Risultati per: Short Acting Opioid

Circulation, Volume 146, Issue Suppl_1, Page A12401-A12401, November 8, 2022. Introduction:Several strategies based on immune checkpoint inhibitors (ICIs) have been developed or are under investigation for cancer therapy, opening to advantages in cancer outcomes. However, several ICIs-induced side effects emerged in these patients, especially a rare but clinically significant cardiotoxicity with high rate of mortality.Hypothesis:We analyzed the differential vasculo and cardiotoxicity of Pembrolizumab, Nivolumab and Ipilimumab in preclinical models highlighting on the molecular pathways involved.Methods:C57 female mice were treated with Ipilimumab, Pembrolizumab or Nivolumab (15 mg/kg) through intraperitoneal injection for 10 days. pAMPK expression and vascular p65/NF-kB was analyzed through Immunohistochemistry. Cardiac and systemic levels of IL-1α, IL-1β, IL-2, IL-6 and IL-10 were quantified through ELISA methodResults:In preclinical models, all ICIs increased p65/NF-kB expression in vascular endothelial cells of mice compared to saline group. IHC analysis indicates that ICIs reduced pAMPK expression in myocardial cells. Notably, tissue levels of IL-1α, IL-1β, IL-2, IL-6 were strongly increased in ICIs group vs saline (p

Circulation, Volume 146, Issue Suppl_1, Page A13503-A13503, November 8, 2022. Background:Short-term variability of repolarization derived from the QT-interval (STV-QT) has previously been demonstrated to increase prior to arrhythmias in both humans and animals. To continuously monitor the arrhythmic risk by a cardiovascular implantable electronic device (CIED), a fully automatic method to determine STV on intracardiac electrograms (STV-EGMauto) has been developed. This method demonstrated high effectiveness in monitoring and predicting Torsade de Pointes arrhythmias in the CAVB dog model. However, this technique has not been evaluated in arrhythmias related to ischemia yet.Purpose:To assess the novel automatic method of arrhythmic risk monitoring by CIEDs through STV-EGMautomeasurements in a porcine model of ischemia-induced ventricular fibrillation (VF).Methods:Myocardial infarction was induced in 8 anesthetized pigs by balloon occlusion of the left anterior descending coronary artery for 75 minutes, followed by reperfusion. Monitoring included a 12-lead ECG and a duodecapolar EGM catheter in the right ventricle. STV-EGMautoand STV-QT, our gold standard calculated by the method of fiducial segment averaging, were assessed at baseline, occlusion, one minute before VF and just before VF. The STV values and the percentual changes from baseline to the successive three timepoints were compared between STV-EGMautoand STV-QT.Results:VF occurred 21±8.8 minutes after occlusion. Both STV-EGMautoand STV-QT increased significantly from baseline to VF (1.1±0.8 msvs2.4±1.5 ms, p

Circulation, Volume 146, Issue Suppl_1, Page A331-A331, November 8, 2022. Background:Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is one of effective therapeutic modalities for patients with cardiogenic shock (CS) and acute coronary syndrome (ACS). While VA-ECMO maintains end-organ perfusion, it increases damaged left ventricular (LV) wall tension. Combined treatment of VA-ECMO and a micro-axial Impella pump, referred to as ECPELLA, simultaneously provides systemic circulatory support and LV unloading. However, it remains unknown whether LV unloading effect on ECPELLA support further reduces mortality compared to currently available VA-ECMO+IABP support.Purpose:Investigate whether ECPELLA can reduce mortality in ACS patients with severe cardiogenic shock who required VA-ECMO.Methods:From January 2012 to May 2022, 100 consecutive patients with ACS and CS who received VA-ECMO before or after percutaneous coronary intervention were enrolled. Patients were divided into two groups; 39 patients in the ECPELLA; and 61 patients in the VA-ECMO with IABP. We assessed peak serum CPK-MB levels and 30-day mortality.Results:There were no significant differences in age, rate of male sex, coronary risk factors, ST-elevated ACS, left main trunk (LMT) lesion, multi-vessel disease (MVD), number of coronary lesions, extracorporeal cardiopulmonary resuscitation, and the time from onset to reperfusion between two groups. The ECPELLA had lower peak CPK-MB levels compared to VA-ECMO with IABP, but the difference did not reach statistical significance (p=0.056). Kaplan-Meier analysis revealed that the ECPELLA had significantly lower 30-day mortality (p=0.0016). Multivariable Cox proportional hazard analysis revealed that ECPELLA (HR: 0.22 95% confidence interval:0.11-0.45; p

Circulation, Volume 146, Issue Suppl_1, Page A11138-A11138, November 8, 2022. Introduction:Patients with a ST-Elevation Myocardial Infarction (STEMI) and concomitant lung cancer are an understudied cohort. In this study, we explore the in-hospital outcomes of STEMI patients with and without lung cancer.Methods:We queried the National Inpatient Sample database (2016-2019) to identify patients admitted with a principal diagnosis of STEMI and secondary diagnosis of lung cancer. We conducted propensity score matching using a greedy nearest neighbor 1:1 model. Multivariable logistic regression was used to compare mortality.Results:7020 patients met our inclusion criteria. Patients with a STEMI and lung cancer had 1.84 times higher odds of suffering in-hospital mortality compared to STEMI patients without lung cancer (aOR 1.84, 95% CI: 1.55-2.17; p < 0.001). When separated by race, STEMI patients with lung cancer had a higher mortality rate amongst White (11.5% vs 6.5%, p < 0.001) and Black (11.9% vs 6.5%, p = 0.03, Figure 1) patients. STEMI patients with lung cancer were less likely to undergo percutaneous coronary intervention (22.3% vs 32.0%, p < 0.001). There was no difference in intraoperative and postoperative cardiac arrest, cerebral infarction and respiratory failure. Additionally, STEMI patients with lung cancer had longer hospital stays (4.9 days vs 4.4 days, p < 0.001, Table 1).Conclusions:Patients with a STEMI and lung cancer had higher odds of suffering in-hospital mortality compared to patients with a STEMI without lung cancer. Our findings emphasize the importance of risk-benefit analysis and collaborative discussion amongst the care team prior to choosing the appropriate treatment modality.

Circulation, Volume 146, Issue Suppl_1, Page A10603-A10603, November 8, 2022. Introduction:Doxorubicin-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in breast cancer patients. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently been shown to be of therapeutic value in patients with type 2 diabetes, chronic kidney disease, and heart failure with reduced ejection fraction (HFrEF), conditions that commonly coexist and are interrelated pathophysiologically.Hypothesis:Dapagliflozin (an SGLT2i), administered during doxorubicin, could improve cardiac function in preclinical modelsMethods:Female C57Bl/6 mice were untreated (Sham, n=6) or treated for 10 days with doxorubicin i.p at 2.17 mg/kg (DOXO, n=6), DAPA at 12 mg/kg (DAPA, n=6) or doxorubicin combined to DAPA (DOXO-DAPA, n=6). Ejection fraction, radial and longitudinal strain were analyzed through transthoracic echocardiography (Vevo 2100). Cardiac tissue expression of NLRP3 inflammasome, Myd88, DAMPs (galectine 3 and calgranulinS100) , pAMPK, NF-kB, and 13 chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF) were quantified through ELISA and western blot methods.Results:DAPA improved significantly the EF and prevented the reduction of radial and longitudinal strain after 10 days of treatment with doxorubicin. A reduced expression of NLRP3, MyD88, DAMPs and NF-kB in cardiac tissues was seen in DOXO-DAPA group compared to DOXO mice (p

Circulation, Volume 146, Issue Suppl_1, Page A9881-A9881, November 8, 2022. Background:Sleep-disordered breathing (SDB) and blood pressure (BP) variability are closely associated with cardiovascular diseases. We have recently reported that pulse-transit-time (PTT) has enabled to monitor the beat-to-beat BP, identifying a strong relationship between the severity of SDB and the extent to very short-term BP variability. Here, we investigated the effects of continuous positive airway pressure (CPAP) on very short-term BP variability.Methods:We studied 57 patients (mean age 61 years old, male 42) with SDB who underwent the full polysomnography on two consecutive days for diagnosis (baseline) and CPAP. PTT was continuously monitored together, and PTT-based BP values were measured on a beat-to-beat basis. PTT index was defined as the average number of acute transient rises in BP (≥12 mmHg) within 30 seconds per hour.Results:Apnea-hypopnea index (AHI) was decreased from 46.5±22.4 to 13.7±15.0 (P

Circulation, Volume 146, Issue Suppl_1, Page A12402-A12402, November 8, 2022. Introduction:Doxorubicin-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in breast cancer patients. Sacubitril-valsartan (LCZ 696) is a combination drug, made up of neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan, used for the treatment of heart failure in patients with a reduced ejection fraction.Hypothesis:We hypothesized that LCZ 696, administered during doxorubicin, could improve cardiac functionMethods:Female C57Bl/6 mice were untreated (Sham, n=6) or treated for 10 days with doxorubicin i.p at 2.17 mg/kg (DOXO, n=6), LCZ-696 at 60 mg/kg (LCZ, n=6) or doxorubicin combined to LCZ-696 (DOXO-LCZ, n=6). Ejection fraction, radial and longitudinal strain were analyzed through transthoracic echocardiography (Vevo 2100). Cardiac tissue expression of NLRP3 inflammasome, Myd88, DAMPs (galectine 3 and calgranulinS100) , pAMPK, NF-kB, and 13 chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF) were quantified through ELISA and western blot methods.Results:LCZ 696 improved significantly the EF and prevented the reduction of radial and longitudinal strain after 10 days of treatment with doxorubicin. A reduced expression of NLRP3, MyD88, DAMPs and NF-kB in cardiac tissues was seen in DOXO-LCZ group compared to DOXO mice (p

Circulation, Volume 146, Issue Suppl_1, Page A13963-A13963, November 8, 2022. Introduction:Torsade de Pointe (TdP) is defined as a polymorphic VT (pVT) typically associated with QTc prolongation. However, not all pVT occur in the presence of QTc prolongation and respond to different forms of therapy. Hence defining their etiology is important.Case:A 48-yo Female with H/O resolved peripartum cardiomyopathy, hypertension & obesity presented to the hospital following a syncopal episode. Her BP was 207/125 mmHg, and ECG showed sinus rhythm with a QTc of 436. No history of heart disease or SCD in her family. Physical exam was unremarkable, labs showing K-3.2 without troponin elevation. On day 2, she developed a pVT requiring defibrillation and amiodarone. Telemetry revealed a PVC causing R on T phenomenon with a coupling interval of 260 msec prior to initiation of SVT with QTc 484 and K-2.8. On day 3, despite electrolyte correction, she had multiple non-sustained pVTs with QTc 482. Amiodarone was switched to lidocaine and QTc normalized to 447. TTE and LHC were unremarkable with a small LV aneurysm on cMRI. On day 4, the patient continued to have incessant runs of pulseless pVT requiring defibrillation and started on verapamil. A 12 lead ECG during VT demonstrated left bundle branch mimicry with a left axis consistent with a VT exit site along the RV moderator band. The patient underwent emergent ablation with targets along the right anterolateral papillary muscle. AICD was placed prior to discharge.Discussion:The critical timing of PVC falling on the peak of the preceding T wave differentiates ‘Short-coupled TdP’ from other malignant VTs with normal QTc. These PVCs typically originate from distal ramifications of Purkinje fibers in both ventricles. PVC morphology with LBBB pattern, left axis and late precordial R-S transition points to the moderator band as the source of idiopathic VT. Contrasting with typical TdP, medical management with Quinidine and Verapamil may be efficacious. Catheter ablation is curative in most cases.

Circulation, Volume 146, Issue Suppl_1, Page A13763-A13763, November 8, 2022. Introduction:Transcatheter edge-to-edge repair (TEER) of the mitral valve has become an established therapy for patients with severe mitral regurgitation; however, the impact of institutional variations in the number of edge-to-edge TEER for readmission rates with large-scale data is not well investigated.Objectives:Our study aimed to describe the institutional variations of TEER, and also the association between the institutional volume and readmission rates after the procedure across the US institutions.Methods:We conducted a retrospective cohort study of TEER performed in the US between 2019 using the Nationwide Readmission Database. We divided the patients according to the tertiles based on site-specific case of TEER (Q1 [lowest]-Q3 [highest]) and evaluated its association with 30-day readmission rates using Cox proportional hazard model.Results:Overall, 4,922 patients who underwent TEER (mean age 76.8 ± 11.5 years, and 54.5% male) at 250 institutions were included in the analyses. Patients in Q3 (highest tertile) were more likely to be older, and have comorbidities, albeit risk adjusted 30-day readmission rates were similar in each group (Q1: 13.5%; Q2: 13.6%; Q3: 13.7%). Rather than the volume of the procedure, institutional characteristics, such as teaching hospitals located in metropolitan area (hazard ratio [HR 1.92, confidence interval [CI] 1.41-2.61) and institutions with predominantly non-elective (e.g. urgent or emergent) TEER cases (HR 1.75 95% CI 1.39-2.22), or patient characteristics such as chronic heart failure (HR 1.91 95%CI 1.33-2.73), cancer (HR 1.87 95%CI 1.15-3.06), chronic kidney disease (HR 1.45 95% CI 1.20-1.75), chronic pulmonary disease (HR 1.40 95% CI 1.13-1.72), diabetes mellitus (HR 1.39 95% CI 1.12-1.72), and history of percutaneous coronary intervention (HR 1.37 95% CI 1.07-1.76) were associated with a higher incidence of 30-day readmission.Conclusions:Among patients undergoing TEER in a contemporary representative US cohort, procedure volume variation was not associated with the 30-day readmission rate.

Objectives
Self-reported approaches that assess opioid usage can be subject to social desirability and recall biases that may underestimate actual pill consumption. Our objective was to determine the accuracy of patient self-reported opioid consumption using a 14-day daily paper or electronic diary.

Design
Prospective cohort study.

Setting
Multicentre study conducted in four Québec (Canada) emergency departments (ED): three university-affiliated centres, two of them Level I trauma centres and one urban community hospital.

Participants
ED patients aged ≥18 years with acute pain (≤2 weeks) who were discharged with an opioid prescription. Patients completed a 14-day daily diary (paper or electronic) assessing the quantity of opioids consumed. On diary completion, a random sample from the main cohort was selected for a follow-up visit to the hospital or a virtual video visit where they had to show and count the remaining pills. Patients were blinded to the main objective of the follow-up visit.

Outcomes
Quantity of opioid pills consumed during the 2-week follow-up period self-reported in the 14-day diary (paper or electronic) and calculated from remaining pills counted during the follow-up visit. Intraclass correlation coefficient (ICC) and Bland-Altman plots were used to assess accuracy.

Results
A total of 166 participants completed the 14-day diary as well as the in-person or virtual visit; 49.4% were women and median age was 47 years (IQR=21). The self-reported consumed quantity of opioid in the 14-day diary and the one calculated from counting remaining opioid pills during the follow-up visit were very similar (ICC=0.992; 95% CI: 0.989 to 0.994). The mean difference between both measures from Bland-Altman analysis was almost zero (0.048 pills; 95% CI: –3.77 to 3.87).

Conclusion
Self-reported prescription opioid use in a 14-day diary is an accurate assessment of the quantity of opioids consumed in ED discharged patients.

Trial registration number
NCT03953534.

Introduction
Opioid use disorder (OUD) is a debilitating and persistent disorder. The standard-of-care treatment is daily maintenance dosing of sublingual buprenorphine (BUP-SL) or oral methadone (MET). Monthly, extended-release, subcutaneous injectable buprenorphine (BUP-XR) has been developed to enhance treatment effectiveness. This study aims to investigate the experiences of participants who have been offered BUP-XR (evaluation 1), health-related quality-of-life among participants who have opted to receive BUP-XR longer term (evaluation 2) and the experiences of participants allocated to receive BUP-XR or BUP-SL or MET with the offer of adjunctive personalised psychosocial intervention (evaluation 3).

Methods and analysis
Three qualitative–quantitative (mixed-methods) evaluations embedded in a five-centre, head-to-head, randomised controlled trial of BUP-XR versus BUP-SL and MET in the UK. Evaluation 1 is a four-centre interview anchored on an OUD-related topic guide and conducted after the 24-week trial endpoint. Evaluation 2 is a two-centre interview anchored on medications for opioid use disorder-specific quality-of-life topic guide conducted among participants after 12–24 months. Evaluation 3: single-centre interview after the 24-week trial endpoint. All evaluations include selected trial clinical measures, with evaluation 2 incorporating additional questionnaires. Target participant recruitment for evaluations 1 and 2 is 15 participants per centre (n=60 and n=30, respectively). Recruitment for evaluation 3 is 15 participants per treatment arm (n=30). Each evaluation will be underpinned by theory, drawing on constructs from the behavioural model for health service use or the health-related quality-of-life model. Qualitative data analysis will be by iterative categorisation.

Ethics and dissemination
Study protocol, consent materials and questionnaires were approved by the London-Brighton and Sussex research ethics committee (reference: 19/LO/0483) and the Health Research Authority (IRAS project number 255522). Participants will be provided with information sheets and informed written consent will be obtained for each evaluation. Study findings will be disseminated through peer-reviewed scientific journals.

Trial registration number
2018-004460-63.

Annals of Internal Medicine, Volume 175, Issue 10, Page HO2-HO4, October 2022.

Annals of Internal Medicine, Ahead of Print.

Annals of Internal Medicine, Ahead of Print.

Annals of Internal Medicine, Volume 175, Issue 10, Page W118, October 2022.

Objective
The objective of this study was to evaluate how urine drug screening (UDS) frequency is associated with retention in opioid agonist treatment (OAT).

Methods
Data for this retrospective cohort study of 55 921 adults in OAT in Ontario, Canada, were derived from administrative sources between 1 January 2011 and 31 December 2015. All patient information was linked anonymously across databases using encrypted health card numbers. Descriptive statistics were calculated for comparing UDS frequency groups using standardised differences (d) where d less than 10% indicated a statistically significant difference. A logistic regression model was then used to calculate ORs adjusting for baseline covariates, including sex, age, location of residence, income quintile, mental disorders, HIV status and deep tissue infections.

Results
Over 70% of the cohort had four or more UDS tests per month (weekly or more UDS). Significant associations were observed between UDS frequency and 1-year treatment retention in OAT biweekly (adjusted OR (aOR)=3.20, 95% CI 2.75 to 3.75); weekly UDS (aOR=6.86, 95% CI 5.88 to 8.00) and more than weekly (aOR=8.03, 95% CI 6.87 to 9.38) using the monthly or less groups as the reference.

Conclusion
This study identified an association between weekly UDS and 1-year treatment retention in OAT. There is an active discussion within Canada about the utility of UDS. The lack of evidence for the impact of UDS on retention has left it open to some to argue they simply provide a barrier to patient engagement. Therefore, it is timely of this study to demonstrate that more frequent urine testing is not associated with a reduction in treatment retention.