in hemoglobin status. EBL exhibited a significant decrease in bleeding recurrence when compared with APC. Moreover, shorter hospitalization stays were seen in APC + EBL and EBL groups compared with APC, and a beneficial change in hemoglobin status was also more often seen in APC + EBL and EBL groups compared with APC. Based on this study, EBL was found to have superior efficacy when compared with APC for the treatment of GAVE; however, there was no significant difference in rates of adverse events between APC, EBL, and combination therapy.

Impact of Stenting Long Lesions on Clinical Outcomes in Patients Presenting With Acute Coronary Syndrome and Multivessel Disease: Data From the BIOVASC Trial

An increased total stent length (TSL) might be associated with a higher risk of clinical events, however, in patients with multivessel disease (MVD) a considerable total stent length is often required. In patients presenting with acute coronary syndrome (ACS) and MVD, immediate complete revascularization was associated with shorter TSL in the BIOVASC Trial. This is a sub-analysis of the BIOVASC trial comparing clinical outcomes in patients with either <60mm or ≥60mm total stent length. The primary outcome was a composite of all-cause mortality, myocardial infarction, any unplanned ischemia driven revascularization or cerebrovascular events at 2 years post index procedure. 1525 patients were enrolled in the BIOVASC trial, of whom 855 had a TSL of ≥60mm (long TSL). No significant difference was established when comparing patients treated with either long or short TSL in terms of the primary outcome at 2-year follow up, which occurred in 117 patients (13.7%) in the ≥60 mm group and 69 patients (10.3%) in the <60mm group (adjusted HR 1.25, 95% CI 0.92-1.69, p=0.16). Also, no significant differences were observed in the secondary endpoints. In conclusion, in patients with ACS and MVD, long stenting did not show a significant difference in clinical event rate compared with short stenting.

Feasibility and Outcomes of an Active Osseointegrated Bone Conduction Implant in Children as Young as 5 Years of Age.

This study reviews the feasibility of implanting active osseointegrated bone conduction devices in young children, below the prior age for FDA indication (<12 years), which has recently been reduced to 5 years. Outcomes included differences in adverse event rates and operative time between two groups (<12 and 12 years or older). This study is a retrospective review of children receiving active osseointegrated bone conduction devices at a tertiary referral center academic hospital. One hundred and twenty-four children received 135 active osseointegrated bone conduction devices (May 2018-March 2024). Of 135 devices, 77 (57%) were in children <12 years (mean age (SD) = 7.9 (2.0) years, range = 4.9-11.9 years) and 58 (43%) were in 12 years or older (mean age (SD) = 15.1 (1.7) years, range = 12-18 years). Adverse events were significantly higher in the older group, occurring in 8 (10%) of 77 devices in children <12 years and 15 (26%) of 58 devices in children 12 years and older (26%) (Fisher's exact test = 0.0217 at p < 0.05). Major adverse events occurred in 5/124 (4%) patients, with 2 in patients <12 years (2/73, 3%) and 3 in children 12 and older (3/51, 6%). The proportion of major events between groups was not significantly different (Fisher's exact test = 0.4, p < 0.05). Mean surgical time was significantly less (t = -2.8799, df = 120.26, p = 0.005) in the children <12 years (mean (SD) = 66.5 (22.4) min) compared to those 12 and over (mean (SD) = 78.32 (23.1) min). Implantation of active osseointegrated bone conduction devices is feasible in children as young as 5 years and demonstrates low rates of complication. Further miniaturization may allow even earlier safe intervention.

Apixaban vs rivaroxaban in patients with atrial fibrillation at high or low bleeding risk: A population-based cohort study

BackgroundDespite many atrial fibrillation (AF) patients being at risk of bleeding, very limited data are available on bleeding rates of different direct oral anticoagulants based on the spectrum of bleeding risk. ObjectiveWe aimed to compare the risk of major bleeding and thromboembolic events with apixaban vs rivaroxaban for AF patients stratified by bleeding risk. MethodsWe conducted a population-based, retrospective cohort study of all adult patients (66 years or older) with AF in Ontario, Canada, who were treated with apixaban or rivaroxaban between April 1, 2011, and March 31, 2020. Bleeding risk was estimated by the HAS-BLED score, with high bleeding risk defined as a score of ≥3. The primary safety outcome was major bleeding, and the primary efficacy outcome was thromboembolic events. Comparisons were adjusted for baseline comorbidities by inverse probability of treatment weighting. ResultsThis study included 18,156 AF patients with high bleeding risk and 55,186 AF patients with low bleeding risk. Apixaban use was more common in patients with high bleeding risk; 63% of high-risk patients used apixaban compared with 56% of low-risk patients. Apixaban users had lower rates of major bleeding in high-risk patients (2.9% vs 4.2% per year; hazard ratio [HR], 0.69; 95% CI, 0.58–0.81) and in low-risk patients (1.8% vs 2.9% per year; HR, 0.63; 95% CI, 0.56–0.70) compared with rivaroxaban. There were no differences in rates of thromboembolic events, 3.1% vs 3.0% per year (HR, 1.02; 95% CI, 0.86–1.22) in high-risk patients and 1.9% vs 1.9% per year (HR, 1.00; 95% CI, 0.89–1.14) in low-risk patients. ConclusionIn older AF patients with high or low bleeding risk, treatment with apixaban was associated with lower rates of major bleeding with no difference in risk for thromboembolic events compared with rivaroxaban.

Disability patterns in multiple sclerosis: A meta-analysis on RAW and PIRA in the real-world context

Objective: To summarize the current evidence on relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA) through a quantitative synthesis of real-world studies. Methods: Scientific databases were searched to identify suitable articles. Random-effects meta-analyses, subgroup analyses and meta-regression models were ran to provide pooled estimates of RAW and PIRA events and to identify their potential moderators (PROSPERO registration: CRD42024503895). Results: Eighteen articles met the eligibility criteria, with a pooled sample size of 52,667 patients (93% relapsing–remitting, 6% clinically isolated syndrome and 1% progressive) followed for 2.4 to 12.1 years, yielding to 415,825 patient-years. Pooled event rates for RAW and PIRA were 1.6 (95 confidence interval (CI) = 1.1–2.1) and 3.1 (95% CI = 2.3–3.9) per 100 patient-years, respectively. Less RAW events were found in cohorts including patients with progressive course (β = −0.069, p = 0.006) and under high-efficacy disease-modifying treatments (DMTs) (β = −0.031, p = 0.007), while PIRA events were directly related to older age (β = 0.397, p = 0.027). In addition, we found significant differences in PIRA event rates according to the criteria adopted to define confirmed disability accrual (p < 0.05). Discussion: PIRA accounts for most events causing disability accumulation in the real-world setting, even at the earlier disease stages, whereas RAW represents a less frequent phenomenon, likely due to effective treatments. The detection and statistical analysis of PIRA outcomes pose challenges, raising the risk of erroneous inference. When interpreting our findings, caution is needed given the wide heterogeneity of included studies.

The SMILE study: Study of long-term methotrexate and iguratimod combination therapy in early rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation and joint destruction. Iguratimod (IGU) is a novel conventional synthetic disease-modifying antirheumatic drugs (csDMARD) with good efficacy and safety for the treatment of active RA in China and Japan. However, the long-term effects of IGU on the progression of bone destruction or radiographic progression in patients with active RA remain unknown. We aimed to investigate the efficacy and safety of iguratimod (IGU), a combination of methotrexate (MTX) and IGU, and IGU in patients with active rheumatoid arthritis (RA) who were naïve to MTX. This multicenter, double-blind, randomized, non-inferiority clinical trial was conducted at 28 centers for over 52weeks in China. In total, 911 patients were randomized (1:1:1) to receive MTX monotherapy (10-15mg weekly, n=293), IGU monotherapy (25mg twice daily, n=297), or IGU+MTX (10-15mg weekly for MTX and 25mg twice daily for IGU, n=305) for 52weeks. The patients' clinical characteristics, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), disease activity score in 28 joints-C-reactive protein (DAS28-CRP) level, and erythrocyte sedimentation rate (DAS28-ESR) were assessed at baseline. The primary endpoints were the proportion of patients with≥20% improvement according to the American College of Rheumatology (ACR20) response and changes in the van der Heijde-modified total Sharp score (vdH-mTSS) at week 52. The proportions of patients achieving an ACR20 response at week 52 were 77.44%, 77.05 %, and 65.87% for IGU monotherapy, IGU + MTX, and MTX monotherapy, respectively. The non-inferiority of IGU monotherapy to MTX monotherapy was established with the ACR20 (11.57%; 95% confidence interval [CI], 4.35-18.79%; P<0.001) and vdH-mTSS (-0.37; 95% CI, -1.22-0.47; P=0.022). IGU monotherapy was also superior to MTX monotherapy in terms of ACR20 (P=0.002) but not the vdH-mTSS. The superiority of IGU+MTX over MTX monotherapy was confirmed in terms of the ACR20 (11.18%; 95% CI, 3.99-18.37%; P=0.003), but not in the vdH-mTSS (-0.68; 95% CI, -1.46-0.11; P=0.091). However, the difference in the incidence rates of adverse events was not statistically significant. IGU monotherapy/IGU+MTX showed a more favorable clinical response than did MTX monotherapy. IGU may have some clinical benefits over MTX in terms of radiographic progression, implying that IGU may be considered as an initial therapeutic option for patients with active RA. https://classic.clinicaltrials.gov/, NCT01548001.

A Randomized, Controlled Trial Evaluating Perioperative Risk-Stratification and Risk-Based, Protocol-Driven Management After Elective Major Cancer Surgery.

We evaluated the efficacy of risk-based, protocol-driven management versus (vs) usual management after elective major cancer surgery to reduce 30-day rates of postoperative death or serious complications (DSC) . Major cancer surgery is associated with significant perioperative risks which result in worse long-term outcomes. Adults scheduled for elective major cancer surgery were stratified/randomized to risk-based escalating levels of care, monitoring, and co-management vs usual management. The primary study outcome was 30-day rate of DSC. Additional outcomes included complications, adverse events, health care utilization, health-related quality of life (HRQOL), and disease-free and overall survival (DFS and OS). Between August 2014 and June 2020, 1529 patients were enrolled and randomly allocated to the study arms; 738 patients in the Intervention Arm and 732 patients in the Control Arm were eligible for analysis. 30-day rate of DSC with the intervention was 15.0% (95% CI, 12.5-17.6%) vs 14.1%, (95% CI, 11.6-16.6%) with usual management (P=0.65). There were no differences in 30-day rates of complications or adverse events (including return to the operating room); postoperative length of stay; rate of discharge to home; or 30, 60, or 90-day HRQOL or rates of hospital readmission or receipt of anti-neoplastic therapy between the study arms. At median follow-up of 48 months, OS (P=0.57) and DFS (P=0.91) were similar. Risk-based, protocol-driven management did not reduce 30-day rate of DSC after elective major cancer surgery compared to usual management, nor improve postoperative health care utilization, HRQOL, or cancer outcomes. Trials are needed to identify cost-effective, tailored perioperative strategies to optimize outcomes after major cancer surgery.

Outpatient elective induction of labour at 39 weeks’ gestation (HOME INDUCTION): an open-label, randomised, controlled, phase III, non-inferiority trial

The increased demand for induction of labour (IOL) at 39 weeks' gestation in normal-risk nulliparous patients creates significant logistical challenges for busy maternity units. A potential innovation is commencing induction by means of outpatient cervical ripening, using either a vaginal prostaglandin preparation (Propess) or an osmotic cervical dilator (Dilapan-S). A Phase III, open label, single centre non-inferiority trial (EudraCT number 2019-004697-25) randomised healthy nulliparous women who chose elective IOL at 39 weeks to one of three methods of initial cervical ripening, specifically 12h of Dilapan-S(D12), 24h of Dilapan-S(D24), or 24h of Propess(P24) between November 2020 and July 2023. After initial administration of the IOL agent in the hospital, participants returned home for 12 or 24h, before readmission to complete delivery. The primary outcome was vaginal delivery achieved at any time, and this was compared in a non-inferiority analysis of Dilapan-S compared to Propess, within a 10% non-inferiority margin. Secondary outcomes included pairwise comparisons for each induction agent, and a range of logistical factors, such as time to delivery, the need for an additional cervical ripening agent, and length of hospital stay. Of the 327 women randomised at 38 weeks, 271 (83%) completed the induction intervention. The D24 and P24 groups showed similarly high rates of vaginal delivery, 75% and 76% respectively. D12 had a lower vaginal delivery rate of 64% and consequently the overall comparison of Dilapan-S to Propess did not demonstrate non-inferiority (difference=-6%, 95% CI=-17%, 5%) because the lower 95% CI exceeded the-10% threshold of non-inferiority. The majority of participants across all groups were delivered by any means within 72h of starting the induction process, inclusive of time spent at home (89% of the D24 group, 98% of the D12 group, 95% of the P24 group). There were no differences in rates of adverse events between groups. There were similarly high vaginal delivery rates for D24 and P24, with at least 75% of patients successfully delivering vaginally following outpatient cervical ripening, with no significant adverse maternal or neonatal outcomes. The Rotunda Foundation, Medicem Technology s.r.o.

Comparative Effectiveness and Safety of Apixaban, Rivaroxaban, and Warfarin in Patients With Cirrhosis and Atrial Fibrillation : A Nationwide Cohort Study.

Apixaban, rivaroxaban, and warfarin have shown benefit for preventing major ischemic events, albeit with increased bleeding risk, among patients in the general population with atrial fibrillation (AF). However, data are scarce in patients with cirrhosis and AF. To compare the effectiveness and safety of apixaban versus rivaroxaban and versus warfarin in patients with cirrhosis and AF. Population-based cohort study. Two U.S. claims data sets (Medicare and Optum's de-identified Clinformatics Data Mart Database [2013 to 2022]). 1:1 propensity score (PS)-matched patients with cirrhosis and nonvalvular AF initiating use of apixaban, rivaroxaban, or warfarin. Primary outcomes included ischemic stroke or systemic embolism and major hemorrhage (intracranial hemorrhage or major gastrointestinal bleeding). Database-specific and pooled PS-matched rate differences (RDs) per 1000 person-years (PY) and Cox proportional hazard ratios (HRs) with 95% CIs were estimated, controlling for 104 preexposure covariates. Rivaroxaban initiators had significantly higher rates of major hemorrhagic events than apixaban initiators (RD, 33.1 per 1000 PY [95% CI, 12.9 to 53.2 per 1000 PY]; HR, 1.47 [CI, 1.11 to 1.94]) but no significant differences in rates of ischemic events or death. Consistently higher rates of major hemorrhage were found with rivaroxaban across subgroup and sensitivity analyses. Warfarin initiators also had significantly higher rates of major hemorrhage than apixaban initiators (RD, 26.1 per 1000 PY [CI, 6.8 to 45.3 per 1000 PY]; HR, 1.38 [CI, 1.03 to 1.84]), particularly hemorrhagic stroke (RD, 9.7 per 1000 PY [CI, 2.2 to 17.2 per 1000 PY]; HR, 2.85 [CI, 1.24 to 6.59]). Nonrandomized treatment selection. Among patients with cirrhosis and nonvalvular AF, initiators of rivaroxaban versus apixaban had significantly higher rates of major hemorrhage and similar rates of ischemic events and death. Initiation of warfarin versus apixaban also contributed to significantly higher rates of major hemorrhagic events, including hemorrhagic stroke. National Institutes of Health.

Obesity and Survival After Immune Checkpoint Inhibition for Head and Neck Squamous Cell Carcinoma

For patients treated with immune checkpoint inhibitors (ICIs), recent data suggest that obesity has a beneficial effect on survival outcomes in various cancer types. Reports on this association in head and neck cancer are limited. To compare overall survival (OS) to 5 years and functional outcomes in patients with head and neck squamous cell carcinoma (HNSCC) treated with ICIs based on pretreatment body mass index (BMI). This retrospective population-based cohort study used data obtained from the TriNetX Global Collaborative Network database to identify patients with HNSCC who received ICI treatment between January 1, 2012, and December 31, 2023, resulting in a total of 166 patients (83 with BMI of 20.0-24.9 [normal BMI] and 83 with BMI of ≥30.0 [obesity BMI]) after propensity score matching (PSM) for pretreatment medical comorbidities and oncologic staging. Normal BMI vs obesity BMI. Overall survival and functional outcomes (dysphagia, tracheostomy dependence, and gastrostomy tube dependence) were measured to 5 years after ICI treatment and compared between patients with obesity BMI and normal BMI. Additional analyses compared OS and functional outcomes in the cohort with normal BMI and cohorts with overweight BMI (25.0-29.9) and underweight BMI (<20.0). Among the 166 patients included in the PSM analysis (112 men [67.1%]; mean [SD] age, 62.9 [15.4] years), obesity BMI was associated with significantly improved OS at 6 months (hazard ratio [HR], 0.54 [95% CI, 0.31-0.96]), 3 years (HR, 0.56 [95% CI, 0.38-0.83]), and 5 years (HR, 0.62 [95% CI, 0.44-0.86]) after ICI treatment, compared with patients with normal BMI. Obesity BMI was also associated with decreased risk of gastrostomy tube dependence at 6 months (odds ratio [OR], 0.41 [95% CI, 0.21-0.80]), 1 year (OR, 0.41 [95% CI, 0.21-0.78]), 3 years (OR, 0.35 [95% CI, 0.18-0.65]), and 5 years (OR, 0.34 [95% CI, 0.18-0.65]). Obesity was also associated with decreased risk for tracheostomy dependence at 1 year (OR, 0.52 [95% CI, 0.28-0.90]), 3 years (OR, 0.45 [95% CI, 0.45-0.90]), and 5 years (OR, 0.45 [95% CI, 0.45-0.90]). There were no differences in rates of dysphagia or immune-related adverse events between cohorts at any points. Using population-level data for patients with HNSCC treated with ICIs, these results suggest that having obesity was associated with improved 6-month, 3-year, and 5-year OS compared with having normal BMI. Additionally, obesity was associated with decreased gastrostomy and tracheostomy tube dependence compared with normal BMI. Further investigation is required to understand the mechanism of these findings.

Skeletonized Versus Pedicled Harvesting of the Internal Thoracic Artery and Long-Term Clinical Outcomes in Coronary Artery Bypass Surgery.

The internal thoracic artery (ITA) is the most important conduit for coronary artery bypass grafting. Recent evidence suggests that skeletonized ITA harvesting yields long-term outcomes inferior to those of pedicled harvesting. The aim was to investigate the impact of the ITA harvesting method on 10-year mortality and major adverse cardiovascular events. In this observational cohort study, we identified all patients from the SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) register who underwent isolated coronary artery bypass grafting using at least 1 ITA at Karolinska University Hospital from 2012 to 2021. The main outcome was all-cause mortality, and the secondary outcomes were a combination of myocardial infarction, repeat revascularization, heart failure, and stroke. Outcomes were ascertained using national health data registers and compared between the skeletonized and pedicled groups using weighted flexible parametric survival models. Among 3267 patients, 1657 (51%) underwent pedicled ITA harvesting and 1610 (49%) underwent skeletonized ITA harvesting. The patients' mean age was 66 years, and 15% were women. The weighted all-cause mortality incidence rate in the pedicled versus skeletonized ITA group was 2.6% (95CI, 2.2%-3.0%) versus 2.6% (95% CI, 2.2%-3.1%), respectively (hazard ratio (HR), 1.01 [95% CI, 0.81-1.27]). The weighted major adverse cardiovascular events incidence rate was 7.8% (95% CI, 7.1%-8.6%) versus 7.5% (95% CI, 6.7%-8.4%), respectively (HR, 0.94 [95% CI, 0.82-1.08]). We found no significant differences in all-cause mortality or major adverse cardiovascular events rates between the 2 ITA harvesting methods.

Effect of low-dose tamoxifen on IGF-I/IGFBP-3 and estradiol/SHBG ratio and their prognostic/predictive effect in DCIS/LCIS/ADH.

10510 Background: Babytam (BT), 5 mg/day for 3 years (y) is a popular choice for preventive therapy after breast DCIS/LCIS/ADH given its 10-y efficacy to prevent recurrence without adverse events (1). Here we investigated the effect of BT on serum biomarkers and their role as prognostic and predictive factors. Methods: In a phase-III trial of BT or placebo (P), 406 out of 500 women consented to blood sampling at baseline, 1 and 3 y. Serum estradiol (E2), SHBG, IGF-I, IGFBP-3 and their molar ratios were measured by CLIA. Biomarker changes were estimated with mixed-effects models for repeated measures and Incidence Rate Ratios (IRR) of the primary endpoint (invasive breast cancer or DCIS) were calculated after 5 and 10 y of follow-up with Poisson regression. Subgroup analyses were performed by interaction test. Results: There were no differences in event rates between women with blood samples and those w/out. Compared with P at 1 y, IGF-I/IGFBP-3 decreased by 0.039 (95%CI, 0.027-0.052), relative difference (rd), 22% (15-29) (p&lt;0.001), whereas E2/SHBG increased by 2.967 (1.767-4.166), rd, 79% (47-111) in pre- and decreased by 0.121 (-1.117-0.874), rd, -9% (-84-66), in postmenopausal women on BT (p-interaction=0.001). The mean annual rate of events (x1000 PY) after 5 and 10 y follow-up according to baseline level of IGF-I/IGFBP-3 (all women) and E2/SHBG (postmenopausal). Conclusions: BT significantly lowers IGF-I/IGFBP-3 ratio, increases E2/SHBG in premenopause to a lesser extent than 20 mg/d and is effective in most subgroups regardless of baseline biomarker levels. While lower baseline IGF-I/IGFBP-3 levels were predictive of BT efficacy at 5 and 10 y, higher levels at 10 y were associated with a lower benefit of BT. E2/SHBG had a tendency to be prognostic and predictive of BT efficacy at 5 y, but softened down at 10 y. These biomarkers may help differentiate which women benefit most from BT. The role of IGF-I change as surrogate biomarker of BT effect requires further studies. 1. Lazzeroni et al: JCO 41:3116, 2023. Clinical trial information: NCT01357772 . [Table: see text]