Pancreatic Cancer Action Network's SPARK: A Cloud-Based Patient Health Data and Analytics Platform for Pancreatic Cancer.

PURPOSE: Pancreatic cancer currently holds the position of third deadliest cancer in the United States and the 5-year survival rate is among the lowest for major cancers at just 12%. Thus, continued research efforts to better understand the clinical and molecular underpinnings of pancreatic cancer are critical to developing both early detection methodologies as well as improved therapeutic options. This study introduces Pancreatic Cancer Action Network's (PanCAN's) SPARK, a cloud-based data and analytics platform that integrates patient health data from the PanCAN's research initiatives and aims to accelerate pancreatic cancer research by making real-world patient health data and analysis tools easier to access and use. MATERIALS AND METHODS: The SPARK platform integrates clinical, molecular, multiomic, imaging, and patient-reported data generated from PanCAN's research initiatives. The platform is built on a cloud-based infrastructure powered by Velsera. Cohort exploration and browser capabilities are built using Velsera ARIA, a specialized product for leveraging clinicogenomic data to build cohorts, query variant information, and drive downstream association analyses. Data science and analytic capabilities are also built into the platform allowing researchers to perform simple to complex analysis. RESULTS: Version 1 of the SPARK platform was released to pilot users, who represented diverse end users, including molecular biologists, clinicians, and bioinformaticians. Included in the pilot release of SPARK are deidentified clinical (including treatment and outcomes data), molecular, multiomic, and whole-slide pathology images for over 600 patients enrolled in PanCAN's Know Your Tumor molecular profiling service. CONCLUSION: The pilot release of the SPARK platform introduces qualified researchers to PanCAN real-world patient health data and analytical resources in a centralized location.

Cost-Effectiveness Analysis of Lung Cancer Screening Accounting for the Effect of Indeterminate Findings.

BACKGROUND: Numerous health policy organizations recommend lung cancer screening, but no consensus exists on the optimal policy. Moreover, the impact of the Lung CT screening reporting and data system guidelines to manage small pulmonary nodules of unknown significance (a.k.a. indeterminate nodules) on the cost-effectiveness of lung cancer screening is not well established. METHODS: We assess the cost-effectiveness of 199 screening strategies that vary in terms of age and smoking eligibility criteria, using a microsimulation model. We simulate lung cancer-related events throughout the lifetime of US-representative current and former smokers. We conduct sensitivity analyses to test key model inputs and assumptions. RESULTS: The cost-effectiveness efficiency frontier consists of both annual and biennial screening strategies. Current guidelines are not on the frontier. Assuming 4% disutility associated with indeterminate findings, biennial screening for smokers aged 50-70 years with at least 40 pack-years and less than 10 years since smoking cessation is the cost-effective strategy using $100 000 willingness-to-pay threshold yielding the highest health benefit. Among all health utilities, the cost-effectiveness of screening is most sensitive to changes in the disutility of indeterminate findings. As the disutility of indeterminate findings decreases, screening eligibility criteria become less stringent and eventually annual screening for smokers aged 50-70 years with at least 30 pack-years and less than 10 years since smoking cessation is the cost-effective strategy yielding the highest health benefit. CONCLUSIONS: The disutility associated with indeterminate findings impacts the cost-effectiveness of lung cancer screening. Efforts to quantify and better understand the impact of indeterminate findings on the effectiveness and cost-effectiveness of lung cancer screening are warranted.

Enteral Access Procedures: An 18-Year Analysis of Changing Patterns of Utilization in the Medicare Population.

PURPOSE: To evaluate national trends in enteral access and maintenance procedures for Medicare beneficiaries with regard to utilization rates, specialty group roles, and sites of service. MATERIALS AND METHODS: Using Medicare Physician Supplier Procedure Summary Master Files for the period 1994-2012, claims for gastrostomy and gastrojejunostomy access and maintenance procedures were identified. Longitudinal utilization rates were calculated using annual enrollment data. Procedure volumes by site of service and medical specialty were analyzed. RESULTS: Between 1994 and 2012, de novo enteral access procedure utilization decreased from 61.6 to 42.3 per 10,000 Medicare Part B beneficiaries (-31%). Gastroenterologists and surgeons performed > 80% of procedures (unchanged over study period) with 97% in the hospital setting. Over time, relative use of an endoscopic approach (62% in 1994; 82% in 2012) increased as percutaneous (21% to 12%) and open surgical (17% to 5%) procedures declined. Existing enteral access maintenance services increased 29% (from 20.1 to 25.9 per 10,000 beneficiaries). Radiologists (from 13% to 31%) surpassed gastroenterologists (from 36% to 21%) as dominant providers of maintenance procedures. Emergency physicians (from 8% to 23%) and nonphysician providers (from 0% to 6%) have seen rapid growth as maintenance services providers as these services have transitioned increasingly to the emergency department setting (from 18% to 32%). CONCLUSIONS: Among Medicare beneficiaries, de novo enteral access procedures have declined in the last 2 decades as existing access maintenance services have increased. The latter are increasingly performed by radiologists, emergency physicians, and nonphysician providers.

Comparison of the diagnostic value of MR imaging and ophthalmoscopy for the staging of retinoblastoma.

PURPOSE: To compare the diagnostic value of magnetic resonance (MR) imaging and ophthalmoscopy for staging of retinoblastoma. METHODS: MR and ophthalmoscopic images of 36 patients who underwent enucleation were evaluated retrospectively following institutional review board approval. Histopathology being the standard of reference, the sensitivity and specificity of both diagnostic modalities were compared regarding growth pattern, iris neoangiogenesis, retinal detachment, vitreous seeds and optic nerve invasion. Data were analysed via McNemar's test. RESULTS: Both investigations showed no significant difference in accuracy for the detection of different tumour growth patterns (P = 0.80). Vitreous seeding detection was superior by ophthalmoscopy (P < 0.001). For prelaminar optic nerve invasion, MR imaging showed similar sensitivity as ophthalmoscopy but increased specificity of 40 % (CI 0.12-0.74) vs. 20 % (0.03-0.56). MR detected optic nerve involvement past the lamina cribrosa with a sensitivity of 80 % (0.28-0.99) and a specificity of 74 % (0.55-0.88). The absence of optic nerve enhancement excluded histopathological infiltration, but the presence of optic nerve enhancement included a high number of false positives (22-24 %). CONCLUSIONS: Ophthalmoscopy remains the method of choice for determining extent within the globe while MR imaging is useful for evaluating extraocular tumour extension. Thus, both have their own strengths and contribute uniquely to the staging of retinoblastoma. KEY POINTS: • Ophthalmoscopy: method of choice for determining extent of retinoblastoma within the globe. • MR imaging provides optimal evaluation of extrascleral and extraocular tumour extension. • Positive enhancement of the optic nerve on MRI does not necessarily indicate involvement.

Improving safety in the operating room: a systematic literature review of retained surgical sponges.

PURPOSE OF REVIEW: Gossypibomas are surgical sponges that are unintentionally left inside a patient during a surgical procedure. To improve this patient safety indicator, anesthesiologists will need to work with operating room personnel. This study's goal was to systematically review the literature on retained sponges to identify body location, time to discovery, methods for detection, and risk factors. RECENT FINDINGS: Two hundred and fifty-four gossypiboma cases (147 reports from the period 1963-2008) were identified via the National Library of Medicine's Medline and the Cochrane Library. Gossypibomas (mean patient age 49 years, range 6-92 years) were most commonly found in the abdomen (56%), pelvis (18%), and thorax (11%). Average discovery time equaled 6.9 years (SD 10.2 years) with a median (quartiles) of 2.2 years (0.3-8.4 years). The most common detection methods were computed tomography (61%), radiography (35%), and ultrasound (34%). Pain/irritation (42%), palpable mass (27%), and fever (12%) were the leading signs and symptoms, but 6% of cases were asymptomatic. Complications included adhesion (31%), abscess (24%), and fistula (20%). Risk factors were case specific (e.g. emergency) or related to the surgical environment (e.g. poor communication). Most gossypibomas occurred when the sponge count was falsely pronounced correct at the end of surgery. SUMMARY: More is being discovered about the patterns leading to a retained sponge. Multidisciplinary approaches and new technologies may help reduce this low frequency but clinically significant event. However, given the complexity of surgical care, eliminating retained sponges may prove elusive.

Ritonavir inhibition of calcium-activated neutral proteases.

Calpains (EC 3.4.22.17) are intracellular calcium-activated cysteine proteases that mediate tissue injury following post-ischemic and post-traumatic stress. Both human HIV protease and calpains share a similar secondary structure, where the active site is flanked by hydrophobic regions. The present study demonstrates that ritonavir, a hydrophobic HIV protease inhibitor, also inhibits calpain activity. In PC12 cell extracts assayed for calpain at maximal activity (2mM calcium), ritonavir exhibited competitive inhibition with a K(i) of 11+/-7.0 microM. Experiments with purified enzymes showed inhibition for both m- and mu-calpain isoforms (m-calpain, K(i)=9.2+/-1.2 microM; mu-calpain, K(i)=5.9+/-1.4 microM). Ritonavir also inhibited calcium-stimulated calpain activity in PC12 cells in situ. These results suggest that ritonavir or analogues of the drug should be investigated as cytoprotective agents in conditions where cell death or injury is mediated via calpain activation.