Toward real-time reporting of cancer incidence: methodology, pilot study, and SEER Program implementation.

BACKGROUND: A lag time between cancer case diagnosis and incidence reporting impedes the ability to monitor the impact of recent events on cancer incidence. Currently, the data submission standard is 22 months after a diagnosis year ends, and the reporting standard is 27.5 months after a diagnosis year ends. This paper presents the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program's efforts to minimize the lag and achieve "real-time" reporting, operationalized as submission within 2 months from the end of a diagnosis year. METHODS: Technology for rapidly creating a consolidated tumor case (CTC) from electronic pathology (e-path) reports is described. Statistical methods are extended to adjust for biases in incidence rates due to reporting delays for the most recent diagnosis years. RESULTS: A registry pilot study demonstrated that real-time submissions can approximate rates obtained from 22-month submissions after adjusting for reporting delays. A plan to be implemented across the SEER Program rapidly ascertains unstructured e-path reports and uses machine learning algorithms to translate the reports into the core data items that comprise a CTC for incidence reporting. Across the program, cases were submitted 2 months after the end of the calendar year. Registries with the most promising baseline values and a willingness to modify registry operations have joined a program to become certified as real-time reporting. CONCLUSION: Advances in electronic reporting, natural language processing, registry operations, and statistical methodology, energized by the SEER Program's mobilization and coordination of these efforts, will make real-time reporting an achievable goal.

Machine learning and deep learning tools for the automated capture of cancer surveillance data.

The National Cancer Institute and the Department of Energy strategic partnership applies advanced computing and predictive machine learning and deep learning models to automate the capture of information from unstructured clinical text for inclusion in cancer registries. Applications include extraction of key data elements from pathology reports, determination of whether a pathology or radiology report is related to cancer, extraction of relevant biomarker information, and identification of recurrence. With the growing complexity of cancer diagnosis and treatment, capturing essential information with purely manual methods is increasingly difficult. These new methods for applying advanced computational capabilities to automate data extraction represent an opportunity to close critical information gaps and create a nimble, flexible platform on which new information sources, such as genomics, can be added. This will ultimately provide a deeper understanding of the drivers of cancer and outcomes in the population and increase the timeliness of reporting. These advances will enable better understanding of how real-world patients are treated and the outcomes associated with those treatments in the context of our complex medical and social environment.

SMS reminders to improve outpatient attendance for public dental services: A retrospective study.

Patients who miss scheduled appointments reduce clinical productivity and delay access to care for other patients. Reminders have improved attendance for healthcare appointments previously, but it is not known if short message service (SMS) implementation reduces incidence of patients unable to attend (UTA) or who fail to attend (FTA) appointments in the public dental service. This paper studied the effectiveness of SMS reminders in increasing appointment attendance at outpatient public dental services in Queensland. Data were sourced from the adult service and the children and adolescent oral health service (CAOHS) at West Moreton Hospital and Health Service, a public dental service in Queensland. A total of 63,238 appointments pre-implementation of SMS reminders and 55,028 appointments post-implementation over a period of 2 years were analysed for rates of attendance, UTA and FTA. Characteristics of UTA and FTA appointments were analysed to identify factors that hindered improvement after implementation of reminders. For the CAOHS, the attendance rate decreased 4% (95% CI: 2%, 6%) following SMS implementation. The UTA rate also increased by 20% (95% CI: 15%, 25%). Following SMS implementation in the adult service, the attendance rate increased from 73.5 (95% CI: 72.6, 74.4) to 77.7 (95% CI: 76.6-78.8) per 100 appointments. The FTA rate post-implementation was 1.08 (95% CI: 1.00, 1.16) times that from pre-intervention, and the UTA rate decreased from 21.7 (95% CI: 21.2, 22.2) to 17.1 (95% CI: 16.6, 17.7) per 100 appointments. The SMS reminders had a mixed effect on the attendance, UTA and FTA rates for the CAOHS and adult services. Reminders reduced the rates of UTA for the CAOHS service and increased the rate of attendance for the adult service. There was an increase in the FTA rate for both services.

Interrater and Test-Retest Reliability and Minimal Detectable Change of the Balance Evaluation Systems Test (BESTest) and Subsystems With Community-Dwelling Older Adults.

BACKGROUND AND PURPOSE: Falls are a common cause of injuries and hospital admissions in older adults. Balance limitation is a potentially modifiable factor contributing to falls. The Balance Evaluation Systems Test (BESTest), a clinical balance measure, categorizes balance into 6 underlying subsystems. Each of the subsystems is scored individually and summed to obtain a total score. The reliability of the BESTest and its individual subsystems has been reported in patients with various neurological disorders and cancer survivors. However, the reliability and minimal detectable change (MDC) of the BESTest with community-dwelling older adults have not been reported. The purposes of our study were to (1) determine the interrater and test-retest reliability of the BESTest total and subsystem scores; and (2) estimate the MDC of the BESTest and its individual subsystem scores with community-dwelling older adults. METHODS: We used a prospective cohort methodological design. Community-dwelling older adults (N = 70; aged 70-94 years; mean = 85.0 [5.5] years) were recruited from a senior independent living community. Trained testers (N = 3) administered the BESTest. All participants were tested with the BESTest by the same tester initially and then retested 7 to 14 days later. With 32 of the participants, a second tester concurrently scored the retest for interrater reliability. Testers were blinded to each other's scores. Intraclass correlation coefficients [ICC(2,1)] were used to determine the interrater and test-retest reliability. Test-retest reliability was also analyzed using method error and the associated coefficients of variation (CVME). MDC was calculated using standard error of measurement. RESULTS: Interrater reliability (N = 32) of the BESTest total score was ICC(2, 1) = 0.97 (95% confidence interval [CI], 0.94-0.99). The ICCs for the individual subsystem scores ranged from 0.85 to 0.94. Test-retest reliability (N = 70) of the BESTest total score was ICC(2,1) = 0.93 (95% CI, 0.89-0.96). ICCs for the individual subsystem scores ranged from 0.72 to 0.89. The CVME (N = 70) of the BESTest total score was 4.1%. The CVME for the subsystem scores ranged from 5.0% to 10.7%. MDC (N = 70) for the BESTest total score at the 95% CI was 7.6%, or 8.2 points. MDC at the 95% CI for subsystem scores ranged from 11.7% to 19.0% (2.1-3.4 points). DISCUSSION: Results demonstrated generally good to excellent interrater and test-retest reliability in both the BESTest total and subsystem scores with community-dwelling older adults. CONCLUSIONS: The BESTest total and individual subsystem scores demonstrate good to excellent interrater and test-retest reliability with community-dwelling older adults. A change of 7.6% (8.2 points) or more in the BESTest total and a percentage change ranged from 11.7% to 19.0% (2.1-3.4 points) in the subsystem scores are suggested for clinicians to be 95% confident of true change when evaluating change in this population.

Intraductal Papilloma with Benign Pathology on Breast Core Biopsy: To Excise or Not?

BACKGROUND: The management of intraductal papillomas on core biopsy continues to be controversial. Papillomas with atypia are typically excised. However, it is unclear whether surgical excision is warranted for benign lesions. METHODS: A retrospective review of our institution's pathology and radiology databases from January 2009 through May 2014 identified 119 patients with a diagnosis of benign papilloma without atypia on core biopsy. We determined the rate of carcinoma identification on surgical excision. RESULTS: The average patient age was 52.8 years (range 24-84 years). Indication for core biopsy included: abnormal imaging (n = 106), nipple discharge (n = 21), or palpable mass (n = 24). Seventy-five patients underwent surgical excision after core biopsy. Sixteen patients (21.3 %) had atypia in the excision specimen (combination atypical ductal hyperplasia, n = 11; atypical lobular hyperplasia, n = 8; lobular carcinoma-in situ, n = 3), 15 (93.8 %) of which were in the surrounding breast tissue. Two patients (2.7 %) had malignancy (ductal carcinoma-in situ and micropapillary carcinoma-in situ). As a result of surgical findings, 12 % of patients had a change in management. In comparing those with benign findings on surgical pathology and those whose disease was upstaged, there was no statistically significant difference in family history of breast cancer, indication for core biopsy, mammographic findings, or location of papilloma. CONCLUSIONS: Benign papillomas diagnosed on core biopsy are rarely upstaged to malignancy on surgical excision. However, at least 21 % of patients may have atypical findings in the surrounding tissue, which could change clinical management. Surgical excision should be considered in patients with benign papillomas.

Piloting an approach to rapid and automated assessment of a new research initiative: Application to the National Cancer Institute's Provocative Questions initiative.

Funders of biomedical research are often challenged to understand how a new funding initiative fits within the agency's portfolio and the larger research community. While traditional assessment relies on retrospective review by subject matter experts, it is now feasible to design portfolio assessment and gap analysis tools leveraging administrative and grant application data that can be used for early and continued analysis. We piloted such methods on the National Cancer Institute's Provocative Questions (PQ) initiative to address key questions regarding diversity of applicants; whether applicants were proposing new avenues of research; and whether grant applications were filling portfolio gaps. For the latter two questions, we defined measurements called focus shift and relevance, respectively, based on text similarity scoring. We demonstrate that two types of applicants were attracted by the PQs at rates greater than or on par with the general National Cancer Institute applicant pool: those with clinical degrees and new investigators. Focus shift scores tended to be relatively low, with applicants not straying far from previous research, but the majority of applications were found to be relevant to the PQ the application was addressing. Sensitivity to comparison text and inability to distinguish subtle scientific nuances are the primary limitations of our automated approaches based on text similarity, potentially biasing relevance and focus shift measurements. We also discuss potential uses of the relevance and focus shift measures including the design of outcome evaluations, though further experimentation and refinement are needed for a fuller understanding of these measures before broad application.

(-)Epigallocatechin-3-gallate inhibits the spontaneous firing of rat locus coeruleus neuron.

(-)Epigallocatechin-3-gallate (EGCG), a tea catechin, has been known to cause many biological actions, such as anxiolytic and hypotensive effects in behavioral studies. However, to date, few reports investigate its neuronal modulation. In this study, intracellular recording was used to test the neuronal modulation of different catechins on locus coeruleus (LC) neuron, which has been demonstrated to be affected by cardiovascular function regulation and stressful events. Several catechins (1 -- 1,000 microM) were tested, including: (-)catechin (C), (-)catechingallate (CG), (-)epicatechin (EC), (-)epicatechin-3-gallate (ECG), (?)epigallocatechin (EGC) and EGCG. The results showed that catechins EC, ECG, EGC and EGCG could inhibit the spontaneous firing of the LC neurons; furthermore, these catechins show potency and efficacy in the order of EGCG>ECG>EC approximately EGC. Among the tested catechins, EGCG was the most potent in inhibiting LC's spontaneous firing with IC(50) of 20.5 microM. This caused us to further examine the EGCG's desensitization and tolerance properties. When continuously administering EGCG at 1 -- 300 microM for 20 min, no acute desensitization appeared. However, repeated applications of 300 microM EGCG at 5 min each time showed different results. The second and third applications induced less responses compared to that of the first application, suggesting a development of tolerance towards EGCG in inhibiting LC neuronal activity. Our data suggest that EGCG can inhibit LC neuron's spontaneous firing in a dose-dependent manner, with developed tolerance only when high concentration of EGCG is repeatedly applied.

Real-time detection of epidermal growth factor receptor expression in fresh oral cavity biopsies using a molecular-specific contrast agent.

Early diagnosis of individuals with high risk of developing head and neck squamous carcinoma should lead to decreased morbidity and increased survival. To aid in noninvasive early detection of oral neoplasia in vivo, we have developed a molecular-specific fluorescent contrast agent, consisting of a far-red fluorescent dye coupled to a monoclonal antibody targeted against the epidermal growth factor receptor. In our study, we used organ cultures of normal and neoplastic human oral tissue to evaluate the capabilities of using this contrast agent to enhance clinical diagnosis. Fresh tissue sections were prepared from 34 biopsies of clinically normal and abnormal oral mucosa from 17 consenting patients. Samples were exposed to contrast agent, rinsed and the presence of bound agent was detected using fluorescence confocal microscopy. Simple assays to assess cytotoxicity of the dye used in the agent and to determine labeling efficacy at physiologic temperatures were also performed. Results indicate that the mean fluorescence intensity (MFI) of samples with dysplasia and cancer are higher than that of the normal sample from the same patient, and that this increase in fluorescence could potentially be used in the early detection and delineation of premalignant lesions. Normal tissue could be distinguished from cancer or moderate dysplasia, using either the ratio of the MFI of abnormal to normal tissue or the MFI obtained from the epithelial surface. No detrimental effects from the dye were observed over a 4-day period. These results indicate that the use of this optical contrast agent could yield important clinical advantages for noninvasive early detection and molecular characterization of oral mucosa.

Detection of the molecular changes associated with oral cancer using a molecular-specific fluorescent contrast agent and single-wavelength spectroscopy.

There is currently no standard screening technique for oral cancer and its precursors other than visual identification and biopsy of suspicious lesions. To aid noninvasive early detection of oral neoplasia in vivo, we previously developed a molecular-specific contrast agent targeted against epidermal growth factor receptor. Here, we present a simple fluorescence spectroscopy system to detect the presence of this contrast agent in biological models representative of living tissues in order to demonstrate the feasibility of using a spectroscopy system in conjunction with a contrast agent as a screening technique for oral cancer. The spectroscopy system was tested for the ability to detect the contrast agent in four in vitro models: multilayer tissue phantoms made of cells pre-labeled with the contrast agent, multilayer tissue phantoms labeled with the contrast agent from the surface in conjunction with a permeability enhancing agent, fresh tissue slices from normal and abnormal oral cavity biopsies, and whole normal and abnormal oral cavity biopsies. The optical signal from samples labeled with the contrast agent was 3--32 times stronger compared to controls and was detected with a signal-to-noise ratio greater than 10. These results demonstrate that an inexpensive and simple spectroscopy system can be used in biological models of living systems to detect the optical signal from a contrast agent targeted toward a cancer-related biomarker with good signal-to-noise ratios. Coupling inexpensive fluorescence spectrometers with molecular-specific contrast agents has the potential to improve the early detection of oral neoplasia by providing a low-cost screening tool.