Dynamic changes in cardiovascular and systemic parameters prior to sudden cardiac death in heart failure with reduced ejection fraction: a PARADIGM-HF analysis.

Aims: Prognostic models of sudden cardiac death (SCD) typically incorporate data at only a single time-point. We investigated independent predictors of SCD addressing the impact of integrating time-varying covariates to improve prediction assessment.

Methods And Results: We studied 8399 patients enrolled in the PARADIGM-HF trial and identified independent predictors of SCD (n = 561, 36% of total deaths) using time-updated multivariable-adjusted Cox models, classification and regression tree (CART), and logistic regression analysis.

Camptothecin and Topotecan, Inhibitors of Transcription Factor Fli-1 and Topoisomerase, Markedly Ameliorate Lupus Nephritis in (NZB × NZW)F1 Mice and Reduce the Production of Inflammatory Mediators in Human Renal Cells.

Objective: To examine the therapeutic effects of camptothecin (CPT) and topotecan (TPT), inhibitors of transcription factor Fli-1 and topoisomerase, on lupus nephritis in (NZB × NZW)F1 (NZBWF1) mice, and to examine the effects of CPT and TPT on inflammatory mediators in human renal cells.

Methods: Female NZBWF1 mice were treated with vehicle, cyclophosphamide (CYC), CPT (1 mg/kg or 2 mg/kg), or TPT (0.03 mg/kg, 0.

How the Workload and Outcome of Imaging Examinations Changed During the COVID-19 Pandemic Lockdown.

Background: On March 9th, 2020, the Italian government decided to go into lockdown due to the COVID-19 pandemic, which led to changes in the workflow of radiological examinations.

Aims: Aim of the study is to illustrate how the workload and outcome of radiological exams changed in a community hospital during the pandemic.

Methods And Material: The exams performed in the radiology department from March 9th to March 29th, 2020 were retrospectively reviewed and compared to the exams conducted during the same time-period in 2019.

Microbiome as Mediator of Diet on Colorectal Cancer Risk: The Role of Vitamin D, Markers of Inflammation and Adipokines.

Obesity and diet are associated with colorectal cancer (CRC) risk, and microbiome could mediate this risk factor. To investigate this interaction, we performed a case-control study (34 CRC cases and 32 controls) and analyzed fecal microbiota composition using 16S rRNA metabarcoding and sub-sequential shotgun analyses of genomic bacterial DNA to evaluate the role of microbiome and diet in CRC etiology, taking into account vitamin D and other risk biomarkers. Dietary habits were evaluated using a short questionnaire.

Developing and validating models to predict sudden death and pump failure death in patients with heart failure and preserved ejection fraction.

Background: Sudden death (SD) and pump failure death (PFD) are leading modes of death in heart failure and preserved ejection fraction (HFpEF). Risk stratification for mode-specific death may aid in patient enrichment for new device trials in HFpEF.

Methods: Models were derived in 4116 patients in the Irbesartan in Heart Failure with Preserved Ejection Fraction trial (I-Preserve), using competing risks regression analysis.

Prediction of worsening heart failure events and all-cause mortality using an individualized risk stratification strategy.

Aims: This study aimed to examine the clinical utility of a multisensor, remote, ambulatory diagnostic risk score, TriageHF™, in a real-world, unselected, large patient sample to predict heart failure events (HFEs) and all-cause mortality.

Methods And Results: TriageHF risk score was calculated in patients in the Optum database who had Medtronic implantable cardiac defibrillator device from 2007 to 2016. Patients were categorized into three risk groups based on probability for having an HFE within 6 months (low risk <5.

Effect of Praliciguat on Peak Rate of Oxygen Consumption in Patients With Heart Failure With Preserved Ejection Fraction: The CAPACITY HFpEF Randomized Clinical Trial.

Importance: Heart failure with preserved ejection fraction (HFpEF) is often characterized by nitric oxide deficiency.

Objective: To evaluate the efficacy and adverse effects of praliciguat, an oral soluble guanylate cyclase stimulator, in patients with HFpEF.

Design, Setting, And Participants: CAPACITY HFpEF was a randomized, double-blind, placebo-controlled, phase 2 trial.

Relationship between duration of heart failure, patient characteristics, outcomes, and effect of therapy in PARADIGM-HF.

Aims: Little is known about patient characteristics, outcomes, and the effect of treatment in relation to duration of heart failure (HF). We have investigated these questions in PARADIGM-HF. The aim of the study was to compare patient characteristics, outcomes, and the effect of sacubitril/valsartan, compared with enalapril, in relation to time from HF diagnosis in PARADIGM-HF.

Prognostic value of brain natriuretic peptide vs history of heart failure hospitalization in a large real-world population.

Background: In heart failure (HF) patients, both natriuretic peptides (NP) and previous HF hospitalization (pHFH) have been used to predict prognosis.

Hypothesis: In a large real-world population, both NP levels and pHFH have independent and interdependent predictive value for clinical outcomes of HFH and all-cause mortality.

Methods: Linked electronic health records and insurance claims data from Decision Resource Group were used to identify HF patients that had a BNP or NT-proBNP result between January 2012 and December 2016.

Sacubitril/Valsartan and Sudden Cardiac Death According to Implantable Cardioverter-Defibrillator Use and Heart Failure Cause: A PARADIGM-HF Analysis.

Objectives: The purpose of this study was to investigate the effect of sacubitril/valsartan therapy on sudden cardiac death (SCD) according to the use of and eligibility for an implantable cardioverter-defibrillator (ICD), stratified by heart failure cause.

Background: SCD still accounts for a significant proportion of overall mortality in heart failure with reduced ejection fraction (HFrEF).

Methods: Patients enrolled in the PARADIGM-HF (Prospective Comparison of ARNI with an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial (n = 8,399) were evaluated to assess patterns of ICD implantation and eligibility according to clinical guidelines.

Improving Adherence to Adjuvant Hormonal Therapy Among Disadvantaged Women Diagnosed with Breast Cancer in South Carolina: Proposal for a Multimethod Study.

Background: Current clinical guidelines recommend that hormone receptor-positive breast cancer survivors take adjuvant hormonal therapy (AHT) for 5 to 10 years, following the end of definitive treatment. However, fewer than half of patients adhere to the guidelines, and suboptimal adherence to AHT is associated with an increased risk of breast cancer mortality. Research has extensively documented sociodemographic and disease-specific factors associated with adherence to AHT, but very little evidence exists on behavioral factors (eg, knowledge, patient-provider communication) that can be modified and targeted by interventions.

Serum uric acid, influence of sacubitril-valsartan, and cardiovascular outcomes in heart failure with preserved ejection fraction: PARAGON-HF.

Aims: This study aimed to determine the prognostic value of serum uric acid (SUA) on outcomes in heart failure (HF) with preserved ejection fraction (HFpEF), and whether sacubitril-valsartan reduces SUA and use of SUA-related therapies.

Methods And Results: We analysed 4795 participants from the Prospective Comparison of ARNI [angiotensin receptor-neprilysin inhibitor] with ARB [angiotensin-receptor blockers] Global Outcomes in HF with Preserved Ejection Fraction (PARAGON-HF) trial. We related baseline hyperuricaemia (using age and gender adjusted assay definitions) to the primary outcome [cardiovascular (CV) death and total HF hospitalizations].

Serum potassium in the PARADIGM-HF trial.

Aims: The associations between potassium level and outcomes, the effect of sacubitril-valsartan on potassium level, and whether potassium level modified the effect of sacubitril-valsartan in patients with heart failure and a reduced ejection fraction were studied in PARADIGM-HF. Several outcomes, including cardiovascular death, sudden death, pump failure death, non-cardiovascular death and heart failure hospitalization, were examined.

Methods And Results: A total of 8399 patients were randomized to either enalapril or sacubitril-valsartan.

Prediction of heart failure hospitalizations based on the direct measurement of intrathoracic impedance.

Aims: OptiVol fluid index was developed as a transthoracic impedance-based indicator of short-term risk for heart failure hospitalization (HFH). OptiVol is calculated as the accumulating difference between daily impedance (measured impedance) and long-term average impedance (reference impedance). Measured impedance alone was thought to have limited prognostic utility; however, measured impedance has the advantage of being simple, direct, and possibly additive to OptiVol fluid index in establishing long-term HFH risk.

Prevalence and incidence of intra-ventricular conduction delays and outcomes in patients with heart failure and reduced ejection fraction: insights from PARADIGM-HF and ATMOSPHERE.

Aims: The importance of intra-ventricular conduction delay (IVCD), the incidence of new IVCD and its relationship to outcomes in heart failure and reduced ejection fraction (HFrEF) are not well studied. We addressed these questions in the PARADIGM-HF and ATMOSPHERE trials.

Methods And Results: The risk of the primary composite outcome of cardiovascular death or heart failure hospitalization and all-cause mortality were estimated by use of Cox regression according to baseline QRS duration and morphology in 11 861 patients without an intracardiac device.

Measuring Apathy in Alzheimer's Disease in the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2): A Comparison of Instruments.

Background: Diagnostic criteria for apathy have been published but have yet to be evaluated in the context of clinical trials. The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) operationalized the diagnostic criteria for apathy (DCA) into a clinician-rated questionnaire informed by interviews with the patient and caregiver.

Objective: The goal of the present study was to compare the classification of apathy using the DCA with that using the Neuropsychiatric Inventory-apathy (NPI-apathy) subscale in ADMET 2.

Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium.

Background: PTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study.

Methods: Tumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran-Mantel-Haenszel tests.

Avoidance of tobacco health warnings? An eye-tracking approach.

Aims: Among three eye-tracking studies, we examined how cigarette pack features affected visual attention and self-reported avoidance of and reactance to warnings.

Design: Study 1: smoking status × warning immediacy (short-term versus long-term health consequences) × warning location (top versus bottom of pack). Study 2: smoking status × warning framing (gain-framed versus loss-framed) × warning format (text-only versus pictorial).

Changes in Myocardial Microstructure and Mechanics With Progressive Left Ventricular Pressure Overload.

This study assessed the regional changes in myocardial geometry, microstructure, mechanical behavior, and properties that occur in response to progressive left ventricular pressure overload (LVPO) in a large animal model. Using an index of local biomechanical function at early onset of LVPO allowed for prediction of the magnitude of left ventricular chamber stiffness (Kc) and left atrial area at LVPO late timepoints. Our study found that LV myocardial collagen content alone was insufficient to identify mechanisms for LV myocardial stiffness with progression to heart failure with preserved ejection fraction (HFpEF).

Neurobiologic Rationale for Treatment of Apathy in Alzheimer's Disease With Methylphenidate.

The public health burden of Alzheimer's disease (AD) is related not only to cognitive symptoms, but also to neuropsychiatric symptoms, including apathy. Apathy is defined as a quantitative reduction of goal-directed activity in comparison to a previous level of functioning and affects 30%-70% of persons with AD. Previous attempts to treat apathy in AD-both nonpharmacologically and pharmacologically-have been wanting.

Liver function and prognosis, and influence of sacubitril/valsartan in patients with heart failure with reduced ejection fraction.

Aims: The prevalence of liver function abnormalities is common in patients with heart failure (HF) with reduced ejection fraction (HFrEF). We assessed the impact of liver function on prognosis and the effect of sacubitril/valsartan on measures of liver function in patients with HFrEF.

Methods And Results: The PARADIGM-HF trial was a randomized, double-blind, active treatment-controlled trial.

COVID-19 Pandemic and Beyond: Considerations and Costs of Telehealth Exercise Programs for Older Adults With Functional Impairments Living at Home-Lessons Learned From a Pilot Case Study.

Objective: The purpose of this study was to describe the process and cost of delivering a physical therapist-guided synchronous telehealth exercise program appropriate for older adults with functional limitations. Such programs may help alleviate some of the detrimental impacts of social distancing and quarantine on older adults at-risk of decline.

Methods: Data were derived from the feasibility arm of a parent study, which piloted the telehealth program for 36 sessions with 1 participant.

The prevalence and importance of frailty in heart failure with reduced ejection fraction - an analysis of PARADIGM-HF and ATMOSPHERE.

Aims: Frailty, characterized by loss of homeostatic reserves and increased vulnerability to physiological decompensation, results from an aggregation of insults across multiple organ systems. Frailty can be quantified by counting the number of 'health deficits' across a range of domains. We assessed the frequency of, and outcomes related to, frailty in patients with heart failure and reduced ejection fraction (HFrEF).