Symptomatic Events Research Articles

Clinical results of 30 consecutive patients of carotid artery stenosis treated with CASPER stent placement: 1-year follow-up and in-stent findings on intravascular ultrasound examination immediately and 6 months after treatment

BackgroundThe CASPER stent is expected to reduce periprocedural ischemic complications, but there is concern about restenosis in the early period. One-year follow-up results of CASPER stenting and findings on intravascular...

Early postoperative acetylsalicylic acid administration does not increase the risk of postoperative intracranial bleeding in patients with spontaneous intracerebral hemorrhage.

Administration of acetylsalicylic acid (ASA) at early stage after surgery for spontaneous intracerebral hemorrhage (SICH) may increase the risk of postoperative intracranial bleeding (PIB), because of potential inhibition of platelet function. This study aimed to investigate whether early ASA administration after surgery was related to increased risk of PIB. This retrospective study enrolled SICH patients receiving surgery from September 2019 to December 2022 in seven medical institution. Based on postoperative ASA administration, patients who continuously received ASA more than three days within seven days post-surgery were identified as ASA users, otherwise as non-ASA users. The primary outcome was symptomatic PIB events within seven days after surgery. Incidence of PIB was compared between ASA users and non-ASA users using survival analysis. This study included 744 appropriate patients from 794 SICH patients. PIB occurred in 42 patients. Survival analysis showed no statistical difference between ASA users and non-ASA users in incidence of PIB (P = 0.900). Multivariate Cox analysis demonstrated current smoker (hazard ratio [HR], 2.50, 95%CI, 1.33-4.71, P = 0.005), dyslipidemia (HR = 3.03; 95%CI, 1.31-6.99; P = 0.010) and pre-hemorrhagic antiplatelet therapy (HR = 3.05; 95% CI, 1.64-5.68; P < 0.001) were associated with PIB. Subgroup analysis manifested no significant difference in incidence of PIB between ASA users and non-ASA users after controlling the effect from factors of PIB (i.e., sex, age, current smoker, regular drinker, dyslipidemia, pre-hemorrhagic antiplatelet therapy and hematoma location). This study revealed that early ASA administration to SICH patients after surgery was not related to increased risk of PIB.

PREVALENCE OF SYMPTOMATIC VENOUS THROMBOEMBOLISM IN PATIENTS WITH DIABETIC FEET TREATED IN TOTAL CONTACT CAST IN A TERTIARY REFERRAL DIABETIC FOOT UNIT

IntroductionTotal contact casting (TCC) is one of the most commonly utilized modalities in the management of diabetic feet. We undertook a retrospective review to determine the prevalence of symptomatic VTE events in patients treated in a weight bearing TCC in our diabetic foot unit, and to formulate guidelines for VTE prophylaxis.MethodsElectronic records were reviewed to identify all patients treated in a TCC between 2014 and 2021. Data collection included patient demographics, comorbidities, period of immobilization in TCC, the incidence of VTE events, and any VTE prophylaxis prescribed during their period in TCC.Results549 patients were identified who had at least one episode of TCC. Mean age was 67 years (range 28 to 94 years) and the mean duration in cast was 10.2 weeks (range 0.3–46 weeks). Only 6 patients (1.1%) were prescribed chemical thrombo-prophylaxis during their period in TCC. Mean body mass index (BMI) for these patients was 32.3 (Range 18.4–58.9). Other significant comorbidities: 81% (n-444) of patients had associated cardio-vascular comorbidities; 54 % (n-296) had renal comorbidities including 22% (n-121) having had dialysis and 4.2% (n-23) with renal transplants. Eight of the 549 patients (1.5%) had suffered a VTE event of which only 2 (0.36%) were during the period of immobilization in TCC. One was a symptomatic DVT (0.18%) and the another was an asymptomatic (incidental) finding of pulmonary embolism (PE). There was no mortality related to the VTE episodes.ConclusionNICE guidelines state that one should “Consider pharmacological VTE prophylaxis for patients with lower limb immobilization”. Our study finds that patients treated in a weight bearing TCC do not require routine pharmacological VTE prophylaxis, in spite of an extended period of lower limb immobilization and significant medical comorbidities.

Patient-reported outcomes corresponding to most common symptomatic adverse events in lung cancer clinical trials.

11103 Background: FDA recommends assessing the most relevant expected symptomatic adverse events (AEs) with patient-reported outcomes (PROs) in cancer clinical trials (CTs) to complement traditional safety data. To inform selection of symptomatic AEs, we previously identified the most common (i.e., all-grade, clinician-reported in ≥20% of patients) symptomatic AEs from FDA-approved lung cancer product approvals from 2015 through 2021 based on CT monotherapy experimental arm safety data from US Prescribing Information (USPI). The present research aims to assess whether these CTs included PROs which adequately captured common symptomatic AEs. Methods: We assessed 30 CTs that supported lung cancer approvals from 2015 through 2021. We reviewed the study protocol, statistical analysis plan, and/or clinical study report to determine the PRO measures included. We matched symptoms included within PRO measures and items to the most common clinician-reported symptomatic AEs per the USPI to determine the extent to which the PROs and symptomatic AEs corresponded. Results: Twenty-three out of 30 (77%) CTs supporting non-small cell lung cancer (NSCLC) approvals included PRO(s). Nineteen included more than one PRO measure. The most frequently used PRO measures were the European Organisation for Research and Treatment of Cancer-Core Questionnaire (EORTC QLQ-C30; n=19), EORTC-Lung Cancer (EORTC QLQ-L13; n=17), EuroQoL 5-Dimension (EQ-5D; n=12), and selected items from the Patient-reported Outcomes version of the Common Terminology Criteria for Adverse Events item library (PRO-CTCAE; n=4). Nearly all (20 of 23) CTs included PRO items corresponding to more than half of the common symptomatic AEs reported. Symptomatic AEs for types of pain corresponded to general pain PRO items (e.g., “musculoskeletal pain” matched to EORTC item for “pain”). However, PRO items for specific types of pain were not often used. While important symptomatic AEs such as fatigue, diarrhea, nausea, and decreased appetite were often assessed by PROs, others including rash and edema were not usually captured. Ultimately, only 4 of 23 (17%) CTs with PROs included items that assessed all symptomatic AEs that occurred in ≥20% of patients. Of the 4 CTs which included an item library, 3 (75%) comprehensively assessed patient-reported symptomatic AEs, compared to 3 of 19 (16%) CTs that did not employ an item library for patient-reported symptom collection. Conclusions: Based on USPI safety data and PRO measures from CT monotherapy experimental arms of recently approved NSCLC cancer drugs, we determined that while the majority of CTs include PRO items for some relevant symptomatic AEs, other important expected symptomatic AEs (e.g., edema, rash, specific types of pain) were not measured. Future NSCLC CTs should include PRO items for common expected symptomatic AEs which is feasible using well-established PRO item libraries.

Feasibility and utilization of electronic patient-reported outcome measures for lung cancer in routine clinical care.

11107 Background: Prior studies have shown the value of Patient-Reported Outcomes (PRO) in cost burden, quality of life (QoL), and survival in cancer care. To facilitate focus on patient-centricity and value-based care, the International Consortium for Health Outcomes Measurements (ICHOM) and European Health Outcomes Observatory (H2O) developed a Core Outcomes Set (COS) in lung cancer. We explored the feasibility of deploying standardized PRO measures among patients with lung cancer in US clinical practice. Methods: A retrospective database study was conducted, with IRB waiver, using Carevive PROmPT, an electronic PRO (ePRO) remote symptom monitoring platform with weekly surveys comparable in scope to ICHOM/H2O COS, of symptomatic adverse events (PRO-CTCAE), physical function (PROMIS 4A Physical Function), and QoL items (EORTC QLQ-C30 items #29,30). Severe PRO-CTCAE symptom scores triggered care team alerts. From 9/2020 to 5/2023, 207 patients enrolled across 9 US cancer centers. Patients were ≥18 years, with lung cancer, and in current treatment. Patient engagement was measured by survey compliance, follow-up time, and completeness; clinician engagement was measured by platform utilization time, time to alert response, and clinical action taken. Results: Participants were 50% female, 86% White, 12% African American, median age 68, 81% NSCLC, and 26% with metastatic disease. Median survey persistence: 8 weeks, with 85% compliance over that time. Of domains assessed, 37 (58%) from Carevive data overlapped with ICHOM/H2O COS, with 19 measured over time. Overlapping domains included 15 clinical outcomes with 60% median completion rate and 22 PRO domains with 98% median completion. Of 19 domains assessed longitudinally, median compliance was 76%. Of patients triggering ≥1 ePRO symptom alert, 87% were within 4 weeks, with 46% requesting call-backs. Median clinician follow-up to alerts was 20 hours, with 69.3% addressed within 48 hours. Clinicians accessed the platform 2-3 times weekly, for median 2 minutes (range: 1-14 minutes) per login for nurses and Advanced Practitioners (AP). 89% of alerts were addressed by nurses and AP. Of alert responses, 66% indicated continuation of treatment, 12% were escalated to the clinical team, and 1% were escalated to hospitalization or ER visit. Conclusions: Results support the feasibility of integrating a standard set of multi-domain ePRO measures, comparable to the ICHOM/H2O COS, into routine cancer care, across multiple sites, with consistent patient engagement and provider utilization. One limitation is that clinical and financial impact were not directly assessed. Future research should explore direct clinician feedback, systematic implementation of PRO measures, and impacts on patient outcomes, resource utilization, and health systems.

Patient-reported outcomes (PROs) from the DREAMM-7 randomized phase 3 study comparing belantamab mafodotin, bortezomib, and dexamethasone (BVd) vs daratumumab, bortezomib, and dexamethasone (DVd) in patients with relapsed/refractory multiple myeloma (RRMM).

7543 Background: Belantamab mafodotin(belamaf), a first-in-class antibody-drug conjugate targeting B-cell maturation antigen, acts through a multimodal mechanism including direct cell killing and immune-mediated mechanisms. The global, phase 3, open-label, randomized, DREAMM-7 trial (NCT04246047) met its primary endpoint of demonstrating statistically significant progression-free survival benefit favoring BVd vs DVd in patients with RRMM who had received ≥1 prior line of therapy; here, we report PRO findings for BVd vs DVd. Methods: Patients were randomized (1:1) to receive BVd or DVd and completed electronic PRO measures at baseline and every 3 weeks (Q3W) during treatment. PRO measures included EORTC-QLQ-C30, EORTC-QLQ-MY20 disease symptoms (pain), PRO-CTCAE patient-reported tolerability, and OSDI vision-related functioning (Q3W up to the sixth dose of belamaf, then Q6W). Each domain was summarized using descriptive statistics. Results: Among 494 patients (BVd, n=243; DVd, n=251), adherence to PRO assessments was &gt;90% for most study visits. There was no difference in EORTC QLQ-C30 global health status/quality-of-life assessments between the study arms over time. Similarly, role functioning, physical functioning, fatigue, and pain were stable (change from baseline in EORTC score was within 10 points) over time and consistent between arms. Most symptomatic adverse events evaluated by PRO-CTCAE were reported at no to low severity, frequency, and interference (PRO-CTCAE ratings ≤2) in both arms throughout the study. The severity and interference of blurred vision and frequency of watery eyes were reported at higher levels (PRO-CTCAE ratings ≥3) in the BVd arm. Among patients in the BVd arm with a clinically meaningful deterioration in vision-related functioning (a change from baseline of ≥12.5 points), EORTC-QLQ-C30 global health status, role functioning, and physical functioning were comparable to the DVd arm over time. Conclusions: Overallquality of life, role functioning, physical functioning, fatigue, and pain were comparable in patients treated with BVd vs DVd. In patients treated with BVd who reported a clinically meaningful deterioration in vision-related functioning, overall quality of life was consistent with the DVd arm.

Comparative patient-reported tolerability (PRT): A multiplicity-controlled analysis of LIBRETTO-531, a randomized controlled trial (RCT) in medullary thyroid cancer (MTC).

11111 Background: In cancers with longer natural histories, progression free survival (PFS) alone may not adequately capture the impact of treatment side effects (SE) and may, therefore, be complemented by robust measures of patient-reported tolerability (PRT) to quantify overall SE burden. Here, we pioneer the use of a novel, scalable, quantitative PRT metric as a key secondary endpoint to support the regulatory review and inform clinical decision-making of selpercatinib use in LIBRETTO-531 (NCT04211337), an RCT that demonstrated the PFS benefit (HR=0.28) of selpercatinib over vandetanib/cabozantinib (control) in RET-mutant MTC. Methods: We first assessed PRT using the single Functional Assessment of Cancer Therapy (FACT) item GP5, asking patients to rate “bothered by treatment side effects” from 0 to 4. Patients who reported “3=quite a bit” or “4=very much” on GP5 were classified as “high SE bother,” a validated meaningful cutoff for treatment SE burden. In a second pre-specified step, PRT was defined as the proportion of time on treatment (PTOT) with “high SE bother” and was compared between selpercatinib vs. control arms in the tolerability evaluable population. PRT was tested at a 1-sided significance level of 0.025, conditional on achieving statistical significance for PFS and treatment failure-free survival by BICR. To complement PRT, other patient-reported outcomes including health-related quality of life (HRQoL, using EORTC QLQ-C30) and symptomatic adverse events (AEs; using PRO-CTCAE) were evaluated. We calculated the PTOT that patients reported clinically meaningful impairment of HRQoL (using pre-specified cutoff scores) and highly symptomatic AEs (scores of 3 or 4). Results: Patients on selpercatinib (n=161) had a significantly better PRT (lower PTOT with high SE bother) than control (n=81) (8% vs. 24%, p&lt;.0001). Sensitivity analyses using different cutoffs for high SE bother showed consistent results (p&lt;.0001). On QLQ-C30, patients on selpercatinib reported significantly less PTOT with HRQoL impairment across physical (36% vs. 52%), role (2% vs. 11%), cognitive (4% vs. 8%), emotional (6% vs. 11%), and social (2% vs. 8%) functions (all p&lt;0.01) vs. control. On PRO-CTCAE, patients on selpercatinib reported significantly less PTOT with diarrhea (5% vs. 38%), fatigue (6% vs. 21%), taste change (3% vs. 15%), decreased appetite (2% vs. 15%), hand/foot syndrome (2% vs. 9%) (all p&lt;.001) vs. control. Conclusions: Through the incorporation of a novel, single question and quantifiable metric that measured time on treatment under high SE bother into the LIBRETTO-531 study, we demonstrated superior PRT and improved PFS for selpercatinib in patients with RET-mutant MTC versus vandetanib/cabozantinib. This simplified PRT metric deserves further adoption as a quantitative endpoint to complement PFS in future RCTs.

Sex influence on cancer immunotherapy efficacy and safety in advanced non-small cell lung cancer (NSCLC): A Canadian institution real-world experience.

e20618 Background: Males and females differ in innate and adaptive immune responses. This difference may also be reflected in their response to cancer immunotherapies. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment for advanced NSCLC, however the impact of sex on treatment outcomes in these patients remains unclear. The aim of this retrospective cohort study was to evaluate sex-related differences in immunotherapy outcome in a real-world population of NSCLC patients treated with ICIs. Methods: Demographics, clinical, pathological and treatment characteristics were assessed. Treatment-related variables were analyzed to understand the differences in efficacy and safety outcomes including response rates, PFS, OS and all-cause treatment discontinuation (TD) in relation to sex. Results: 152 advanced NSCLC patients receiving first-line immunotherapy, either alone or in conjunction with chemotherapy, were included in the study cohort. Females were younger age, were more likely to be non-smokers, have non-squamous tumors and had a higher prevalence of pre-existing autoimmune diseases compared to males. Disease control (CR/PR/SD) was achieved in 65.8% of patients. Median PFS was 12.0 mo in females and 14.1 mo in males. Median OS for all patients was 15.8 mo; 16.1 and 15.7 mo in females and males respectively. No statistical differences based on gender were observed in PFS and OS (P = 0.767 and P = 0.657). In regression analysis older age and presence of liver metastases were independent poor prognostic factors. Gender was not an independent prognostic factor in PFS and OS. Notably, 44 or 28.9% patients developed symptomatic immune-related adverse events (ir-AEs) that led to TD (Table 1). ir-AE-related TD occurred at a significantly higher rate in females compared with males (Table 1; 38.2% vs 19.7%, RR = 1.90; 95% CI: 1.12 to 3.26; p = 0.018). GI toxicity, including hepatitis and colitis was predominantly observed in females, whereas pneumonitis was the most frequent ir-AE leading to TD in males. Conclusions: Despite no significant differences based on gender were observed in PFS and OS, our study showed that female patients with advanced NSCLC receiving ICIs are at a substantially greater risk of severe symptomatic ir-AEs and TD. This finding indicates that broad-based sex differences in this context could potentially exist and emphasizes the need for further investigations into the role played by gender in immunity and cancer immunotherapy treatment.[Table: see text]

A phase 1, randomized, double-blind, placebo-controlled trial investigating the pharmacokinetics, pharmacodynamics, safety and tolerability of oral semaglutide in healthy Chinese subjects.

The trial (NCT04016974) investigated the pharmacokinetics, pharmacodynamics, safety and tolerability of oral semaglutide, the first orally administered glucagon-like peptide-1 analogue for type 2 diabetes, in healthy Chinese subjects. This single-centre, multiple-dose, placebo-controlled trial randomized 32 healthy Chinese adults to once-daily oral semaglutide (3 mg escalating to 14 mg) or placebo for 12 weeks. Blood samples were collected regularly during treatment and follow-up. The primary endpoint was the area under the semaglutide concentration-time curve over a dosing interval (0-24 h) at steady state (AUC0-24h,sema,SS). Secondary pharmacokinetic endpoints included the maximum observed semaglutide plasma concentration at steady state (Cmax,sema,SS). Supportive secondary pharmacodynamics endpoints included changes in body weight and fasting plasma glucose. Treatment with all oral semaglutide doses showed dose-dependent increases in semaglutide exposure in healthy Chinese subjects at steady state, determined by AUC0-24h,sema,SS (233, 552 and 1288 h·nmol/L for 3, 7 and 14 mg of oral semaglutide, respectively) and Cmax,sema,SS. Oral semaglutide treatment was associated with significant reductions in body weight (p = .0001) and fasting plasma glucose (p = .0011) versus placebo at the end of treatment. The safety and tolerability of oral semaglutide were consistent with the known profile of glucagon-like peptide-1 receptor agonists, with no severe or blood-glucose-confirmed symptomatic hypoglycaemic events, serious adverse events or deaths. The most frequent adverse events were gastrointestinal disorders. At steady state, oral semaglutide exposure was dose dependent and close to dose proportionality in healthy Chinese subjects. This is consistent with previous clinical pharmacology results for oral semaglutide.

Patient-reported symptomatic events do not adequately reflect atrial arrhythmia

BackgroundManagement of atrial fibrillation is frequently geared toward improving symptoms. Yet, the magnitude of symptom-rhythm discordance is not well known in the setting of monitoring by ambulatory electrocardiography (AECG). ObjectiveWe aimed to quantify the symptom-rhythm correlation (SRC) for atrial arrhythmia (atrial tachycardia/atrial fibrillation [AT/AF]) events. MethodsThis was a retrospective cohort analysis of AECG data at a tertiary care center. All AECGs of ≥7 days with at least 1 AT/AF were included. Patient-triggered symptoms included shortness of breath, tiredness, palpitations, dizziness, or passing out with or without concurrent AT/AF. SRC was calculated for each patient. In addition, AT/AF-symptom association was evaluated at the event level by multivariable mixed effects logistic regression. ResultsWe identified 742 patients with qualifying AECG data; mean age was 64 years, 50% were female, and 22% had heart failure. The mean CHA2DS2-VASc score was 2.5. There were 6289 symptomatic events and 6900 AT/AF episodes. Of symptomatic events, 1013 (16%) had shortness of breath, 839 (13%) tiredness, 2640 (42%) palpitations, 783 (12%) dizziness, and 93 (1%) passing out. Overall SRC was 0.39 (range, 0–1.0), but presence of AT/AF increased odds of symptoms by ∼8.3 times in adjusted analyses (P < .01). In multivariable analysis, prior AF rhythm control treatment and lower heart rate were associated with worse SRC (P < .01). ConclusionWhereas AT/AF events increase the chances of symptoms, there is poor overall correlation between symptomatic events and documented AT/AF. Patient factors and prior treatments influence SRC. An improved understanding of this relationship correlation is needed to optimize clinical outcomes and to improve the rigor of AF research.

Diagnostic yield of cardiac monitors in patients with suspected arrhythmias: systematic literature review and network meta-analysis

Abstract Objective To demonstrate the diagnostic yield (DY) across cardiac rhythm monitors stratified by monitoring duration for symptomatic patients with suspected cardiac arrhythmias (palpitations, dizziness, syncope, presyncope, lightheadedness). Methods PubMed, Embase, and Scopus were searched to identify published randomized and observational studies between January 1, 2000, and November 28th, 2021. DY data were extracted for comparative studies. The DY of cardiac monitors in these patients was reviewed for Any Arrhythmia, Clinically Relevant Arrhythmia, Explained Episodes (symptomatic and clinically relevant), New Onset Atrial Fibrillation, and Symptomatic Events. Clinically Relevant Arrhythmia was defined by the study and included atrial fibrillation, atrial flutter, atrial tachycardia, other SVT, VT, pause, and bradycardia. Patients who had a history of prior stroke or transient ischemic attack were excluded. Network meta-analysis (NMA) was used to pool estimates. Cardiac monitoring duration was categorized into the following 3 timeframes: 3 days or less (≤3 d), greater than 3 days to less than 30 days (&amp;gt;3 d), and 30 days or greater (≥ 30 d). Results Inclusion and exclusion criteria identified a pooled population of 1696 patients in 6 comparative studies, 2 Randomized Controlled Trials (RCTs) and 4 non-RCTs (Figure 1). NMA results for comparative studies show that monitoring durations of &amp;gt;3 d and ≥30 d provided significant better DY than ≤3 d (Table 1). The odds ratio for DY of &amp;gt;3 d as compared to ≤3 d was 5.75 (95% CI 2.05-19.38) in patients with Any Arrhythmias, 5.99 (95% CI 2.10 - 7.79) in patients with Clinically Relevant Arrhythmias, 10.22 (95% CI 0.61 - 4343.00) in patients with Explained Episodes, and 2.74 (95% CI 1.12 - 7.53) in patients with New Onset Atrial Fibrillation. As only a single study provided results on Symptomatic Events, NMA was not possible for this measure. The odds ratio for DY of &amp;gt;3 d as compared to ≥30 d was 0.02 (95% CI 0.00 - 0.15) in patients with Any Arrhythmias, 0.03 (95% CI 0.00 - 0.10) in patients with Clinically Relevant Arrhythmias, 0.04 (95% CI 0.01 - 0.13) in patients with Explained Episodes, and 0.17 (95% CI 0.03 - 0.66) in patients with diagnosis of New Onset Atrial Fibrillation. Conclusion NMA indicates that &amp;gt;3 d and ≥30 d provide significantly better DY than ≤3 d for identifying Any Arrhythmia, Clinically Relevant Arrhythmia, and New Onset AF. Despite favorable odds ratios for ≥30 d over &amp;gt;3 d, these values were associated with uncertainty due to the limited studies available for monitoring durations of ≥30 d. Overall, in patients experiencing symptoms of palpitations, dizziness, syncope, and without prior stroke or transient ischemic arrest, &amp;gt;3 d of monitoring improved DY compared with shorter monitoring durations.Figure 1.Prisma Flow DiagramTable 1.Diagnostic Yield Comparison.

Utilization of implantable cardiac monitors in detecting type 1 patterns in brugada syndrome

Abstract Introduction In individuals with Brugada syndrome, the presence of the type 1 pattern (BP1) is linked to an elevated risk of severe arrhythmias. However, the identification and measurement of BP1 can be challenging due to its intermittent nature. Implantable cardiac monitors (ICMs) provide extended continuous monitoring, potentially overcoming the limitations of intermittent ambulatory ECG monitoring in detecting spontaneous BP1. Nevertheless, their specific application for this purpose remains unevaluated. Methods From November 2022 to September 2023, all patients presenting with pharmacologically induced BP1 were enrolled at our centre. An ICM was surgically placed in the left second intercostal space at a 45° angle, enabling readings with a morphology similar to the right precordial ECG leads during ajmaline testing (AT). Patients were remotely monitored, and in addition to routine automatic transmissions, each patient was provided with a remote control to transmit in case of fever or symptomatic events. Transmissions were scrutinized to detect: 1) ST-segment elevation; 2) ventricular arrhythmias; 3) burden of ventricular extrasystoles (PVC). A reading was classified as positive for BP1 if it bore a similar morphology to that recorded during AT. The frequency of BP1-positive transmissions was evaluated across four hourly intervals. Results The ICM was successfully implanted in 21 patients (male-to-female ratio 1.62:1, mean age 43.9±13.1 years). Over an average follow-up of 168±70.6 days, a total of 7818 transmissions were received, evenly spread across hourly intervals (minimum of 1296 transmissions per interval). Among these, 173 transmissions were identified as BP1 positive (2.2%), originating from 6 patients (28.6% of the total, all newly diagnosed with spontaneous BP1). The median duration between implantation and the diagnosis of spontaneous BP1 was 16.5 days (range 2-23). The median number of days with at least one positive transmission was 30.2 (range 13.4-73.9). The evening period (6 pm to midnight) displayed a significantly higher rate of positive transmissions compared to the morning (p=0.04) and afternoon (p=0.01); however, not in contrast to the nighttime (p=0.8). No sustained ventricular arrhythmias were observed, and there were no significant differences in PVC burden among patients. Conclusions The utilization of ICM for continuous monitoring in patients with pharmacologically induced BP1 led to the identification of spontaneous BP1 patterns in almost 30% of cases during an approximately 6-month follow-up. Evening and nighttime periods exhibited the highest incidence of BP1. This methodology shows promise in quantifying BP1 incidence and could serve as a tool for stratifying arrhythmic risk in individuals with Brugada syndrome.

Economic burden of generalized myasthenia gravis (MG) in the United States and the impact of common comorbidities and acute MG-events

Background This study assessed the incremental healthcare costs and resource utilization (HRU) associated with generalized myasthenia gravis (gMG), as well as variability in these outcomes among patients with gMG and common comorbidities and acute MG-related events. Methods Adults with gMG and without MG were identified from a large US database (2017–2021). The index date was the first MG diagnosis (gMG cohort) or random date (non-MG cohort). Cohorts were propensity score matched 1:1. The gMG cohort included subgroups of patients with a 12-month pre-index (baseline) cardiometabolic or psychiatric comorbidity, or a post-index MG exacerbation/crisis. Monthly healthcare costs (2021 USD) and HRU were compared post-index between gMG and non-MG cohorts. Results The gMG and matched non-MG cohorts each contained 2,739 patients. Mean incremental healthcare costs associated with MG were $4,155 (gMG: $5,567; non-MG: $1,411), with differences driven by incremental inpatient costs of $2,166 (gMG: $2,617; non-MG: $452); all p < 0.001. The gMG versus non-MG cohort had 4.36 times more inpatient admissions and 2.26 times more outpatient visits; all p < 0.001. Among patients with gMG in cardiometabolic (n = 1,859), psychiatric (n = 1,308), and exacerbation/crisis (n = 419) subgroups, mean monthly healthcare costs were $6,660, $7,443, and $17,330, respectively. Conclusions gMG is associated with substantial incremental costs and HRU, with inpatient costs driving the total incremental costs. Costs increased by 20% and 34% among patients with cardiometabolic and psychiatric conditions, respectively, and over three times among those with acute MG-related events. gMG is a complex disease requiring management of comorbidities and treatment options that can prevent acute symptomatic events.

Final Results of RIGHT Choice: Ribociclib Plus Endocrine Therapy Versus Combination Chemotherapy in Premenopausal Women With Clinically Aggressive Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer.

A head-to-head comparison of efficacy between a cyclin-dependent kinase 4/6 inhibitor plus endocrine therapy (ET) versus combination chemotherapy (CT) has never been reported in patients with clinically aggressive hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). In this open-label, multicenter, randomized phase II trial, pre/perimenopausal women with clinically aggressive HR+/HER2- ABC were randomly assigned 1:1 to first-line ribociclib (600 mg once daily; 3 weeks on, 1 week off) plus letrozole/anastrozole and goserelin or investigator's choice of combination CT (docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine). The primary end point was progression-free survival (PFS). Among 222 patients randomly assigned to ribociclib plus ET (n = 112) or combination CT (n = 110), 150 (67.6%) had symptomatic visceral metastases, 41 (18.5%) had rapid disease progression per investigator's judgment, and 31 (14.0%) had symptomatic nonvisceral disease. Overall, 106 (47.7%) patients had investigator-assessed visceral crisis. The median follow-up time was 37.0 months. At data cutoff, 31.3% (ribociclib arm) and 15.5% (CT arm) of patients had completed study treatment and transitioned to post-trial access. The median PFS was 21.8 months (ribociclib plus ET; [95% CI, 17.4 to 26.7]) and 12.8 months (combination CT; [95% CI, 10.1 to 18.4); hazard ratio, 0.61 [95% CI, 0.43 to 0.87]; P = .003. The overall response rates and the median time to response in the ribociclib versus CT arms, respectively, were 66.1% and 61.8% and 4.9 months and 3.2 months (hazard ratio, 0.76 [95% CI, 0.55 to 1.06]). Lower rates of symptomatic adverse events were observed in the ribociclib versus CT arm. First-line ribociclib plus ET showed a significant PFS benefit, similar response rates, and better tolerability over combination CT in patients with clinically aggressive HR+/HER2- ABC.

The Use of Computed Tomography to Quantify Renal Calculi Strain to Estimate Potential Symptomatic Incidents

This study investigates into the historical evolution and contemporary applications of Computed Tomography (CT) in renal stone estimation, with a focus on the innovative use of CT to quantify renallcalculiistrain for estimating potentiallsymptomatic incidents. Historically, CT has played a pivotal role in diagnosing renal calculi, offering unparalleled sensitivity and specificity in detecting stones of varying composition and size. However, the clinical significance of renal calculi extends beyond mere detection, prompting researchers to explore novel approaches to predict symptomatic events associated with stone disease. This research aimed to determine the right way to classify asymptomatic radiographic calculi strain on computed tomography (CT) scans in Al-Hussein Teaching Hospital, Al-Muthanna, Iraq. A survey was made available to calculi formers who had a CT scan during asymptomatic after a calculi clinical assessment. A survey and a study of medical records revealed symptomatic calculi route incidents after a CT scan. The amount of calculus, the biggest calculi thickness, electronic total calculi size (TSV), and two-pronged calculus were measured radiographically and linked as predictors of calculi events. There were 55 calculi formers in the study, and 61% had a calculi event one year after the CT scan. The calculus number was (0–1, 2–3, 4–6, 7), the highest calculi diameter was (0–2, 3–4, 5–7, 8 mm), and 48% had bilateral calculus. The number of calculus per quartile had a danger ratio of 1.30 (p = 0.001), the largest calculi diameter had a hazard ratio of 1.26 (p 0.001), TSV had a hazard ratio of 1.38 (p = 0.001), and bilateral calculus had a hazard ratio of 1.80 (p = 0.001). Only TSV wass an unbiased measure offsymptomaticceventssin multivariable regression (HR = 1.35 per quartile, p = 0.01). TSV-related incidents were also unaffected by demographics, urinary chemistry, or calculi composition. A drastic rise in TSV between CT scans (&gt; 31 mm3/year) expected additional eventssin the 49 patients with interim events (HR = 2.8, p = 0.05). For calculating calculi pressure on CT scan, automated TSV is more accurate for asymptomatic events than physical approaches.

Long-term Monitoring to Detect Risk of Sudden Cardiac Death in Inherited Arrhythmia Patients

BackgroundRisk stratification in inherited arrhythmia syndromes is challenging. Implantable cardioverter defibrillators (ICDs) are effective in the prevention of sudden cardiac death but are associated with significant complications. We aimed to determine the value of long-term implantable loop recorder (ILR) monitoring to determine risk factors for arrhythmias in inherited arrhythmia patients. MethodsWe conducted a prospective multicentre study between 2015 and 2020 recruiting inherited arrhythmia probands and family members at intermediate arrhythmic risk, with no class 1 indication for ICD implantation. The primary endpoint was the detection by ILR of nonsustained ventricular tachycardia over ≥ 10 consecutive beats. Secondary endpoints included ICD insertion during follow-up, all-cause mortality, and ILR complication rates. ResultsA total of 45 individuals (30 female participants) were enrolled in the study. The most common diagnoses were long-QT syndrome (28%), Brugada syndrome (26%), and arrhythmogenic cardiomyopathy (11%). Following ILR insertion (mean follow-up 633 days; range, 387-969), cardiac symptoms occurred in 19 of 45 patients (42%), 5 of whom had nonsustained ventricular tachycardias (11%), which were symptomatic in 3 individuals. This situation led to ICD implantation based on ILR in 5 of 45 patients (11%). Fifty percent of symptomatic events occurred in ARVC patients. The median time from ILR insertion to ICD implantation was 152 days (interquartile range (25th, 75th percentiles) 55 of 209). No patient experienced sudden cardiac death. ConclusionsILRs enable the detection of high-risk arrhythmic features and facilitate selection of ICD candidates in inherited arrhythmia patients with borderline indications.

Health-related quality of life with sacituzumab govitecan in HR+/HER2- metastatic breast cancer in the phase III TROPiCS-02 trial.

The TROPiCS-02 study (NCT03901339) demonstrated that sacituzumab govitecan (SG) has superior clinical outcomes over treatment of physician's choice (TPC) chemotherapy in patients with hormone receptor-positive, human epidermal growth factor 2 receptor-negative (HR+/HER2-) metastatic breast cancer (mBC). Here, we present health-related quality of life (HRQoL) patient-reported outcome (PRO) findings from this study. Eligible adults with HR+/HER2- mBC who previously received a taxane, endocrine-based therapy, a CDK4/6 inhibitor, and 2-4 lines of chemotherapy were randomized 1:1 to receive SG or TPC until progression or unacceptable toxicity. PROs were assessed at baseline and on day 1 of each cycle, using the European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 (EORTC QLQ-C30), EQ-5D-5L, and PRO Common Terminology Criteria for Adverse Events (PRO-CTCAE). Compared to TPC, overall least square mean change from baseline was significantly better for SG for physical functioning and dyspnea, but worse for diarrhea. Time to first clinically meaningful worsening or death was significantly longer for SG in global health status/quality of life, physical functioning, fatigue, emotional functioning, dyspnea, insomnia, and financial difficulties of the EORTC QLQ-C30 and the EQ-VAS, but longer for TPC in diarrhea. Few patients in both arms reported experiencing any worsening to level 3 or 4 treatment-related symptomatic events during treatment, as assessed by 16 PRO-CTCAE items, except for diarrhea frequency and amount of hair loss, which favored TPC. SG was associated with an HRQoL benefit in most symptoms and functioning, compared with TPC. This supports the favorable profile of SG as a treatment option for patients with pretreated HR+/HER2- mBC.

Association of preprocedural antiplatelet use with decreased thromboembolic complications for intracranial aneurysms undergoing intrasaccular flow disruption.

This study was conducted to investigate the impact of antiplatelet administration in the periprocedural period on the occurrence of thromboembolic complications (TECs) in patients undergoing treatment using the Woven EndoBridge (WEB) device for intracranial wide-necked bifurcation aneurysms. The primary objective was to assess whether the use of antiplatelets in the pre- and postprocedural phases reduces the likelihood of developing TECs, considering various covariates. A retrospective multicenter observational study was conducted within the WorldWideWEB Consortium and comprised 38 academic centers with endovascular treatment capabilities. Univariable and multivariable logistic regression analyses were performed to determine the association between antiplatelet use and TECs, adjusting for covariates. Missing predictor data were addressed using multiple imputation. The study comprised two cohorts: one addressing general thromboembolic events and consisting of 1412 patients, among whom 103 experienced TECs, and another focusing on symptomatic thromboembolic events and comprising 1395 patients, of whom 50 experienced symptomatic TECs. Preprocedural antiplatelet use was associated with a reduced likelihood of overall TECs (OR 0.32, 95% CI 0.19-0.53, p < 0.001) and symptomatic TECs (OR 0.49, 95% CI 0.25-0.95, p = 0.036), whereas postprocedural antiplatelet use showed no significant association with TECs. The study also revealed additional predictors of TECs, including stent use (overall: OR 4.96, 95% CI 2.38-10.3, p < 0.001; symptomatic: OR 3.24, 95% CI 1.26-8.36, p = 0.015), WEB single-layer sphere (SLS) type (overall: OR 0.18, 95% CI 0.04-0.74, p = 0.017), and posterior circulation aneurysm location (symptomatic: OR 18.43, 95% CI 1.48-230, p = 0.024). The findings of this study suggest that the preprocedural administration of antiplatelets is associated with a reduced likelihood of TECs in patients undergoing treatment with the WEB device for wide-necked bifurcation aneurysms. However, postprocedural antiplatelet use did not show a significant impact on TEC occurrence.

Circulating microRNAs and therapy-associated cardiac events in HER2-positive breast cancer patients: an exploratory analysis from NeoALTTO

PurposeThe relevance of cardiotoxicity in the context of HER2-positive breast cancer is likely to increase with increasing patient treatment exposure, number of treatment lines, and prolonged survival. Circulating biomarkers to early identify patients at risk of cardiotoxicity could allow personalized treatment and follow-up measures. The aim of this study is to examine the relationship between circulating microRNAs and adverse cardiac events in HER2-positive breast cancer patients.MethodsWe based our work on plasma samples from NeoALTTO trial obtained at baseline, after 2 weeks of anti-HER2 therapy, and immediately before surgery. Eleven patients experienced either a symptomatic or asymptomatic cardiac event. Circulating microRNAs were profiled in all patients presenting a cardiac event (case) and in an equal number of matched patients free of reported cardiac events (controls) using microRNA-Ready-to-Use PCR (Human panel I + II). Sensitivity analyses were performed by increasing the number of controls to 1:2 and 1:3. Normalized microRNA expression levels were compared between cases and controls using the non-parametric Kruskal–Wallis test.ResultsEight circulating microRNAs resulted differentially expressed after 2 weeks of anti-HER2 therapy between patients experiencing or not a cardiac event. Specifically, the expression of miR-125b-5p, miR-409-3p, miR-15a-5p, miR-423-5p, miR-148a-3p, miR-99a-5p, and miR-320b increased in plasma of cases as compared to controls, while the expression of miR-642a-5p decreases. Functional enrichment analysis revealed that all these microRNAs were involved in cardiomyocyte adrenergic signaling pathway.ConclusionThis study provides proof of concept that circulating microRNAs tested soon after treatment start could serve as biomarkers of cardiotoxicity in a very early stage in breast cancer patients receiving anti-HER2 therapy.

Frequency of hypoglycaemia with basal insulin treatments in adults with type 1 diabetes treated with basal-bolus insulin regimens in treat-to-target trials: A narrative review.

To summarise, in a narrative review, published data on hypoglycaemia occurrence with basal insulin therapy in adults with type 1 diabetes treated with basal-bolus insulin regimens in treat-to-target randomised controlled trials. Data were included from 21 eligible trials, which mainly used self-measured blood glucose or plasma glucose to detect hypoglycaemia. All-day self-measured blood glucose or plasma glucose level 2 (glucose threshold of 3.1 or 3.0 mmol/L) and level 3 (severe, requiring assistance) hypoglycaemic events were reported, respectively, by a range of 69.0%-97.5% and 0%-13.4% adults when receiving basal-bolus insulin therapy, with rates of 10.6-68.1 and 0.0-0.4 events per patient-year of exposure, respectively. Hypoglycaemia rates measured using continuous glucose monitoring (three studies) were numerically, yet consistently, higher than with either other method, except when limiting to symptomatic events. Nocturnal hypoglycaemia rates were generally less than 30% of the equivalent all-day rates. Differences across the studies in design (e.g., titration targets) and participant characteristics hindered comparison of hypoglycaemia rates by insulin formulation. Consequently, few trends were identified by insulin formulation, study methodology or individuals' characteristics, suggesting that further research is required to identify treatment strategies that facilitate development of individualised recommendations to lower hypoglycaemia risk. These findings are useful to understand hypoglycaemia risk with available basal insulin therapies when used in a multiple daily injection regimen, as well as to provide context for the results of ongoing and future clinical trials, including those for two once-weekly basal insulins, insulin icodec and basal insulin Fc.