A High-Reliability Organization Framework for Health Care: A Multiyear Implementation Strategy and Associated Outcomes.

OBJECTIVES: Applying high-reliability organization (HRO) principles to health care is complex. No consensus exists as to an effective framework for HRO implementation or the direct impact of adoption. METHODS: The Veterans Health Administration (VHA) National Center for Patient Safety established the high-reliability hospital (HRH) model for HRO adoption and piloted HRH in collaboration with the Truman VA Medical Center (Truman) during a 3-year intervention period (January 1, 2016-December 31, 2018). High-reliability hospital components are as follows: annual patient safety (PS) assessment, annual PS culture survey, annual root cause analysis training, daily leadership walk-arounds, monthly PS forum, annual processes standardization review, Just Culture training, unit-based Clinical Team Training, unit-based continuous improvement projects, and annual Clinical Team Training simulation education. The impact of HRH was examined using a PS Culture Survey, PS event reporting, and quality outcomes of standardized mortality rate and complication rate. RESULTS: Truman internally improved PS culture and PS event reporting rates resulting in outcomes better than all VHA facilities (All VHA; P < 0.001 and P < 0.001, respectively). Low-harm PS event reporting increased (P < 0.001); however, serious safety event rate remained unchanged versus All VHA. Significant improvement in Truman standardized mortality rate and complication rate versus All VHA occurred immediately and were sustained through intervention (slopes, P < 0.001 and P < 0.020; respectively). CONCLUSIONS: High-reliability hospital is an effective framework for HRO implementation and will be applied to 18 additional VHA sites. Based on these results, the expected outcome will be improved PS culture and overall PS event reporting. The impact of HRH on serious safety event rate and quality measures requires further study.

Discharge independence with minimally invasive lobectomy.

BACKGROUND: The effects of video-assisted thoracic surgery (VATS) pulmonary lobectomy on after-hospital care are not well known. METHODS: In a retrospective case-control study, 20 consecutive VATS cases were matched to 38 standard thoracotomies (open cases). RESULTS: Ages were 73.8 +/- 7.8 years with no initial differences between the groups. No hospital deaths occurred. Excluding 2 VATS and 6 open outliers, VATS cases had fewer hospital days (4.6 +/- 1.9 vs. 6.4 +/- 2.2, P <0.01), chest tube days (3.0 +/- 1.1 vs. 4.2 +/- 1.7, P = 0.01), and prolonged pain complaints (28% vs. 56%, P = 0.05). Transfer to care facilities or home nursing support was needed for 63% of open patients and only 20% of VATS patients (P = 0.015). Less personal care (10% vs. 21%), wound/medical care (0% vs. 13%), occupational/physical therapy (5% vs. 13%), or other home support (5% vs. 18%) was needed for VATS patients. CONCLUSIONS: In older populations, more independence and fewer resources after discharge favor VATS lobectomy over standard thoracotomy.

Upregulation of the tissue inhibitor of metalloproteinase-1 protein is associated with progression of human non-small-cell lung cancer.

PURPOSE: Tissue inhibitors of metalloproteinases (TIMPs) are naturally occurring inhibitors of matrix metalloproteinases (MMPs). It has been shown that TIMP-1 may be a multifunctional protein. Little is known about the role of TIMP-1 in progression and metastasis of human lung cancer (tumor inhibiting or tumor promoting), although studies using a variety of techniques have analyzed the expression of TIMP-1 mRNA and/or protein in human cancers. PATIENTS AND METHODS: We examined the expression of TIMP-1 protein by immunohistochemistry in patients (n = 160) with primary respectable (stage I to IIIA) non-small-cell lung cancer (NSCLC). RESULTS: Twenty-seven percent of the tumors (43 of 160) demonstrated elevated expression of this protein. We demonstrate that overexpression of TIMP-1 protein is associated with an adverse outcome. In addition, disease stage, patient's age, and performance status were all significantly related to survival. In multivariate analyses, patients with high TIMP-1 expression had a 90% increased risk of death when compared with those with low expression (relative risk, 1.92; 95% CI, 1.19 to 3.09; P =.008). TIMP-1 expression did not correlate with expression of MMP-2 and MMP-9. CONCLUSION: These results suggest that TIMP-1, independent of its inhibiting activity of MMPs, may have other function(s) critical for NSCLCs. The significance of our results is two-fold. The adverse outcome in patients with overexpression of TIMP-1 indicates its potential prognostic value in NSCLC. Thus, TIMP-1 overexpression may serve to help identify patients with particularly aggressive disease for adjuvant treatments. In addition, the TIMP-1 molecule may represent a novel therapeutic target for treatment of some NSCLCs.

Photodynamic therapy for sarcoma pulmonary metastases: a preclinical toxicity study.

BACKGROUND: Intraoperative pleural and interstitial PDT accompanying resection may reduce peripheral micrometastatic foci and preclude lobectomy when applied to hilar lesions. MATERIALS AND METHODS: Fourteen beagles were used to determine the safety and histologic changes resulting from PDT. Photosensitizers HPPH (0.3 mg/kg) or Photofrin (2.0 mg/kg) were administered i.v. 48 hours prior to thoracotomy and light delivery. At thoracotomy interstitial or pleural light was given. They underwent necropsy at eight and 30 days. RESULTS: The significant toxicitities occurred with pleural PDT using high dose HPPH (15 & 30 J/cm2) including pyrexia, elevated WBC and CPK, and respiratory distress. However, using single beam pleural surface treatment all light doses for HPPH and Photofrin (5-40 J/cm2) were tolerated with depths of treatment effect up to 10 mm with HPPH. CONCLUSION: Histologic and clinical changes associated with interstitial and pleural PDT were acceptable after dosimetry was adjusted. PDT holds promise as an adjuvant treatment for sarcoma pulmonary metastases.

Human CD4+ T cells present within the microenvironment of human lung tumors are mobilized by the local and sustained release of IL-12 to kill tumors in situ by indirect effects of IFN-gamma.

By implanting nondisrupted pieces of human lung tumor biopsy tissues into SCID mice, it has been possible to establish viable grafts of the tumor, as well as the tumor-associated microenvironment, including inflammatory cells, fibroblasts, tumor vasculature, and the extracellular matrix. Using this xenograft model, we have evaluated and characterized the effects of a local and sustained release of human rIL-12 (rhIL-12) from biodegradable microspheres. In response to rhIL-12, the human CD45+ inflammatory cells present within the xenograft mediate the suppression or the complete arrest of tumor growth in SCID mice. Analysis of the cellular events reveals that human CD4+ and CD8+ T cells are induced by rhIL-12 to produce and secrete IFN-gamma. Serum levels of human IFN-gamma in mice bearing rhIL-12-treated tumor xenografts correlate directly with the degree of tumor suppression, while neutralizing Abs to human IFN-gamma abrogate the IL-12-mediated tumor suppression. Gene expression profiling of tumors responding to intratumoral rhIL-12 demonstrates an up-regulation of IFN-gamma and IFN-gamma-dependent genes not observed in control-treated tumors. Genes encoding a number of proinflammatory cytokines, chemokines (and their receptors), adhesion molecules, activation markers, and the inducible NO synthase are up-regulated following the introduction of rhIL-12, while genes associated with tumor growth, angiogenesis, and metastasis are decreased in expression. NO contributes to the tumor killing because an inhibitor of inducible NO synthase prevents IL-12-induced tumor suppression. Cell depletion studies reveal that the IL-12-induced tumor suppression, IFN-gamma production, and the associated changes in gene expression are all dependent upon CD4+ T cells.

The evolution of lung cancer screening.

In the 1970s, four trials failed to demonstrate any mortality reduction using a combination of chest X-ray (CXR) and/or sputum cytology. The recent early lung cancer action project (ELCAP) demonstrated that modern screening is capable of detecting Stage I lung cancers. Bronchial epithelial changes leading up to cancers are now being understood to include histologic changes and genetic alterations. Emerging molecular markers detected in sputum and serum show promise in the future of lung cancer screening.

Pulmonary lymphatic mapping in dogs: use of technetium sulfur colloid and isosulfan blue for pulmonary sentinel lymph node mapping in dogs.

Lung cancer is the most frequent cause of cancer death in the United States. The pattern of regional lymph node involvement is a major prognostic factor in a patient with nonsmall cell lung cancer. The accuracy of information obtained about the lymph node status of lung cancer patients can be potentially increased by sentinel node lymphatic mapping. This technique has been well studied in melanoma and breast cancer. It may be useful in increasing the detection of micrometastases and in decreasing the morbidity from complete mediastinal lymphadenectomy. We report an animal pilot study of pulmonary lymphatic mapping. The aim of our study was to gain experience in the surgical techniques for pulmonary sentinel node lymphatic mapping in an animal model prior to its application in humans. Technetium sulfur colloid and isosulfan blue dye were injected into different lobes of the lung followed by attempts to identify the sentinel node draining that specific portion of the lung. Technetium sulfur colloid identified the sentinel node in five of six dogs within 20 min after the radiotracer was injected into the lung parenchyma. Isosulfan blue dye identified the sentinel node in three of six dogs within 5 min. Both the agents are potentially useful, but we found greater technical ease in identifying the sentinel node with technetium sulfur colloid. Two single-institution pilot studies in humans have been performed. A multicentered study to validate and further refine this technique is necessary. Advanced pathologic techniques such as immunohistochemistry and reverse transcriptase-polymerase chain reaction can be used to enhance the accuracy of staging. This may facilitate proper application of novel therapeutic strategies to improve the current dismal prognosis of this disease.