Urban-rural inequalities in IV thrombolysis for acute ischemic stroke: A nationwide study.

INTRODUCTION: Rural residency has been associated with lower reperfusion treatment rates for acute ischemic stroke in many countries. We aimed to explore urban-rural differences in IV thrombolysis rates in a small country with universal health care, and short transport times to stroke units. PATIENTS AND METHODS: In this nationwide cohort study, adult ischemic stroke patients registered in the Danish Stroke Registry (DSR) between 2015 and 2020 were included. The exposure was defined by residence rurality. Data from the DSR, Statistics Denmark, and the Danish Health Data Authority, were linked on the individual level using the Civil Registration Number. Adjusted treatment rates were calculated by balancing baseline characteristics using inverse probability of treatment weights. RESULTS: Among the included 56,175 patients, prehospital delays were shortest for patients residing in capital municipalities (median 4.7 h), and longest for large town residents (median 7.1 h). Large town residents were predominantly admitted directly to a comprehensive stroke center (98.5%), whereas 30.9% of capital residents were admitted to a hospital with no reperfusion therapy available (non-RT unit). Treatment rates were similar among all non-rural residents (18.5%-18.7%), but slightly lower among rural residents (17.2% [95% CI 16.5-17.8]). After adjusting for age, sex, immigrant status, and educational attainment, rural residents reached treatment rates comparable to capital and large town residents at 18.5% (95% CI 17.7-19.4). DISCUSSION AND CONCLUSION: While treatment rates varied minimally by urban-rural residency, substantial differences in median prehospital delay and admission to non-RT units underscored marked urban-rural differences in potential obstacles to reperfusion therapies.

2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease" provides an update to and consolidates new evidence since the "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease" and the corresponding "2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease." METHODS: A comprehensive literature search was conducted from September 2021 to May 2022. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. STRUCTURE: This guideline provides an evidenced-based and patient-centered approach to management of patients with chronic coronary disease, considering social determinants of health and incorporating the principles of shared decision-making and team-based care. Relevant topics include general approaches to treatment decisions, guideline-directed management and therapy to reduce symptoms and future cardiovascular events, decision-making pertaining to revascularization in patients with chronic coronary disease, recommendations for management in special populations, patient follow-up and monitoring, evidence gaps, and areas in need of future research. Where applicable, and based on availability of cost-effectiveness data, cost-value recommendations are also provided for clinicians. Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease" provides an update to and consolidates new evidence since the "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease" and the corresponding "2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease." METHODS: A comprehensive literature search was conducted from September 2021 to May 2022. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. STRUCTURE: This guideline provides an evidenced-based and patient-centered approach to management of patients with chronic coronary disease, considering social determinants of health and incorporating the principles of shared decision-making and team-based care. Relevant topics include general approaches to treatment decisions, guideline-directed management and therapy to reduce symptoms and future cardiovascular events, decision-making pertaining to revascularization in patients with chronic coronary disease, recommendations for management in special populations, patient follow-up and monitoring, evidence gaps, and areas in need of future research. Where applicable, and based on availability of cost-effectiveness data, cost-value recommendations are also provided for clinicians. Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

The role of hemostatic agents after tooth extractions: A systematic review and meta-analysis.

BACKGROUND: Hemostatic agents are used to control bleeding after tooth extraction and have been compared with conventional measures (that is, sutures or gauze pressure) in several studies. The objective of this systematic review was to evaluate the benefits of topical hemostatic agents for controlling bleeding after tooth extractions, especially in patients receiving antithrombotic therapy. TYPES OF STUDIES REVIEWED: The authors conducted a literature search in MEDLINE (PubMed), Scopus, and the Cochrane Central Register of Controlled Trials, including prospective human randomized clinical trials in which researchers compared hemostatic agents with conventional methods and reported the time to achieve hemostasis and postoperative bleeding events. RESULTS: Seventeen articles were eligible for inclusion. Hemostatic agents resulted in a significantly shorter time to achieve hemostasis in both healthy patients and patients taking antithrombotic drugs (standardized mean difference, -1.02; 95% CI, -1.70 to -0.35; P = .003 and standardized mean difference, -2.30; 95% CI, -3.20 to -1.39; P < .00001, respectively). Significantly fewer bleeding events were noted when hemostatic agents were used (risk ratio, 0.62; 95% CI, 0.44 to 0.88; P = .007). All forms of hemostatic agents (that is, mouthrinse, gel, hemostatic plug, and gauze soaked with the agent) had better efficacy in reducing the number of postoperative bleeding events than conventional hemostasis measures, except for hemostatic sponges. However, this was based on a small number of studies in each subgroup. CONCLUSIONS: The use of hemostatic agents seemed to offer better bleeding control after tooth extractions in patients on antithrombotic drugs than conventional measures. PRACTICAL IMPLICATIONS: Findings of this systematic review may help clinicians attain more efficient hemostasis in patients requiring tooth extraction. This systematic review is registered in the PROSPERO database. The registration number is CRD42021256145.

Biosimilar Tenecteplase Versus Alteplase in Acute Ischemic Stroke: A Real World Study.

Background and Purpose: There is an unmet need for a more effective thrombolytic agent in acute ischemic stroke (AIS) management. Various studies and meta-analysis suggest tenecteplase (TNK) as non-inferior over alteplase (rTPA). The present single-center study compares biosimilar TNK and rTPA in a tertiary care setting. Methods: Data of patients who presented with AIS and underwent intravenous thrombolysis (IVT) were recruited retrospectively from January 2018 to July 2021. Primary efficacy outcome was a modified Rankin score (mRS) at 90 days dichotomized at < = 2. Qualitative and quantitative variables were assessed using Chi-square test and Student's t-test, respectively. Results: A total of 160 patients, 103 in the rTPA and 57 in TNK group, were analyzed. The baseline characteristics were well matched apart from hypertension. Large artery atherosclerosis was the most frequent subtype of stroke among the two groups. Good functional outcome was seen in 47.92% of patients TNK and 64.77% of patients in rTPA group (p = 0.069). No difference was seen in the rates of any ICH (p = 0.29) and mortality at 3 months (p = 0.32) among the two groups. Conclusion: This present study observed no difference in the efficacy and safety between biosimilar TNK and rTPA. Our findings are in concordance with published trials showing equivalence between the two molecules.

Impact of Time to Intervention on Catheter-Directed Therapy for Pulmonary Embolism.

Cather-directed therapies (CDTs) are an evolving therapeutic option for patients with intermediate-risk pulmonary embolism (PE). Although many techniques have been studied, there is limited evidence for the impact of timing of intervention on patient outcomes. Our objective was to assess the association between time to CDT in patients presenting with PE on patient-related outcomes such as length of stay (LOS) and mortality. DESIGN: Retrospective cohort study. SETTING: Single academic center. PATIENTS: We identified patients for which the PE response team had been activated from January 2014 to October 2021. Patients were split into two cohorts depending on whether they went to CDT less than 24 hours from admission (early) versus greater than 24 hours (late). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data on demographics, timing of interventions, pulmonary hemodynamics, and outcomes were collected. Sixty-four patients were included in analysis. Thirty-nine (63.8%) underwent their procedure less than 24 hours from admission, whereas 25 (36.2%) underwent the procedure after 24 hours. The time from admission to CDT was 15.9 hours (9.1-20.3 hr) in the early group versus 33.4 (27.9-41) in the late group (p ≤ 0.001). There was a greater decrease in pulmonary artery systolic pressure after intervention in the early cohort (14 mm Hg [6-20 mm Hg] vs 6 mm Hg [1-10 mm Hg]; p = 0.022). Patients who received earlier intervention were found to have shorter hospital LOS (4 vs 7 d; p = 0.038) and ICU LOS (3 vs 5 d; p = 0.004). There was no difference in inhospital mortality between the groups (17.9% vs 12%; p = 0.523). CONCLUSIONS: Patients who underwent CDT within 24 hours of admission were more likely to have shorter hospital and ICU LOS. The magnitude of change in LOS between the two cohorts was not fully explained by the difference in time to CDT. There were modest improvements in pulmonary hemodynamics in the patients who underwent CDT earlier.

Postoperative Bleeding Risk after Gastric Endoscopic Submucosal Dissection in Patients Receiving a P2Y12 Receptor Antagonist.

Background/Aims: The safety of gastric endoscopic submucosal dissection (ESD) in users of a P2Y12 receptor antagonist (P2Y12RA) under current guidelines has not been verified. Methods: Patients treated by gastric ESD at Okayama University Hospital between January 2013 and December 2020 were registered. The postoperative bleeding rates of patients (group A) who did not receive any antithrombotic drugs; patients (group B) receiving aspirin or cilostazol monotherapy; and P2Y12RA users (group C) those on including monotherapy or dual antiplatelet therapy were compared. The risk factors for post-ESD bleeding were examined in a multivariate analysis of patient background, tumor factors, and antithrombotic drug management. Results: Ultimately, 1,036 lesions (847 patients) were enrolled. The bleeding rates of group B and C were significantly higher than that of group A (p=0.012 and p<0.001, respectively), but there was no significant difference between group B and C (p=0.11). The postoperative bleeding rate was significantly higher in dual antiplatelet therapy than in P2Y12RA monotherapy (p=0.014). In multivariate analysis, tumor diameter ≥12 mm (odds ratio [OR], 4.30; 95% confidence interval [CI], 1.99 to 9.31), anticoagulant use (OR, 4.03; 95% CI, 1.64 to 9.86), and P2Y12RA use (OR, 3.40; 95% CI, 1.07 to 10.70) were significant risk factors for postoperative bleeding. Conclusions: P2Y12RA use is a risk factor for postoperative bleeding in patients who undergo ESD even if receiving drug management according to guidelines. Dual antiplatelet therapy carries a higher risk of bleeding than monotherapy.

Intrapleural Instillation of Sodium Bicarbonate versus Urokinase in Management of Complicated Pleural Effusion: A Comparative Cohort Study.

Aim: The main target is evacuation; however, with evidence about the value of intrapleural instillation of different fibrinolytic agents still under evaluation, our aim was comparing the effectiveness and safety of intrapleural instillation of sodium bicarbonate (NaHCO3) in comparison with urokinase in patients with infected pleural effusion. Methods: Our prospective cohort study included 40 patients with complicated empyema; the diagnosis was based on analysis of aspirated fluid in association with radiological and bacteriological culture. The patients were subjected to instillation of two different fibrinolytic agents; the first one was NaHCO3, the second was urokinase. Results: The commonest underlying chest infection that was visualized by CT was pneumonia 70%. Nearly half of cases had community-acquired infection (45%), and more than half of them (55%) had anaerobic infection, and only five cases had TB pleural effusion based on ADA-positive, tuberculin skin test in addition to Abram's needles closed biopsy. The rate of repeated therapeutic thoracentesis success in each group was 85%; 80% in NaHCO3 group, and 90% in urokinase group, both of them was significantly equal, P=0.37. Moreover, the frequency of complications in all patients was less than 13%, hence hemothorax and iatrogenic pneumothorax was 12.5%, and only 10% of cases were admitted in ICU after the maneuver, with insignificant difference in between the groups. However, looking at the smaller rate of RTT failure of NaHCO3 or urokinase, the logistic regression model showed that RTT-NaHCO3 was insignificantly related to failure in both unadjusted and adjusted models, P=0.37 and 0.32, respectively, and only smoking habits increase the likelihood of failure 9-fold (OR=8.9, P=0.04) with respect to age, sex, and treatment methods. Conclusion: The efficacy of repeated therapeutic thoracentesis (RTT) with intrapleural instillation of NaHCO3 was effective and safe, the same as urokinase, with consideration that NaHCO3 was much more available and affordable than urokinase.

Risk of Bleeding after Transcatheter Aortic Valve Replacement: impact of Preoperative Antithrombotic Regimens

Abstract Introduction: Bleeding after transcatheter aortic valve replacement (TAVR) has a negative impact on the outcome of the procedure. Risk factors for bleeding vary widely in the literature, and the impact of preoperative antithrombotic agents has not been fully established. The objectives of our study were to assess bleeding after TAVR as defined by the Valve Academic Research Consortium-2 (VARC-2), identify its risk factors, and correlate with antithrombotic treatment in addition to its effect on procedural mortality. Methods: The study included 374 patients who underwent TAVR from 2009 to 2018. We grouped the patients into four groups according to the VARC-2 definition of bleeding. Group 1 included patients without bleeding (n=265), group 2 with minor bleeding (n=22), group 3 with major bleeding (n=61), and group 4 with life-threatening bleeding (n=26). The median age was 78 (25th-75th percentiles: 71-82), and 226 (60.4%) were male. The median EuroSCORE was 3.4 (2-6.3), and there was no difference among groups (P=0.886). The TAVR approach was transfemoral (90.9%), transapical (5.6%), and trans-subclavian (1.9%). Results: Predictors of bleeding were stroke (OR: 2.465; P=0.024) and kidney failure (OR: 2.060; P=0.046). Preoperative single and dual antiplatelet therapy did not increase the risk of bleeding (P=0.163 and 0.1, respectively). Thirty-day mortality occurred in 14 patients (3.7%), and was significantly higher in patients with life-threatening bleeding (n=8 [30.8%]; P<0.001). Conclusion: Bleeding after TAVR is common and can be predicted based on preprocedural comorbidities. Preprocedural antithrombotic therapy did not affect bleeding after TAVR in our population.

Impact of the COVID-19 pandemic on cardiovascular heart disease medication use: time-series analysis of England's prescription data during the COVID-19 pandemic (January 2019 to October 2020).

BACKGROUND: Management of high blood pressure (BP) typically requires adherence to medication regimes. However, it is known that the COVID-19 pandemic both interrupted access to some routine prescriptions and changed some patient health behaviours. AIM: This study, therefore, retrospectively investigated prescription reimbursement of cardiovascular (CVD) medicines as a proxy measure for patient adherence and access to medicines during the pandemic. METHODS: A cohort study of all primary care patients in England prescribed CVD medicines. The exposure was to the global pandemic. Prescriptions were compared before and after the pandemic's onset. Statistical variation was the outcome of interest. RESULTS: Descriptive statistics show changes to monthly prescriptions, with wide confidence intervals indicating varying underlying practice. Analysis of variance reveals statistically significant differences for bendroflumethiazide, potassium-sparing diuretics, nicorandil, ezetimibe, ivabradine, ranolazine, colesevelam and midodrine. After the pandemic began (March-October 2020), negative parameters are observed for ACE inhibitors, beta-blockers, calcium channel blockers, statins, antiplatelet, antithrombotics, ARBs, loop diuretics, doxazosin, bendroflumethiazide, nitrates and indapamide, indicating decelerating monthly prescription items (statistically significant declines of calcium channel blockers, antithrombotic, adrenoreceptor blockers and diuretics) of CVD medicines within the general population. Many data points are not statistically significant, but fluctuations remain clinically important for the large population of patients taking these medications. CONCLUSION: A concerning decline in uptake of CVD therapies for chronic heart disease was observed. Accessible screening and treatment alongside financial relief on prescription levies are needed. A video abstract is (4 min 51 s) available: https://bit.ly/39gvEHi.

Alteplase or tenecteplase for thrombolysis in ischemic stroke: An illustrated review.

Intravenous thrombolysis is a standard of care treatment for patients with acute ischemic stroke. Tissue plasminogen activator (tPA) has been the main thrombolytic agent used since the publication of the seminal National Institutes of Neurological Disorders and Stroke trial in 1995. There is now mounting evidence to support the routine use of Tenecteplase (TNK) to treat acute ischemic stroke. TNK is a genetically modified tPA with higher fibrin specificity, longer half-life, and reduced systemic coagulopathy. In this illustrated review, we compare the indications, doses, mechanisms of action, efficacy and safety of TNK and tPA. We provide an overview of published clinical trials studying TNK in acute ischemic stroke, including dose-escalation studies and head-to-head comparisons with tPA. Finally, we summarize current acute stroke guideline recommendations and suggest treatment algorithms to manage the two main complications of intravenous thrombolysis: symptomatic intracerebral hemorrhage and angioedema.

Medical students' confidence and competence with prescribing in ST-elevation myocardial infarction: a mixed-methods study.

Objectives: To explore factors associated with prescribing confidence and competence of final-year medical students for prescribing antiplatelet and fibrinolytic agents in ST-segment elevation myocardial infarction (STEMI). Methods: The study was conducted among final-year medical students with a triangular convergent mixed-methods approach. First, an online survey was conducted using a voluntary sampling method with concurrent in-depth interviews performed. The survey data was analysed using descriptive statistics and paired t-tests, while survey factors were compared using the chi-squared or Fisher's exact test. The interview data were coded and analysed thematically. The relations between the qualitative and quantitative findings were finally described. Results: Totally 92 validly replied to the questionnaire, and 20 participated in the interviews. The quantitative analysis indicated that they had high competence in the diagnosis of STEMI and prescribing antiplatelet and fibrinolytic agents. The mean confidence score of prescribing for both was medium and was significantly lower in fibrinolytic agents. (M=3.3, SD=1.1 vs. M=2.8, SD=1.0, t(91)=5.39, p<0.01). Their experience, knowledge, and mentoring were accounted for, considering the prescribing confidence factors in both approaches. Besides, providing guidelines and standing orders were derived from the interview data. Conclusions: This study has demonstrated that final-year medical students have a high ability to diagnose and prescribe essential medications in STEMI but tend to have low confidence in prescribing fibrinolytic agents. Experiential learning, mentorship and providing guidelines can help them, especially in emergency settings to prescribe confidently and safely. Further multicenter studies on undergraduate and graduate medical students' confidence and perspective of prescribing are required, especially for high-alert medications.

Intravenous thrombolysis prior to mechanical thrombectomy does not affect clinical or procedural outcomes in patients with large vessel occlusion acute ischemic stroke.

Mechanical thrombectomy (MT) has revolutionized the care of large vessel occlusion acute ischemic strokes (LVOAIS). However, the benefit of intravenous thrombolysis prior to MT remains unproven. Two recent trials showed equivocal results regarding the benefits of pre-MT intravenous thrombolysis in predominantly Asian populations. We evaluated clinical outcomes and procedural metrics for patients with LVOAIS who were treated with MT alone compared to those who were treated with both intravenous tPA and MT. In a retrospective study, LVOAIS patients treated with MT, with or without preceding intravenous thrombolysis, between January of 2017 and December of 2019 were identified. Patients were treated according to contemporary guidelines. Baseline demographic and clinical characteristics, procedural metrics, and clinical outcomes were collected. Among LVOAIS patients, those treated with intravenous thrombolysis and MT did not differ from those with MT alone on clinical outcomes at three months. Further, the two groups did not differ on thrombectomy procedure times, recanalization rates, and symptomatic intracranial hemorrhage rates. In our patients with LVOAIS, intravenous thrombolysis combined with MT offered no advantage compared to MT alone in clinical outcomes or recanalization rates. Our results are consistent with earlier studies in other populations. In addition, our results suggest that IV tPA does not impact the ease of clot removal by MT. Further studies will evaluate how newly available thrombolytic agents may benefit patients eligible for MT.

Trombolisis sistémica complicada en embolia cerebral múltiple por trombo intraventricular / Systemic thrombolysis following multiple embolic cerebral lesions in a patient with myocardial infarction and intraventricular thrombus

RESUMEN Se presenta un caso de trombólisis sistémica complicada con transformación hemorrágica en paciente con evento isquémico cerebral sintomático por embolia múltiple a partir de trombo intraventricular en contexto de infarto agudo de miocardio por oclusión total de arteria descendente anterior con deterioro severo de función sistólica de ventrículo izquierdo.

ABSTRACT: We describe a case of complicated systemic thrombolysis with hemorrhagic transformation in a patient with a cerebral ischemic event due to multiple embolisms from intraventricular thrombus in the context of acute myocardial infarction due to total occlusion of the anterior descending artery and severe deterioration of left ventricular systolic function.