Cervical cancer screening preference among Inuit women in Nunavik, Quebec.

Self-sampling for oncogenic human papillomavirus (HPV) offers an alternative to the Papanicolaou (Pap) test for cervical cancer screening. We aimed to assess Inuit women's cervical cancer screening preferences. Eligible Inuit women aged between 25 and 65 in 2022-2023 were given the choice between self-sampling, sampling performed solely by the nurse or the Pap test and were administered a questionnaire on screening preference.

Multicenter, Phase 2, Randomized Controlled Study of the Efficacy and Safety of Etripamil Nasal Spray for the Acute Reduction of Rapid Ventricular Rate in Patients With Symptomatic Atrial Fibrillation (ReVeRA-201).

Background: Despite chronic therapies, atrial fibrillation (AF) leads to rapid ventricular rates (RVR) often requiring intravenous treatments. Etripamil is a fast-acting, calcium-channel blocker administered intranasally affecting the atrioventricular node within minutes.

Methods: Reduction of Ventricular Rate in Patients with Atrial Fibrillation evaluated the efficacy and safety of etripamil for the reduction of ventricular rate (VR) in patients presenting urgently with AF-RVR (VR ≥110 beats per minute [bpm]), was randomized, double-blind, placebo-controlled, and conducted in Canada and the Netherlands.

Pan-Arctic soil moisture control on tundra carbon sequestration and plant productivity.

Long-term atmospheric CO concentration records have suggested a reduction in the positive effect of warming on high-latitude carbon uptake since the 1990s. A variety of mechanisms have been proposed to explain the reduced net carbon sink of northern ecosystems with increased air temperature, including water stress on vegetation and increased respiration over recent decades. However, the lack of consistent long-term carbon flux and in situ soil moisture data has severely limited our ability to identify the mechanisms responsible for the recent reduced carbon sink strength.

Comparison of Outcomes of Invasive or Conservative Management of Chronic Coronary Disease in Four Randomized Controlled Trials.

Revascularization and medical therapy for chronic coronary disease have both evolved significantly over the last 50 years. A total of 4 contemporary randomized controlled trials- Clinical Outcomes Utilizing Revascularization and Aggressive drug Evaluation (COURAGE), Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D), Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2 (FAME 2), and International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA)-have assessed the incremental benefit of revascularization when added to secondary prevention with intensive pharmacologic and lifestyle intervention. We reviewed these 4 seminal studies with the objective of marshaling evidence to better frame how these results should apply to clinical decision making.

Inhibitors of HIV-1 Nef: applications and developments for a practical cure.

Antiretroviral therapy can control human immunodeficiency virus type 1 (HIV-1) replication in people living with HIV; however, these treatments are not curative and no practical approach for an HIV-1 cure has yet shown success in clinical trials. Counteracting the multiple barriers HIV-1 presents against a practical cure is a direct means to functionalize these curative approaches in vivo. Pharmacological inhibition of the HIV-1 accessory protein, Nef, represents a particularly promising and ambitious approach, with Nef inhibitors holding the potential to reverse HIV-1-related defects in T cell receptor and kinase signaling, apoptosis, autophagy and most importantly, antigen presentation.

[Not Available].

Résumé La thérapie anti-rétrovirale peut contrôler la réplication du virus de l'immunodéficience humaine de type 1 (VIH-1) chez les individus vivant avec le VIH. Par contre, ces traitements ne constituent pas une guérison et aucune approche pour une guérison du VIH-1 n'a encore montré de succès lors des études cliniques. Les approches de guérison sont souvent contrées in vivo par des barrières développées par le VIH-1.

Comparison of Days Alive Out of Hospital With Initial Invasive vs Conservative Management: A Prespecified Analysis of the ISCHEMIA Trial.

Importance: Traditional time-to-event analyses rate events occurring early as more important than later events, even if later events are more severe, eg, death. Days alive out of hospital (DAOH) adds a patient-focused perspective beyond trial end points.

Objective: To compare DAOH between invasive management and conservative management, including invasive protocol-assigned stays, in the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) randomized clinical trial.

CT Angiography Followed by Invasive Angiography in Patients With Moderate or Severe Ischemia-Insights From the ISCHEMIA Trial.

Objectives: This study aimed to examine the concordance of coronary computed tomographic angiography (CCTA) assessment of coronary anatomy and invasive coronary angiography (ICA) as the reference standard in patients enrolled in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches).

Background: Performance of CCTA compared with ICA has not been assessed in patients with very high burdens of stress-induced ischemia and a high likelihood of anatomically significant coronary artery disease (CAD). A blinded CCTA was performed after enrollment to exclude patients with left main (LM) disease or no obstructive CAD before randomization to an initial conservative or invasive strategy, the latter guided by ICA and optimal revascularization.

Initial Invasive or Conservative Strategy for Stable Coronary Disease.

Background: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain.

Methods: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest.

Health-Status Outcomes with Invasive or Conservative Care in Coronary Disease.

Background: In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients.

Methods: We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.

Association of Sex With Severity of Coronary Artery Disease, Ischemia, and Symptom Burden in Patients With Moderate or Severe Ischemia: Secondary Analysis of the ISCHEMIA Randomized Clinical Trial.

Importance: While many features of stable ischemic heart disease vary by sex, differences in ischemia, coronary anatomy, and symptoms by sex have not been investigated among patients with moderate or severe ischemia. The enrolled ISCHEMIA trial cohort that underwent coronary computed tomographic angiography (CCTA) was required to have obstructive coronary artery disease (CAD) for randomization.

Objective: To describe sex differences in stress testing, CCTA findings, and symptoms in ISCHEMIA trial participants.

Baseline Predictors of Low-Density Lipoprotein Cholesterol and Systolic Blood Pressure Goal Attainment After 1 Year in the ISCHEMIA Trial.

Background: Risk factor control is the cornerstone of managing stable ischemic heart disease but is often not achieved. Predictors of risk factor control in a randomized clinical trial have not been described.

Methods And Results: The ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) randomized individuals with at least moderate inducible ischemia and obstructive coronary artery disease to an initial invasive or conservative strategy in addition to optimal medical therapy.

Clinical outcomes of bioresorbable vascular scaffold to treat all-comer patients. Are patients with acute coronary syndrome better candidates for bioresorbable vascular scaffold?

Background: Scaffold thromboses (ST) and adverse events and have been associated with bioresorbable vascular scaffolds (BVS) at long-term, but their mechanism remains unclear. We sought to evaluate patient and lesion characteristics associated with mid- to long-term outcomes in patients treated with BVS.

Methods: This is an observational single-center, single-arm, retrospective study evaluating the performance of BVS in an all-comer population, including complex lesions (chronic total occlusions, long lesions), small vessels, and acute coronary syndromes (ACS).

Simplifying the assessment of coronary artery stenosis by enhancing instantaneous wave free ratio.

Background: Instantaneous wave free ratio (iFR) does not require adenosine, but has a relatively wide intermediate range where functional assessment remains inconclusive. In this pilot study, we sought to enhance iFR through with the use of intracoronary (IC) saline (iFRs) and contrast media (iFRc) and determine whether these techniques correlated well with fractional flow reserve (FFR).

Methods: Patients with coronary artery stenosis (CAS) associated with an iFR in the intermediate zone (≥0.

The discovery of IDX21437: Design, synthesis and antiviral evaluation of 2'-α-chloro-2'-β-C-methyl branched uridine pronucleotides as potent liver-targeted HCV polymerase inhibitors.

Herein we describe the discovery of IDX21437 35b, a novel Rd-aminoacid-based phosphoramidate prodrug of 2'-α-chloro-2'-β-C-methyluridine monophosphate. Its corresponding triphosphate 6 is a potent inhibitor of the HCV NS5B RNA-dependent RNA polymerase (RdRp). Despite showing very weak activity in the in vitro Huh-7 cell based HCV replicon assay, 35b demonstrated high levels of active triphosphate 6 in mouse liver and human hepatocytes.

Use of troponin assay 99th percentile as the decision level for myocardial infarction diagnosis.

Background: The Universal Definition of Myocardial Infarction recommends the 99th percentile concentration of cardiac troponin in a normal reference population as part of the decision threshold to diagnose type 1 spontaneous myocardial infarction. Adoption of this recommendation in contemporary worldwide practice is not well known.

Methods: We performed a cohort study of 276 hospital laboratories in 31 countries participating in the National Heart, Lung, and Blood Institute-sponsored International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial.

Escherichia coli O157:H7 Infections Associated with Contaminated Pork Products - Alberta, Canada, July-October 2014.

During July-October 2014, an outbreak of 119 Escherichia coli O157:H7 infections in Alberta, Canada was identified through notifiable disease surveillance and investigated by local, provincial, and federal public health and food regulatory agencies. Twenty-three (19%) patients were hospitalized, six of whom developed hemolytic uremic syndrome; no deaths were reported. Informed by case interviews, seven potential food sources were identified and investigated.

O157:H7 Infections associated with contaminated pork products - Alberta, Canada, July-October 2014.

What Is Already Known About This Topic?: Pork is a known, although infrequent, source of human O157:H7 infection. O157:H7 infections often result in clinically severe illness with serious complications in humans.

What Is Added By This Report?: During July-October 2014, an outbreak of 119 cases of O157:H7 infections associated with exposure to contaminated pork products occurred in Alberta, Canada.

Optimal medical therapy with or without percutaneous coronary intervention in women with stable coronary disease: A pre-specified subset analysis of the Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluation (COURAGE) trial.

Objectives: To determine whether sex-based differences exist in clinical effectiveness of percutaneous coronary intervention (PCI) when added to optimal medical therapy (OMT) in patients with stable coronary artery disease.

Background: A prior pre-specified unadjusted analysis from COURAGE showed that women randomized to PCI had a lower rate of death or myocardial infarction during a median 4.6-year follow-up with a trend for interaction with respect to sex.

The value of core lab stress echocardiography interpretations: observations from the ISCHEMIA Trial.

Background: Stress echocardiography (SE) is dependent on subjective interpretations. As a prelude to the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) Trial, potential sites were required to submit two SE, one with moderate or severe left ventricular (LV) myocardial ischemia and one with mild ischemia. We evaluated the concordance of site and core lab interpretations.

The Benefits Conferred by Radial Access for Cardiac Catheterization Are Offset by a Paradoxical Increase in the Rate of Vascular Access Site Complications With Femoral Access: The Campeau Radial Paradox.

Objectives: The purpose of this study was to assess whether the benefits conferred by radial access (RA) at an individual level are offset by a proportionally greater incidence of vascular access site complications (VASC) at a population level when femoral access (FA) is performed.

Background: The recent widespread adoption of RA for cardiac catheterization has been associated with increased rates of VASCs when FA is attempted.

Methods: Logistic regression was used to calculate the adjusted VASC rate in a contemporary cohort of consecutive patients (2006 to 2008) where both RA and FA were used, and compared it with the adjusted VASC rate observed in a historical control cohort (1996 to 1998) where only FA was used.

Design, synthesis and antiviral evaluation of 2'-C-methyl branched guanosine pronucleotides: the discovery of IDX184, a potent liver-targeted HCV polymerase inhibitor.

Background: Ribonucleoside analogs possessing a β-methyl substituent at the 2'-position of the d-ribose moiety have been previously discovered to be potent and selective inhibitors of hepatitis C virus (HCV) replication, their triphosphates acting as alternative substrate inhibitors of the HCV RdRp NS5B. Results/methodology: In this article, the authors detail the synthesis, anti-HCV evaluation in cell-based replicon assays and structure-activity relationships of several phosphoramidate diester derivatives of 2'-C-methylguanosine (2'-MeG).

Conclusion: The most promising compound, namely the O-[S-(hydroxyl)pivaloyl-2-thioethyl]{abbreviated as O-[(HO)tBuSATE)]} N-benzylamine phosphoramidate diester derivative (IDX184), was selected for further in vivo studies, and was the first clinical pronucleotide evaluated for the treatment of chronic hepatitis C up to Phase II trials.