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1.
J Gen Intern Med ; 38(10): 2236-2244, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36849864

RESUMO

BACKGROUND: Prior evaluation at our hospital demonstrated that, compared to White patients, Black and Latinx patients with congestive heart failure (CHF) were less likely to be admitted to the cardiology service rather than the general medicine service (GMS). Patients admitted to GMS (compared to cardiology) had inferior rates of cardiology follow-up and 30-day readmission. OBJECTIVE: To develop and test the feasibility and impacts of using quality improvement (QI) methods, in combination with the Public Health Critical Race Praxis (PHCRP) framework, to engage stakeholders in developing an intervention for ensuring guideline-concordant inpatient CHF care across all patient groups. METHODS: We compared measures for all patients admitted with CHF to GMS between September 2019 and March 2020 (intervention group) to CHF patients admitted to GMS in the previous year (pre-intervention group) and those admitted to cardiology during the pre-intervention and intervention periods (cardiology group). Our primary measures were 30-day readmissions and 14- and 30-day post-discharge cardiology follow-up. RESULTS: There were 79 patients admitted with CHF to GMS during the intervention period, all of whom received the intervention. There were similar rates of Black and Latinx patients across the three groups. Compared to pre-intervention, intervention patients had a significantly lower 30-day readmission rate (18.9% vs. 24.8%; p=0.024), though the cardiology group also had a decrease in 30-day readmissions from the pre-intervention to intervention period. Compared to pre-intervention, intervention patients had significantly higher 14-day and 30-day post-discharge follow-up visits scheduled with cardiology (36.7% vs. 24.8%, p=0.005; 55.7% vs. 42.3%, p=0.0029), but no improvement in appointment attendance. CONCLUSION: This study provides a first test of applying the PHCRP framework within a stakeholder-engaged QI initiative for improving CHF care across races and ethnicities. Our study design cannot evaluate causation. However, the improvements in 30-day readmission, as well as in processes of care that may affect it, provide optimism that inclusion of a racism-conscious framework in QI initiatives is feasible and may enhance QI measures.


Assuntos
Insuficiência Cardíaca , Melhoria de Qualidade , Humanos , Pacientes Internados , Assistência ao Convalescente , Saúde Pública , Alta do Paciente , Readmissão do Paciente , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia
2.
J Med Internet Res ; 22(4): e15573, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32343248

RESUMO

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.


Assuntos
Cuidadores/normas , Registros Eletrônicos de Saúde/normas , Alta do Paciente/tendências , Adulto , Feminino , Humanos , Masculino , Inquéritos e Questionários
3.
Genes Dev ; 26(19): 2154-68, 2012 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-23028142

RESUMO

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.


Assuntos
Regulação da Expressão Gênica , Lactação/fisiologia , Prolactina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição STAT5/metabolismo , Animais , Comunicação Autócrina/fisiologia , Diferenciação Celular , Células Cultivadas , Regulação para Baixo , Feminino , Deleção de Genes , Lactação/genética , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/metabolismo , Camundongos , Proteínas do Leite/metabolismo , PTEN Fosfo-Hidrolase/genética , Gravidez , Prolactina/genética , Proteínas Proto-Oncogênicas c-akt/genética
4.
Jt Comm J Qual Patient Saf ; 43(12): 676-685, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29173289

RESUMO

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.


Assuntos
Registros Eletrônicos de Saúde/organização & administração , Pacientes Internados , Segurança do Paciente/normas , Qualidade da Assistência à Saúde/organização & administração , Interface Usuário-Computador , Comunicação , Comportamento Cooperativo , Registros Eletrônicos de Saúde/normas , Humanos , Cultura Organizacional , Participação do Paciente , Indicadores de Qualidade em Assistência à Saúde
6.
Nat Cell Biol ; 9(5): 493-505, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17450133

RESUMO

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.


Assuntos
Transformação Celular Neoplásica/metabolismo , Senescência Celular , Células Epiteliais/metabolismo , Glândulas Mamárias Animais/metabolismo , Neoplasias Mamárias Experimentais/metabolismo , Proteína Oncogênica p21(ras)/metabolismo , Lesões Pré-Cancerosas/metabolismo , Fatores de Ribosilação do ADP/metabolismo , Animais , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Senescência Celular/efeitos dos fármacos , Senescência Celular/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Relação Dose-Resposta a Droga , Doxiciclina/farmacologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Hiperplasia , Glândulas Mamárias Animais/efeitos dos fármacos , Glândulas Mamárias Animais/patologia , Neoplasias Mamárias Experimentais/genética , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Transgênicos , Mutação , Proteína Oncogênica p21(ras)/genética , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Regiões Promotoras Genéticas/efeitos dos fármacos , Transporte Proteico , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Transdução de Sinais , Fatores de Tempo , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima
7.
Circ Cardiovasc Qual Outcomes ; 17(1): e010031, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38054286

RESUMO

BACKGROUND: Overall outcomes and the escalation rate for home hospital admissions for heart failure (HF) are not known. We report overall outcomes, predict escalation, and describe care provided after escalation among patients admitted to home hospital for HF. METHODS: Our retrospective analysis included all patients admitted for HF to 2 home hospital programs in Massachusetts between February 2020 and October 2022. Escalation of care was defined as transfer to an inpatient hospital setting (emergency department, inpatient medical unit) for at least 1 overnight stay. Unexpected mortality was defined as mortality excluding those who desired to pass away at home on admission or transitioned to hospice. We performed the least absolute shrinkage and selection operator logistic regression to predict escalation. RESULTS: We included 437 hospitalizations; patients had a median age of 80 (interquartile range, 69-89) years, 58.1% were women, and 64.8% were White. Of the cohort, 29.2% had reduced ejection fraction, 50.9% had chronic kidney disease, and 60.6% had atrial fibrillation. Median admission Get With The Guidelines HF score was 39 (interquartile range, 35-45; 1%-5% predicted inpatient mortality). Escalation occurred in 10.3% of hospitalizations. Thirty-day readmission occurred in 15.1%, 90-day readmission occurred in 33.8%, and 6-month mortality occurred in 11.5%. There was no unexpected mortality during home hospitalization. Patients who experienced escalation had significantly longer median length of stays (19 versus 7.5 days, P<0.001). The most common reason for escalation was progressive renal dysfunction (36.2%). A low mean arterial pressure at the time of admission to home hospital was the most significant predictor of escalation in the least absolute shrinkage and selection operator regression. CONCLUSIONS: About 1 in 10 home hospital patients with HF required escalation; none had unexpected mortality. Patients requiring escalation had longer length of stays. A low mean arterial pressure at the time of admission to home hospital was the most important predictor of escalation of care in the least absolute shrinkage and selection operator logistic regression model.


Assuntos
Insuficiência Cardíaca , Hospitalização , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Estudos Retrospectivos , Readmissão do Paciente , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/complicações , Hospitais
8.
Chest ; 163(4): 891-901, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36372302

RESUMO

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.


Assuntos
Asma , Transtornos Respiratórios , Doenças Respiratórias , Humanos , Feminino , Estados Unidos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Estudos Retrospectivos , Hospitalização , Alta do Paciente , Doença Aguda , Hospitais
9.
Cancer Cell ; 6(6): 577-86, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15607962

RESUMO

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.


Assuntos
Adenocarcinoma/patologia , Neoplasias Mamárias Experimentais/patologia , Proteínas Proto-Oncogênicas c-myc/genética , Adenocarcinoma/genética , Animais , Apoptose , Northern Blotting , Análise Mutacional de DNA , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Marcação In Situ das Extremidades Cortadas , Neoplasias Mamárias Experimentais/genética , Camundongos , Camundongos Transgênicos , Mutação , Proteínas Proto-Oncogênicas c-myc/fisiologia , Proteínas Proto-Oncogênicas p21(ras) , Recidiva , Indução de Remissão , Fatores de Tempo , Proteínas ras/genética
10.
JAMA Netw Open ; 5(8): e2229067, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-36040741

RESUMO

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.


Assuntos
COVID-19 , Serviços de Assistência Domiciliar , Médicos , Adulto , Idoso , COVID-19/epidemiologia , Feminino , Hospitais Comunitários , Humanos , Masculino , Readmissão do Paciente
11.
Cell Metab ; 4(6): 475-90, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17141631

RESUMO

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.


Assuntos
Transportador de Glucose Tipo 1/metabolismo , Glucose/metabolismo , Lactação/metabolismo , Lipídeos/biossíntese , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Feminino , Isoenzimas/deficiência , Isoenzimas/metabolismo , Lactação/genética , Camundongos , Camundongos Knockout , Leite/metabolismo , Transporte Proteico/genética , Proteínas Proto-Oncogênicas c-akt/deficiência
12.
Neurology ; 97(9): 434-442, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34158383

RESUMO

Over the last century, attending rounds have shifted away from the bedside. Despite evidence for greater patient satisfaction rates and improved nursing perception of teamwork with bedside presentations, residents and attending physicians are apprehensive of the bedside approach. There is lack of data to guide rounding practices within neurology, and therefore, optimal rounding methods remain unclear. The objective of this study was to compare bedside rounding with hallway rounding on an academic neurology inpatient service and assess efficiency, trainee education, and satisfaction among patients and staff. We conducted a single-center prospective randomized study of bedside vs hallway rounding on new inpatient neurology admissions over 1-week blocks. The bedside team presented patients at the bedside, whereas the hallway team presented patients outside of the patient's room. We evaluated the 2 approaches with time-motion analysis, which investigated the rounding style's effect on composition and timing of rounds (primary outcome) and surveys of patients, nurses, residents, and attending physicians on both teams (secondary outcomes). The mean rounding time per newly admitted patient in the bedside group (n = 38 patients) and hallway group (n = 41 patients) was 23 minutes and 23.2 minutes, respectively (p = 0.93). The bedside group spent on average 56.4% of patient rounding time in the patient's room, whereas the hallway group spent 39.5% of rounding time in the patient's room (p = 0.036). Residents perceived hallway rounding to be more efficient and associated it with a superior educational experience and more effective data review. Nurses had improved perception of their participation in bedside rounds. Although patients' views of bedside and hallway rounds were similar, patients who had experienced bedside rounds preferred it. In conclusion, bedside rounding was perceived less favorably by most residents but was as efficient as hallway rounding. Although bedside rounding limited the use of technology for data review, it promoted nursing participation and resulted in more time spent with the patient. CLINICAL TRIAL REGISTRATION NUMBER: Registered retrospectively per the editors' suggestion (NCT04754828).


Assuntos
Educação de Pós-Graduação em Medicina/métodos , Neurologia/educação , Visitas de Preceptoria/métodos , Humanos , Enfermeiras e Enfermeiros , Satisfação do Paciente
13.
Breast Cancer Res ; 12(5): R72, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20849614

RESUMO

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.


Assuntos
Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição STAT5/metabolismo , Animais , Diferenciação Celular , Proliferação de Células , Sobrevivência Celular , Feminino , Janus Quinases/metabolismo , Lactação , Camundongos , Camundongos Knockout , Proteínas do Leite/biossíntese , Técnicas de Cultura de Órgãos , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais
14.
Trop Med Int Health ; 15(1): 33-40, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19912592

RESUMO

OBJECTIVES: To assess the therapeutic efficacy of chloroquine (CQ) treatment against uncomplicated Plasmodium falciparum infections in a tribal population of central India (Madhya Pradesh) and to investigate the prevalence of mutant P. falciparum chloroquine-resistant transporter (pfcrt) gene in the parasite population. METHODS: Clinical and parasitological response was determined by in-vivo testing. For molecular testing, the parasite DNA was extracted from blood samples and used to amplify and sequence parts of the pfcrt (44-177 codons), MSP1 (block 2) and MSP2 (central repeat region) genes. RESULTS: Of 463 patients presenting fever, 137 tested positive for P. falciparum. They were treated with CQ. Of these, 58% participated in the study. Overall, treatment failure occurred in 53% of participants. Children under 5 years of age showed significantly more CQ resistance than adults. Mutant genotype S(72)V(73)M(74)N(75)T(76) was prevalent among both CQ responders (61.29%) and non-responders (66.7%). Interestingly, several patients from the CQ non-responder group (33.3%, n = 39) were harbouring parasite with wild type C(72)V(73)M(74)N(75)K(76) genotype of the pfcrt gene. Microsatellite sequences downstream of exon 2 varied widely among both wild type and mutant pfcrt haplotypes. CONCLUSION: The high rate of treatment failure in the present study clearly indicates the need to reassess the use of CQ as first-line antimalarial therapy in central India. This is supported by the presence of mutant pfcrt genotype among majority of the parasite population of the CQ non-responder group of patients. However, the presence of wild type amino acid at codon 76 of the pfcrt gene among several patients with CQ non-responders requires further investigations.


Assuntos
Antimaláricos/uso terapêutico , Cloroquina/uso terapêutico , Malária Falciparum/tratamento farmacológico , Proteínas de Membrana Transportadoras/genética , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Adolescente , Adulto , Fatores Etários , Animais , Antígenos de Protozoários/genética , Criança , Pré-Escolar , Análise Mutacional de DNA/métodos , DNA de Protozoário/genética , Resistência a Medicamentos/genética , Feminino , Humanos , Índia/epidemiologia , Lactente , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Masculino , Proteína 1 de Superfície de Merozoito/genética , Pessoa de Meia-Idade , Mutação , Reação em Cadeia da Polimerase/métodos , Falha de Tratamento , Adulto Jovem
15.
Appl Clin Inform ; 11(5): 792-801, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33241547

RESUMO

OBJECTIVE: We deployed a Remote Patient Monitoring (RPM) program to monitor patients with coronavirus disease 2019 (COVID-19) upon hospital discharge. We describe the patient characteristics, program characteristics, and clinical outcomes of patients in our RPM program. METHODS: We enrolled COVID-19 patients being discharged home from the hospital. Enrolled patients had an app, and were provided with a pulse oximeter and thermometer. Patients self-reported symptoms, O2 saturation, and temperature daily. Abnormal symptoms or vital signs were flagged and assessed by a pool of nurses. Descriptive statistics were used to describe patient and program characteristics. A mixed-effects logistic regression model was used to determine the odds of a combined endpoint of emergency department (ED) or hospital readmission. RESULTS: A total of 295 patients were referred for RPM from five participating hospitals, and 225 patients were enrolled. A majority of enrolled patients (66%) completed the monitoring period without triggering an abnormal alert. Enrollment was associated with a decreased odds of ED or hospital readmission (adjusted odds ratio: 0.54; 95% confidence interval: 0.3-0.97; p = 0.039). Referral without enrollment was not associated with a reduced odds of ED or hospital readmission. CONCLUSION: RPM for COVID-19 provides a mechanism to monitor patients in their home environment and reduce hospital utilization. Our work suggests that RPM reduces readmissions for patients with COVID-19 and provides scalable remote monitoring capabilities upon hospital discharge. RPM for postdischarge patients with COVID-19 was associated with a decreased risk of readmission to the ED or hospital, and provided a scalable mechanism to monitor patients in their home environment.


Assuntos
Assistência ao Convalescente/métodos , COVID-19 , Alta do Paciente , Adulto , Idoso , COVID-19/epidemiologia , COVID-19/terapia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Readmissão do Paciente/estatística & dados numéricos
16.
Appl Clin Inform ; 11(1): 34-45, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31940670

RESUMO

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.


Assuntos
Registros Eletrônicos de Saúde , Segurança do Paciente , Humanos , Pesquisa
17.
Mol Cell Biol ; 26(21): 8109-21, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16908535

RESUMO

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.


Assuntos
Isoenzimas/metabolismo , Neoplasias Mamárias Experimentais/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Transdução de Sinais/fisiologia , Proteína Wnt1/metabolismo , Animais , Transformação Celular Neoplásica , Ativação Enzimática , Feminino , Humanos , Isoenzimas/genética , Neoplasias Mamárias Experimentais/genética , Camundongos , Camundongos Transgênicos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Mutação , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Transgenes , Proteína Supressora de Tumor p53/metabolismo , Proteína Wnt1/genética
18.
J Am Med Inform Assoc ; 26(12): 1488-1492, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31504592

RESUMO

OBJECTIVE: To investigate the effects of adjusting the default order set settings on telemetry usage. MATERIALS AND METHODS: We performed a retrospective, controlled, before-after study of patients admitted to a house staff medicine service at an academic medical center examining the effect of changing whether the admission telemetry order was pre-selected or not. Telemetry orders on admission and subsequent orders for telemetry were monitored pre- and post-change. Two other order sets that had no change in their default settings were used as controls. RESULTS: Between January 1, 2017 and May 1, 2018, there were 1, 163 patients admitted using the residency-customized version of the admission order set which initially had telemetry pre-selected. In this group of patients, there was a significant decrease in telemetry ordering in the post-intervention period: from 79.1% of patients in the 8.5 months prior ordered to have telemetry to 21.3% of patients ordered in the 7.5 months after (χ2 = 382; P < .001). There was no significant change in telemetry usage among patients admitted using the two control order sets. DISCUSSION: Default settings have been shown to affect clinician ordering behavior in multiple domains. Consistent with prior findings, our study shows that changing the order set settings can significantly affect ordering practices. Our study was limited in that we were unable to determine if the change in ordering behavior had significant impact on patient care or safety. CONCLUSION: Decisions about default selections in electronic health record order sets can have significant consequences on ordering behavior.


Assuntos
Sistemas de Registro de Ordens Médicas , Padrões de Prática Médica , Telemetria , Centros Médicos Acadêmicos , Humanos , Internato e Residência , Corpo Clínico Hospitalar , Estudos Retrospectivos
19.
Circ Heart Fail ; 12(11): e006214, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31658831

RESUMO

BACKGROUND: Racial inequities for patients with heart failure (HF) have been widely documented. HF patients who receive cardiology care during a hospital admission have better outcomes. It is unknown whether there are differences in admission to a cardiology or general medicine service by race. This study examined the relationship between race and admission service, and its effect on 30-day readmission and mortality Methods: We performed a retrospective cohort study from September 2008 to November 2017 at a single large urban academic referral center of all patients self-referred to the emergency department and admitted to either the cardiology or general medicine service with a principal diagnosis of HF, who self-identified as white, black, or Latinx. We used multivariable generalized estimating equation models to assess the relationship between race and admission to the cardiology service. We used Cox regression to assess the association between race, admission service, and 30-day readmission and mortality. RESULTS: Among 1967 unique patients (66.7% white, 23.6% black, and 9.7% Latinx), black and Latinx patients had lower rates of admission to the cardiology service than white patients (adjusted rate ratio, 0.91; 95% CI, 0.84-0.98, for black; adjusted rate ratio, 0.83; 95% CI, 0.72-0.97 for Latinx). Female sex and age >75 years were also independently associated with lower rates of admission to the cardiology service. Admission to the cardiology service was independently associated with decreased readmission within 30 days, independent of race. CONCLUSIONS: Black and Latinx patients were less likely to be admitted to cardiology for HF care. This inequity may, in part, drive racial inequities in HF outcomes.


Assuntos
Centros Médicos Acadêmicos , Negro ou Afro-Americano , Serviço Hospitalar de Cardiologia , Acessibilidade aos Serviços de Saúde , Disparidades em Assistência à Saúde/etnologia , Insuficiência Cardíaca/terapia , Hispânico ou Latino , Admissão do Paciente , População Branca , Idoso , Idoso de 80 Anos ou mais , Boston/epidemiologia , Feminino , Disparidades nos Níveis de Saúde , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etnologia , Insuficiência Cardíaca/mortalidade , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
20.
J Hosp Med ; 12(3): 150-156, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28272590

RESUMO

BACKGROUND: Attending rounds at academic medical centers are often disconnected from patients and team members who are not physicians. Regionalization of care teams may facilitate bedside rounding and more frequent interactions among doctors, nurses, and patients. OBJECTIVE: We used time-motion analysis to investigate how regionalization of medical teams and encouragement of bedside rounds affect participants on rounds and rounding time. DESIGN AND SETTING: We used pre-post analysis to study the effects of care redesign on teams' daily rounds on a general medicine service at an academic medical center. PARTICIPANTS: Four general medical teams were evaluated before the intervention and 5 teams afterward. INTERVENTIONS: General medical teams were regionalized to specific units, the admitting structure was changed to facilitate regionalization, and teams were encouraged to round bedside. MEASUREMENTS: Primary outcomes included proportion of time each team member was present on rounds and proportion of bedside rounding time. Secondary outcomes included round duration and non-patient time during rounds. RESULTS: Proportion of time the nurse was present on rounds increased from 24.1% to 67.8% (P ⟨ 0.001), and proportion of total bedside rounding time increased from 39.9% to 55.8% (P ⟨ 0.001). Mean total rounding time decreased from 3.0 hours to 2.4 hours (P = 0.01), despite a higher patient census. CONCLUSIONS: Creating regionalized care teams and encouraging interdisciplinary bedside rounds increased the proportion of bedside rounding time and the presence of nurses on rounds while decreasing total rounding time. Journal of Hospital Medicine 2017;12:150-156.


Assuntos
Eficiência Organizacional/normas , Corpo Clínico Hospitalar/normas , Equipe de Assistência ao Paciente/normas , Visitas de Preceptoria/normas , Centros Médicos Acadêmicos/métodos , Centros Médicos Acadêmicos/normas , Idoso , Feminino , Humanos , Medicina Interna/métodos , Medicina Interna/normas , Relações Interprofissionais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Visitas de Preceptoria/métodos , Fatores de Tempo
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