Hospital-Level Care at Home for Patients With Acute Respiratory Disease: A Descriptive Analysis.

BACKGROUND: Home hospital (HH) care is hospital-level substitutive care delivered at home for acutely ill patients who traditionally would be cared for in the hospital. Despite HH care programs operating successfully for years and scientific evidence of similar or better outcomes compared with bricks-and-mortar care, HH care outcomes in the United States for respiratory disease have not been evaluated. RESEARCH QUESTION: Do outcomes differ between patients admitted to HH care with acute respiratory illness vs those with other acute general medical conditions? STUDY DESIGN AND METHODS: This was a retrospective evaluation of prospectively collected data of patients admitted to HH care (2017-2021). We compared patients requiring admission with respiratory disease (asthma exacerbation [26%], acute exacerbation of COPD [33%], and non-COVID-19 pneumonia [41%]) to all other patients admitted to HH care. During HH care, patients received two nurse and one physician visit daily, IV medications, advanced respiratory therapies, and continuous heart and respiratory rate monitoring. Main outcomes were acute and postacute health care use and safety. RESULTS: We analyzed 1,031 patients; 24% were admitted for respiratory disease. Patients with and without respiratory disease were similar: mean age, 68 ± 17 years, 62% women, and 48% White. Patients with respiratory disease more often were active smokers (21% vs 9%; P < .001). Eighty percent of patients showed an FEV1 to FVC ratio of ≤ 70; 28% showed a severe or very severe obstructive pattern (n = 118). During HH care, patients with respiratory disease showed less health care use: length of stay (mean, 3.4 vs 4.6 days), laboratory orders (median, 0 vs 2), IV medication (43% vs 73%), and specialist consultation (2% vs 7%; P < .001 for all). Ninety-six percent of patients completed the full admission at home with no mortality in the respiratory group. Within 30 days of discharge, both groups showed similar readmission, ED presentation, and mortality rates. INTERPRETATION: HH care is as safe and effective for patients with acute respiratory disease as for those with other acute general medical conditions. If scaled, it can generate significant high-value capacity for health systems and communities, with opportunities to advance the complexity of care delivered.

Remote vs In-home Physician Visits for Hospital-Level Care at Home: A Randomized Clinical Trial.

Importance: Home hospital care is the substitutive provision of home-based acute care services usually associated with a traditional inpatient hospital. Many home hospital models require a physician to see patients at home daily, which may hinder scalability. Whether remote physician visits can safely substitute for most in-home visits is unknown. Objective: To compare remote and in-home physician care. Design, Setting, and Participants: This randomized clinical trial assessed 172 adult patients at an academic medical center and community hospital who required hospital-level care for select acute conditions, including infection, heart failure, chronic obstructive pulmonary disease, and asthma, between August 3, 2019, and March 26, 2020; follow-up ended April 26, 2020. Interventions: All patients received acute care at home, including in-home nurse or paramedic visits, intravenous medications, remote monitoring, and point-of-care testing. Patients were randomized to receive physician care remotely (initial in-home visit followed by daily video visit facilitated by the home hospital nurse) vs in-home care (daily in-home physician visit). In the remote care group, the physician could choose to see the patient at home beyond the first visit if it was felt to be medically necessary. Main Outcomes and Measures: The primary outcome was the number of adverse events, compared using multivariable Poisson regression at a noninferiority threshold of 10 events per 100 patients. Adverse events included a fall, pressure injury, and delirium. Secondary outcomes included the Picker Patient Experience Questionnaire 15 score (scale of 0-15, with 0 indicating worst patient experience and 15 indicating best patient experience) and 30-day readmission rates. Results: A total of 172 patients (84 receiving remote care and 88 receiving in-home physician care [control group]) were randomized; enrollment was terminated early because of COVID-19. The mean (SD) age was 69.3 (18.0) years, 97 patients (56.4%) were female, 77 (45.0%) were White, and 42 (24.4%) lived alone. Mean adjusted adverse event count was 6.8 per 100 patients for remote care patients vs 3.9 per 100 patients for control patients, for a difference of 2.8 (95% CI, -3.3 to 8.9), supporting noninferiority. For remote care vs control patients, the mean adjusted Picker Patient Experience Questionnaire 15 score difference was -0.22 (95% CI, -1.00 to 0.56), supporting noninferiority. The mean adjusted 30-day readmission absolute rate difference was 2.28% (95% CI, -3.23% to 7.79%), which was inconclusive. Of patients in the remote group, 16 (19.0%) required in-home visits beyond the first visit. Conclusions and Relevance: In this study, remote physician visits were noninferior to in-home physician visits during home hospital care for adverse events and patient experience, although in-home physician care was necessary to support many patients receiving remote care. Our findings may allow for a more efficient, scalable home hospital approach but require further research. Trial Registration: ClinicalTrials.gov Identifier: NCT04080570.

Interactive Digital Health Tools to Engage Patients and Caregivers in Discharge Preparation: Implementation Study.

BACKGROUND: Poor discharge preparation during hospitalization may lead to adverse events after discharge. Checklists and videos that systematically engage patients in preparing for discharge have the potential to improve safety, especially when integrated into clinician workflow via the electronic health record (EHR). OBJECTIVE: This study aims to evaluate the implementation of a suite of digital health tools integrated with the EHR to engage hospitalized patients, caregivers, and their care team in preparing for discharge. METHODS: We used the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework to identify pertinent research questions related to implementation. We iteratively refined patient and clinician-facing intervention components using a participatory process involving end users and institutional stakeholders. The intervention was implemented at a large academic medical center from December 2017 to July 2018. Patients who agreed to participate were coached to watch a discharge video, complete a checklist assessing discharge readiness, and request postdischarge text messaging with a physician 24 to 48 hours before their expected discharge date, which was displayed via a patient portal and bedside display. Clinicians could view concerns reported by patients based on their checklist responses in real time via a safety dashboard integrated with the EHR and choose to open a secure messaging thread with the patient for up to 7 days after discharge. We used mixed methods to evaluate our implementation experience. RESULTS: Of 752 patient admissions, 510 (67.8%) patients or caregivers participated: 416 (55.3%) watched the video and completed the checklist, and 94 (12.5%) completed the checklist alone. On average, 4.24 concerns were reported per each of the 510 checklist submissions, most commonly about medications (664/2164, 30.7%) and follow-up (656/2164, 30.3%). Of the 510 completed checklists, a member of the care team accessed the safety dashboard to view 210 (41.2%) patient-reported concerns. For 422 patient admissions where postdischarge messaging was available, 141 (33.4%) patients requested this service; of these, a physician initiated secure messaging for 3 (2.1%) discharges. Most patient survey participants perceived that the intervention promoted self-management and communication with their care team. Patient interview participants endorsed gaps in communication with their care team and thought that the video and checklist would be useful closer toward discharge. Clinicians participating in focus groups perceived the value for patients but suggested that low awareness and variable workflow regarding the intervention, lack of technical optimization, and inconsistent clinician leadership limited the use of clinician-facing components. CONCLUSIONS: A suite of EHR-integrated digital health tools to engage patients, caregivers, and clinicians in discharge preparation during hospitalization was feasible, acceptable, and valuable; however, important challenges were identified during implementation. We offer strategies to address implementation barriers and promote adoption of these tools. TRIAL REGISTRATION: ClinicalTrials.gov NCT03116074; https://clinicaltrials.gov/ct2/show/NCT03116074.

Use, Perceived Usability, and Barriers to Implementation of a Patient Safety Dashboard Integrated within a Vendor EHR.

BACKGROUND: Preventable adverse events continue to be a threat to hospitalized patients. Clinical decision support in the form of dashboards may improve compliance with evidence-based safety practices. However, limited research describes providers' experiences with dashboards integrated into vendor electronic health record (EHR) systems. OBJECTIVE: This study was aimed to describe providers' use and perceived usability of the Patient Safety Dashboard and discuss barriers and facilitators to implementation. METHODS: The Patient Safety Dashboard was implemented in a cluster-randomized stepped wedge trial on 12 units in neurology, oncology, and general medicine services over an 18-month period. Use of the Dashboard was tracked during the implementation period and analyzed in-depth for two 1-week periods to gather a detailed representation of use. Providers' perceptions of tool usability were measured using the Health Information Technology Usability Evaluation Scale (rated 1-5). Research assistants conducted field observations throughout the duration of the study to describe use and provide insight into tool adoption. RESULTS: The Dashboard was used 70% of days the tool was available, with use varying by role, service, and time of day. On general medicine units, nurses logged in throughout the day, with many logins occurring during morning rounds, when not rounding with the care team. Prescribers logged in typically before and after morning rounds. On neurology units, physician assistants accounted for most logins, accessing the Dashboard during daily brief interdisciplinary rounding sessions. Use on oncology units was rare. Satisfaction with the tool was highest for perceived ease of use, with attendings giving the highest rating (4.23). The overall lowest rating was for quality of work life, with nurses rating the tool lowest (2.88). CONCLUSION: This mixed methods analysis provides insight into the use and usability of a dashboard tool integrated within a vendor EHR and can guide future improvements and more successful implementation of these types of tools.

User-Centered Collaborative Design and Development of an Inpatient Safety Dashboard.

Patient safety remains a key concern in hospital care. This article summarizes the iterative participatory development, features, functions, and preliminary evaluation of a patient safety dashboard for interdisciplinary rounding teams on inpatient medical services. This electronic health record (EHR)-embedded dashboard collects real-time data covering 13 safety domains through web services and applies logic to generate stratified alerts with an interactive check-box function. The technological infrastructure is adaptable to other EHR environments. Surveyed users perceived the tool as highly usable and useful. Integration of the dashboard into clinical care is intended to promote communication about patient safety and facilitate identification and management of safety concerns.

Autocrine prolactin induced by the Pten-Akt pathway is required for lactation initiation and provides a direct link between the Akt and Stat5 pathways.

Extrapituitary prolactin (Prl) is produced in humans and rodents; however, little is known about its in vivo regulation or physiological function. We now report that autocrine prolactin is required for terminal mammary epithelial differentiation during pregnancy and that its production is regulated by the Pten-PI3K-Akt pathway. Conditional activation of the PI3K-Akt pathway in the mammary glands of virgin mice by either Akt1 expression or Pten deletion rapidly induced terminal mammary epithelial differentiation accompanied by the synthesis of milk despite the absence of lobuloalveolar development. Surprisingly, we found that mammary differentiation was due to the PI3K-Akt-dependent synthesis and secretion of autocrine prolactin and downstream activation of the prolactin receptor (Prlr)-Jak-Stat5 pathway. Consistent with this, Akt-induced mammary differentiation was abrogated in Prl(-/-), Prlr(-/-), and Stat5(-/-) mice. Furthermore, cells treated with conditioned medium from mammary glands in which Akt had been activated underwent rapid Stat5 phosphorylation in a manner that was blocked by inhibition of Jak2, treatment with an anti-Prl antibody, or deletion of the prolactin gene. Demonstrating a physiological requirement for autocrine prolactin, mammary glands from lactation-defective Akt1(-/-);Akt2(+/-) mice failed to express autocrine prolactin or activate Stat5 during late pregnancy despite normal levels of circulating serum prolactin and pituitary prolactin production. Our findings reveal that PI3K-Akt pathway activation is necessary and sufficient to induce autocrine prolactin production in the mammary gland, Stat5 activation, and terminal mammary epithelial differentiation, even in the absence of the normal developmental program that prepares the mammary gland for lactation. Together, these findings identify a function for autocrine prolactin during normal development and demonstrate its endogenous regulation by the PI3K-Akt pathway.

Akt is required for Stat5 activation and mammary differentiation.

INTRODUCTION: The Akt pathway plays a central role in regulating cell survival, proliferation and metabolism, and is one of the most commonly activated pathways in human cancer. A role for Akt in epithelial differentiation, however, has not been established. We previously reported that mice lacking Akt1, but not Akt2, exhibit a pronounced metabolic defect during late pregnancy and lactation that results from a failure to upregulate Glut1 as well as several lipid synthetic enzymes. Despite this metabolic defect, however, both Akt1-deficient and Akt2-deficient mice exhibit normal mammary epithelial differentiation and Stat5 activation. METHODS: In light of the overlapping functions of Akt family members, we considered the possibility that Akt may play an essential role in regulating mammary epithelial development that is not evident in Akt1-deficient mice due to compensation by other Akt isoforms. To address this possibility, we interbred mice bearing targeted deletions in Akt1 and Akt2 and determined the effect on mammary differentiation during pregnancy and lactation. RESULTS: Deletion of one allele of Akt2 in Akt1-deficient mice resulted in a severe defect in Stat5 activation during late pregnancy that was accompanied by a global failure of terminal mammary epithelial cell differentiation, as manifested by the near-complete loss in production of the three principal components of milk: lactose, lipid, and milk proteins. This defect was due, in part, to a failure of pregnant Akt1(-/-);Akt2(+/-) mice to upregulate the positive regulator of Prlr-Jak-Stat5 signaling, Id2, or to downregulate the negative regulators of Prlr-Jak-Stat5 signaling, caveolin-1 and Socs2. CONCLUSIONS: Our findings demonstrate an unexpected requirement for Akt in Prlr-Jak-Stat5 signaling and establish Akt as an essential central regulator of mammary epithelial differentiation and lactation.

Dose-dependent oncogene-induced senescence in vivo and its evasion during mammary tumorigenesis.

Activating Ras mutations can induce either proliferation or senescence depending on the cellular context. To determine whether Ras activation has context-dependent effects in the mammary gland, we generated doxycycline-inducible transgenic mice that permit Ras activation to be titrated. Low levels of Ras activation - similar to those found in non-transformed mouse tissues expressing endogenous oncogenic Kras2 - stimulate cellular proliferation and mammary epithelial hyperplasias. In contrast, high levels of Ras activation - similar to those found in tumours bearing endogenous Kras2 mutations - induce cellular senescence that is Ink4a-Arf- dependent and irreversible following Ras downregulation. Chronic low-level Ras induction results in tumour formation, but only after the spontaneous upregulation of activated Ras and evasion of senescence checkpoints. Thus, high-level, but not low-level, Ras activation activates tumour suppressor pathways and triggers an irreversible senescent growth arrest in vivo. We suggest a three-stage model for Ras-induced tumorigenesis consisting of an initial activating Ras mutation, overexpression of the activated Ras allele and, finally, evasion of p53-Ink4a-Arf-dependent senescence checkpoints.

Isoform-specific requirement for Akt1 in the developmental regulation of cellular metabolism during lactation.

The metabolic demands and synthetic capacity of the lactating mammary gland exceed that of any other tissue, thereby providing a useful paradigm for understanding the developmental regulation of cellular metabolism. By evaluating mice bearing targeted deletions in Akt1 or Akt2, we demonstrate that Akt1 is specifically required for lactating mice to synthesize sufficient quantities of milk to support their offspring. Whereas cellular proliferation, differentiation, and apoptosis are unaffected, loss of Akt1 disrupts the coordinate regulation of metabolic pathways that normally occurs at the onset of lactation. This results in a failure to upregulate glucose uptake, Glut1 surface localization, lipid synthesis, and multiple lipogenic enzymes, as well as a failure to downregulate lipid catabolic enzymes. These findings demonstrate that Akt1 is required in an isoform-specific manner for orchestrating many of the developmental changes in cellular metabolism that occur at the onset of lactation and establish a role for Akt1 in glucose metabolism.

Isoform-specific ras activation and oncogene dependence during MYC- and Wnt-induced mammary tumorigenesis.

We have previously shown that c-MYC-induced mammary tumorigenesis in mice proceeds via a preferred secondary pathway involving spontaneous activating mutations in Kras2 (C. M. D'Cruz, E. J. Gunther, R. B. Boxer, J. L. Hartman, L. Sintasath, S. E. Moody, J. D. Cox, S. I. Ha, G. K. Belka, A. Golant, R. D. Cardiff, and L. A. Chodosh, Nat. Med. 7:235-239, 2001). In contrast, we now demonstrate that Wnt1-induced mammary tumorigenesis proceeds via a pathway that preferentially activates Hras1. In addition, we find that expression of oncogenic forms of Kras2 and Hras1 from their endogenous promoters has markedly different consequences for the progression of tumors to oncogene independence. Spontaneous activating Kras2 mutations occurring in either MYC- or Wnt1-induced tumors were strongly associated with oncogene-independent tumor growth following MYC or Wnt1 downregulation. In contrast, Hras1-mutant Wnt1-induced tumors consistently remained oncogene dependent. Additionally, Kras2-mutant tumors exhibited substantially higher levels of ras-GTP, phospho-Erk1/2, and phospho-Mek1/2 compared to Hras1-mutant tumors, suggesting the involvement of the ras/mitogen-activated protein kinase (MAPK) pathway in the acquisition of oncogene independence. Consistent with this, by use of carcinogen-induced ras mutations as well as knock-in mice harboring a latent activated Kras2 allele, we demonstrate that Kras2 activation strongly synergizes with both c-MYC and Wnt1 in mammary tumorigenesis and promotes the progression of tumors to oncogene independence. Together, our findings support a model for tumorigenesis in which c-MYC and Wnt1 select for the outgrowth of cells harboring mutations in specific ras isoforms and that these secondary mutations, in turn, determine the extent of ras/MAPK pathway activation and the potential for oncogene-independent growth.

Lack of sustained regression of c-MYC-induced mammary adenocarcinomas following brief or prolonged MYC inactivation.

Recent studies of oncogene dependence in conditional transgenic mice have suggested the exciting possibility that transient or prolonged MYC inactivation may be sufficient for sustained reversal of the tumorigenic process. In contrast, we report here that following oncogene downregulation, the majority of c-MYC-induced mammary adenocarcinomas grow in the absence of MYC overexpression. In addition, residual neoplastic cells persist from virtually all tumors that do regress to a nonpalpable state and these residual cells rapidly recover their malignant properties following MYC reactivation or spontaneously recur in a MYC-independent manner. Thus, MYC-induced mammary tumor cells subjected to either brief or prolonged MYC inactivation remain exquisitely sensitive to its oncogenic effects and characteristically progress to a state in which growth is MYC-independent.

A novel doxycycline-inducible system for the transgenic analysis of mammary gland biology.

Normal developmental events such as puberty, pregnancy, and parity influence the susceptibility of the mammary gland to tumorigenesis in both humans and rodent model systems. Unfortunately, constitutive transgenic mouse models that rely on mammary-specific promoters to control transgene expression have limited utility for studying the effect of developmental events on breast cancer risk since the hormonal signals governing these events also markedly influence transgene expression levels. A novel transgenic mouse system is described that uses the MMTV-LTR to drive expression of the reverse tetracycline-dependent transactivator rtTA. Transgenic mice expressing rtTA in the mammary epithelium were crossed with reporter lines bearing tet operator-controlled transgenes. We tested the ability to spatially, temporally, and quantitatively control reporter gene expression after administration of doxycycline to bitransgenic mice. Transgene expression using this system can be rapidly induced and deinduced, is highly mammary specific, can be reproducibly titrated over a wide range of expression levels, and is essentially undetectable in the uninduced state. Homogeneous transgene expression throughout the mammary epithelium can be achieved. This system permits transgene expression to be restricted to any desired stage of postnatal mammary gland development. We have developed a mammary-specific, doxycycline-inducible transgenic mouse model for studying the effect of mammary gland development on transgene-mediated phenotypes. Unlike other mammary-specific, transgenic systems that have been described, this system combines spatially homogeneous transgene expression in the mammary epithelium during puberty, pregnancy, lactation, and involution with the use of an orally administered, inexpensive, and widely available inducing agent. This system offers new opportunities for the transgenic analysis of mammary gland biology in vivo.