bluuebunny/crossref_metadata_2025_split huggingface dataset:
Should the Use of Acid Reducing Agents in Conjunction with Ribociclib be Avoided? An Integrated QbD Approach for Assessment of pH-Mediated Interaction
Authors: Desai Mrunal , Patil Prajakta Harish , Rao Rajat Radhakrishna , Shenoy Gurupur Gautham , Rao Mahadev , Mutalik Srinivas , Jagadish Puralae Channabasavaiah 
Published: October 2022

Abstract
The objective of the study was to evaluate the possible pH-dependent interaction of ribociclib succinate with acid-reducing agents, which are concomitantly administered as supportive care medicines in cancer. Quality by Design-based analytical method development for a weakly basic drug ribociclib succinate supposedly having the characteristic ability of pH-dependent solubility was carried out for analyzing micro-dissolution experiment samples in biorelevant media to study pH-dependent interaction. An accurate and robust analytical method was developed using a three-level three-factorial box–behnken design for quantification of ribociclib succinate in micro-dissolution samples by the implementation of the Analytical Quality by Design approach. Here, pH of aqueous mobile phase and flow rate proved to be critical process parameters. The gastric compartment solubility was found to be 814.05 μg/mL, which dropped down to 494.71 μg/mL after a pH shift from pH 1.2–6.5. In the intestinal compartment, initial solubility was 717.58 μg/mL, which reduced to 463.20 μg/mL after a pH shift from 6.5 to 6.8. Concluded results state that pH shift does not impact the solubility or the absorption of the drug to a significant extent in the presence of acid-reducing agents. However, the study would prove to be a practical approach for examination of the behavior of the drugs at the initial stages.
Engaging writing in the Arab EFL classroom
Authors: Hayik Rawia 
Published: October 2022

AbstractThe PhotoVoice tool invites participants to create photographs that reflect aspects of their surroundings that they find problematic and to elaborate on them in writing. Participants then share their photographs and written accounts with an influential audience with the hope of resolving the highlighted concerns. Aiming to connect the classroom to the students’ community, the author, a teacher-educator, and her college students implemented PhotoVoice at Palestinian-Israeli schools, guiding small groups of elementary-level EFL pupils throughout the writing process. Children’s powerful presentations to the invited audience proved how creative and proficient EFL learners can be when provided with sufficient support to write and discuss social issues pertinent to their lives. Inspired by critical literacy pedagogy, this approach for improving literacy skills while promoting change challenges the teaching of EFL as a set of linguistic skills detached from reality. This tool can foster an engaging approach to language education that connects literacy teaching with social action.
Teacher perspectives on addressing environmental issues in ELT
Authors: Mercer Sarah , Correia Ibrahim Nayr , Bilsborough Katherine , Jones Ceri , Potzinger Chiara 
Published: October 2022

Abstract
In this article, we report on a mixed-methods study which investigated teachers’ attitudes towards and experiences with teaching environmental issues within their ELT classes. Given the rising importance of ecoliteracy and its inclusion as a transversal learning objective for all subjects in many national state curricula, it is critically important to understand how ELT educators can be best supported in addressing simultaneously both linguistic and environmentally related teaching goals. Data were collected via an online international survey (n = 91) and a series of in-depth, semi-structured interviews (n = 5). Analysis of the data reveals the specific strategies ELT teachers employ when integrating environmental issues alongside linguistic issues, what their motivations for doing so are, what resources and materials they use, and what challenges they face. The article offers valuable insights into the factors that facilitate the sustainable and effective teaching of both language and environmental issues in diverse ELT contexts across the globe.
The mitral to aortic/pulmonary velocity-time integral ratio is a simple, feasible and accurate discriminator for echocardiographic evaluation of severe isolated mitral regurgitation
Authors: Ramkumar S , Nerlekar N , Maggiore P , Teng J , Cimenkaya C , Be K , Baumann A , Nicholls S , Moir S 
Published: October 2022

Abstract

Background
Echocardiographic quantification of mitral regurgitation (MR) remains challenging, requiring dedicated image acquisition, and is limited by potential error from geometric assumptions of annular dimensions. Volume is a product of area and flow and assuming proportional mitral/aortic areas, an increased mitral-inflow volume compared to LV/RV-outflow semi-quantitatively represents greater MR regurgitant volume. Therefore, we investigated the feasibility and diagnostic performance of the mitral-aortic velocity-time integral (VTI) ratio in isolated MR. We also investigated the use of the mitral-pulmonary VTI ratio as an alternative in clinical situations where the LV outflow tract (LVOT) VTI could not be used.

Methods
We reviewed 166 consecutive patients (54 (33% severe MR by multi-parameter integrated expert opinion)). Pulsed-Doppler VTI at the mitral leaflet tips and the left ventricular outflow and continuous-wave Doppler of the right ventricular outflow tract were measured individually and independently by blinded readers (expert and trainee status) to derive the ratio. Receiver operator characteristic area under the curve (AUC) comparison was calculated and compared with effective regurgitant orifice area (EROA &gt;40 mm), regurgitant volume (RVol &gt;6 0mL), vena contracta (VC &gt;0.7 cm), E-velocity &gt;1.2 cm, systolic flow reversal (SFR), left atrial and ventricular dilatation.

Results
Increasing ratio was associated with severe MR (AUC 0.94) with optimal threshold defined at 1.3. This provided significant discrimination for severe MR (AUC 0.81) compared to EROA (0.68), VC (0.52), LV dilatation (0.69), LA dilatation (0.70), SFR (0.73), E-velocity (0.68) all p&lt;0.05, with sensitivity 82% and specificity 94%. The mitral-pulmonary VTI ratio demonstrated similar discrimination (AUC 0.92) with optimal threshold defined at 1.14. Excellent inter-observer reproducibility (intra-class correlation 0.97) was seen between trainee and expert readers. There was no difference in AUC comparison by MR mechanism or patient rhythm.

Conclusions
The mitral-aortic or mitral-pulmonary VTI ratio is a simple, geometric-free parameter feasibly reproducible from routine echocardiographic datasets and is an excellent discriminative tool for severe MR. Readers should consider integration of this parameter in routine reporting.

Funding Acknowledgement
Type of funding sources: None.
Suboptimal coronary flow after PCI in STEMI patients: clinical implications and predictors
Authors: Barradas M , Duarte F , Coutinho Dos Santos I , Resendes De Oliveira L , Serena C , Xavier Fontes A , Viveiros Monteiro A , Machado C , Dourado R , Santos E , Pelicano N , Pacheco M , Tavares A , Martins D 
Published: October 2022

Abstract

Background
Even in experienced angioplasty centers, percutaneous coronary intervention (PCI) in the acute setting of ST-elevation myocardial infarctions (STEMI) is associated with a low, but still significant rate of suboptimal coronary flow. Identification of its clinical impact and potential modifiable risk factors is important.

Purpose
To evaluate the clinical impact of suboptimal coronary flow after PCI in STEMI patients and to access potential predictors of suboptimal coronary flow.

Methods
We retrospectively evaluated 103 hospitalized patients with acute STEMI who were admitted to our center between 2018 and 2019 and underwent PCI. Coronary flow was accessed using the Thrombolysis in myocardial infarction (TIMI) Flow Grading System. Patients were divided into suboptimal patency of the culprit-vessel, defined as TIMI flow ≤2 (group 1, n=8 (7,8%)) and optimal patency of the culprit-vessel defined as TIMI flow 3 (group 2, n=95 (92,2%)). Glomerular filtration rate (GFR) was calculated using the Modification of Diet in Renal Disease (MDRD) formula.

Results
Mean age 58,15±12,6 years and 85,4% were males. Seventy-eight patients (75,7%) had history of smoking, 45 (43,7%) dyslipidemia, 20 (19,4%) previous acute coronary syndrome, 18 (17,5%) diabetes, 17 (15,5%) were obese and 4 (3,9%) had chronic kidney disease. The revascularization strategy was primary PCI in 55 (54,4%) patients and fibrinolytic therapy with facilitated PCI in 48 (46,6%) patients. Infarct-related artery was the left anterior descending artery in 45 (45,5%) and multivessel disease was present in 38 (38,0%). Angiographic no-reflow after PCI was 3,0%. Intrahospital cardiovascular death occurred in 4 (3,9%) patients and was significantly associated with suboptimal flow (p=0,036) and there was no association with stent thrombosis. Predictors of suboptimal flow were higher blood urea nitrogen, creatinine and GFR at hospital admission (p=0,017 and p=0,012), peak creatinine (p=0,012) and stent length (p=0,038). Suboptimal flow was associated with higher Zwolle score (p=0,010) and ischemic Paris score (p=0,036).

Conclusion
Failure to achieve optimal culprit-vessel patency after PCI in STEMI patients, although infrequent, is associated with increased hospital cardiovascular death. Longer stents could be and important modified risk factor. Renal dysfunction is an important comorbidity that should be promptly identified and could be partially improved with medical treatment.

Funding Acknowledgement
Type of funding sources: None.
Evolution and clinical implications of right ventricular dysfunction in ischemic cardiomyopathy with or without coronary artery bypass surgery
Authors: Zhou Z , Liang M , Jian B , Fu G , Wu Z 
Published: October 2022

Abstract

Background
The Surgical Treatment of Ischemic Heart Failure (STICH) trial demonstrated that coronary artery bypass grafting (CABG) provides additional survival benefits to patients with ischemic cardiomyopathy. However, it remains unclear whether this benefit is affected by preoperative right ventricular (RV) function and how post-therapeutic evolution of RV function influences long-term outcomes.

Purpose
We sought to investigate the implications of baseline RV function on therapeutic decision-making in patients with ischemic cardiomyopathy, and to evaluate the prognostic implications of post-therapeutic evolution of RV function.

Methods
Patients with available baseline echocardiographic RV function assessed by experienced Echocardiography Core Laboratory physicians were included from the hypothesis 1 of the STICH trial. The primary outcome was long-term all-cause mortality.

Results
A total of 1042 patients were included, among them 757 (72.7%) had normal RV function, 143 (13.7%) mild right ventricular dysfunction (RVD), and 142 (13.6%) moderate to severe RVD. After a median follow-up of 9.8 years, patients with RVD had a higher risk of all-cause mortality compared with patients with normal RV function [mild RVD: adjusted hazard ratio (aHR) 1.32; 95% confidence interval (CI) 1.06–1.64; moderate to severe RVD: aHR, 1.74; 95% CI 1.39–2.18]. Although no significant interaction was detected between RVD degree and treatment allocation (P for interaction = 0.399), a gradually decreasing survival benefit associated with CABG was observed among patients with normal RV function (aHR: 0.79; 95% CI: 0.65–0.96), mild RVD (aHR: 0.85; 95% CI: 0.56–1.29), and moderate to severe RVD (aHR: 0.97; 95% CI: 0.67–1.43). Among 746 patients with available RV function assessed at baseline and post-therapeutic 4-month follow-up, there was a gradient of increasing risk for all-cause mortality across patients with consistent normal RV function, recovery of RVD (aHR: 1.20; 95% CI: 0.88–1.64), newly developed RVD (aHR: 1.59; 95% CI: 1.18–2.14), and consistent RVD (aHR: 2.06; 95% CI: 1.60–2.67). Independent predictors of RVD recovery included baseline left ventricular ejection fraction (per 1-percent increment, adjusted odds ratio: 1.04; 95% CI: 1.00–1.09) and mitral regurgitation ≥ grade 2 (adjusted odds ratio: 0.42; 95% CI: 0.21–0.84).

Conclusions
Baseline RVD was associated with an increased risk of long-term mortality in patients with ischemic cardiomyopathy, and adding CABG to medical therapy might provide limited survival benefits in patients with moderate to severe RVD. A gradient of increasing risk for mortality was observed across different categories of RV function evolution, which emphasizes the necessity of pre- and post-therapeutic RV assessment for prognostic evaluation.

Funding Acknowledgement
Type of funding sources: None.
ST Segment myocardial infarction due to totally occluded unprotected left main coronary artery (TOULM): an insight from nationwide database
Authors: Arabi A , Rafie I , Arafa S , Alqahtani A , Altamimi O , Abujalala S , Hamid T , Ali M , Alkindi F , Alkhani M , Al-Hijji M , Altamimi H , Al Suwaidi J 
Published: October 2022

Abstract

Objective
This study sought to describe the clinical profile, management and short-term outcomes of patients with ST elevation myocardial infraction (STEMI) due to totally occluded unprotected left main coronary artery (TOULM).

Methods
This is a retrospective analysis of nationwide STEMI database of patients who underwent primary percutaneous intervention (PPCI). Patients with TOULM are defined as having 100% acute thrombotic occlusion of the left main artery or subtotal occlusion with no more than TIMI 1 flow.

Results
Between January 2011 and February 2022, 7107 patients underwent Primary Percutaneous Intervention for STEMI. 35 cases (0.5%) of all STEMI were due to TOULM. The average age of patients with TOULM was 51±14 years, predominantly male (94%) and had no prior cardiac history (94%). 11 patients (31%) suffered cardiac arrest and 16 (45%) were on mechanical ventilation prior to arrival to cardiac catheterization laboratory.
The right coronary artery was the dominant vessel in 29 (89%) patients. Right to left collaterals were present in 15 (42%), absent in 8 (23%) and unknown (the right coronary artery was injected after TOULM intervention or not injected) in 12 (34%) patients. Mechanical circulatory support was used in 37% of the cases (IABP 8, ECMO 3 and ECMO plus IABP 2). Revascularization was achieved with PCI and stenting in 30 patients (86%). Five patients underwent urgent CABG after balloon angioplasty. Survival to hospital discharge was 55%.

Conclusions
STEMI due to TOULM is a rare occurrence and involved mainly male with no prior cardiac history. Despite all the patients in our series undergoing revascularization, the in-hospital mortality is almost 50%. One major limitations of our study is we had no post-mortem data of any patient who died prior to coronary angiography, which potentially will lead to higher recorded cases of TOULM related mortality.

Funding Acknowledgement
Type of funding sources: None.
Bleeding complications in patients undergoing percutaneous coronary intervention in coronary artery bypass grafts: the impact of clinical presentation, access site and selection bias
Authors: Bimal T , Bhuiyan M , Fishbein J , Gandotra P , Selim S , Ong L , Gruberg L 
Published: October 2022

Abstract

Background
Percutaneous coronary intervention (PCI) in patients with prior coronary artery bypass graft (CABG) surgery is commonly done via the femoral approach. Relatively few cases are done via the radial approach.

Purpose
To assess bleeding complications in patients with either radial/brachial or femoral access when undergoing graft PCI, saphenous vein graft or internal mammary artery (IMA) graft.

Method
Data was collected for quality control on all patients that underwent PCI between 2010 and 2018 at 6 tertiary care hospitals in our system. Outcomes were classified and reported in accordance with the Bleeding Academic Research Consortium (BARC) criteria. BARC Type 4 (CABG-related) and BARC Type 5 (fatal) bleeds were excluded. Major bleeding was defined as BARC Type ≥3. Major adverse cardiac and cerebrovascular events (MACCE) was the combined endpoint of hospital death; post procedural myocardial infarction; cerebrovascular events (ischemic and hemorrhagic) and major bleeding complications. Due to the high intraclass correlation of procedures within patients, only the first procedure within the study period was selected from each patient for analysis. The two-sample t-test, Wilcoxon rank sum test, chi-square or Fisher's exact test were used as appropriate.

Results
A total of 1153 of 1196 patients who underwent graft intervention had BARC outcome data. Of these only 81 (7%) was via radial/brachial access. Baseline clinical characteristics are shown in the Table. A higher percentage of BARC ≥3 patients presented with NSTEMI/STEMI or had IMA graft intervention. Access site was not associated with bleeding complications. However, MACCE, post procedural heart failure (HF) and post procedural myocardial infarction (MI) rates were higher in patients who had femoral access (Figure).

Conclusions
In a large contemporary dataset of post CABG patients undergoing graft interventions: 1) the majority of patients (93%) underwent graft PCI via femoral access; 2) clinical presentation and acuity was associated with more severe bleeding complications; 3) access site did not seem to be associated with bleeding complications (possible selection bias); and 4) there was a trend towards higher MACCE rates in patients who had a femoral access. Additional analysis will be done to further investigate our findings.

Funding Acknowledgement
Type of funding sources: None.
Long-term risk factor control after acute coronary syndrome; results from the Swedish primary care cardiovascular database
Authors: Bentzel S , Ljungman C , Hjerpe P , Schioler L , Manhem K , Mourtzinis G 
Published: October 2022

Abstract

Background
Most secondary prevention studies after acute coronary syndrome (ACS) have relatively short follow-up time, and less is known about long-term risk factor control in patients after ACS.

Purpose
We aimed to study and describe the long-term risk factor control, treatment adherence and outcome after ACS.

Methods
We identified 3765 patients (mean age 75 years, 40% women) with an incident ACS between 2006 and 2010 in the Swedish Primary Care Cardiovascular Database. All participants were followed from index ACS until 31 December 2014 or death. We annually recorded blood pressure, low density lipoprotein cholesterol (LDL-C), dispensed prescription of drugs, recurrent ACS, and death. Data were collected from electronic medical records at the primary care centres, the Swedish Prescribed Drug Register, the Swedish Patient Register, and the Cause of Death Register. We calculated annually proportion of days covered (PDC) for secondary prevention medication. PDC value of ≥80% was considered cut off for medication adherence.

Results
The median follow-up time was 4.8 years (min 1.8 and max 8.0). 1890 new ACS-events were recorded during the follow up; the annual incidence of recurrent ACS was 17.3%, 12.9%, 8.9%, 8.0%, 7.6%, 6.5%, 5.2%, and 5.0% (for year 1 to year 8 respectively). 1859 (49.4%) patients died during the follow up. The annual incidence of death was 19.9%, 7.9%, 7.1%, 8.3%, 7.9%, 8.2%, 6.7%, and 6.4% (for year 1 to year 8 respectively). The annual proportion of patients that achieved the blood pressure target &lt;140/90 mm Hg was 57.8%, 60.9%, 62.7%, 63.3%, 64.9%, 63.1%, 62.4%, and 66.1% (for year 1 to year 8 respectively). The annual mean number of antihypertensive medications for each patient was 1.5, 1.3, 1.3, 1.3, 1.4, 1.4, 1.4, and 1.5 (for year 1 to year 8 respectively). The annual proportion of patients that achieved LDL-C &lt;1.8 mmol/L was 23.1%, 21.7%, 19.8%, 18.2%, 15.7%, 19.6%, 18.3%, and 16.7% (for year 1 to year 8 respectively). The annual proportion of patients in treatment with statins was 55.3%, 57.5%, 58.7%, 59.2%, 63.0%, 63.7%, 64.1%, and 67.7% (for year 1 to year 8 respectively). The annual proportion of patients in treatment with acetylsalicylic acid was 79.6%, 76.4%, 76.2%, 78.9%, 78.3%, 79.2%, and 80.8% % (for year 1 to year 8 respectively). The annual proportion of patients in treatment with P2Y12-inhibitors was 24.3%, 7.2%, 5.4%, 6.0%, 7.2%, 8.1%, 7.9% and 8.2% (for year 1 to year 8 respectively).

Conclusion
This retrospective long-term real-world study from primary care demonstrates a large potential for improvement of risk factor control in patients after ACS. More specific, this study demonstrates underutilized treatment with antihypertensive medication and statins, while adherence to antiplatelet therapy was found to be high.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Astra Zeneca
Cardiovascular disease risk in males and females with new onset diabetes: a population-based study in universal health care setting
Authors: Kaul P , Manh Chu L , Dover D C , Eurich D T , Yeung R O , Senior P , Butalia S 
Published: October 2022

Abstract

Background
The evidence on whether long-term cardiovascular disease (CVD) outcomes differ among males and females with incident diabetes remains equivocal.

Objective
To examine sex-differences in the association between incident diabetes and 5-year risk of CVD and mortality at the population-level.

Methods
The study population consisted of an inception cohort of individuals between 40 and 80 years without diabetes or CVD on April 1, 2013 in the province of Alberta, Canada (N=1,315,885). Incident diabetes during a 3-year period was used to categorize males and females by diabetes status as of March 31, 2016. Primary outcome of interest was a combination of CVD hospitalization (defined as a hospitalization with a primary diagnosis of heart failure, acute coronary syndromes, cerebrovascular disorders, atrial fibrillation and flutter, ventricular arrhythmia, or sudden cardiac death) or all-cause mortality over a 5-year period until March 31, 2021. Inverse probability of treatment weighting (IPTW) was used to reduce the impact of confounders between individuals with and without diabetes. Kaplan-Meier curves were used to examine unadjusted outcomes and Cox-proportional hazards models were used to examine the impact of diabetes on outcomes in males and females after adjusting for the following: age, hypertension, material deprivation, urban/rural residence, and comorbidity burden.

Results
Among 672,881 females and 643,004 males, 27,082 (4.0%) and 33,054 (5.1%) developed incident diabetes, respectively. Regardless of sex, individuals with diabetes were older and had higher rates of hypertension and other comorbidities. Overall, CVD hospitalization/mortality rates per 1000 person years were 7.5% (95% confidence interval (CI): 7.4–7.6) among females compared to 11.7% (95% CI: 11.6–11.8) among males. When stratified by diabetes status, the rates of the combined endpoint were 7.2% (95% CI: 7.1–7.3) among females with no diabetes (F w/o DM), 11.2% (95% CI: 11.1–11.3) among males with no diabetes (M w/o DM), 14.7% (95% CI: 14.0–15.3) among females with diabetes (F with DM) and 20.9% (95% CI: 20.1–21.6) among males with diabetes (M with DM, Figure 1). The adjusted hazard ratio (aHR) associated with diabetes on outcomes was similar among males (aHR 1.38 95% confidence interval (CI): 1.36–1.41) and females (aHR 1.39 95% CI: 1.36–1.42).

Conclusions
The presence of diabetes weakens the possible cardio-protection of female sex with respect to CVD outcomes. Future work aims to assess CVD prevention, management and treatment among males with females with incident diabetes.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Canadian Institutes of Health Research (CIHR) Sex and Gender Science Chair