Risultati per: Short Acting Opioid

The American Academy of Pediatrics (AAP) released its first clinical guidance on prescribing opioids for outpatient acute pain management to youth. Although it cautions against the dangers of rising opioid use disorder among children and teens, it also notes that a decrease in opioid prescription rates may leave some youth with pain that is not adequately treated.

We write in response to the Letter to the Editor by van den Berg et al1 commenting on our recent article ‘Gut microbiota predicts severity and reveals novel metabolic signatures in acute pancreatitis’.2 We greatly appreciate the interest in our work and are grateful to clarify some aspects of the study. The primary endpoint of our study investigated whether microbial compositions can be employed as early predictors for severity of acute pancreatitis (AP). Patients with revised Atlanta classification III (RAC III) showed highly significant microbial differences compared with RAC I and RAC II. Further analysis revealed a higher abundance of species that are known producers of short-chain fatty acids (SCFA) in severe AP. Van den Berg et al mention the lack of a healthy control cohort, however, it is already known from previous studies that the microbial composition in stool samples of patients with AP…

With great interest, we read the paper by Ammer-Hermenau et al, which features a multicentre microbiome study that included buccal and rectal samples taken at admission from 450 patients with acute pancreatitis.1 Severe acute pancreatitis was post hoc defined as persistent organ failure and/or collections that required drainage. These patients were propensity score matched with patients with mild acute pancreatitis. Remarkedly, over-representation of 10 known short-chain fatty acid (SCFA)-producing bacteria was found in the severe group. The authors conclude that SCFAs might be associated with worse outcomes and speculate that the increased mortality that was observed in the intervention group of the Probiotics in Pancreatitis Trial (PROPATRIA) could be explained by SCFA producers in the probiotics formula.2 There are, however, some limitations to this study, and we believe the author’s statements are in need of nuance. First, the authors did not include a control group…

Objective
In patients with Crohn’s disease (CD) on combination therapy (infliximab and immunosuppressant) and stopping infliximab (cohort from the study of infliximab diSconTinuation in CrOhn’s disease patients in stable Remission on combined therapy with Immunosuppressors (STORI)), the risk of short-term (≤6 months) and mid/long-term relapse ( >6 months) was associated with distinct blood protein profiles. Our aim was to test the external validity of this finding in the SPARE cohort (A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn’s Disease Patients in Sustained Steroid-free Remission on Combination Therapy).

Design
In SPARE, patients with CD in sustained steroid-free clinical remission and on combination therapy were randomly allocated to three arms: continuing combination therapy, stopping infliximab or stopping immunosuppressant. In the baseline serum of the STORI and SPARE (arm stopping infliximab) cohorts, we studied 202 immune-related proteins. The proteins associated with time to relapse (univariable Cox model) were compared between STORI and SPARE. The discriminative ability of biomarkers (individually and combined in pairs) was evaluated by the c-statistic (concordance analysis) which was compared with C-reactive protein (CRP), faecal calprotectin and a previously validated model (CEASE).

Results
In STORI and SPARE, distinct blood protein profiles were associated with the risk of short-term (eg, high level: CRP, haptoglobin, interleukin-6, C-type lectin domain family 4 member C) and mid/long-term relapse (eg, low level: Fms-related tyrosine kinase 3 ligand, kallistatin, fibroblast growth factor 2). At external validation, the top 10 biomarker pairs showed a higher c-statistic than the CEASE model, CRP and faecal calprotectin in predicting short-term (0.76–0.80 vs 0.74 vs 0.71 vs 0.69, respectively) and mid/long-term relapse (0.66–0.68 vs 0.61 vs 0.52 vs 0.59, respectively).

Conclusion
In patients with CD stopping infliximab, we confirm that the risk of short-term and mid/long-term relapse is associated with distinct blood protein profiles showing the potential to guide infliximab withdrawal.

Trial registration number
NCT00571337 and NCT02177071.

We appreciate the constructive dialogue from Cheng on our study’s findings.1 We agree that any clinical database study has limitations that necessitate careful interpretation of results. Manual medical records review is a logical next step to mitigate these shortcomings and allow a more thorough examination of each patient’s course. Nevertheless, we re-analysed our data in response to points raised. The analyses in our original paper suggest an elevated risk of undergoing an esophagogastroduodenoscopy (EGD) in patients treated with glucagon-like peptide-1 receptor agonists (GLP-1 RA) compared with control. As mentioned in our prior reply,2 we recognise that there is a potential diagnostic bias from this observation. We re-ran our cohorts and found that the rate of undergoing an EGD in the propensity-score matched cohort receiving short-acting GLP-1 RA was 6.13% compared with 5.22% in the matched control cohort (OR 1.185; 95% CI 1.131 to 1.241), reflecting the…

Circulation, Volume 150, Issue Suppl_1, Page A4136932-A4136932, November 12, 2024. Introduction:Annually, over 500,000 Americans are hospitalized due to heart failure (HF), marking it as a major contributor to morbidity and mortality. It also poses a significant financial burden and leads to considerable losses in productivity.Objective:This study investigates the predictive accuracy of different socioeconomic metrics on the risk and outcomes of HF in Maryland.Methodology:A retrospective analysis of the Maryland State Inpatient Database (2016-2020) was conducted to assess the predictive accuracy of race/ethnicity, insurance status, household median income, and neighborhood poverty level (measured by the Distressed Communities Index) on the risk of heart failure-related hospital admissions and outcomes. Multivariate logistic regression models were also used to adjust for confounders.Result:During the study period, a total of 389,220 cases of HF were reported in the Maryland SID. The majority of these patients were white (56.8%) and female (51.1%), with a median age of 73 years (interquartile range [IQR] 62-82 years). The in-hospital mortality rate was 5.1%, while rates of atrial fibrillation, cardiac arrest and prolonged hospital stay were 34.4%, 0.3%, and 48.4%, respectively. Multivariate analysis revealed a substantial area under the ROC curve (AUC) indicating good model performance: 0.88 for predicting HF, 0.64 for atrial fibrillation, 0.64 for cardiac arrest 0.57 for prolonged hospital stays, 0.63 for mortality. Subgroup analyses showed variable predictiveness by race (AUC = 0.4378), payment method (AUC = 0.5754), income quartile (AUC = 0.5202), and deprivation composite score (AUC = 0.4751). Patients with private insurance had the highest risk of stress cardiomyopathy (odds ratio [OR] = 1.98; 95% confidence interval [CI] 1.70-2.29). Socioeconomic metrics, including neighborhood distress, showed varying predictive accuracy for the HF-related admissions and selected short-term outcomes, with the highest predictive accuracy for neighborhood distress on the risk of HF (AUC = 0.50, std: 0.006), atrial fibrillation (AUC = 0.48, std: 0.0007), cardiac arrest (AUC = 0.51, std: 0.007), and prolonged hospital stays (AUC = 0.53, std: 0.0005) and mortality (AUC = 0.50, std: 0.0015).Conclusion:Neighborhood poverty level demonstrates significant predictive power for assessing the risk of HF-related hospital admissions and the short-term outcomes among Maryland residents, exceeding factors like insurance and race/ethnicity.

Circulation, Volume 150, Issue Suppl_1, Page A4145819-A4145819, November 12, 2024. Introduction:Despite early mitigation efforts, the opioid pandemic in the United States has persisted and affected many Americans. A public health emergency was declared urging all prescribers to use caution in prescribing opioids. Alternative approaches to postoperative pain management during transvenous cardiac device implants (TCDI) in adults have not been described.Methods:We report a single-center retrospective analysis of 612 consecutive patients that underwent TCDI between January 2021 and January 2024 with ultrasound guided pectoral nerve block (PNB) using liposomal bupivacaine prior to implant for postoperative pain management. Pain scores (0-10) were recorded systematically in the postoperative period, at discharge, and at wound check follow-up. Any need for opioid use in the postoperative period was recorded as well.Results:A total of 612 patients were evaluated, 50% female with a mean age of 71.2 years. All patients received PNB successfully with no device site infection or hematomas. The mean Visualized Analog Scale (VAS) pain scores at 1, 3, and 5 hours after the procedure, at discharge, and at the follow-up visit were 1.93, 1.22, 1.10, 1.05, and 0.13 respectively. During follow-up, no patients required opioids for pain control throughout the entire postoperative period of 14 days.Conclusion:Pectoral nerve block with liposomal bupivacaine can be performed safely preoperatively during TCDI and provides adequate pain control without need for opioid use postoperatively. Further research is needed to assess broad scale implications of this approach to larger patient populations.

Circulation, Volume 150, Issue Suppl_1, Page A4139216-A4139216, November 12, 2024. Introduction:TX000045 (TX45) is a long-acting Fc-relaxin fusion protein with vasodilatory, anti-fibrotic and anti-inflammatory activity due to selective agonism of the G protein-coupled relaxin family peptide receptor 1 (RXFP1). It is being developed for Group 2 pulmonary hypertension associated with heart failure with preserved ejection fraction (HFpEF). This first-in-human study evaluated the safety/tolerability, pharmacokinetic and pharmacodynamic profile of TX45 in healthy volunteers after single doses.Methods:This phase 1a, randomized, double-blind, placebo-controlled single ascending dose study was performed in seven cohorts of healthy volunteers. Six cohorts consisted of eight patients receiving intravenously (IV) or subcutaneously (SC) one of several doses of TX45 (n=6 on treatment) or placebo (n=2), including 0.3 mg/kg IV, 1 mg/kg IV, 3 mg/kg IV, 150 mg SC (x2 cohorts), and 300 mg SC. One cohort consisted of seven patients receiving 600 mg SC TX45 (n=5 patients) or placebo (n=2 patients). The goals of the study were to assess the tolerability and safety, immunogenicity, pharmacokinetic (PK) and pharmacodynamic (PD = renal plasma flow, RPF) properties of TX45 in healthy volunteers after single doses. RPF was determined by analysis of steady-state para-aminohippurate (PAH) blood levels in response to a PAH IV infusion.Results:55 healthy volunteers were randomized. TX45 was well tolerated. Most adverse events were mild to moderate in intensity. The most common treatment emergent adverse event was transient orthostatic tachycardia, not associated with hypotension. TX45 demonstrated linear pharmacokinetics across the dose range with a terminal half-life estimated to be 13-23 days. Treatment with TX45, across dose levels, increased renal plasma flow by 16-42%, consistent with known relaxin effects. Leveraging repeated measures of renal plasma flow post dose, TX45 demonstrated prolonged maintenance of a pharmacodynamic effect. There was no evidence of immune mediated clearance of TX45.Conclusions:TX45 was generally well tolerated with a safety, pharmacokinetic and pharmacodynamic profile to support further clinical development. Its maximum effect on RPF is similar to previously described effects of native relaxin. Its half-life will support a prolonged dosing interval. These findings support further evaluation of TX45 in patients with Group 2 pulmonary hypertension associated with HFpEF.

Circulation, Volume 150, Issue Suppl_1, Page A4138674-A4138674, November 12, 2024. Introduction:Urocortin-2 (UCN-2), a peptide which is part of the corticotropin-releasing factor (CRF) family, functions as an autocrine and paracrine factor, exerting its effects on cardiac and pulmonary function through agonism of CRF2 receptors. Although acute administration of UCN-2 has shown promise by improving heart and lung function in conditions like heart failure (HF) and pulmonary hypertension (PH), its limited stability impedes its chronic therapeutic use.Hypothesis:In this study, we explored the efficacy of COR-1389, a potent, selective and long-acting CRF2 agonist peptide, in the Sugen 5416 (VEGFR2 inhibitor, Su) combined with hypoxia (Hx) rat model of PH and right heart failure (RHF).Methods:To this aim, male adult Sprague Dawley rats were divided into three groups: Control rats (normoxia) were compared with rats injected subcutaneously with 20 mg/kg Sugen 5416 and exposed to chronic hypoxia for 3 weeks, followed by 2 weeks of normoxia. At 5 weeks, control rats and one SuHx group received subcutaneously vehicle (control and SuHx), while the third group received COR-1389 at a dose of 100 μg/kg every 4 days subcutaneously for 3 weeks (SuHx + COR-1389). At 8 weeks, cardiac and pulmonary hemodynamic functions of the three groups were evaluated using echocardiography and right heart catheterization, and heart and lung tissue were evaluated by histology and immunohistochemistry.Results:Compared to controls (n=10), SuHx exhibited increased mean pulmonary arterial pressure (mPAP), right ventricle (RV) hypertrophy (Fulton Index/body weight), muscularization of distal pulmonary arteries, RV fibrosis and cardiomyocyte hypertrophy, alongside reduced RV systolic function (Tricuspid Annular Plane Systolic Excursion, TAPSE) and cardiac output (CO). Conversely, compared to the SuHx + vehicle group (n=11), curative treatment with COR-1389 for 3 weeks in SuHx rats (n=13) led to enhanced RV systolic function (TAPSE) and CO, together with reductions in mPAP, RV hypertrophy, muscularization of pulmonary arteries, RV fibrosis and cardiomyocyte hypertrophy. Systolic blood pressure remained unchanged across all groups.Conclusion:These findings indicate that COR-1389 ameliorates the deteriorating cardiopulmonary parameters observed in the SuHx model and represents a promising approach for the treatment of PH and RHF.

Circulation, Volume 150, Issue Suppl_1, Page A4146327-A4146327, November 12, 2024. Background:Despite advances in treatment strategies for out-of-hospital cardiac arrest (OHCA), prognosis remains poor. The MIRACLE2 score is an established risk stratification tool for cardiogenic OHCA, but its utility in acute coronary syndrome (ACS), a leading OHCA etiology, is unclear.Aims:To validate the prognostic performance of the MIRACLE2 score in OHCA patients with ACS undergoing urgent/emergent percutaneous coronary intervention (PCI).Methods:We conducted a single-center, observational study (COEDO-CPA registry) of consecutive cardiogenic OHCA patients from 2018-2024. Patients with OHCA due to ACS who underwent urgent/emergent PCI were stratified into high-risk (MIRACLE2 score >5), medium-risk (3-4), and low-risk (0-2) groups based on their MIRACLE2 scores. The primary endpoint was 30-day all-cause mortality, compared among risk groups using Kaplan-Meier analysis.Results:Of 124 cardiogenic OHCA patients, 80 with ACS-related OHCA undergoing PCI were analyzed (mean age 64.7 years, 89% male). The mean MIRACLE2 score was 3.2, with 18 high-risk, 30 medium-risk, and 32 low-risk patients. Mechanical circulatory support was used in 58%. The high-risk group tended to be older with higher lactate levels, worse renal function, elevated D-dimer, and longer cardiopulmonary resuscitation duration compared to lower-risk groups. Kaplan-Meier analysis demonstrated a graded increase in 30-day mortality across risk groups, with effective risk stratification by the MIRACLE2 score (log-rank p=0.003).Conclusion:Among OHCA patients with ACS undergoing PCI, the MIRACLE2 score effectively stratified short-term mortality risk. This validated risk stratification tool could guide treatment strategies and resource allocation in this critically ill population. Incorporating the MIRACLE2 score into OHCA management pathways may optimize care for ACS-related OHCA.

Circulation, Volume 150, Issue Suppl_1, Page A4145933-A4145933, November 12, 2024. Introduction:Cardiogenic shock (CS) remains a clinical challenge with a high mortality rate. An escalation strategy from intra-aortic balloon pump (IABP) to Impella has been proposed for patients with CS refractory to IABP therapy, but clinical data on this approach are lacking. This study aimed to elucidate the short-term clinical outcomes after IABP-Impella escalation in patients with CS.Methods and Results:From the Japanese nationwide registry of Impella (J-PVAD) database between 2020 and 2022, a total of 2,578 patients with CS who received Impella support were classified into the IABP-Impella group (n=189) or the Primary Impella group (n=2,389). We applied a 1:3 propensity score matching, selecting 180 patients in the IABP-Impella group and 540 patients in the Primary Impella group. Before matching, the IABP-Impella group presented significantly longer shock-to-Impella time, worse laboratory data indicating multiorgan damage, and more frequent inotrope use compared to the Primary Impella group. After matching, the baseline characteristics were well-balanced between the two groups. The clinical outcomes within 30 days after the initiation of Impella were compared between the matched groups. The IABP-Impella group showed a significantly higher rate of additional mechanical circulatory support (MCS) use than the Primary Impella group (33.9% vs. 25.6%, p=0.034). Although the incidence of mortality was similar between the two groups (30.6% vs. 30.9%, p >0.99), the incidence of major complications (a composite of bleeding, hemolysis, infection, stroke, myocardial infarction, limb ischemia, and vascular injury) tended to be higher in the IABP-Impella group (43.0% vs. 36.3%, p=0.053). Notably, the incidence of infection was significantly higher in the IABP-Impella group than in the Primary Impella group (10.0% vs. 4.8%, p=0.018). Kaplan-Meier estimates revealed that infection occurred more frequently in the IABP-Impella group during the 30-day follow-up period (log-rank p=0.016).Conclusions:Patients undergoing the IABP-Impella escalation strategy showed poorer baseline clinical conditions in baseline and were associated with a higher likelihood of further MCS upgrade and an increased risk of infection.

Circulation, Volume 150, Issue Suppl_1, Page A4136013-A4136013, November 12, 2024. Introduction:The use of Transcatheter Aortic Valve Replacement(TAVR) has provided a safer alternative to open surgical approaches. The introduction of frailty scoring systems has proven effective in improving healthcare approaches and outcomes in various aspects of medicine. As there is a paucity of data on the impact of frailty among TAVR patients, we aim to conduct a retrospective study to investigate further.Methods:Our study analyzed adult cases with a primary procedural code for TAVR among hospitalizations between 2016 and 2021 through the National Inpatient Sample(NIS). Frailty status was explored through the criteria of Gilbert’s frailty index. Multivariable regression models helped evaluate differences in short-term outcomes and complications between them.Results:Our study involved 374200 cases of TAVR that were divided into LFR(285425 cases, 76.3%), IFR(86005 cases, 23.0%), and HFR(2770 cases, 0.7%). Compared to patients with LFR, patients with MFR and HFR showed higher odds of several complications, including cardiogenic shock(MFR: aOR 6.933, p

Circulation, Volume 150, Issue Suppl_1, Page A4145961-A4145961, November 12, 2024. Introduction:Approximately 20% of ischemic strokes are linked to a cardioembolic source, with 80% of cardioembolic strokes being attributed to atrial fibrillation. This study aimed to investigate the impact of non-valvular atrial fibrillation (NVAF) on mortality and recurrent stroke following a minor stroke event, considering AF as the most prevalent sustained cardiac rhythm disorder associated with stroke.Methods and Materials:Consecutive patients experiencing minor acute ischemic stroke (NIHSS

Circulation, Volume 150, Issue Suppl_1, Page A4147011-A4147011, November 12, 2024. Introduction:Guidelines recommend dual antiplatelet therapy (DAPT) for 12 months following percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). However, prolonged DAPT may increase bleeding risk. Monotherapy with the potent P2Y12 inhibitor ticagrelor after short DAPT offers a promising strategy to balance thrombotic and bleeding risks.Objective:To compare outcomes of short DAPT (≤3 months) followed by ticagrelor monotherapy until 12 months vs. 12-month DAPT in patients undergoing PCI for ACS.Methods:We systematically searched PubMed, Scopus, and Cochrane Central databases for studies comparing short DAPT followed by ticagrelor monotherapy vs. 12-month DAPT following PCI. Outcomes of interest included net adverse clinical events (NACE), major adverse cardiovascular/cerebrovascular events (MACCE), and any bleeding at 12 months post-PCI. Statistical analysis was done using R software. Random effects models were used to generate risk ratios (RRs) with 95% confidence intervals (CIs). Heterogeneity was assessed using I2statistics. Analysis followed the PRISMA guideline.Results:The systematic review identified 4 randomized controlled trials including 5,293 patients. Ticagrelor monotherapy was used in 2,667 (50.38%) patients. At 12 months, NACE (RR 0.81; 95%CI 0.57-1.14; p=0.227; I2=45%), MACCE (RR 1.11; 95%CI 0.86-1.42; p=0.415; I2=3%), and any bleeding (RR 0.68; 95%CI 0.46-1.01; p=0.055; I2=34%) were comparable between the two groups.Conclusion:After PCI for STEMI, short DAPT for ≤3 months followed by ticagrelor monotherapy was non-inferior to 12-month DAPT in terms of NACE, MACCE, and bleeding. Ticagrelor monotherapy following short DAPT may be considered for STEMI patients after PCI.

Circulation, Volume 150, Issue Suppl_1, Page A4144700-A4144700, November 12, 2024. Background:Long term right ventricular apex pacing has been reported to affect myocardial metabolism and perfusion to lead to impaired left ventricular function. However, there is little information available on the effect on fatty acid metabolism, myocardial perfusion and function in RV septal or His bundle pacing.Methods and Results:We studied 94 patients (mean age 77±11 years, male 40%, AV block 71%) admitted for pacemaker implantation in our prospective cohort study, excluding patients with coronary artery disease who had past histories of coronary arterial revascularization and severe stenosis in coronary CT or coronary angiography. Forty-five patients had right ventricular apex pacing (RVA; n=10) or right ventricular septal pacing (RVS; n=35), 17 had selective or non-selective His bundle pacing (HIS) and, as a control, 32 had right atrial pacing (RA). The patients underwent 123I-β-methyl-P-iodophenyl-pentadecanoic acid (BMIPP) SPECT imaging and Tc-99m- methoxyisobutylisonitrile (MIBI) SPECT imaging between 3 months and 1 year after implantation. The uptakes of both tracers were displayed on a polar map, which was divided into 17 segments. Regional tracer activity at each segment was quantified as %uptake. Left ventricular ejection fraction (LVEF) was also obtained in MIBI imaging.There were no significant differences in baseline characteristics such as age, gender, or underlying heart disease between the four groups. LVEF in MIBI rest imaging in RVA group was significantly lower than RA group (58.3±2.1% vs 64.9±1.2%, p=0.013), while there was no significant difference in LVEF among RVS, HIS and RA groups, with non-significantly (p=0.25) lower LVEF in RVS (62.5±1.1%) than HIS (65.3±1.6%) groups. The average of BMIPP %uptake in 17 segments significantly correlated with LVEF (r=-0.259, p=0.01). BMIPP and MIBI (stress and rest) %uptake were significantly lower in RVA group and RVS group than RA group in the septal or anterolateral area. Especially, BMIPP %uptake in RVA group was significantly lower at the broad area. On the other hand, BMIPP and MIBI (stress and rest) %uptake in HIS group were almost similar to those in RA group.Conclusion:His bundle pacing, but not RV septal pacing, maintains myocardial metabolism, perfusion and function.

Circulation, Volume 150, Issue Suppl_1, Page A4118341-A4118341, November 12, 2024. Background:Opioid use has increased significantly in the past few decades, impacting cardiac and non-cardiac patients. As heart failure with preserved ejection fraction (HFpEF) comprises half of all heart failure cases, understanding its management and effect on outcomes is crucial. This study aims to evaluate the outcomes of chronic opioid therapy on HFpEF patients.Methods:Studying the National Inpatient Sample (2016-2020), we identified adult HFpEF patients using the appropriate ICD-10 codes -after excluding patients with end-stage renal disease (ESRD)- and compared outcomes between chronic opioid users and non-users. Multivariate logistic and linear regression analyses were performed, adjusting for multiple patient and hospital confounders. The primary outcome was all-cause in-hospital mortality while secondary outcomes included acute kidney injury/hemodialysis (AKI/HD), cardiogenic shock, cardiac arrest, mechanical ventilation, length of stay, and total charges.Results:Among 1,557,344 HFpEF patients, 21,655 (1.4%) were on opioids chronically. Inpatient mortality was not significantly different between patients who were on opioids and those who were not. (adjusted odds ratio [aOR] 1.01, 95% CI 0.85 – 1.2, p=0.89). There was a non-significant increased risk of cardiogenic shock (aOR 1.14, 95% CI 0.87 – 1.5, p=0.35) and cardiac arrest (aOR 1.05, 95% CI 0.8 – 1.36, p=0.74) in patients on chronic opioids. Chronic opioids were associated with increased risk of AKI/HD (aOR 1.12, 95% CI 1.04 – 1.2, p=0.002) and mechanical ventilation (aOR 1.29, 95% CI 1.16 – 1.43, p< 0.001). Opioid use was also associated with longer hospital stay (adjusted MD [aMD] 1.07 days, 95% CI 0.75 - 1.39, p