Applications of Remote Patient Monitoring.

Remote patient monitoring programs collect and analyze a variety of health-related data to detect clinical deterioration with the goal of early intervention. There are many program designs with various deployed devices, monitoring schemes, and escalation protocols. Although several factors are considered, the disease state plays a foundational role when designing a specific program. Remote patient monitoring is used both in chronic disease states and patients with acute self-limited conditions. These programs use health-related data to identify early deterioration and then successfully intervene to improve clinical outcomes and decrease costs of care.

Key Factors Promoting Rapid Implementation of Virtual Screening Modalities for the COVID-19 Pandemic Response.

BACKGROUND: The COVID-19 (C-19) pandemic required swift response from health care organizations to mitigate spread and impact. A large integrated health network rapidly deployed and operationalized multiple access channels to the community, allowing assessment and triage to occur virtually. These channels were characterized by swift implementation of virtual models, including asynchronous e-visits and video visits for C-19 screening. PURPOSE: (1) Evaluate implementation characteristics of C-19 screening e-visits and video visits. (2) Identify volume of C-19 screening and other care provided via e-visits and video visits. (3) Discuss future implications of expanded virtual access models. METHODS: Retrospective analysis of implementation data for C-19 screening e-visits and video visits, including operational characteristics and visit/screening volumes conducted. RESULTS: Virtual channels were implemented and rapidly expanded during the first week C-19 testing was made available. During the study period, primary care clinicians conducted 10,673 e-visits and 31,226 video visits with 9,126 and 26,009 patients, respectively. Within these 2 virtual modalities, 4,267 C-19 tests were ordered (10% of visits). Four hundred forty-eight clinicians supported 24/7 access to these virtual modalities. DISCUSSION: Given ongoing patient interest and opportunity, virtual health care services will continue to be available for an expanded number of symptoms and diagnoses.

Physician-directed smoking cessation using patient "opt-out" approach in the emergency department: A pilot program.

OBJECTIVE: Using a physician-directed, patient "opt-out" approach to prescriptive smoking cessation in the emergency department (ED) setting, we set out to describe patient actions as they related to smoking cessation behaviors. METHODS: A convenience sample of smokers at 2 Pennsylvania hospital EDs who met inclusion/exclusion criteria were approached to participate in a brief intervention known as screening, treatment initiation, and referral (STIR) counseling that included phone follow-up. Demographic information, current smoking status, and specific physician prescription and follow-up recommendations were collected. Approximately 3 months later, patients were contacted to determine current smoking status and actions taken since their ED visit. RESULTS: One hundred six patients were approached and 7 (6.6%) opted out of the intervention. Patients who did not opt out were evaluated for appropriate use of smoking cessation-related medications; 35 (35.4%) opted out of the prescription(s) and 6 (6.1%) were not indicated. Twenty-one (21.2%) patients opted out of ambulatory referral follow-ups with primary care and/or tobacco treatment program; one (1.0%) was not indicated for referral. Nineteen (32.8%) patients who received prescription(s) for smoking cessation-related medications initially also followed the prescription(s). Seventeen (22.1%) patients participated in referral follow-up. CONCLUSION: In this small ED pilot, using the STIR concepts in an opt-out method, few smokers opted out of the smoking cessation intervention. About one-third of the patients declined prescriptions for smoking cessation-related medications and less than one-quarter declined ambulatory referrals for follow-up. These findings support a willingness of patients to participate in STIR and the benefits of intervention in this setting.

Investing in New Technology in Pulmonary Medicine: Navigating the Tortuous Path to Success.

The introduction of new technologies offers the promise to advance medicine. This occurs alongside improved efforts to control costs of health care by hospital administrators, the Centers for Medicare & Medicaid Services' (CMS) pivot to value programs, and commercial payers' efforts to reduce reimbursement. These trends present a challenge for the pulmonologist, among others, who must navigate increasingly complex and highly scrutinized evaluation processes used to secure new technology (NT). Health-care providers are turning toward value assessments while simultaneously tasked with the mission of offering state of the art technologies and services. Pulmonologists desiring NT are thus faced with increased scrutiny in their evaluation of costs and clinical data to support investments. Consideration of this scrutiny and further evidence to temper the evaluation will improve the likelihood of adoption and patient access to clinically impactful technology. The identification of this evidence may provide a comprehensive view of the clinical and economic benefits of such technologies to both administrators and pulmonary clinicians. It is imperative that all parties involved in the decision process work collaboratively to deploy value added and clinically impactful technologies. Although a physician group might invest in such NT, the capital required often leads such decisions to a larger organization such as a hospital, health-care system, or privately owned entity. This article aims to provide a framework for pulmonary clinicians to better understand the processes that purchasers use to evaluate NT, the pressures that influence their consideration, and what resources may be leveraged toward success.

Effectiveness of a thoracic multidisciplinary clinic in the treatment of stage III non-small-cell lung cancer.

INTRODUCTION: The Institute of Medicine, the American Society of Clinical Oncology, and the European Society of Medical Oncology promote a multidisciplinary approach for the treatment of cancer. Stage III non-small-cell lung cancer (NSCLC) represents a heterogeneous group of diseases necessitating coordination of care among medical, radiation, and surgical oncology. The optimal care of stage III NSCLC underscores the need for a multidisciplinary approach. METHODS: From tumor registry data, we identified all cases of stage III NSCLC seen at Lehigh Valley Health Network between March 2010 and March 2013. The care received by patients when seen in the thoracic multidisciplinary clinic (MDC) was compared with the care received when not seen in the thoracic MDC. RESULTS: All patients seen in the MDC, compared to <50% of patients seen outside the MDC, were evaluated by more than one physician prior to beginning the treatment. Time to initiate treatment was shorter in MDC patients than in non-MDC patients. Patients seen in the MDC had a greater concordance with clinical pathways. A greater percentage of patients seen in the thoracic MDC had pathologic staging of their mediastinum. Patients seen in the MDC were more likely to receive all of their care at Lehigh Valley Health Network. CONCLUSION: Multidisciplinary care is essential in the treatment of patients with stage III NSCLC. Greater utilization of MDCs for this complex group of patients will result in more efficient coordination of care, pretreatment evaluation, and therapy, which in turn should translate to improve patients' outcomes.

Stent-mediated gene delivery for site-specific transgene administration to the airway epithelium and management of tracheobronchial tumors.

BACKGROUND: Gene therapy is currently under investigation as a means of managing a variety of pulmonary diseases. Unfortunately, gene transfer to bronchial epithelium has been hampered by the lack of stable and efficient transduction. Recent studies have shown that gene vectors could be tethered to the metallic surfaces of intra-arterial stents. This approach enables efficacious and site-specific adenoviral gene delivery to the vascular endothelium. OBJECTIVES: We hypothesized that airway mesh stents impregnated with viral gene vectors could be used for local gene delivery to benign and malignant bronchial epithelium. METHODS: Serotype 5 adenoviral vectors (Ad5, E1-/E3-) containing the reporter genes green fluorescent protein (Ad.GFP) or ß-galactoside/LacZ (Ad.LacZ), or a therapeutic gene, Ad.INF-ß, were coupled to either metallic mesh disks or stents via anti-Ad knob antibodies. These platforms were assessed for their ability to transfect bronchial epithelial cells from both rats and humans, as well as murine (L1C2) and human (A549) lung cancer cell lines. Gene transfer was quantified by fluorescent microscopy, scanning fluorimetry for Ad.GFP, and light microscopy studies assessing ß-galactosidase staining for Ad.LacZ. Metallic mesh and stent-mediated gene transfer was also performed in a murine flank tumor model and in a rat endotracheal tumor model in order to evaluate the therapeutic potential. RESULTS: In these studies, murine and human non-small cell lung cancer (NSCLC) cells were successfully transfected with reporter genes in vitro. Ad.LacZ-complexed mesh successfully transfected reporter genes into established murine flank NSCLC tumors. In addition, Ad.LacZ-tethered stents could effectively transfect both tracheobronchial epithelium and submucosal glands in rats. Similar epithelial transfection was achieved in ex vivo human bronchial epithelium. Pilot in vivo experimentation provided data supporting the concept that therapeutic genes could also be delivered with this technology. In additional pilot in vivo experiments, the growth of murine flank tumors was inhibited by placement of mesh disks coupled with Ad.muINF-ß, and rats bearing endotracheal tumors demonstrated a trend towards prolonged survival with insertion of Ad.ratINF-ß-tethered stents. CONCLUSIONS: Stent-mediated gene delivery successfully enabled site-specific vector administration to target rat and human airway cells in cell culture, organ culture and in vivo. Local tracheobronchial gene delivery via stents could provide a viable clinical solution for overcoming the difficulties encountered with vector delivery within the lungs, in particular by lowering requisite vector titers and by directing desired vectors to areas of interest. This strategy may prove valuable for treating tumors involving the tracheobronchial tree, as well as other nonmalignant tracheobronchial disorders.

Clinical and financial considerations for implementing an ICU telemedicine program.

As the population in the United States increases and ages, the need to provide high-quality, safe, and cost-effective care to the most critically ill patients will be of great importance. With the projected shortage of intensivists, innovative changes to improve efficiency and increase productivity will be necessary. Telemedicine programs in the ICUs (tele-ICUs) are a successful strategy to improve intensivist access to critically ill patients. Although significant capital and maintenance costs are associated with tele-ICUs, these costs can be offset by indirect financial benefits, such as decreased length of stay. To achieve the positive clinical outcomes desired, tele-ICUs must be carefully designed and implemented. In this article, we discuss the clinical benefits of tele-ICUs. We review the financial considerations, including direct and indirect reimbursement and development and maintenance costs. Finally, we review design and implementation considerations for tele-ICUs.

Transbronchial needle injection: a systematic review of a new diagnostic and therapeutic paradigm.

BACKGROUND AND OBJECTIVE: Transbronchial needle catheters are commonly used during flexible and rigid bronchoscopy for needle aspiration. The use of these catheters can be expanded by employing the technique of transbronchial needle injection. METHODS AND RESULTS: By injecting lesions in the airways, peribronchial structures, mediastinum, or lung parenchyma, transbronchial needle injection has been applied to the treatment of lung cancer, inflammatory disorders of the airways, recurrent respiratory papillomatosis, as well as bronchopleural fistulas. Diagnostic applications have included the localization of peripheral lung nodules as well as sentinel lymph nodes. CONCLUSIONS: Our review defines this bronchoscopic technique and summarizes its various reported applications.

Treatment of lung cancer using clinically relevant oral doses of the cyclooxygenase-2 inhibitor rofecoxib: potential value as adjuvant therapy after surgery.

OBJECTIVE: To investigate the uses and limitations of cyclooxygenase- (COX) 2 inhibition using clinically relevant doses of oral rofecoxib in the treatment of murine models of non-small-cell lung cancer (NSCLC). SUMMARY BACKGROUND DATA: Overexpression of COX-2 has been reported in lung cancer. Several studies have demonstrated that high doses of COX-2 inhibitors could inhibit the growth of rodent and human lung cancer cell lines. The potential uses and limitations of COX-2 inhibition at doses equivalent to those currently approved for use in humans have not been well studied. METHODS: Three murine NSCLC cell lines were injected into the flanks of mice to establish tumor xenografts. Mice were treated orally with low doses of a COX-2 inhibitor (rofecoxib chow, 0.0075%). Mechanisms were evaluated by analysis of tumor-infiltrating lymphocytes. To study rofecoxib as adjuvant therapy, large established tumors (14-18 days after tumor inoculation) were surgically debulked and animals were treated with rofecoxib starting 3 days before surgery. Recurrence of the tumor after debulking was monitored. RESULTS: Rofecoxib significantly slowed the growth of small (0-120 mm) tumors (P < 0.01-0.05) in all 3 cell lines, with higher efficacy in the more immunogenic tumors. Minimal responses were noted in larger tumors. Rofecoxib appeared to augment CD8 T cell infiltration in immunogenic tumors. Rofecoxib significantly reduced the recurrence rate after debulking (P < 0.01). CONCLUSIONS: Clinically relevant doses of the COX-2 inhibitor rofecoxib given orally were effective in inhibiting the growth of small (but not large) tumors in 3 murine NSCLC cell lines tested and in preventing recurrences after surgical debulking. Depending on the immunogenicity of human tumors, COX-2 inhibition might be useful as adjuvant therapy for surgically resectable NSCLC.

Immuno-gene therapy with interferon-beta before surgical debulking delays recurrence and improves survival in a murine model of malignant mesothelioma.

OBJECTIVES: Immuno-gene therapy of mesothelioma with an adenovirus encoding interferon-beta mediated strong antitumor responses in murine models with low but not high tumor burden. Our goals were to determine the mechanisms responsible for this loss of efficacy and to test the hypothesis that the combination of preoperative adenovirus encoding interferon-beta and surgical resection would be effective in treating bulky tumors. METHODS: Flank tumors of a mouse mesothelioma cell line were treated with adenovirus encoding interferon-beta or adenoviral vector encoding the bacterial protein beta-galactosidase. Cytotoxic T lymphocytes and tumor infiltration by T lymphocytes were measured. Tumors were surgically excised 72 hours later and tumor cells were injected in the contralateral flank to create a model of a metastatic focus. Tumor-free survival and distant metastatic disease were assessed. RESULTS: Immuno-gene therapy effectively treated small tumors (<200 mm(3)) but did not reduce the size of large (>800 mm(3)) flank tumors. Although treatment with adenovirus encoding interferon-beta resulted in the generation of tumor-neutralizing splenocytes in large tumors, the number of T cells visualized within the tumors was minimal. Tumors treated with adenovirus encoding interferon-beta (versus adenoviral vector encoding the bacterial protein beta-galactosidase or phosphate-buffered saline solution) prior to debulking increased long-term tumor-free survival and resulted in two- to sixfold smaller foci of implanted tumor cells at 2 weeks postoperatively. CONCLUSIONS: The use of adenovirus encoding interferon-beta or surgical debulking alone is ineffective in treating large tumors, but combining preoperative adenovirus encoding interferon-beta and surgical debulking significantly reduces tumor recurrence and improves long-term tumor-free survival. We postulate that adenovirus encoding interferon-beta amplifies the cytotoxic T-lymphocyte antitumor response, allowing elimination of residual tumor cells.

Endobronchial gene therapy.

Gene therapy for pulmonary disease, a field still in the experimental stage, has nonetheless progressed considerably in the past decade. There have been significant advances in pre-clinical studies, as well as important developments resulting from multiple early-phase human clinical trials for a variety of respiratory disorders. Although there are several ways of delivering therapeutic genes to the lungs, the primary delivery modality remains flexible bronchoscopy. The flexible bronchoscope, because of its unique access to both large and small airways, serves as an ideal instrument to deliver therapeutic genes to the tracheobronchial tree, even to small airways and alveoli that are beyond the reach of the bronchoscope. In addition, bronchoscopic gene delivery has the capacity to treat pulmonary vascular disorders because delivery of marker and therapeutic genes via the airways has been demonstrated to successfully transduce the pulmonary vascular endothelium. This article describes the various methods and disease targets of bronchoscopically mediated gene therapy, focusing in particular on the results of clinical studies and providing a glimpse into the future of the field.

Differentially expressed apoptotic genes in early stage lung adenocarcinoma predicted by expression profiling.

OBJECTIVE: In undiseased lung epithelial cells, apoptosis is an evolutionarily conserved and genetically regulated form of cell suicide which plays an important role in development and in the maintenance of tissue homeostasis. Neoplastic lung cells develop the ability to deregulate growth by alterations in these genes which control apoptosis. Genomic profiling was used to compare gene expression levels in early stage lung adenocarcinomas and nonneoplastic pulmonary tissue in order to comprehensively identify alterations in the process of apoptosis. METHODS: RNA extracted from node negative, poorly differentiated lung adenocarcinomas (15 patients) and nonneoplastic pulmonary tissue (5 patients) was hybridized to oligonucleotide microarray filters containing 44,363 genes. Ontological classification was used to extract genes involved with apoptosis. Further analysis discovered a subset of differentially expressed genes for further study. RESULTS: Of the 308 apoptotic genes on the microarray filters, 24 genes were predicted to be differentially expressed in lung adenocarcinomas. Alterations in several genes (i.e., Akt, BcL-xL, PTEN, FAS) are consistent with the literature. We also identified 10 novel genes that have not been described in nonsmall cell lung cancer (i.e., RIP, Caspase 1, PDK-1). CONCLUSIONS: These results identified several potential apoptotic genes altered in lung cancer.

Alterations in cell cycle genes in early stage lung adenocarcinoma identified by expression profiling.

In normal lung epithelial cells, cellular division is an ordered, tightly regulated process involving multiple checkpoints that assess extracellular growth signals, cell size, and DNA integrity. In contrast, neoplastic lung cells develop the ability to bypass several of these checkpoints, particularly at the G1/S and G2/M boundaries. We used genomic profiling to compare gene expression levels in early stage lung adenocarcinomas and non-neoplastic pulmonary tissue in order to comprehensively identify alterations in the process of cell cycling. RNA extracted from node negative, poorly differentiated lung adenocarcinomas (15 patients) and non-neoplastic pulmonary tissue (5 patients) was hybridized to oligonu-cleotide microarray filters containing 44,363 genes. Ontological classification was used to extract genes involved with cell cycle progression. Further analysis discovered a subset of differentially expressed genes for further study. Of the 624 cell cycle genes on the microarray filters, 40 genes were predicted to be differentially expressed in lung adeno-carcinomas. Alterations in several genes (i.e., cyclin B1, cyclin D1, p21, MDM2) are consistent with published data in the literature. We also identified 19 novel genes that have neither been described in non-small cell lung cancer (i.e., cdc2, cullin 4A, ZAC, p57, DP-1, GADD45, PISSLRE, cdc20) nor in any other tumors (i.e., cyclin F, cullin 5, p34). These results identified several potential cell cycle genes altered in lung cancer.