Implementation of Perioperative Music Using the Consolidated Framework for Implementation Research.

BACKGROUND: Complementary integrative health therapies have a perioperative role in the reduction of pain, analgesic use, and anxiety, and increasing patient satisfaction. However, long implementation lags have been quantified. The Consolidated Framework for Implementation Research (CFIR) can help mitigate this translational problem. METHODS: We reviewed evidence for several nonpharmacological treatments (CFIR domain: characteristics of interventions) and studied external context and organizational readiness for change by surveying providers at 11 Veterans Affairs (VA) hospitals (domains: outer and inner settings). We asked patients about their willingness to receive music and studied the association between this and known risk factors for opioid use (domain: characteristics of individuals). We implemented a protocol for the perioperative use of digital music players loaded with veteran-preferred playlists and evaluated its penetration in a subgroup of patients undergoing joint replacements over a 6-month period (domain: process of implementation). We then extracted data on postoperative recovery time and other outcomes, comparing them with historic and contemporary cohorts. RESULTS: Evidence varied from strong and direct for perioperative music and acupuncture, to modest or weak and indirect for mindfulness, yoga, and tai chi, respectively. Readiness for change surveys completed by 97 perioperative providers showed overall positive scores (mean >0 on a scale from -2 to +2, equivalent to >2.5 on the 5-point Likert scale). Readiness was higher at Durham (+0.47) versus most other VA hospitals (range +0.05 to +0.63). Of 3307 veterans asked about willingness to receive music, approximately 68% (n = 2252) answered "yes." In multivariable analyses, a positive response (acceptability) was independently predicted by younger age and higher mean preoperative pain scores (>4 out of 10 over 90 days before admission), factors associated with opioid overuse. Penetration was modest in the targeted subset (39 received music out of a possible 81 recipients), potentially reduced by device nonavailability due to diffusion into nontargeted populations. Postoperative recovery time was not changed, suggesting smooth integration into workflow. CONCLUSIONS: CFIR-guided implementation of perioperative music was feasible at a tertiary VA hospital, with moderate penetration in a high-risk subset of patients. Use of digital music players with preferred playlists was supported by strong evidence, tension for change, modest readiness among providers, good acceptability among patients (especially those at risk for opioid overuse), and a protocolized approach. Further study is needed to identify similar frameworks for effective knowledge-translation activities.

Oncogene-dependent control of miRNA biogenesis and metastatic progression in a model of undifferentiated pleomorphic sarcoma.

Undifferentiated pleomorphic sarcoma (UPS) is one of the most common soft tissue malignancies. Patients with large, high-grade sarcomas often develop fatal lung metastases. Understanding the mechanisms underlying sarcoma metastasis is needed to improve treatment of these patients. Micro-RNAs (miRNAs) are a class of small RNAs that post-transcriptionally regulate gene expression. Global alterations in miRNAs are frequently observed in a number of disease states including cancer. The signalling pathways that regulate miRNA biogenesis are beginning to emerge. To test the relevance of specific oncogenic mutations in miRNA biogenesis in sarcoma, we used primary soft tissue sarcomas expressing either Braf(V600E) or Kras(G12D). We found that Braf(V600E) mutant tumours, which have increased MAPK signalling, have higher levels of mature miRNAs and enhanced miRNA processing. To investigate the relevance of oncogene-dependent alterations in miRNA biogenesis, we introduced conditional mutations in Dicer and showed that Dicer haploinsufficiency promotes the development of distant metastases in an oncogene-dependent manner. These results demonstrate that a specific oncogenic mutation can cooperate with mutation in Dicer to promote tumour progression in vivo.

A novel imaging system permits real-time in vivo tumor bed assessment after resection of naturally occurring sarcomas in dogs.

BACKGROUND: Treatment of soft tissue sarcoma (STS) includes complete tumor excision. However, in some patients, residual sarcoma cells remain in the tumor bed. We previously described a novel hand-held imaging device prototype that uses molecular imaging to detect microscopic residual cancer in mice during surgery. QUESTIONS/PURPOSES: To test this device in a clinical trial of dogs with naturally occurring sarcomas, we asked: (1) Are any adverse clinical or laboratory effects observed after intravenous administration of the fluorescent probes? (2) Do canine sarcomas exhibit fluorescence after administration of the cathepsin-activated probe? (3) Is the tumor-to-background ratio sufficient to distinguish tumor from tumor bed? And (4) can residual fluorescence be detected in the tumor bed during surgery and does this correlate with a positive margin? METHODS: We studied nine dogs undergoing treatment for 10 STS or mast cell tumors. Dogs received an intravenous injection of VM249, a fluorescent probe that becomes optically active in the presence of cathepsin proteases. After injection, tumors were removed by wide resection. The tumor bed was imaged using the novel imaging device to search for residual fluorescence. We determined correlations between tissue fluorescence and histopathology, cathepsin protease expression, and development of recurrent disease. Minimum followup was 9 months (mean, 12 months; range, 9-15 months). RESULTS: Fluorescence was apparent from all 10 tumors and ranged from 3 × 10(7) to 1 × 10(9) counts/millisecond/cm(2). During intraoperative imaging, normal skeletal muscle showed no residual fluorescence. Histopathologic assessment of surgical margins correlated with intraoperative imaging in nine of 10 cases; in the other case, there was no residual fluorescence, but tumor was found at the margin on histologic examination. No animals had recurrent disease at 9 to 15 months. CONCLUSIONS: These initial findings suggest this imaging system might be useful to intraoperatively detect residual tumor after wide resections. CLINICAL RELEVANCE: The ability to assess the tumor bed intraoperatively for residual disease has the potential to improve local control.

Intraoperative detection and removal of microscopic residual sarcoma using wide-field imaging.

BACKGROUND: The goal of limb-sparing surgery for a soft tissue sarcoma of the extremity is to remove all malignant cells while preserving limb function. After initial surgery, microscopic residual disease in the tumor bed will cause a local recurrence in approximately 33% of patients with sarcoma. To help identify these patients, the authors developed an in vivo imaging system to investigate the suitability of molecular imaging for intraoperative visualization. METHODS: A primary mouse model of soft tissue sarcoma and a wide field-of-view imaging device were used to investigate a series of exogenously administered, near-infrared (NIR) fluorescent probes activated by cathepsin proteases for real-time intraoperative imaging. RESULTS: The authors demonstrated that exogenously administered cathepsin-activated probes can be used for image-guided surgery to identify microscopic residual NIR fluorescence in the tumor beds of mice. The presence of residual NIR fluorescence was correlated with microscopic residual sarcoma and local recurrence. The removal of residual NIR fluorescence improved local control. CONCLUSIONS: The authors concluded that their technique has the potential to be used for intraoperative image-guided surgery to identify microscopic residual disease in patients with cancer.