An overview of real-world data sources for oncology and considerations for research.

Generating evidence on the use, effectiveness, and safety of new cancer therapies is a priority for researchers, health care providers, payers, and regulators given the rapid pace of change in cancer diagnosis and treatments. The use of real-world data (RWD) is integral to understanding the utilization patterns and outcomes of these new treatments among patients with cancer who are treated in clinical practice and community settings. An initial step in the use of RWD is careful study design to assess the suitability of an RWD source. This pivotal process can be guided by using a conceptual model that encourages predesign conceptualization. The primary types of RWD included are electronic health records, administrative claims data, cancer registries, and specialty data providers and networks. Careful consideration of each data type is necessary because they are collected for a specific purpose, capturing a set of data elements within a certain population for that purpose, and they vary by population coverage and longitudinality. In this review, the authors provide a high-level assessment of the strengths and limitations of each data category to inform data source selection appropriate to the study question. Overall, the development and accessibility of RWD sources for cancer research are rapidly increasing, and the use of these data requires careful consideration of composition and utility to assess important questions in understanding the use and effectiveness of new therapies.

Association of SARS-CoV-2 Seropositive Antibody Test With Risk of Future Infection.

Importance: Understanding the effect of serum antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on susceptibility to infection is important for identifying at-risk populations and could have implications for vaccine deployment. Objective: The study purpose was to evaluate evidence of SARS-CoV-2 infection based on diagnostic nucleic acid amplification test (NAAT) among patients with positive vs negative test results for antibodies in an observational descriptive cohort study of clinical laboratory and linked claims data. Design, Setting, and Participants: The study created cohorts from a deidentified data set composed of commercial laboratory tests, medical and pharmacy claims, electronic health records, and hospital chargemaster data. Patients were categorized as antibody-positive or antibody-negative according to their first SARS-CoV-2 antibody test in the database. Main Outcomes and Measures: Primary end points were post-index diagnostic NAAT results, with infection defined as a positive diagnostic test post-index, measured in 30-day intervals (0-30, 31-60, 61-90, >90 days). Additional measures included demographic, geographic, and clinical characteristics at the time of the index antibody test, including recorded signs and symptoms or prior evidence of coronavirus 2019 (COVID) diagnoses or positive NAAT results and recorded comorbidities. Results: The cohort included 3 257 478 unique patients with an index antibody test; 56% were female with a median (SD) age of 48 (20) years. Of these, 2 876 773 (88.3%) had a negative index antibody result, and 378 606 (11.6%) had a positive index antibody result. Patients with a negative antibody test result were older than those with a positive result (mean age 48 vs 44 years). Of index-positive patients, 18.4% converted to seronegative over the follow-up period. During the follow-up periods, the ratio (95% CI) of positive NAAT results among individuals who had a positive antibody test at index vs those with a negative antibody test at index was 2.85 (95% CI, 2.73-2.97) at 0 to 30 days, 0.67 (95% CI, 0.6-0.74) at 31 to 60 days, 0.29 (95% CI, 0.24-0.35) at 61 to 90 days, and 0.10 (95% CI, 0.05-0.19) at more than 90 days. Conclusions and Relevance: In this cohort study, patients with positive antibody test results were initially more likely to have positive NAAT results, consistent with prolonged RNA shedding, but became markedly less likely to have positive NAAT results over time, suggesting that seropositivity is associated with protection from infection. The duration of protection is unknown, and protection may wane over time.

Real-world data suggest antibody positivity to SARS-CoV-2 is associated with a decreased risk of future infection.

Importance There is limited evidence regarding whether the presence of serum antibodies to SARS-CoV-2 is associated with a decreased risk of future infection. Understanding susceptibility to infection and the role of immune memory is important for identifying at-risk populations and could have implications for vaccine deployment. Objective The purpose of this study was to evaluate subsequent evidence of SARS-CoV-2 infection based on diagnostic nucleic acid amplification test (NAAT) among individuals who are antibody-positive compared with those who are antibody-negative, using real-world data. Design This was an observational descriptive cohort study. Participants The study utilized a national sample to create cohorts from a de-identified dataset composed of commercial laboratory test results, open and closed medical and pharmacy claims, electronic health records, hospital billing (chargemaster) data, and payer enrollment files from the United States. Patients were indexed as antibody-positive or antibody-negative according to their first SARS-CoV-2 antibody test recorded in the database. Patients with more than 1 antibody test on the index date where results were discordant were excluded. Main Outcomes/Measures Primary endpoints were index antibody test results and post-index diagnostic NAAT results, with infection defined as a positive diagnostic test post-index, as measured in 30-day intervals (0-30, 31-60, 61-90, >90 days). Additional measures included demographic, geographic, and clinical characteristics at the time of the index antibody test, such as recorded signs and symptoms or prior evidence of COVID-19 (diagnoses or NAAT+) and recorded comorbidities. Results We included 3,257,478 unique patients with an index antibody test. Of these, 2,876,773 (88.3%) had a negative index antibody result, 378,606 (11.6%) had a positive index antibody result, and 2,099 (0.1%) had an inconclusive index antibody result. Patients with a negative antibody test were somewhat older at index than those with a positive result (mean of 48 versus 44 years). A fraction (18.4%) of individuals who were initially seropositive converted to seronegative over the follow up period. During the follow-up periods, the ratio (CI) of positive NAAT results among individuals who had a positive antibody test at index versus those with a negative antibody test at index was 2.85 (2.73 - 2.97) at 0-30 days, 0.67 (0.6 - 0.74) at 31-60 days, 0.29 (0.24 - 0.35) at 61-90 days), and 0.10 (0.05 - 0.19) at >90 days. Conclusions Patients who display positive antibody tests are initially more likely to have a positive NAAT, consistent with prolonged RNA shedding, but over time become markedly less likely to have a positive NAAT. This result suggests seropositivity using commercially available assays is associated with protection from infection. The duration of protection is unknown and may wane over time; this parameter will need to be addressed in a study with extended duration of follow up.

Comparisons of high versus low emergency department utilizers in sickle cell disease.

STUDY OBJECTIVE: Patients with sickle cell disease often receive a substantial amount of their health care in the emergency department (ED) and some come to the ED frequently, seeking treatment for pain. As a result, patients with sickle cell disease are often stigmatized as opioid-seeking ED overutilizers. We describe the proportion of sickle cell disease patients who are high utilizers of the ED and compare them with other sickle cell disease patients on demographics, pain characteristics, health data, psychosocial characteristics, and quality of life. METHODS: Two hundred thirty-two patients completed baseline data and at least 30 days of daily diary data. Baseline data included demographics, health data, and quality of life (Medical Outcome Study 36 Item Short Form). Daily diary data included ED utilization for sickle cell pain and descriptors of pain and distress. RESULTS: Eighty-two (35.5%) patients were found to be high ED utilizers. Clinically important and statistically significant differences were found between high ED utilizers and all other sickle cell disease patients: lower hematocrit level, more transfusions, more pain days, more pain crises, higher mean pain and distress, and worse quality of life on Medical Outcome Study 36 Item Short Form physical function summary scales. After controlling for severity and frequency of pain, high ED utilizers did not use opioids more frequently than other sickle cell disease patients. CONCLUSION: A substantial minority of sickle cell disease patients are high ED utilizers. However, high ED utilizers with sickle cell disease are more severely ill as measured by laboratory variables, have more pain, more distress, and have a lower quality of life.

Daily assessment of pain in adults with sickle cell disease.

BACKGROUND: Researchers of sickle cell disease have traditionally used health care utilization as a proxy for pain and underlying vaso-occlusion. However, utilization may not completely reflect the amount of self-reported pain or acute, painful episodes (crises). OBJECTIVE: To examine the prevalence of self-reported pain and the relationship among pain, crises, and utilization in adults with sickle cell disease. DESIGN: Prospective cohort study. SETTING: Academic and community practices in Virginia. PATIENTS: 232 patients age 16 years or older with sickle cell disease. MEASUREMENTS: Patients completed a daily diary for up to 6 months, recording their maximum pain (on a scale of 0 to 9); whether they were in a crisis (crisis day); and whether they used hospital, emergency, or unscheduled ambulatory care for pain on the previous day (utilization day). Summary measures included both simple proportions and adjusted probabilities (for repeated measures within patients) of pain days, crisis days, and utilization days, as well as mean pain intensity. RESULTS: Pain (with or without crisis or utilization of care) was reported on 54.5% of 31 017 analyzed patient-days (adjusted probability, 56%). Crises without utilization were reported on 12.7% of days and utilization on only 3.5% (unadjusted). In total, 29.3% of patients reported pain in greater than 95% of diary days, whereas only 14.2% reported pain in 5% or fewer diary days (adjusted). The frequency of home opiate use varied and independently predicted pain, crises, and utilization. Mean pain intensity on crisis days, noncrisis pain days, and total pain days increased as the percentage of pain days increased (P < 0.001). Intensity was significantly higher on utilization days (P < 0.001). However, utilization was not an independent predictor of crisis, after controlling for pain intensity. LIMITATIONS: The study was done in a single state. Patients did not always send in their diaries. CONCLUSION: Pain in adults with sickle cell disease is the rule rather than the exception and is far more prevalent and severe than previous large-scale studies have portrayed. It is mostly managed at home; therefore, its prevalence is probably underestimated by health care providers, resulting in misclassification, distorted communication, and undertreatment.

Depression and anxiety in adults with sickle cell disease: the PiSCES project.

OBJECTIVE: Depression and anxiety are common in sickle cell disease (SCD) but relatively little is known about their impact on SCD adults. This study measured prevalence of depression and anxiety in SCD adults, and their effects on crisis and noncrisis pain, quality-of-life, opioid usage, and healthcare utilization. METHODS: The Pain in Sickle Cell Epidemiology Study is a prospective cohort study in 308 SCD adults. Baseline variables included demographics, genotype, laboratory data, health-related quality-of-life, depression, and anxiety. Subjects completed daily diaries for up to 6 months, reporting sickle cell pain intensity, distress, interference, whether they were in a sickle cell crisis, as well as health care and opioid utilization. RESULTS: Two hundred thirty-two subjects who completed at least 1 month of diaries were studied; 27.6% were depressed and 6.5% had any anxiety disorder. Depressed subjects had pain on significantly more days than nondepressed subjects (mean pain days 71.1% versus 49.6%, p < .001). When in pain on noncrisis days, depressed subjects had higher mean pain, distress from pain, and interference from pain. Both depressed and anxious subjects had poorer functioning on all eight SF-36 subscales, even after controlling for demographics, hemoglobin type, and pain. The anxious subjects had more pain, distress from pain, and interference from pain, both on noncrisis pain days and on crisis days, and used opioids more often. CONCLUSIONS: Depression and anxiety predicted more daily pain and poorer physical and mental quality-of-life in adults with SCD, and accounted for more of the variance in all domains of quality-of-life than hemoglobin type.

Patient satisfaction in specialized versus nonspecialized adult sickle cell care centers: the PiSCES study.

BACKGROUND: Sickle cell disease (SCD) patients can receive their ambulatory care from either SCD specialists (caregivers with sickle cell-only clinics) or nonspecialized care centers. Patient satisfaction, an important factor that may influence compliance and outcome, can differ between the two groups because of the perceived quality of care, outcomes or practice style. METHODS: We administered a patient satisfaction survey to 308 participants in an SCD prospective cohort study. Of the 308 patients, 133 (43.2%) received the majority of their SCD care at specialized centers, 152 (49.3%) received their care from nonspecialized centers and 26 (7.5) did not provide information. The satisfaction surveys measured general satisfaction (GS), technical quality (TQ), interpersonal manner (IM), communication (CM), financial aspects (FA), time spent with doctor (TA), and accessibility and convenience (AC). Patients reported their levels of satisfaction using a five-point Likert scale. We compared unadjusted group means, as well as means adjusted for potential confounders such as marital status, on patient satisfaction between specialized and nonspecialized centers. RESULTS: SCD patients who received their care from specialized centers had significantly higher mean satisfaction scores, compared to those who received their care from nonspecialized centers: GS 4.00(+/-0.93) vs. 3.66 (+/- 01.16, p=0.0326), TQ 3.98 (+/- 0.77) vs. 3.65 (+/- 0.91, p=0.0058), AC 3.83 (+/-0.79) vs. 3.51 (+/- 1.02, p=0.0142) , FA 3.88 (+/-0.96) vs. 3.49 (+/-1.25, p=0.0120). There were no statistically significant group differences in IM, TA and CM. CONCLUSION: SCD patients who received most of their SCD care from specialized centers had somewhat higher satisfaction scores in some areas when compared with patients who received their care from nonspecialized centers.

Gender differences in pain and healthcare utilization for adult sickle cell patients: The PiSCES Project.

BACKGROUND: Many studies have found gender differences in frequency and intensity of pain. Women often report lower pain thresholds, higher pain ratings, and lower tolerance for pain. People with sickle cell disease (SCD) experience both chronic and acute pain throughout life. OBJECTIVES: To compare adult men and women with SCD in terms of reported pain, crises, healthcare utilization, and opioid usage. METHODS: Two hundred twenty-six adults with SCD in Virginia were enrolled in a prospective cohort study of pain and completed daily diaries for 1-6 months. Subjects reported for the previous day their maximum SCD-related pain, distress, and interference (0-9 scale), whether they were in a sickle cell crisis, had unplanned utilization (clinic, emergency room, or hospitalization), or used opioids. Episodes of pain, crisis, or utilization were defined as consecutive days of such. Men and women were compared, using analysis of covariance (ANCOVA), controlling for age, SCD genotype, depression, and education. RESULTS: There were no significant differences between men and women in the percentage of days subjects experienced pain (men 58.6% vs. women 56.5%) or the number of pain episodes/6 months (7.7 vs. 9.6). Mean pain scores were comparable, when subjects were in crisis (5.5 vs. 5.6) or not (2.5 vs. 2.2). Distress and interference results were similar. Men with the SS genotype reported a higher percentage of days with crisis(18.5% vs. 11.6%) and utilization (5.1% vs. 2.7%) than women with the SS genotype. CONCLUSIONS: Contrary to many studies of pain, particularly chronic pain, men and women with SCD reported generally similar pain experiences.

Health related quality of life in sickle cell patients: the PiSCES project.

BACKGROUND: Sickle cell disease (SCD) is a chronic disease associated with high degrees of morbidity and increased mortality. Health-related quality of life (HRQOL) among adults with sickle cell disease has not been widely reported. METHODS: We administered the Medical Outcomes Study 36-item Short-Form to 308 patients in the Pain in Sickle Cell Epidemiology Study (PiSCES) to assess HRQOL. Scales included physical function, physical and emotional role function, bodily pain, vitality, social function, mental health, and general health. We compared scores with national norms using t-tests, and with three chronic disease cohorts: asthma, cystic fibrosis and hemodialysis patients using analysis of variance and Dunnett's test for comparison with a control. We also assessed whether SCD specific variables (genotype, pain, crisis and utilization) were independently predictive of SF-36 subscales, controlling for socio-demographic variables using regression. RESULTS: Patients with SCD scored significantly worse than national norms on all subscales except mental health. Patients with SCD had lower HRQOL than cystic fibrosis patients except for mental health. Scores were similar for physical function, role function and mental health as compared to asthma patients, but worse for bodily pain, vitality, social function and general health subscales. Compared to dialysis patients, sickle cell disease patients scored similarly on physical role and emotional role function, social functioning and mental health, worse on bodily pain, general health and vitality and better on physical functioning. Surprisingly, genotype did not influence HRQOL except for vitality. However, scores significantly decreased as pain levels increased. CONCLUSION: SCD patients experience health related quality of life worse than the general population, and in general, their scores were most similar to patients undergoing hemodialysis. Practitioners should regard their HRQOL as severely compromised. Interventions in SCD should consider improvements in health related quality of life as important outcomes.

Understanding pain and improving management of sickle cell disease: the PiSCES study.

Until recent decades, sickle cell disease (SCD) was associated with recurrent, disabling pain, organ failure and death in childhood or early adulthood. SCD treatment advances have now decreased pain and prolonged survival, but episodic or chronic pain may still require substantial analgesic use and frequent hospitalization for pain episodes. This pain is poorly characterized and often poorly treated. Adult patients may face barriers to comprehensive SCD care, stigmatization of their care-seeking behavior by providers and lack of family support, forcing them into maladaptive coping strategies. The Pain in Sickle Cell Epidemiology Study (PiSCES) attempts to develop and validate a biopsychosocial model of SCD pain, pain response and healthcare utilization in a large, multisite adult cohort. PiSCES participants complete a baseline survey and six months of daily pain diaries in which they record levels of SCD-related pain and related disability and distress as well as responses to pain (e.g., medication use, hospital visits). PiSCES will advance methods of measuring pain and pain response in SCD by better describing home-managed as well as provider-managed pain. PiSCES will assess the relative contributions of biological (disease-related), psychosocial and environmental (readiness to utilize) factors to overall pain and pain response in SCD, suggesting targets for biobehavioral interventions over time. Importantly, PiSCES will also identify "triggers" of SCD pain episodes and healthcare utilization in the moment of pain, suggesting targets for timely care that mutes pain episodes.

Daily home opioid use in adults with sickle cell disease: The PiSCES project.

BACKGROUND: Although opioid prescribing in sickle cell disease (SCD) can be controversial, little is published about patterns of opioid use. OBJECTIVE: To report on home opioid use among adults with SCD. DESIGN: Cohort study. PARTICIPANTS: Adults with SCD (n=219) who completed daily pain diaries for up to 6 months and had at least one home pain day. MAIN MEASURES: Use of long-acting or short-acting opioids, other analgesics, or adjuvants; the proportion of home days, home pain days, and home crisis days with opioid use; these two outcomes according to patient characteristics. KEY RESULTS: Patients used opioids on 12,311 (78 percent) of 15,778 home pain days. Eighty-five patients (38.8 percent) used long-acting opioids with or without short-acting opioids and 103 (47.0 percent) used only short-acting opioids. Twenty-one (9.6 percent) patients used only non-opioid analgesics and 10 (4.6 percent) used no analgesics. Both pain intensity and pain frequency were higher among opioid users (analysis of variance [ANOVA], p<0.0001). Opioid users used hydroxyurea more often than nonusers, even when controlling for mean pain on pain days. Among all patients, significant relationships were found between any opioid use and somatic symptom burden, SCD stress, negative coping, and physical and mental quality of life (QOL); the relationship with SCD stress and physical QOL remained when controlled for mean pain. Among opioid users, similar associations were found between frequency of opioid use and some disease-related and psychosocial variables. CONCLUSIONS: In this adult SCD sample, opioids were used by the majority of patients. Pain was the overwhelming characteristic associated with use, but disease-related and psychosocial variables were also associated.

Collaborative Initiatives in the Care of Early Stage Breast Cancer: Reduction in Variation of Breast-Conserving Therapy.

Breast-conserving therapy (BCT) has survival results comparable to those obtained with modified radical mastectomy (MST). However, studies suggest variations in the rates of breast-conserving therapy that are not explained by comorbidities or age. The Virginia Health Quality Center collaborated with 40 Virginia hospitals to address patterns of breast cancer treatment. Medicare Peer Review Organization data files were used to identify all Medicare beneficiaries with a primary diagnosis of breast cancer from January 1, 1992, through June 30, 1993. Explicit chart review was performed on a random sample of patients with early stage disease receiving either BCT or MST. At baseline, the BCT rate was 21.1% after controlling for access to radiation facilities, medical conditions, and demographic variables. Hospitals with the highest rates of appropriate BCT served as resources for the project. We provided data on BCT rates to 40 participating hospitals. Hospitals then submitted comprehensive plans to address the performance of BCT. A four-step cooperative improvement intervention was employed to initiate and sustain changes at the hospital level. Interventions included individual hospital feedback, dissemination of model cancer care processes at high-performing institutions, and integration of oncology services for breast cancer treatment decisions. One year after implementation, the overall BCT rate in Virginia increased to 25.5%. Hospitals with the lowest BCT rates increased their average rate from 6.6% to 21.2%. Middle tercile hospitals increased BCT rates by 10%. Variation between the lowest and highest terciles was reduced to 9%. Variation in BCT rates can be reduced by a collaborative program centered on addressing processes of care for breast cancer treatment for Medicare patients with early stage disease.

SEER cancer registry biospecimen research: yesterday and tomorrow.

The National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) registries have been a source of biospecimens for cancer research for decades. Recently, registry-based biospecimen studies have become more practical, with the expansion of electronic networks for pathology and medical record reporting. Formalin-fixed paraffin-embedded specimens are now used for next-generation sequencing and other molecular techniques. These developments create new opportunities for SEER biospecimen research. We evaluated 31 research articles published during 2005 to 2013 based on authors' confirmation that these studies involved linkage of SEER data to biospecimens. Rather than providing an exhaustive review of all possible articles, our intent was to indicate the breadth of research made possible by such a resource. We also summarize responses to a 2012 questionnaire that was broadly distributed to the NCI intra- and extramural biospecimen research community. This included responses from 30 investigators who had used SEER biospecimens in their research. The survey was not intended to be a systematic sample, but instead to provide anecdotal insight on strengths, limitations, and the future of SEER biospecimen research. Identified strengths of this research resource include biospecimen availability, cost, and annotation of data, including demographic information, stage, and survival. Shortcomings include limited annotation of clinical attributes such as detailed chemotherapy history and recurrence, and timeliness of turnaround following biospecimen requests. A review of selected SEER biospecimen articles, investigator feedback, and technological advances reinforced our view that SEER biospecimen resources should be developed. This would advance cancer biology, etiology, and personalized therapy research. See all the articles in this CEBP Focus section, "Biomarkers, Biospecimens, and New Technologies in Molecular Epidemiology." Cancer Epidemiol Biomarkers Prev; 23(12); 2681-7. ©2014 AACR.

Automated determination of metastases in unstructured radiology reports for eligibility screening in oncology clinical trials.

Enrolling adequate numbers of patients that meet protocol eligibility criteria in a timely manner is critical, yet clinical trial accrual continues to be problematic. One approach to meet these accrual challenges is to utilize technology to automatically screen patients for clinical trial eligibility. This manuscript reports on the evaluation of different automated approaches to determine the metastatic status from unstructured radiology reports using the Clinical Trials Eligibility Database Integrated System (CTED). The study sample included all patients (N = 5,523) with radiologic diagnostic studies (N = 10,492) completed in a two-week period. Eight search algorithms (queries) within CTED were developed and applied to radiology reports. The performance of each algorithm was compared to a reference standard which consisted of a physician's review of the radiology reports. Sensitivity, specificity, positive, and negative predicted values were calculated for each algorithm. The number of patients identified by each algorithm varied from 187 to 330 and the number of true positive cases confirmed by physician review ranged from 171 to 199 across the algorithms. The best performing algorithm had sensitivity 94%, specificity 100%, positive predictive value 90%, negative predictive value 100%, and accuracy of 99%. Our evaluation process identified the optimal method for rapid identification of patients with metastatic disease through automated screening of unstructured radiology reports. The methods developed using the CTED system could be readily implemented at other institutions to enhance the efficiency of research staff in the clinical trials eligibility screening process.

Effort required in eligibility screening for clinical trials.

PURPOSE: Determining eligibility for a clinical trial (CT) typically requires a lengthy manual review of data for a single evaluation. The cost associated with eligibility screening is typically not compensated through contracts supporting CTs. METHODS: We used a real-time tracking system that captures CT evaluations and provides information on evaluation outcomes and time spent on each eligibility screening by research staff. Using these data, we describe the effort and costs of eligibility screening overall and per enrolled patient for cancer CTs. The study sample included all completed eligibility assessment (evaluation) records for the 18-month study period. We used generalized multinomial modeling to predict evaluation outcomes and then used the resulting parameter coefficients to estimate the effort associated with each participant, adjusted for probability of being enrolled. From these data, we calculated cost associated with eligibility screening. RESULTS: We found substantial variation in attributed cost by study type and phase. The cost of eligibility screening ranged by study phase from $129.15 to $336.48 per enrolled patient. The estimated annual cost of screening was more than $90,000. CONCLUSION: This study provides results based on prospectively captured effort to estimate the largely nonreimbursed costs of eligibility screening and suggests that screening can be a significant financial burden to an institution. Centers performing CTs may need to acknowledge the differences in screening costs for different study types when negotiating contracts with funding organizations. Information such as that captured here could support such negotiations to reduce the gap between reimbursed and nonreimbursed costs.

Impact of automated data collection from urology offices: improving incidence and treatment reporting in urologic cancers.

BACKGROUND: Urologic cancers represent a substantial proportion of the total cancer burden, yet the true burden of these cancers is unknown due to gaps in current cancer surveillance systems. Prostate and bladder cancers in particular may be underreported due to increased availability of outpatient care. Thus, there is a critical need to develop systems to completely and accurately capture longitudinal data to understand the true patterns of care and outcomes for these cancers. METHODS: We determined the accuracy and impact of automated software to capture and process billing data to supplement reporting of cancers diagnosed and treated in a large community urology practice. From these data, we estimated numbers of unreported cancers for an actively reporting and for a non-reporting practice and the associated impact for a central cancer registry. RESULTS: The software automatically processed billing data representing 26,133 visits for 15,495 patients in the 3.5-month study period. Of these, 2,275 patients had a cancer diagnosis and 87.2% of these matched with a central registry case. The estimated annual number of prostate and bladder cancers remaining unreported from this practice was 158. If the practice were not actively reporting, the unreported cases were estimated at 1,111, representing an increase of 12% to the registry. Treatments added from billing varied by treatment type with the largest proportion of added treatments for biologic response modifiers (BRMs) (127%-166%) and chemotherapy (22%). CONCLUSION: Automated processing of billing data from community urology practices offers an opportunity to enhance capture of missing prostate and bladder cancer surveillance data with minimal effort to a urology practice. IMPACT: Broader implementation of automated reporting could have a major impact nationally considering the more than 12,000 practicing urologists listed as members of the American Urological Association.

Genes involved in radiation therapy response in head and neck cancers.

OBJECTIVES: This is a pilot study designed to identify gene expression profiles able to stratify head and neck squamous cell carcinoma (HNSCC) tumors that may or may not respond to chemoradiation or radiation therapy. STUDY DESIGN: We prospectively evaluated 14 HNSCC specimens, arising from patients undergoing chemoradiotherapy or radiotherapy alone with curative intent. A complete response was assessed by clinical evaluation with no evidence of gross tumor after a 2-year follow-up period. METHODS: Residual biopsy samples from eight complete responders (CR) and six nonresponders (NR) were evaluated by genome-wide gene expression profiling using HG-U133A 2.0 arrays. Univariate parametric t-tests with proportion of false discoveries controlled by multivariate permutation tests were used to identify genes with significantly different gene expression levels between CR and NR cases. Six different prediction algorithms were used to build gene predictor lists. Three representative genes showing 100% crossvalidation support after leave-one-out crossvalidation (LOOCV) were further validated using real-time QRT-PCR. RESULTS: We identified 167 significant probe sets that discriminate between the two classes, which were used to build gene predictor lists. Thus, 142 probe sets showed an accuracy of prediction ranging from 93% to 100% across all six prediction algorithms. The genes represented by these 142 probe sets were further classified into different functional networks that included cellular development, cellular movement, and cancer. CONCLUSIONS: The results presented herein offer encouraging preliminary data that may provide a basis for a more precise prognosis of HNSCC, as well as a molecular-based therapy decision for the management of these cancers.

Pain site frequency and location in sickle cell disease: the PiSCES project.

Treatment options for sickle cell disease (SCD) pain could be tailored to pain locations. But few epidemiologic descriptions of SCD pain location exist; these are based on few subjects over short time periods. We examined whether SCD pain locations vary by disease genotype, gender, age, frequency of pain, depression, pain crisis or healthcare utilization. We enrolled 308 adults with SCD in 2002-2004. Subjects kept daily pain diaries for up to 6months, including a body chart. Mixed model and generalized estimating equations were employed for analyses. Two hundred and sixty subjects completed at least one body chart. An average of 3.3/16 sites (25%) were painful. The number of pain sites varied by age, depression, frequent pain days, crisis and unplanned hospital/ED utilization. Lower back, knee/shin and hip, hurt on average more than a third of pain days, while jaw and pelvis hurt on fewer than 10% of days. Odds of a crisis were increased substantially when pain was in the arm, shoulder, upper back, sternum, clavicle, chest or pelvis (OR>1.5) while the odds of unplanned utilization were substantially increased for the sternum, clavicle and chest (OR>2.0). Pain in SCD varies considerably both within and between subjects, although it occurs most commonly in the lower back and lower extremities. The number and location of pain sites vary significantly by age, frequent pain, crisis and utilization. Identification and understanding of combinations of pain location and intensity may help to understand the etiology of SCD and improve SCD management.

Alcohol abuse in sickle cell disease: the Pisces Project.

Alcohol abuse is common in patients with chronic painful medical disorders, but it has not been studied in sickle cell disease (SCD). In a prospective cohort study of SCD adults, 31.4% were identified as abusing alcohol. There were no significant differences between alcohol abusers and nonabusers on demographics, biological variables, depression, anxiety, measures of crisis and noncrisis pain, or opioid use, but abusers reported more pain relief from opioids than nonabusers did. Alcohol abusers had fewer unscheduled clinic visits, emergency room visits, hospital days, and any health care utilization for SCD, but this was only significant for emergency room visits. Quality of life was similar between both groups, except that alcohol abusers unexpectedly had better overall physical summary scores. Alcohol abusers were more likely to report coping by ignoring pain, diverting attention, and using particular self-statements.

The role of catastrophizing in sickle cell disease--the PiSCES project.

In several types of chronic pain, catastrophizing has been related to higher pain intensity, and health care utilization but it has not been explored extensively in sickle cell disease (SCD). The objective of the study was to identify the role of catastrophizing in SCD, specifically in relation to painful crises, non-crisis pain, and responses to pain. Two hundred and twenty SCD adults were enrolled in a prospective cohort study of pain and completed between 30 and 188 daily diaries in 6 months. The Catastrophizing subscale (CAT) of the Coping Strategy Questionnaire (CSQ) was administered at baseline and at study exit. Depression and quality of life were measured by the Patient Health Questionnaire and SF-36, respectively, at baseline. The CAT mean was 13.6 (SD=8.4) and higher CAT was correlated with greater depression severity (r=0.48; p<0.001) and poorer quality of life in all domains (r=-0.24 to -0.47; p<0.001). There was no significance difference between CAT mean baseline and exit scores, and the measures were strongly correlated within patients (r=0.69; p<0.001). No difference was found between higher and lower catastrophizers in intensity of pain, distress, interference, and health service utilization, both on crisis or non-crisis SCD-related pain days, after controlling for depression. Adults with SCD had a higher mean catastrophizing score than found in studies of other chronic pain conditions that are not lifelong and life-threatening. CAT scores were not correlated with pain parameters or utilization. The role of catastrophizing in other conditions cannot be generalized to SCD.