Metabolic Drivers and Rescuers of Heart Failure.

Cardiac hypertrophy and heart failure involve a number of metabolic alterations. Human genetic mutations and murine genetic deficiency models of metabolic enzymes or transporters largely suggest that these alterations in metabolism are maladaptive and contribute to the cardiac remodeling and dysfunction. Here, we discuss insights into metabolic alterations identified in cardiac hypertrophy and failure, as well as dietary and pharmacologic therapies that counteract these metabolic alterations and have been shown to significantly improve heart failure.

Inpatient Understanding of Their Care Team and Receipt of Mixed Messages: a Two-Site Cross-Sectional Study.

BACKGROUND: Patient understanding of their care, supported by physician involvement and consistent communication, is key to positive health outcomes. However, patient and care team characteristics can hinder this understanding. OBJECTIVE: We aimed to assess inpatients' understanding of their care and their perceived receipt of mixed messages, as well as the associated patient, care team, and hospitalization characteristics. DESIGN: We administered a 30-item survey to inpatients between February 2020 and November 2021 and incorporated other hospitalization data from patients' health records. PARTICIPANTS: Randomly selected inpatients at two urban academic hospitals in the USA who were (1) admitted to general medicine services and (2) on or past the third day of their hospitalization. MAIN MEASURES: Outcome measures include (1) knowledge of main doctor and (2) frequency of mixed messages. Potential predictors included mean notes per day, number of consultants involved in the patient's care, number of unit transfers, number of attending physicians, length of stay, age, sex, insurance type, and primary race. KEY RESULTS: A total of 172 patients participated in our survey. Most patients were unaware of their main doctor, an issue related to more daily interactions with care team members. Twenty-three percent of patients reported receiving mixed messages at least sometimes, most often between doctors on the primary team and consulting doctors. However, the likelihood of receiving mixed messages decreased with more daily interactions with care team members. CONCLUSIONS: Patients were often unaware of their main doctor, and almost a quarter perceived receiving mixed messages about their care. Future research should examine patients' understanding of different aspects of their care, and the nature of interactions that might improve clarity around who's in charge while simultaneously reducing the receipt of mixed messages.

Treatment outcomes and patient satisfaction of a virtual partial hospital program: A mixed-method study.

OBJECTIVE: Despite a proliferation of virtual partial hospital programs (PHP) during the COVID-19 pandemic, there is a dearth of research on such programs. In the current study, we compared treatment outcomes and patient satisfaction between an in-person and a virtual PHP. Further, we examined patients' qualitative feedback about the virtual PHP. METHOD: Participants included 282 patients attending a virtual PHP during the COVID-19 pandemic and 470 patients attending an in-person PHP one year prior. Patients completed daily measures of symptom severity, and post-treatment measures of patient satisfaction and treatment outcomes. Patients in the virtual PHP provided feedback about virtual care. Quantitative data were analyzed using multilevel modeling, and qualitative data were analyzed using the principles of inductive analysis. RESULTS: Patients experienced a reduction in depression (b = -.28, p < .001) and anxiety symptoms (b = -.25, p < .001) over time and reported high satisfaction in both the in-person and virtual PHPs. There were no significant differences across programs. Virtual PHP patients identified unique advantages and disadvantages of virtual care. CONCLUSION: Our results suggest that virtual PHPs should be explored as an ongoing model of care that may help to systematically reduce barriers to accessing mental health services.

Mechanistic insight into CdSe nanoplatelet-sensitized upconversion: size and stacking induced effects.

CdSe nanoplatelets (NPLs) have been reported as triplet sensitizers for photon upconversion (UC). However, their UC quantum yields lag behind more conventional systems. Here, we take advantage of their one-dimensional quantum confinement to decouple effects caused by the energetic driving force and lateral size. A surprising anti-correlation between the power threshold Ith and the UC quantum yield based on the NPL size is found. We attribute this result to two distinct triplet-triplet annihilation mechanisms based on the NPL lateral dimension and degree of NPL stacking-mediated either by molecular diffusion or triplet energy diffusion.

The essential menopause curriculum for healthcare professionals: A European Menopause and Andropause Society (EMAS) position statement.

INTRODUCTION: The menopause, or the cessation of menstruation, is a stage of the life cycle which will occur in all women. Managing perimenopausal and postmenopausal health is a key issue for all areas of healthcare, not just gynecology. AIM: To provide recommendations for the curriculum of education programs for healthcare professionals worldwide, so that all can receive high quality training on menopause. MATERIALS AND METHODS: Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS: Training programs for healthcare professionals worldwide should include menopause and postmenopausal health in their curriculum. It should include assessment, diagnosis and evidence-based management strategies.

Scratching the Surface: Passivating Perovskite Nanocrystals for Future Device Integration.

Metal halide perovskite materials have recently upended the field of photovoltaics and are aiming to make waves across a multitude of other fields and applications. Recently, perovskite nanocrystals have been synthesized and are rapidly outpacing traditional semiconductor nanocrystals in application driven fields due to their inherent defect tolerance and facile tunability, resulting in high photoluminescent quantum yields and efficient devices. Future improvements to perovskite nanocrystals toward device driven applications must come at the perovskite surface. The last half decade has resulted in considerable progress in tailoring the perovskite nanocrystal/ligand surface toward maximizing the optoelectronic performance. Here, we review the current progress and discuss how further improvements could be made to further improve this bright class of materials.

A Sensitizer of Purpose: Generating Triplet Excitons with Semiconductor Nanocrystals.

The process of photon upconversion promises importance for many optoelectronic applications, as it can result in higher efficiencies and more effective photon management. Upconversion via triplet-triplet annihilation (TTA) occurs at low incident powers and at high efficiencies, requirements for integration into existing optoelectronic devices. Semiconductor nanocrystals are a diverse class of triplet sensitizers with advantages over traditional molecular sensitizers such as energetic tunability and minimal energy loss during the triplet sensitization process. In this Perspective, we review current progress in semiconductor nanocrystal triplet sensitization, specifically focusing on the nanocrystal, the ligand shell which surrounds the nanocrystal, and progress in solid-state sensitization. Finally, we discuss potential areas of improvement which could result in more efficient upconversion systems sensitized by semiconductor nanocrystals. Specifically, we focus on the development of solid-state TTA upconversion systems, elucidation of the energy transfer mechanisms from nanocrystal to transmitter ligand which underpin the upconversion process and propose novel configurations of nanocrystal-sensitized systems.

Mixed halide bulk perovskite triplet sensitizers: Interplay between band alignment, mid-gap traps, and phonons.

Photon upconversion, particularly via triplet-triplet annihilation (TTA), could prove beneficial in expanding the efficiencies and overall impacts of optoelectronic devices across a multitude of technologies. The recent development of bulk metal halide perovskites as triplet sensitizers is one potential step toward the industrialization of upconversion-enabled devices. Here, we investigate the impact of varying additions of bromide into a lead iodide perovskite thin film on the TTA upconversion process in the annihilator molecule rubrene. We find an interplay between the bromide content and the overall device efficiency. In particular, a higher bromide content results in higher internal upconversion efficiencies enabled by more efficient charge extraction at the interface likely due to a more favorable band alignment. However, the external upconversion efficiency decreases as the absorption cross section in the near infrared is reduced. The highest upconversion performance is found in our study for a bromide content of 5%. This result can be traced back to a high absorption cross section in the near infrared and higher photoluminescence quantum yield in comparison to the iodide-only perovskite and an increased driving force for charge transfer.

REGEN-COV® antibody cocktail bioanalytical strategy: comparison of LC-MRM-MS and immunoassay methods for drug quantification.

Aim: In response to the COVID-19 pandemic, Regeneron developed the anti-SARS-CoV-2 monoclonal antibody cocktail, REGEN-COV® (RONAPREVE® outside the USA). Drug concentration data was important for determination of dose, so a two-part bioanalytical strategy was implemented to ensure the therapy was rapidly available for use. Results & methodology: Initially, a liquid chromatography-multiple reaction monitoring-mass spectrometry (LC-MRM-MS) assay, was used to analyze early-phase study samples. Subsequently, a validated electrochemiluminescence (ECL) immunoassay was implemented for high throughput sample analysis for all samples. A comparison of drug concentration data from the methods was performed which identified strong linear correlations and for Bland-Altman, small bias. In addition, pharmacokinetic data from both methods produced similar profiles and parameters. Discussion & conclusion: This novel bioanalytical strategy successfully supported swift development of a critical targeted therapy during the COVID-19 public health emergency.

A Patient-Centered Environmental Scan of Inpatient Visitor Policies During the COVID-19 Pandemic.

Researchers and patients conducted an environmental scan of policy documents and public-facing websites and abstracted data to describe COVID-19 adult inpatient visitor restrictions at 70 academic medical centers. We identified variations in how centers described and operationalized visitor policies. Then, we used the nominal group technique process to identify patient-centered information gaps in visitor policies and provide key recommendations for improvement. Recommendations were categorized into the following domains: 1) provision of comprehensive, consistent, and clear information; 2) accessible information for patients with limited English proficiency and health literacy; 3) COVID-19 related considerations; and 4) care team member methods of communication.

Bioanalytical Challenges due to Prior Checkpoint Inhibitor Exposure: Interference and Mitigation in Drug Concentration and Immunogenicity Assays.

Monoclonal antibodies (mAbs) are a leading class of biotherapeutics. In oncology, patients often fail on early lines of biologic therapy to a specific target. Some patients may then enroll in a new clinical trial with a mAb specific for the same target. Therefore, immunoassays designed to quantify the current mAb therapy or assess immunogenicity to the drug may be susceptible to cross-reactivity or interference with residual prior biologics. The impact of two approved anti-PD-1 mAbs, pembrolizumab and nivolumab, was tested in several immunoassays for cemiplimab, another approved anti-PD-1 mAb. The methods included a target-capture drug concentration assay, a bridging anti-drug antibody (ADA) assay and a competitive ligand-binding neutralizing antibody (NAb) assay. We also tested bioanalytical strategies to mitigate cross-reactivity or interference in these assays from other anti-PD-1 biologics. Both pembrolizumab and nivolumab cross-reacted in the cemiplimab drug concentration assay. This was mitigated by addition of antibodies specific to pembrolizumab or nivolumab. ADA specific for pembrolizumab and nivolumab did not interfere in the cemiplimab ADA assay. However, pembrolizumab and nivolumab generated a false-positive response in a target-capture NAb assay. Our results demonstrate that similar exogenous pre-existing anti-PD-1 mAbs (biotherapeutics) such as pembrolizumab and nivolumab are detected and accurately quantified in the cemiplimab drug concentration assay. However, once steady state is achieved for the new therapy, prior biologics would likely not be detected. Cross-reactivity and interference in immunoassays from previous treatment with class-specific biotherapeutic(s) pose significant bioanalytical challenges, especially in immuno-oncology.

Liquid Chromatography-Multiple Reaction Monitoring-Mass Spectrometry Assay for Quantitative Measurement of Therapeutic Antibody Cocktail REGEN-COV Concentrations in COVID-19 Patient Serum.

REGEN-COV is a cocktail of two human IgG1 monoclonal antibodies (REGN10933 + REGN10987) that targets severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and has shown great promise to reduce the SARS-CoV-2 viral load in COVID-19 patients enrolled in clinical studies. A liquid chromatography-multiple reaction monitoring-mass spectrometry (LC-MRM-MS)-based method, combined with trypsin and rAspN dual enzymatic digestion, was developed for the determination of total REGN10933 and total REGN10987 concentrations in several hundreds of pharmacokinetic (PK) serum samples from COVID-19 patients participating in phase I, II, and III clinical studies. The performance characteristics of this bioanalytical assay were evaluated with respect to linearity, accuracy, precision, selectivity, specificity, and analyte stability before and after enzymatic digestion. The developed LC-MRM-MS assay has a dynamic range from 10 to 2000 µg/mL antibody drug in the human serum matrix, which was able to cover the serum drug concentration from day 0 to day 28 after drug administration in two-dose groups for the clinical PK study of REGEN-COV. The concentrations of REGEN-COV in the two-dose groups measured by the LC-MRM-MS assay were comparable to the concentrations measured by a fully validated electrochemiluminescence (ECL) immunoassay.

Global consensus recommendations on menopause in the workplace: A European Menopause and Andropause Society (EMAS) position statement.

INTRODUCTION: Worldwide, there are 657 million women aged 45-59 and around half contribute to the labor force during their menopausal years. There is a diversity of experience of menopause in the workplace. It is shaped not only by menopausal symptoms and context but also by the workplace environment. It affects quality of life, engagement, performance, motivation and relations with employers. AIM: To provide recommendations for employers, managers, healthcare professionals and women to make the workplace environment more menopause supportive, and to improve women's wellbeing and their ability to remain in work. MATERIALS AND METHODS: Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS: Workplace health and wellbeing frameworks and policies should incorporate menopausal health as part of the wider context of gender and age equality and reproductive and post-reproductive health. Workplaces should create an open, inclusive and supportive culture regarding menopause, involving, if available, occupational health professionals and human resource managers working together. Women should not be discriminated against, marginalized or dismissed because of menopausal symptoms. Health and allied health professionals should recognize that, for some women, menopausal symptoms can adversely affect the ability to work, which can lead to reduction of working hours, underemployment or unemployment, and consequently financial insecurity in later life.

Discharge Practices for COVID-19 Patients: Rapid Review of Published Guidance and Synthesis of Documents and Practices at 22 US Academic Medical Centers.

BACKGROUND: There are currently no evidence-based guidelines that provide standardized criteria for the discharge of COVID-19 patients from the hospital. OBJECTIVE: To address this gap in practice guidance, we reviewed published guidance and collected discharge protocols and procedures to identify and synthesize common practices. DESIGN: Rapid review of existing guidance from US and non-US public health organizations and professional societies and qualitative review using content analysis of discharge documents collected from a national sample of US academic medical centers with follow-up survey of hospital leaders SETTING AND PARTICIPANTS: We reviewed 65 websites for major professional societies and public health organizations and collected documents from 22 Academic Medical Centers (AMCs) in the US participating in the HOspital MEdicine Reengineering Network (HOMERuN). RESULTS: We synthesized data regarding common practices around 5 major domains: (1) isolation and transmission mitigation; (2) criteria for discharge to non-home settings including skilled nursing, assisted living, or homeless; (3) clinical criteria for discharge including oxygenation levels, fever, and symptom improvement; (4) social support and ability to perform activities of daily living; (5) post-discharge instructions, monitoring, and follow-up. LIMITATIONS: We used streamlined methods for rapid review of published guidance and collected discharge documents only in a focused sample of US academic medical centers. CONCLUSION: AMCs studied showed strong consensus on discharge practices for COVID-19 patients related to post-discharge isolation and transmission mitigation for home and non-home settings. There was high concordance among AMCs that discharge practices should address COVID-19-specific factors in clinical, functional, and post-discharge monitoring domains although definitions and details varied.

Patient stakeholder engagement in research: A narrative review to describe foundational principles and best practice activities.

BACKGROUND: Health research is evolving to include patient stakeholders (patients, families and caregivers) as active members of research teams. Frameworks describing the conceptual foundations underlying this engagement and strategies detailing best practice activities to facilitate engagement have been published to guide these efforts. OBJECTIVE: The aims of this narrative review are to identify, quantify and summarize (a) the conceptual foundational principles of patient stakeholder engagement in research and (b) best practice activities to support these efforts. SEARCH STRATEGY, INCLUSION CRITERIA, DATA EXTRACTION AND SYNTHESIS: We accessed a publicly available repository of systematically identified literature related to patient engagement in research. Two reviewers independently screened articles to identify relevant articles and abstracted data. MAIN RESULTS: We identified 990 potentially relevant articles of which 935 (94.4%) were excluded and 55 (5.6%) relevant. The most commonly reported foundational principles were "respect" (n = 25, 45%) and "equitable power between all team members" (n = 21, 38%). Creating "trust between patient stakeholders and researchers" was described in 17 (31%) articles. Twenty-seven (49%) articles emphasized the importance of providing training and education for both patient stakeholder and researchers. Providing financial compensation for patient stakeholders' time and expertise was noted in 19 (35%) articles. Twenty articles (36%) emphasized regular, bidirectional dialogue between patient partners and researchers as important for successful engagement. DISCUSSION AND CONCLUSIONS: Engaging patient stakeholders in research as partners presents an opportunity to design, implement and disseminate patient-centred research. This review creates an overarching foundational framework for authentic and sustainable partnerships between patient stakeholders and researchers.

Associations of Physician Empathy with Patient Anxiety and Ratings of Communication in Hospital Admission Encounters.

OBJECTIVE: To assess the association between the frequency of empathic physician responses with patient anxiety, ratings of communication, and encounter length during hospital admission encounters. DESIGN: Analysis of coded audio-recorded hospital admission encounters and pre- and postencounter patient survey data. SETTING: Two academic hospitals. PATIENTS: Seventy-six patients admitted by 27 attending hospitalist physicians. MEASUREMENTS: Recordings were transcribed and analyzed by trained coders, who counted the number of empathic, neutral, and nonempathic verbal responses by hospitalists to their patients' expressions of negative emotion. We developed multivariable linear regression models to test the association between the number of these responses and the change in patients' State Anxiety Scale (STAI-S) score pre- and postencounter and encounter length. We used Poisson regression models to examine the association between empathic response frequency and patient ratings of the encounter. RESULTS: Each additional empathic response from a physician was associated with a 1.65-point decline in the STAI-S anxiety scale (95% confidence interval [CI], 0.48-2.82). Frequency of empathic responses was associated with improved patient ratings for covering points of interest, feeling listened to and cared about, and trusting the doctor. The number of empathic responses was not associated with encounter length (percent change in encounter length per response 1%; 95% CI, -8%-10%). CONCLUSIONS: Responding empathically when patients express negative emotion was associated with less patient anxiety and higher ratings of communication but not longer encounter length.

Aggression Protects Against the Onset of Major Depressive Episodes in Individuals With Bipolar Spectrum Disorder.

A growing body of research suggests that bipolar spectrum disorders (BSDs) are associated with high aggression. However, little research has prospectively examined how aggression may affect time to onset of hypomanic/manic versus major depressive episodes. In a longitudinal study, we tested the hypothesis that aggression would prospectively predict a shorter time to the onset of hypomanic/manic episodes and a longer time to the onset of major depressive episodes, based on the behavioral approach system theory of BSDs. Young adults (N = 120) diagnosed with cyclothymia, bipolar II disorder, or bipolar disorder not otherwise specified were followed every 4 months for an average of 3.55 years. Participants completed measures of depressive and manic symptoms, family history of mood disorder, impulsivity, and aggression at baseline and were followed prospectively with semistructured diagnostic interview assessments of hypomanic/manic and major depressive episodes and treatment seeking for mood problems. Cox proportional hazard regression analyses indicated that overall, physical, and verbal aggression predicted a longer time to major depressive episode onset, even after controlling for baseline depressive and manic symptoms, family history of mood disorder, treatment seeking for mood problems, and impulsivity. Aggression, however, did not significantly predict time to onset of hypomanic/manic episodes, controlling for the same covariates. The findings suggest that approach-related behaviors may be utilized to delay the onset of major depressive episodes among people with BSDs.

Kindling of Life Stress in Bipolar Disorder: Effects of Early Adversity.

Most theoretical frameworks regarding the role of life stress in bipolar disorders (BD) do not incorporate the possibility of a changing relationship between psychosocial context and episode initiation across the course of the disorder. The kindling hypothesis theorizes that over the longitudinal course of recurrent affective disorders, the relationship between major life stressors and episode initiation declines (Post, 1992). The present study aimed to test an extension of the kindling hypothesis in BD by examining the effect of early life adversity on the relationship between proximal life events and prospectively assessed mood episodes. Data from 145 bipolar participants (59.3% female, 75.2% Caucasian, and mean age of 20.19 years; SD = 1.75 years) were collected as part of the Temple-Wisconsin Longitudinal Investigation of Bipolar Spectrum Project (112 Bipolar II; 33 Cyclothymic disorder). Participants completed a self-report measure of early adversity at baseline and interview-assessed mood episodes and life events at regular 4-month follow-ups. Results indicate that early childhood adversity sensitized bipolar participants to the effects of recent stressors only for depressive episodes and not hypomanic episodes within BD. This was particularly the case with minor negative events. The current study extends prior research examining the kindling model in BD using a methodologically rigorous assessment of life stressors and mood episode occurrence. Clinicians should assess experiences of early adversity in individuals with BD as it may impact reactivity to developing depressive episodes in response to future stressors.