Integrating Out-of-Pocket Costs Into Shared Decision-Making for Heart Failure With Reduced Ejection Fraction: A Stepped-Wedge Trial (POCKET-COST-HF).

Background: Guideline-directed medical therapy for heart failure (HF) with reduced ejection fraction can entail high out-of-pocket (OOP) costs, prompting concerns about financial toxicity and access. OOP costs are generally unavailable during encounters. This trial assessed the impact of providing patient-specific OOP costs to patients and clinicians.

Integrating Cost into Shared Decision-Making for Heart Failure with Reduced Ejection Fraction (POCKET-COST-HF): A Trial Providing Out-of-Pocket Costs for Heart Failure Medications during Clinical Encounters.

Background: Evidence-based medical therapy for heart failure with reduced ejection fraction (HFrEF) often entails substantial out-of-pocket costs that can vary appreciably between patients. This has raised concerns regarding financial toxicity, equity, and adherence to medical therapy. In spite of these concerns, cost discussions in the HFrEF population appear to be rare, partly because out-of-pocket costs are generally unavailable during clinical encounters.

Deciding Whether to Take Sacubitril/Valsartan: How Cardiologists and Patients Discuss Out-of-Pocket Costs.

Background Out-of-pocket costs have significant implications for patients with heart failure and should ideally be incorporated into shared decision-making for clinical care. High out-of-pocket cost is one potential reason for the slow uptake of newer guideline-directed medical therapies for heart failure with reduced ejection fraction. This study aims to characterize patient-cardiologist discussions involving out-of-pocket costs associated with sacubitril/valsartan during the early postapproval period.

Research recruitment through the patient portal: perspectives of community focus groups in Seattle and Atlanta.

Objective: Research recruitment through patient portals (ie, patient-facing, web-based clinical interfaces) has the potential to be effective, efficient, and inclusive, but best practices remain undefined. We sought to better understand how patients view this recruitment approach.

Materials And Methods: We conducted 6 focus groups in Atlanta, GA and Seattle, WA with members of patient advisory committees and the general public.

Experimenting with modifications to consent forms in comparative effectiveness research: understanding the impact of language about financial implications and key information.

Background: Informed consent forms are intended to facilitate research enrollment decisions. However, the technical language in institutional templates can be unfamiliar and confusing for decision-makers. Standardized language describing financial implications of participation, namely compensation for injury and costs of care associated with participating, can be complex and could be a deterrent for potential participants.

Getting the Most out of Consent: Patient-Centered Consent for an Acute Stroke Trial.

Informed consent for clinical trials in acute stroke is characterized by challenges related to urgency, cognitive impairment, and geographical separation. Context-appropriate approaches are needed for this setting. We conducted a mixed-methods project involving focus groups and interviews as well as collaboration with a patient advisory panel and a central institutional review board (CIRB) to design and implement a patient-driven consent process for a multicenter trial incorporating adaptive randomization.

Framing Benefits in Decision Aids: Effects of Varying Contextualizing Statements on Decisions About Sacubitril-Valsartan for Heart Failure.

Presenting numeric data alone may result in patients underappreciating clinically significant benefits. Contextualizing statements to counter this may raise concern about absence of neutrality. These issues arose during construction of a decision aid for sacubitril-valsartan, a heart failure medication associated with a ∼3% absolute reduction in 2-year mortality that carries high out-of-pocket cost.

Reframing Recruitment: Evaluating Framing in Authorization for Research Contact Programs.

Background: The changing clinical research recruitment landscape involves practical challenges but introduces opportunities. Researchers can now identify large numbers of eligible patients through electronic health record review and can directly contact those who have authorized contact. Applying behavioral science-driven strategies to design and frame communication could affect patients' willingness to authorize contact and their understanding of these programs.

Show Me the Money: Patients' Perspectives on a Decision Aid for Sacubitril/Valsartan Addressing Out-of-Pocket Cost.

Background: Out-of-pocket medication costs for patients who have heart failure with reduced ejection fraction may be an important part of shared decision-making, but cost has generally been excluded from clinical discussions. This study reports patients' perspectives on a decision aid for sacubitril/valsartan that explicitly addresses out-of-pocket costs.

Methods: Structured, in-depth interviews were conducted with 20 patients with heart failure with reduced ejection fraction from 2 medical centers to elicit their views on a publicly available decision aid for sacubitril/valsartan that explicitly incorporates considerations related to out-of-pocket costs.

Structural insights into loss of function of a pore forming toxin and its role in pneumococcal adaptation to an intracellular lifestyle.

The opportunistic pathogen Streptococcus pneumoniae has dual lifestyles: one of an asymptomatic colonizer in the human nasopharynx and the other of a deadly pathogen invading sterile host compartments. The latter triggers an overwhelming inflammatory response, partly driven via pore forming activity of the cholesterol dependent cytolysin (CDC), pneumolysin. Although pneumolysin-induced inflammation drives person-to-person transmission from nasopharynx, the primary reservoir for pneumococcus, it also contributes to high mortality rates, creating a bottleneck that hampers widespread bacterial dissemination, thus acting as a double-edged sword.

Public attitudes toward an authorization for contact program for clinical research.

We conducted an online experimental survey to evaluate attitudes toward an authorization for contact (AFC) program allowing researchers to contact patients about studies based on electronic record review. A total of 1070 participants were randomly assigned to 1 of 3 flyers varying in design and framing. Participants were asked to select concerns about and reasons for signing up for AFC.

Patient and Surrogate Postenrollment Perspectives on Research Using the Exception From Informed Consent: An Integrated Survey.

Study Objective: It is important for researchers interested in trials using the exception from informed consent to understand the views and experiences of enrolled individuals. Previous studies have shown that patient and surrogate attitudes are generally positive. These studies were small and did not include pediatric patients, and interviews were often conducted long after trial enrollment.

Partnering With Patients to Bridge Gaps in Consent for Acute Care Research.

Clinical trials for acute conditions such as myocardial infarction and stroke pose challenges related to informed consent due to time limitations, stress, and severe illness. Consent processes should be sensitive to the context in which trials are conducted and to needs of patients and surrogate decision-makers. This manuscript describes a collaborative effort between ethicists, researchers, patients, and surrogates to develop patient-driven, patient-centered approaches to consent for clinical trials in acute myocardial infarction and stroke.

Placental transfer of iodinated humanized immunoglobulin G2Δa in the cynomolgus monkey.

Antibody-like biopharmaceuticals cross the placenta by utilizing existing transport pathways (e.g., FcRn receptor).

Emergency Consent: Patients' and Surrogates' Perspectives on Consent for Clinical Trials in Acute Stroke and Myocardial Infarction.

Background Emergent informed consent for clinical trials in acute myocardial infarction (AMI) and stroke is challenging. The role and value of consent are controversial, and insufficient data exist regarding patients' and surrogates' experiences. Methods and Results We conducted structured interviews with patients (or surrogates) enrolled in AMI or acute stroke trials at 6 sites between 2011 and 2016.

Discussing Out-of-Pocket Costs With Patients: Shared Decision Making for Sacubitril-Valsartan in Heart Failure.

Background "Financial toxicity" is a concern for patients, but little is known about how patients consider out-of-pocket cost in decisions. Sacubitril-valsartan provides a contemporary scenario to understand financial toxicity. It is guideline recommended for heart failure with reduced ejection fraction, yet out-of-pocket costs can be considerable.

Flavin Reductase Contributes to Pneumococcal Virulence by Protecting from Oxidative Stress and Mediating Adhesion and Elicits Protection Against Pneumococcal Challenge.

Pneumococcal flavin reductase (FlaR) is known to be cell-wall associated and possess age dependent antigenicity in children. This study aimed at characterizing FlaR and elucidating its involvement in pneumococcal physiology and virulence. Bioinformatic analysis of FlaR sequence identified three-conserved cysteine residues, suggesting a transition metal-binding capacity.

and lytic antibiotic therapy: are we adding insult to injury during invasive pneumococcal disease and sepsis?

(), otherwise known as 'the pneumococcus', is a fascinating microbe that continues to pose a significant problem to public health. Currently there are no specific National Institute for Clinical Excellence (NICE) or British Thoracic Society (BTS) clinical guidelines referring to the treatment of invasive pneumococcal infection. NICE clinical guidelines suggest the use of lytic β-lactam antibiotic regimens for the management of community-acquired pneumonia and bacterial meningitis; infections for which is a likely causative organism.

Streptococcus pneumoniae Cell-Wall-Localized Phosphoenolpyruvate Protein Phosphotransferase Can Function as an Adhesin: Identification of Its Host Target Molecules and Evaluation of Its Potential as a Vaccine.

In Streptococcus pneumonia, phosphoenolpyruvate protein phosphotransferase (PtsA) is an intracellular protein of the monosaccharide phosphotransferase systems. Biochemical and immunostaining methods were applied to show that PtsA also localizes to the bacterial cell-wall. Thus, it was suspected that PtsA has functions other than its main cytoplasmic enzymatic role.

Inflammation drives thrombosis after Salmonella infection via CLEC-2 on platelets.

Thrombosis is a common, life-threatening consequence of systemic infection; however, the underlying mechanisms that drive the formation of infection-associated thrombi are poorly understood. Here, using a mouse model of systemic Salmonella Typhimurium infection, we determined that inflammation in tissues triggers thrombosis within vessels via ligation of C-type lectin-like receptor-2 (CLEC-2) on platelets by podoplanin exposed to the vasculature following breaching of the vessel wall. During infection, mice developed thrombi that persisted for weeks within the liver.