Impact of Digital Health Technology on Quality of Life in Patients With Heart Failure.

BACKGROUND: Digital health tools may improve quality of life (QoL) in patients with heart failure (HF) by promoting self-care, knowledge, and engagement. OBJECTIVES: This study evaluates the effect of 3 digital technologies on QoL in patients with HF. METHODS: A total of 182 patients were randomized to usual care or one of the technologies promoting self-care: Bodyport (cardiac scale), Conversa (conversational platform), or Noom (smartphone application). The primary outcome was 90-day change in QoL, as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score (OSS). RESULTS: A total of 151 participants (83%) completed their 90-day surveys. The median age of enrolled participants was 61 years (IQR: 53-69 years), and 37.9% were women. No group had any significant change in KCCQ OSS or improvement relative to usual care. However, symptoms and physical function at 90 days, as assessed by the Total Symptom Score (TSS) and Clinical Summary Score (CSS), were significantly improved in the Noom group relative to usual care: TSS median change of +4.2 points (IQR -1 to +16.7) vs -1 points (IQR: -13.5 to +7.8; P = 0.006); CSS median change of +2.8 points (IQR: -1 to +14.6) vs -3.1 points (IQR: -10.2 to +3; P = 0.002). CONCLUSIONS: Three digital interventions showed no independent effect on QoL as assessed by the KCCQ OSS. However, participants randomized to the Noom technology demonstrated improved KCCQ TSS and CSS relative to usual care. Although digital tools may be an important component of longitudinal care for patients with HF, larger studies are needed to better understand their effectiveness and optimal deployment. (Evaluating Efficacy of Digital Health Technology in the Treatment of Congestive Heart Failure; NCT04394754).

Behavioral interventions for vaccination uptake: A systematic review and meta-analysis.

BACKGROUND: Human behavior and more specifically behavioral insight-based approaches to vaccine uptake have often been overlooked. While there have been a few narrative reviews indexed in Medline on behavioral interventions to increase vaccine uptake, to our knowledge, none have been systematic reviews and meta-analyses covering not just high but also low-and-middle income countries. METHODS: We included 613 studies from the Medline database in our systematic review and meta-analysis categorizing different behavioral interventions in 9 domains: education campaigns, on-site vaccination, incentives, free vaccination, institutional recommendation, provider recommendation, reminder and recall, message framing, and vaccine champion. Additionally, considering that there is variability in the acceptance of vaccines among different populations, we assessed studies from both high-income countries (HICs) and low- to middle-income countries (LMICs), separately. FINDINGS: Our results showed that behavioral interventions can considerably improve vaccine uptake in most settings. All domains that we examined improved vaccine uptake with the highest effect size associated with provider recommendation (OR: 3.4 (95%CI: 2.5-4.6); Domain: motivation) and on-site vaccination (OR: 2.9 (95%CI: 2.3-3.7); Domain: practical issues). While the number of studies conducted in LMICs was smaller, the quality of studies was similar with those conducted in HICs. Nevertheless, there were variations in the observed effect sizes. INTERPRETATION: Our findings indicate that "provider recommendation" and "on-site vaccination" along with other behavioral interventions can be employed to increase vaccination rates globally.

A randomized clinical trial assessing the effect of automated medication-targeted alerts on acute kidney injury outcomes.

Acute kidney injury is common among hospitalized individuals, particularly those exposed to certain medications, and is associated with substantial morbidity and mortality. In a pragmatic, open-label, National Institutes of Health-funded, parallel group randomized controlled trial (clinicaltrials.gov NCT02771977), we investigate whether an automated clinical decision support system affects discontinuation rates of potentially nephrotoxic medications and improves outcomes in patients with AKI. Participants included 5060 hospitalized adults with AKI and an active order for any of three classes of medications of interest: non-steroidal anti-inflammatory drugs, renin-angiotensin-aldosterone system inhibitors, or proton pump inhibitors. Within 24 hours of randomization, a medication of interest was discontinued in 61.1% of the alert group versus 55.9% of the usual care group (relative risk 1.08, 1.04 - 1.14, p = 0.0003). The primary outcome - a composite of progression of acute kidney injury, dialysis, or death within 14 days - occurred in 585 (23.1%) of individuals in the alert group and 639 (25.3%) of patients in the usual care group (RR 0.92, 0.83 - 1.01, p = 0.09). Trial Registration Clinicaltrials.gov NCT02771977.

Wearables in Cardiovascular Disease.

Wearable devices stand to revolutionize the way healthcare is delivered. From consumer devices that provide general health information and screen for medical conditions to medical-grade devices that allow collection of larger datasets that include multiple modalities, wearables have a myriad of potential uses, especially in cardiovascular disorders. In this review, we summarize the underlying technologies employed in these devices and discuss the regulatory and economic aspects of such devices as well as the future implications of their use.

Urine Uromodulin as a Biomarker of Kidney Tubulointerstitial Fibrosis.

BACKGROUND AND OBJECTIVES: Uromodulin, produced exclusively in the kidney's thick ascending limb, is a biomarker of kidney tubular health. However, the relationship between urine uromodulin and histologic changes in the kidney tubulointerstitium has not been characterized. In this study, we test the association of urine uromodulin with kidney histologic findings in humans and mice. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We investigated the independent association of urine uromodulin measured at the time of kidney biopsy with histologic features in 364 participants at two academic medical centers from 2015 to 2018 using multivariable linear regression models. This relationship was further examined by comparison of uromodulin staining in murine models of kidney fibrosis and repair. RESULTS: We found urine uromodulin to be correlated with serum creatinine (rho=-0.43; P<0.001), bicarbonate (0.20; P<0.001), and hemoglobin (0.11; P=0.03) at the time of biopsy but not with urine albumin (-0.07; P=0.34). Multivariable models controlling for prebiopsy GFR, serum creatinine at biopsy, and urine albumin showed higher uromodulin to be associated with lower severity of interstitial fibrosis/tubular atrophy and glomerulosclerosis (interstitial fibrosis/tubular atrophy: -3.5% [95% confidence intervals, -5.7% to -1.2%] and glomerulosclerosis: -3.3% [95% confidence intervals, -5.9% to -0.6%] per two-fold difference in uromodulin). However, when both interstitial fibrosis/tubular atrophy and glomerulosclerosis were included in multivariable analysis, only interstitial fibrosis/tubular atrophy was independently associated with uromodulin (interstitial fibrosis/tubular atrophy: -2.5% [95% confidence intervals, -4.6% to -0.4%] and glomerulosclerosis: -0.9% [95% confidence intervals, -3.4% to 1.5%] per two-fold difference in uromodulin). In mouse kidneys, uromodulin staining was found to be lower in the fibrotic model than in normal or repaired models. CONCLUSIONS: Higher urine uromodulin is independently associated with lower tubulointerstitial fibrosis in both human kidney biopsies and a mouse model of fibrosis. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_08_10_CJN04360422.mp3.

Pragmatic randomized trial assessing the impact of digital health technology on quality of life in patients with heart failure: Design, rationale and implementation.

BACKGROUND: Self-care and patient engagement are important elements of heart failure (HF) care, endorsed in the guidelines. Digital health tools may improve quality of life (QOL) in HF patients by promoting care, knowledge, and engagement. This manuscript describes the rationale and challenges of the design and implementation of a pragmatic randomized controlled trial to evaluate the efficacy of three digital health technologies in improving QOL for patients with HF. HYPOTHESIS: We hypothesize that digital health interventions will improve QOL of HF patients through the early detection of warning signs of disease exacerbation, the opportunity of self-tracking symptoms, and the education provided, which enhances patient empowerment. METHODS: Using a fully electronic enrollment and consent platform, the trial will randomize 200 patients across HF clinics in the Yale New Haven Health system to receive either usual care or one of three digital technologies designed to promote self-management and provide critical data to clinicians. The primary outcome is the change in QOL as assessed by the Kansas City Cardiomyopathy Questionnaire at 3 months. RESULTS: First enrollment occurred in September 2021. Recruitment was anticipated to last 6-8 months and participants were followed for 6 months after randomization. Our recruitment efforts have highlighted the large digital divide in our population of interest. CONCLUSION: Assessing clinical outcomes, patient usability, and ease of clinical integration of digital technologies will be beneficial in determining the feasibility of the integration of such technologies into the healthcare system.

Urine testing to differentiate glomerular from tubulointerstitial diseases on kidney biopsy.

Background: Differentiating between glomerular and tubulointerstitial diseases can guide selection of appropriate patients for kidney biopsy. The aim of this study is to identify urine tests that can differentiate between these histological diagnoses. Methods: In this sub-study of a prospectively enrolled cohort of participants with urine samples concurrent with their kidney biopsy, we tested the association of 24 features on urinalysis, urine sediment microscopy, and biomarkers of glomerular and tubular injury and inflammation with histological diagnosis of glomerular or tubulointerstitial disease. We selected a combination of features associated with glomerular disease using stepwise forward and backward regression, and LASSO algorithm after dividing the cohort into training (70%) and test (30%) sets. Results: Of 359 participants, 121 had glomerular, 89 had tubulointerstitial diseases, and 149 were classified as mixed. Compared to patients with tubulointerstitial diseases, those with glomerular diseases had more dipstick hematuria (3+ vs. 1+, P < 0.001) and urine albumin (1.25 vs. 0.09 mg/mg, P < 0.001). Patients with glomerular diseases had higher levels of tubular health biomarkers (Uromodulin, 1.22 vs. 0.92, P = 0.03). In a multivariable model, higher urine albumin, dipstick blood, and urine uromodulin were independently associated with higher odds of glomerular diseases (test set AUC, 0.81 (0.69, 0.93)). Conclusion: Urine tests, including urine albumin, dipstick blood, and urine uromodulin, were associated with the histological diagnosis of glomerular disease. These findings can help clinicians differentiate between glomerular and tubulointerstitial diseases and guide clinical decisions regarding a kidney biopsy.

A guide to molecular and functional investigations of platelets to bridge basic and clinical sciences.

Platelets have been shown to be associated with pathophysiological process beyond thrombosis, demonstrating critical additional roles in homeostatic processes, such as immune regulation, and vascular remodeling. Platelets themselves can have multiple functional states and can communicate and regulate other cells including immune cells and vascular smooth muscle cells, to serve such diverse functions. Although traditional platelet functional assays are informative and reliable, they are limited in their ability to unravel platelet phenotypic heterogeneity and interactions. Developments in methods such as electron microscopy, flow cytometry, mass spectrometry, and 'omics' studies, have led to new insights. In this Review, we focus on advances in platelet biology and function, with an emphasis on current and promising methodologies. We also discuss technical and biological challenges in platelet investigations. Using coronavirus disease 2019 (COVID-19) as an example, we further describe the translational relevance of these approaches and the possible 'bench-to-bedside' utility in patient diagnosis and care.

Role of Platelet Mitochondria: Life in a Nucleus-Free Zone.

Platelets are abundant, small, anucleate circulating cells, serving many emerging pathophysiological roles beyond hemostasis; including active critical roles in thrombosis, injury response, and immunoregulation. In the absence of genomic DNA transcriptional regulation (no nucleus), platelets require strategic prepackaging of all the needed RNA and organelles from megakaryocytes, to sense stress (e.g., hyperglycemia), to protect themselves from stress (e.g., mitophagy), and to communicate a stress response to other cells (e.g., granule and microparticle release). Distinct from avian thrombocytes that have a nucleus, the absence of a nucleus allows the mammalian platelet to maintain its small size, permits morphological flexibility, and may improve speed and efficiency of protein expression in response to stress. In the absence of a nucleus, platelet lifespan of 7-10 days, is largely determined by the mitochondria. The packaging of 5-8 mitochondria is critical in aerobic respiration and yielding metabolic substrates needed for function and survival. Mitochondria damage or dysfunction, as observed with several disease processes, results in greatly attenuated platelet survival and increased risk for thrombovascular events. Here we provide insights into the emerging roles of platelets despite the lack of a nucleus, and the key role played by mitochondria in platelet function and survival both in health and disease.