Patient Perspectives on Digital Interventions to Manage Heart Failure Medications: The VITAL-HF Pilot.

Use of guideline-directed medical therapy (GDMT) for treatment of heart failure with reduced ejection fraction (HFrEF) remains unacceptably low. The purpose of this study was to determine whether a digital health tool can augment GDMT for patients with HFrEF. Participants ≥ 18 years old with symptomatic HFrEF (left ventricular ejection fraction ≤ 40%) and with access to a mobile phone with internet were included. Participants were given a blood pressure cuff, instructed in its use, and given regular symptom surveys via cell-phone web-link. Data were transmitted to the Story Health web-based platform, and automated alerts were triggered based on pre-specified vital sign and laboratory data. Health coaches assisted patients with medication education, pharmacy access, and lab access through text messages and phone calls. GDMT titration plans were individually created in the digital platform by local clinicians based on entry vitals and labs. Twelve participants enrolled and completed the study. The median age and LVEF were 52.5 years (IQR, 46.5-63.5) and 25% (IQR, 22.5-35.5), respectively. There were 10 GDMT initiations, 52 up-titrations, and 13 down-titrations. Five participants engaged in focus-group interviews following study completion to understand first-hand perspectives regarding the use of digital tools to manage GDMT. Participants expressed comfort knowing that there were clinicians regularly reviewing their data. This alleviated concerns of uncertainty in daily living, led to an increased feeling of security, and empowered patients to understand decision-making regarding GDMT. Frequent medication changes, and the associated financial impact, were common concerns. Remote titration of GDMT for HFrEF is feasible and appears to be a patient-centered approach to care.

Building a Real-Time Remote Patient Monitoring Patient Safety Program for COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) pandemic has forced providers to rapidly adopt telehealth tools to reduce staff exposure to ill persons, preserve personal protective equipment, and minimize impact of patient surges on facilities. Remote patient monitoring (RPM) can be used to monitor high-risk patients from their homes and open up hospital bed availability. The authors describe a pilot program to evaluate the impact of RPM in postdischarge monitoring of COVID-19 patients. High-risk patients discharging from the hospital received a wearable vital sign monitoring device to be worn for 8 consecutive days, allowing real-time data transmission to a virtual health center (VHC), which had been established prior to the pandemic, via a smart phone application. The data were monitored 24 hours a day by a VHC tech with built-in escalation protocols to a nurse and/or an attending physician if needed. Eighty patients were enrolled, 48% women with an age range of 19-83 years. Languages included Spanish (49%), English (47%), Burmese (2%), and Swahili (1%). The most common comorbidities included hypertension (48%) and diabetes mellitus (48%). Oxygen was the most common addressed need; 8% requiring new oxygen and 8% benefitting from oxygen-weaning during the RPM time period. Ten percent patients had emergency department (ED) visits and 4% were readmitted within 30 days of discharge. The authors built and deployed an RPM program for postdischarge monitoring of high-risk patients. RPM can be quickly deployed to support COVID-19 patients postdischarge and assist with hospital capacity. RPM can be rapidly and successfully deployed during the COVID 19 pandemic to aid in transitions of care.

The Case for Virtual Sepsis Surveillance and Intervention.

Study Objective:To determine whether deployment of an integrated virtual sepsis surveillance program could improve time to antibiotics and mortality in a longitudinal cohort of non-present on admission (NPOA) sepsis cases.Methods:We used an uncontrolled pre- and poststudy design to compare time to antibiotics and mortality between a time-based cohort of NPOA sepsis cases separated by the deployment of a virtual sepsis surveillance program.Results:A total of 566 NPOA sepsis cases were included in this study. Three hundred and thirty-five cases compromised the preintervention arm, whereas the postintervention cohort included 231 cases. After deployment of the virtual sepsis surveillance program, median time to antibiotics improved from 92 to 59 min (p < 0.001). Mortality was reduced from 30% to 21% (p = 0.015).Conclusion:Deployment of a virtual sepsis surveillance program resulted in a decreased time to antibiotics and an overall reduction in NPOA sepsis mortality.

Mutant NR5A1/SF-1 in patients with disorders of sex development shows defective activation of the SOX9 TESCO enhancer.

Nuclear receptor subfamily 5 group A member 1/Steroidogenic factor 1 (NR5A1; SF-1; Ad4BP) mutations cause 46,XY disorders of sex development (DSD), with phenotypes ranging from developmentally mild (e.g., hypospadias) to severe (e.g., complete gonadal dysgenesis). The molecular mechanism underlying this spectrum is unclear. During sex determination, SF-1 regulates SOX9 (SRY [sex determining region Y]-box 9) expression. We hypothesized that SF-1 mutations in 46,XY DSD patients affect SOX9 expression via the Testis-specific Enhancer of Sox9 core element, TESCO. Our objective was to assess the ability of 20 SF-1 mutants found in 46,XY DSD patients to activate TESCO. Patient DNA was sequenced for SF-1 mutations and mutant SF-1 proteins were examined for transcriptional activity, protein expression, sub-cellular localization and in silico structural defects. Fifteen of the 20 mutants showed reduced SF-1 activation on TESCO, 11 with atypical sub-cellular localization. Fourteen SF-1 mutants were predicted in silico to alter DNA, ligand or cofactor interactions. Our study may implicate aberrant SF-1-mediated transcriptional regulation of SOX9 in 46,XY DSDs.

Interface Passivation and Trap Reduction via a Solution-Based Method for Near-Zero Hysteresis Nanowire Field-Effect Transistors.

In this letter, we demonstrate a solution-based method for a one-step deposition and surface passivation of the as-grown silicon nanowires (Si NWs). Using N,N-dimethylformamide (DMF) as a mild oxidizing agent, the NWs' surface traps density was reduced by over 2 orders of magnitude from 1×10(13) cm(-2) in pristine NWs to 3.7×10(10) cm(-2) in DMF-treated NWs, leading to a dramatic hysteresis reduction in NW field-effect transistors (FETs) from up to 32 V to a near-zero hysteresis. The change of the polyphenylsilane NW shell stoichiometric composition was confirmed by X-ray photoelectron spectroscopy analysis showing a 35% increase in fully oxidized Si4+ species for DMF-treated NWs compared to dry NW powder. Additionally, a shell oxidation effect induced by DMF resulted is a more stable NW FET performance with steady transistor currents and only 1.5 V hysteresis after 1000 h of air exposure.

Gut bacteria require neutrophils to promote mammary tumorigenesis.

Recent studies suggest that gastrointestinal tract microbiota modulate cancer development in distant non-intestinal tissues. Here we tested mechanistic hypotheses using a targeted pathogenic gut microbial infection animal model with a predilection to breast cancer. FVB-Tg(C3-1-TAg)cJeg/JegJ female mice were infected by gastric gavage with Helicobacter hepaticus at three-months-of-age putting them at increased risk for mammary tumor development. Tumorigenesis was multifocal and characterized by extensive infiltrates of myeloperoxidase-positive neutrophils otherwise implicated in cancer progression in humans and animal models. To test whether neutrophils were important in etiopathogenesis in this bacteria-triggered model system, we next systemically depleted mice of neutrophils using thrice weekly intraperitoneal injections with anti-Ly-6G antibody. We found that antibody depletion entirely inhibited tumor development in this H. hepaticus-infected model. These data demonstrate that host neutrophil-associated immune responses to intestinal tract microbes significantly impact cancer progression in distal tissues such as mammary glands, and identify gut microbes as novel targets for extra-intestinal cancer therapy.