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Dense breasts are associated with a higher risk of breast cancer diagnosis, which has impacted risk prediction tools and patient notification policies. However, given that mammography is less sensitive for women with dense breasts and these women may be subject to different confirmation testing pathways, the true association between breast density and cancer risk is unknown. We investigated the relationship between breast density and onset using a natural history model that accounts for differential sensitivity and rates of exams by breast density. Data consisted of Breast Cancer Surveillance Consortium mammogram and cancer outcomes among women aged 40-54 with a first digital mammogram between 2000-2018 (N=33,542). Of these, 15,092 had non-dense (almost entirely fatty or scattered fibroglandular densities) and18,450 had dense (heterogeneously dense or extremely dense) breasts. We estimated the empirical sensitivity of mammograms in dense and non-dense breasts (fraction of diagnosed cancers that were screen detected) and examined rates of mammograms by density. We estimated the relative risk of breast cancer diagnosis five years after the first exam using Kaplan Meier methods and the relative risk of breast cancer onset from a natural history model, assuming density-specific sensitivity was equal to the empirical sensitivity. Empirical sensitivity was .88 in women with non-dense and .78 in women with dense breasts. Mammogram utilization was somewhat higher in women with dense breasts (HR for subsequent mammograms 1.10 (95% CI [1.07, 1.12]). The relative risk of diagnosis for dense versus non-dense breasts was 1.80 (95% CI [1.46,2.57]); based on the natural history model the relative risk of onset was 1.73 [1.43,2.25]. The estimated relative risk of onset ranged from 1.67 to 2.03 under assumptions that the relative sensitivity of the screening episode for dense versus non-dense breasts was 1.0 to 0.4. In conclusion, the association of risk of breast cancer onset with breast density is robust to assumptions about the relative sensitivity in dense and non-dense breasts. Citation Format: Jane M. Lange, Charlotte Gard, Ellen O’meara, Ruth Etzioni. Elevated Risk of Breast Cancer Diagnosis in Women with Dense Breasts reflects a similarly Elevated Risk of Breast Cancer Onset that is Robust to the Effect of Density on Mammography Sensitivity [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-03.

Background Studies conducted in Swedish populations have shown that men with lowest prostate-specific antigen (PSA) levels at ages 44–50 years and 60 years have very low risk of future distant metastasis or death from prostate cancer. This study investigates benefits and harms of screening strategies stratified by PSA levels. Methods PSA levels and diagnosis patterns from two microsimulation models of prostate cancer progression, detection, and mortality were compared against results of the Malmö Preventive Project, which stored serum and tracked subsequent prostate cancer diagnoses for 25 years. The models predicted the harms (tests and overdiagnoses) and benefits (lives saved and life-years gained) of PSA-stratified screening strategies compared with biennial screening from age 45 years to age 69 years. Results Compared with biennial screening for ages 45–69 years, lengthening screening intervals for men with PSA less than 1.0 ng/mL at age 45 years led to 46.8–47.0% fewer tests (range between models), 0.9–2.1% fewer overdiagnoses, and 3.1–3.8% fewer lives saved. Stopping screening when PSA was less than 1.0 ng/mL at age 60 years and older led to 12.8–16.0% fewer tests, 5.0–24.0% fewer overdiagnoses, and 5.0–13.1% fewer lives saved. Differences in model results can be partially explained by differences in assumptions about the link between PSA growth and the risk of disease progression. Conclusion Relative to a biennial screening strategy, PSA-stratified screening strategies investigated in this study substantially reduced the testing burden and modestly reduced overdiagnosis while preserving most lives saved. Further research is needed to clarify the link between PSA growth and disease progression.

Importance The benefit of prostate-specific antigen screening may be greatest in high-risk populations, including men of African descent in the Caribbean. However, organized screening may not be sustainable in low- and middle-income countries.Objective To evaluate the expected population outcomes and resource use of conservative prostate-specific antigen screening programs in the Bahamas.Design, Setting, and Participants Prostate cancer incidence from GLOBOCAN and prostate-specific antigen screening data for 4300 men from the Bahamas were used to recalibrate 2 decision analytical models previously used to study prostate-specific antigen screening for Black men in the United States. Data on age and results obtained from prostate-specific antigen screening tests performed in Nassau from 2004 to 2018 and in Freeport from 2013 to 2018 were used. Data were analyzed from January 15, 2021, to March 23, 2022.Interventions One or 2 screenings for men aged 45 to 60 years and conservative criteria for biopsy (prostate-specific antigen level >10 ng/mL) and curative treatment (Gleason score ≥8) were modeled. Categories of Gleason scores were 6 or lower, 7, and 8 or higher, with higher scores indicating higher risk of cancer progression and death.Main Outcomes and Measures Projected numbers of tests and biopsies, prostate cancer (over)diagnoses, lives saved, and life-years gained owing to screening from 2022 to 2040.Results In this decision analytical modeling study, screening histories from 4300 men (median age, 54 years; range, 13-101 years) tested between 2004 and 2018 at 2 sites in the Bahamas were used to inform the models. Screening once at 60 years of age was projected to involve 40 000 to 42 000 tests (range between models) and prevent 500 to 600 of 10 000 to 14 000 prostate cancer deaths. Screening at 50 and 60 years doubled the number of tests but increased lives saved by only 15% to 16%. Among onetime strategies, screening once at 60 years of age involved the fewest tests per life saved (74-84 tests) and curative treatments per life saved (1.2-2.8 treatments).Conclusions and Relevance The findings of this decision analytical modeling study of prostate cancer screening in the Bahamas suggest that limited screening offered modest benefits that varied with screening ages and number of tests. The results can be combined with data on capacity constraints and evaluated relative to competing national public health priorities.

Background Trials of cancer screening present results in terms of deaths prevented, but metastasis is also a key endpoint that screening seeks to prevent. We developed a framework for projecting overall (de novo and progressive) metastases prevented in a screening trial using prostate cancer screening as a case study. Methods Mechanistic simulation model in which screening shifts a fraction of cases that would be metastatic at diagnosis to being non-metastatic. This shift increases the incidence of non-overdiagnosed, organ-confined cases. We use estimates of the risk of metastatic progression for these cases to project how many progress to metastasis after diagnosis and tally the projected de novo and progressive metastatic cases with and without screening. We use data on stage shift from the European Randomized Study of Screening for Prostate Cancer (ERSPC) and data on the risk of metastatic progression from the Scandinavian Prostate Cancer Group-4 trial. We estimate the relative risk and absolute risk reductions in metastatic disease at diagnosis and compare these with reductions in overall metastases. Results Assuming no effect of screening beyond initial stage shift at diagnosis, the model projects a 43% reduction in metastasis at diagnosis but a 22% reduction in the cumulative probability of metastasis over 12 years in favor of screening. These results are consistent with the empirical findings from the ERSPC. Conclusion Any reduction in metastatic disease at diagnosis under screening is likely to be an overly optimistic predictor of the impact of screening on overall metastasis and disease-specific mortality.

Background There is a need for automated approaches to incorporate information on cancer recurrence events into population-based cancer registries. Objective The aim of this study is to determine the accuracy of a novel data mining algorithm to extract information from linked registry and medical claims data on the occurrence and timing of second breast cancer events (SBCE). Methods We used supervised data from 3092 stage I and II breast cancer cases (with 394 recurrences), diagnosed between 1993 and 2006 inclusive, of patients at Kaiser Permanente Washington and cases in the Puget Sound Cancer Surveillance System. Our goal was to classify each month after primary treatment as pre- versus post-SBCE. The prediction feature set for a given month consisted of registry variables on disease and patient characteristics related to the primary breast cancer event, as well as features based on monthly counts of diagnosis and procedure codes for the current, prior, and future months. A month was classified as post-SBCE if the predicted probability exceeded a probability threshold (PT); the predicted time of the SBCE was taken to be the month of maximum increase in the predicted probability between adjacent months. Results The Kaplan-Meier net probability of SBCE was 0.25 at 14 years. The month-level receiver operating characteristic curve on test data (20% of the data set) had an area under the curve of 0.986. The person-level predictions (at a monthly PT of 0.5) had a sensitivity of 0.89, a specificity of 0.98, a positive predictive value of 0.85, and a negative predictive value of 0.98. The corresponding median difference between the observed and predicted months of recurrence was 0 and the mean difference was 0.04 months. Conclusions Data mining of medical claims holds promise for the streamlining of cancer registry operations to feasibly collect information about second breast cancer events.

Objective: Opioid surveillance in response to the opioid epidemic will benefit from scalable, automated algorithms for identifying patients with clinically documented signs of problem prescription opioid use. Existing algorithms lack accuracy. We sought to develop a high-sensitivity, high-specificity classification algorithm based on widely available structured health data to identify patients receiving chronic extended-release/long-acting (ER/LA) therapy with evidence of problem use to support subsequent epidemiologic investigations. Methods: Outpatient medical records of a probability sample of 2,000 Kaiser Permanente Washington patients receiving ≥60 days’ supply of ER/LA opioids in a 90-day period from 1 January 2006 to 30 June 2015 were manually reviewed to determine the presence of clinically documented signs of problem use and used as a reference standard for algorithm development. Using 1,400 patients as training data, we constructed candidate predictors from demographic, enrollment, encounter, diagnosis, procedure, and medication data extracted from medical claims records or the equivalent from electronic health record (EHR) systems, and we used adaptive least absolute shrinkage and selection operator (LASSO) regression to develop a model. We evaluated this model in a comparable 600-patient validation set. We compared this model to ICD-9 diagnostic codes for opioid abuse, dependence, and poisoning. This study was registered with ClinicalTrials.gov as study NCT02667262 on 28 January 2016. Results: We operationalized 1,126 potential predictors characterizing patient demographics, procedures, diagnoses, timing, dose, and location of medication dispensing. The final model incorporating 53 predictors had a sensitivity of 0.582 at positive predictive value (PPV) of 0.572. ICD-9 codes for opioid abuse, dependence, and poisoning had a sensitivity of 0.390 at PPV of 0.599 in the same cohort. Conclusions: Scalable methods using widely available structured EHR/claims data to accurately identify problem opioid use among patients receiving long-term ER/LA therapy were unsuccessful. This approach may be useful for identifying patients needing clinical evaluation.

Of the 50,000 men in the US who elect for radical prostatectomy for prostate cancer, 24% to 40% will have a prostate-specific antigen (PSA) recurrence (PSA-R) within 10 years. Deciding whether to administer salvage therapy (ST) at PSA-R presents challenges, as treatment reduces the risk of progression to clinical metastasis but incurs unnecessary side effects should the man die before metastasis. We have developed a new harm-benefit framework using a clinical cohort to inform shared decision making between patients and physicians at PSA-R.Records of 1,045 Johns Hopkins University Hospital patients diagnosed between 1984 and 2013 who had PSA-R following radical prostatectomy were analyzed using marginal structural models to estimate the baseline risk of metastasis and the effect of ST (radiation therapy with or without hormone therapy) while accounting for selection into ST on the basis of PSA growth. The estimated model predicts the harm-benefit tradeoffs of ST within patient subgroups. The benefit of ST is the absolute reduction in the risk of metastasis within 10 years; the harm is the frequency of cancers that would not have metastasized in the patient's lifetime in the absence of ST (overtreatment).The adjusted hazard ratio associated with ST was 0.41 (95% CI, 0.31 to 0.55). Providing ST to all men at PSA-R reduced the risk of metastasis from 43% to 23% but led to 31% of men being overtreated (harm/benefit = 31/(43-23) = 1.6). Providing ST to men with Gleason score7 reduced the risk of metastasis from 67% to 39%, with 13% of men being overtreated (harm/benefit = 13/(67-39) = 0.5).A quantitative framework that evaluates primary harms and benefits of ST after PSA-R will facilitate informed decision making. Immediate ST may be more appropriate in patient subgroups at elevated risk of metastasis.

Patient expectations may be associated with outcomes of complementary and alternative medicine (CAM) treatments for chronic pain. However, a psychometrically sound measure of such expectations is needed.The purpose of this study was to develop and evaluate a questionnaire to assess individuals' expectations regarding outcomes of CAM treatments for chronic low back pain (CLBP), as well as a short form of the questionnaire.An 18-item draft questionnaire was developed through literature review, cognitive interviews with individuals with CLBP, CAM practitioners, and expert consultation. Two samples completed the questionnaire: (1) a community sample (n = 141) completed it via an online survey before or soon after starting a CAM treatment for CLBP, and (2) participants (n = 181) in randomized clinical trials evaluating CAM treatments for CLBP or fibromyalgia completed it prior to or shortly after starting treatment. Factor structure, internal consistency, test-retest reliability, and criterion validity were examined.Based on factor analyses, 10 items reflecting expectations (used to create a total score) and three items reflecting hopes (not scored) were selected for the questionnaire. The questionnaire had high internal consistency, moderate test-retest reliability, and moderate correlations with other measures of expectations. A three-item short form also had adequate reliability and validity.The Expectations for Complementary and Alternative Medicine Treatments (EXPECT) questionnaire can be used in research to assess individuals' expectations of treatments for chronic pain. It is recommended that the three hope questions are included (but not scored) to help respondents distinguish between hopes and expectations. The short form may be appropriate for clinical settings and when expectation measurement is not a primary focus.

Background Active surveillance (AS) is an accepted means of managing low-risk prostate cancer. Because of the rarity of downstream events, data from existing AS cohorts cannot yet address how differences in surveillance intensity affect metastasis and mortality. This study projected the comparative benefits of different AS schedules in men diagnosed with prostate cancer who had Gleason score (GS) ≤6 disease and risk profiles similar to those in North American AS cohorts. Methods Times of GS upgrading were simulated based on AS data from the University of Toronto, Johns Hopkins University, the University of California at San Francisco, and the Canary Pass Active Surveillance Cohort. Times to metastasis and prostate cancer death, informed by models from the Scandinavian Prostate Cancer Group 4 trial, were projected under biopsy surveillance schedules ranging from watchful waiting to annual biopsies. Outcomes included the risk of metastasis, the risk of death, remaining life-years (LYs), and quality-adjusted LYs. Results Compared with watchful waiting, AS biopsies reduced the risk of prostate cancer metastasis and prostate cancer death at 20 years by 1.4% to 3.3% and 1.0% to 2.4%, respectively; and 5-year biopsies reduced the risk of metastasis and prostate cancer death by 1.0% to 2.4% and 0.6% to 1.6%, respectively. There was little difference between annual and 5-year biopsy schedules in terms of LYs (range of differences, 0.04-0.16 LYs) and quality-adjusted LYs (range of differences, -0.02 to 0.09 quality-adjusted LYs). Conclusions Among men diagnosed with GS ≤6 prostate cancer, obtaining a biopsy every 3 or 4 years appears to be an acceptable alternative to more frequent biopsies. Reducing surveillance intensity for those who have a low risk of progression reduces the number of biopsies while preserving the benefit of more frequent schedules.

Diagnostic evaluation of suspected breast cancer due to abnormal screening mammography results is common, creates anxiety for women and is costly for the healthcare system. Timely evaluation with minimal use of additional diagnostic testing is key to minimizing anxiety and cost. In this paper, we propose a Bayesian semi-Markov model that allows for flexible, semi-parametric specification of the sojourn time distributions and apply our model to an investigation of the process of diagnostic evaluation with mammography, ultrasound and biopsy following an abnormal screening mammogram. We also investigate risk factors associated with the sojourn time between diagnostic tests. By utilizing semi-Markov processes, we expand on prior work that described the timing of the first test received by providing additional information such as the mean time to resolution and proportion of women with unresolved mammograms after 90 days for women requiring different sequences of tests in order to reach a definitive diagnosis. Overall, we found that older women were more likely to have unresolved positive mammograms after 90 days. Differences in the timing of imaging evaluation and biopsy were generally on the order of days and thus did not represent clinically important differences in diagnostic delay. Copyright © 2016 John Wiley & Sons, Ltd.

There is a need for automated approaches to incorporate information on cancer recurrence events into population-based cancer registries.The aim of this study is to determine the accuracy of a novel data mining algorithm to extract information from linked registry and medical claims data on the occurrence and timing of second breast cancer events (SBCE).We used supervised data from 3092 stage I and II breast cancer cases (with 394 recurrences), diagnosed between 1993 and 2006 inclusive, of patients at Kaiser Permanente Washington and cases in the Puget Sound Cancer Surveillance System. Our goal was to classify each month after primary treatment as pre- versus post-SBCE. The prediction feature set for a given month consisted of registry variables on disease and patient characteristics related to the primary breast cancer event, as well as features based on monthly counts of diagnosis and procedure codes for the current, prior, and future months. A month was classified as post-SBCE if the predicted probability exceeded a probability threshold (PT); the predicted time of the SBCE was taken to be the month of maximum increase in the predicted probability between adjacent months.The Kaplan-Meier net probability of SBCE was 0.25 at 14 years. The month-level receiver operating characteristic curve on test data (20% of the data set) had an area under the curve of 0.986. The person-level predictions (at a monthly PT of 0.5) had a sensitivity of 0.89, a specificity of 0.98, a positive predictive value of 0.85, and a negative predictive value of 0.98. The corresponding median difference between the observed and predicted months of recurrence was 0 and the mean difference was 0.04 months.Data mining of medical claims holds promise for the streamlining of cancer registry operations to feasibly collect information about second breast cancer events.

Importance Atypical ductal hyperplasia (ADH) is a known risk factor for breast cancer. Published risk estimates are based on cohorts that included women whose ADH was diagnosed before widespread use of screening mammograms and did not differentiate between the methods used to diagnose ADH, which may be related to the size of the ADH focus. These risks may overestimate the risk in women with presently diagnosed ADH. Objective To examine the risk of invasive cancer associated with ADH diagnosed using core needle biopsy vs excisional biopsy. Design A cohort study was conducted comparing the 10-year cumulative risk of invasive breast cancer in 955 331 women undergoing mammography with and without a diagnosis of ADH. Data were obtained from 5 breast imaging registries that participate in the National Cancer Institute–funded Breast Cancer Surveillance Consortium. Exposures Diagnosis of ADH on core needle biopsy or excisional biopsy in women undergoing mammography. Main Outcomes and Measures Ten-year cumulative risk of invasive breast cancer. Results The sample included 955 331 women with 1727 diagnoses of ADH, 1058 (61.3%) of which were diagnosed by core biopsy and 635 (36.8%) by excisional biopsy. The mean (interquartile range) age of the women at diagnosis was 52.6 (46.9-60.4) years. From 1996 to 2012, the proportion of ADH diagnosed by core needle biopsy increased from 21% to 77%. Ten years following a diagnosis of ADH, the cumulative risk of invasive breast cancer was 2.6 (95% CI, 2.0-3.4) times higher than the risk in women with no ADH. Atypical ductal hyperplasia diagnosed via excisional biopsy was associated with an adjusted hazard ratio (HR) of 3.0 (95% CI, 2-4.5) and, via core needle biopsy, with an adjusted HR of 2.2 (95% CI, 1.5-3.4). Ten years after an ADH diagnosis, an estimated 5.7% (95% CI, 4.3%-10.1%) of the women had a diagnosis of invasive cancer. Women with ADH diagnosed on excisional biopsy had a slightly higher risk (6.7%; 95% CI, 3.0%-12.8%) compared with those with ADH diagnosed via core needle biopsy (5%; 95% CI, 2.2%-8.9%). Conclusions and Relevance Current 10-year risks of invasive breast cancer after a diagnosis of ADH may be lower than those previously reported. The risk associated with ADH is slightly lower for women whose ADH was diagnosed by needle core biopsy compared with excisional biopsy.

BACKGROUND The standard treatment of pulmonary metastases in patients with Wilms tumor (WT) includes 12-gray radiotherapy (RT) to the entire chest. To the authors' knowledge, the risk of breast cancer (BC) in a large cohort of female survivors of WT has not previously been reported. METHODS A total of 2492 female participants in National Wilms Tumor Studies 1 through 4 (1969-1995) were followed from age 15 years through the middle of 2013 for incident BC. The median age at the time of last contact was 27.3 years. The authors calculated cumulative risk at age 40 years (CR40), hazard ratios (HR) by Cox regression, standardized incidence ratios (SIRs) relative to US population rates, and 95% confidence intervals (95% CIs). RESULTS The numbers of survivors with invasive BC divided by the numbers at risk were 16 of 369 (CR40, 14.8% [95% CI, 8.7-24.5]) for women who received chest RT for metastatic WT, 10 of 894 (CR40, 3.1% [95% CI, 1.3-7.41]) for those who received only abdominal RT, and 2 of 1229 (CR40, 0.3% [95% CI, 0.0-2.3]) for those who received no RT. The SIRs for these 3 groups were 27.6 (95% CI, 16.1-44.2) based on 5010 person-years (PY) of follow-up, 6.0 (95% CI, 2.9-11.0) based on 13,185 PY of follow-up, and 2.2 (95% CI, 0.3-7.8) based on 13,560 PY of follow-up, respectively. The risk was high regardless of the use of chest RT among women diagnosed with WT at age ≥10 years, with 9 of 90 women developing BC (CR40, 13.5% [95% CI, 5.6-30.6]; SIR, 23.6 [95% CI, 10.8-44.8] [PY, 1463]). CONCLUSIONS Female survivors of WT who were treated with chest RT had a high risk of developing early BC, with nearly 15% developing invasive disease by age 40 years. Current guidelines that recommend screening only those survivors who received ≥20 Gy of RT to the chest might be reevaluated. Cancer 2014;120:3722–3730. © 2014 American Cancer Society.

Multistate models are used to characterize individuals’ natural histories through diseases with discrete states. Observational data resources based on electronic medical records pose new opportunities for studying such diseases. However, these data consist of observations of the process at discrete sampling times, which may either be pre-scheduled and non-informative, or symptom-driven and informative about an individual’s underlying disease status. We have developed a novel joint observation and disease transition model for this setting. The disease process is modeled according to a latent continuous-time Markov chain; and the observation process, according to a Markov-modulated Poisson process with observation rates that depend on the individual’s underlying disease status. The disease process is observed at a combination of informative and non-informative sampling times, with possible misclassification error. We demonstrate that the model is computationally tractable and devise an expectation-maximization algorithm for parameter estimation. Using simulated data, we show how estimates from our joint observation and disease transition model lead to less biased and more precise estimates of the disease rate parameters. We apply the model to a study of secondary breast cancer events, utilizing mammography and biopsy records from a sample of women with a history of primary breast cancer.

BACKGROUND: Perceptions of injustice are linked with poorer physical and psychological outcomes in the context of pain and injury. Violations of injustice can arise out of violations of just world belief (JWB). However, no study has yet examined whether JWB moderates the effect of justice violation on pain experience. METHODS: The current study examined the effect of an experimental justice violation on acute pain outcomes and whether JWB moderated this effect. Participants completed the JWB scale and then engaged in two cold pressor tasks (CPT). Half the participants were told that the second CPT immersion was part of standard protocol; the other half were told that the painful procedure had to be repeated due to experimenter negligence. Participants provided report of pain intensity following each CPT immersion. Video records of participants undergoing the CPT were coded for presence and duration of pain behaviour. RESULTS: Exposure to the justice violation resulted in elevated pain intensity from the first to the second immersion only among participants with high JWB. For participants with low JWB and participants in the control condition, there was no significant difference in pain intensity across immersions. Control participants showed a decrease in pain behaviour from the first to the second immersion. In the negligence/ justice violation condition, reductions in pain behaviour were observed only among participants with low JWB. CONCLUSIONS: Our results indicate that individuals with high JWB may show particularly adverse reactions in response to justice violations in the context of acute pain experience. Language: en

Purpose This study was undertaken to evaluate the incidence of pulmonary disease among patients treated with radiation therapy (RT) for pulmonary metastases (PM) from Wilms tumor (WT). Patients and Methods We reviewed records of 6,449 patients treated on National Wilms Tumor Studies-1, -2, -3, and -4 whose flow sheets or annual status reports documented one of several pulmonary conditions. Cases were fully evaluable if pulmonary function test (PFT) results were available, pulmonary fibrosis was identified on a chest radiograph or was listed as the primary or a contributing factor to death. Partially evaluable cases were those for whom PFT results could not be obtained. We evaluated the relationship between RT factors and the occurrence of pulmonary disease using hazard ratios (HRs) and cumulative incidence, treating death as a competing risk. Results Sixty-four fully evaluable and 16 partially evaluable cases of pulmonary disease were identified. The cumulative incidence of pulmonary disease at 15 years since WT diagnosis was 4.0% (95% confidence interval [CI] 2.6–5.4%) among fully evaluable and 4.8% (95% CI 3.3–6.4%) among fully and partially evaluable patients who received lung RT for PM at initial diagnosis. Rates of pulmonary disease were substantially higher among those who received lung RT for PM present at initial diagnosis or relapse compared to those who received no RT or only abdominal RT (HR 30.2, 95% CI 16.9–53.9). Conclusion The risk of pulmonary disease must be considered in evaluating the risk:benefit ratio of lung RT for the management of PM from WT. Pediatr Blood Cancer 2013;60:1721–1726. © 2013 Wiley Periodicals, Inc.

Multistate models are used to characterize disease processes within an individual. Clinical studies often observe the disease status of individuals at discrete time points, making exact times of transitions between disease states unknown. Such panel data pose considerable modeling challenges. Assuming the disease process progresses according a standard continuous-time Markov chain (CTMC) yields tractable likelihoods, but the assumption of exponential sojourn time distributions is typically unrealistic. More flexible semi-Markov models permit generic sojourn distributions yet yield intractable likelihoods for panel data in the presence of reversible transitions. One attractive alternative is to assume that the disease process is characterized by an underlying latent CTMC, with multiple latent states mapping to each disease state. These models retain analytic tractability due to the CTMC framework but allow for flexible, duration-dependent disease state sojourn distributions. We have developed a robust and efficient expectation-maximization (EM) algorithm in this context. Our complete data state space consists of the observed data and the underlying latent trajectory, yielding computationally efficient expectation and maximization steps. Our algorithm outperforms alternative methods measured in terms of time to convergence and robustness. We also examine the frequentist performance of latent CTMC point and interval estimates of disease process functionals based on simulated data. The performance of estimates depends on time, functional, and data-generating scenario. Finally, we illustrate the interpretive power of latent CTMC models for describing disease processes on a data-set of lung transplant patients. We hope our work will encourage wider use of these models in the biomedical setting.

Observational learning may contribute to development and maintenance of pain-related beliefs and behaviors. The current study examined whether observation of video primes could impact appraisals of potential back stressing activities, and whether this relationship was moderated by individual differences in pain-related fear. Participants viewed a video prime in which back-stressing activity was associated with pain and injury. Both before and after viewing the prime, participants provided pain and harm ratings of standardized movements drawn from the Photograph of Daily Activities Scale (PHODA). Results indicated that observational learning occurred for participants with high levels of pain-related fear but not for low fear participants. Specifically, following prime exposure, high fear participants showed elevated pain appraisals of activity images whereas low fear participants did not. High fear participants appraised the PHODA-M images as significantly more harmful regardless of prime exposure. The findings highlight individual moderators of observational learning in the context of pain.

Background Characterizing geographic access depends on a broad range of methods available to researchers and the healthcare context to which the method is applied. Globally, travel time is one frequently used measure of geographic access with known limitations associated with data availability. Specifically, due to lack of available utilization data, many travel time studies assume that patients use the closest facility. To examine this assumption, an example using mammography screening data, which is considered a geographically abundant health care service in the United States, is explored. This work makes an important methodological contribution to measuring access—which is a critical component of health care planning and equity almost everywhere. Method We analyzed one mammogram from each of 646,553 women participating in the US based Breast Cancer Surveillance Consortium for years 2005–2012. We geocoded each record to street level address data in order to calculate travel time to the closest and to the actually used mammography facility. Travel time between the closest and the actual facility used was explored by woman-level and facility characteristics. Results Only 35 % of women in the study population used their closest facility, but nearly three-quarters of women not using their closest facility used a facility within 5 min of the closest facility. Individuals that by-passed the closest facility tended to live in an urban core, within higher income neighborhoods, or in areas where the average travel times to work was longer. Those living in small towns or isolated rural areas had longer closer and actual median drive times. Conclusion Since the majority of US women accessed a facility within a few minutes of their closest facility this suggests that distance to the closest facility may serve as an adequate proxy for utilization studies of geographically abundant services like mammography in areas where the transportation networks are well established.

We assessed risk factors for end stage renal disease in patients with Wilms tumor without known WT1 related syndromes. We hypothesized that patients with characteristics suggestive of a WT1 etiology (early onset, stromal predominant histology, intralobar nephrogenic rests) would have a higher risk of end stage renal disease due to chronic renal failure. We predicted a high risk of end stage renal disease due to progressive bilateral Wilms tumor in patients with metachronous bilateral disease.End stage renal disease was ascertained in 100 of 7,950 nonsyndromic patients enrolled in a National Wilms Tumor Study during 1969 to 2002. Risk factors were evaluated with cumulative incidence curves and proportional hazard regressions.The cumulative incidence of end stage renal disease due to chronic renal failure 20 years after Wilms tumor diagnosis was 0.7%. For end stage renal disease due to progressive bilateral Wilms tumor the incidence was 4.0% at 3 years after diagnosis in patients with synchronous bilateral Wilms tumor and 19.3% in those with metachronous bilateral Wilms tumor. For end stage renal disease due to chronic renal failure stromal predominant histology had a HR of 6.4 relative to mixed (95% CI 3.4, 11.9; p0.001), intralobar rests had a HR of 5.9 relative to no rests (95% CI 2.0, 17.3; p=0.001), and Wilms tumor diagnosis at less than 24 months had a HR of 1.7 relative to 24 to 48 months and 2.8 relative to greater than 48 months (p=0.003 for trend).Metachronous bilateral Wilms tumor is associated with high rates of end stage renal disease due to surgery for progressive Wilms tumor. Characteristics associated with a WT1 etiology markedly increased the risk of end stage renal disease due to chronic renal failure despite the low risk in non-WT1 syndromic cases overall.

Purpose This study was undertaken to evaluate the effect of prior treatment with radiation therapy or chemotherapy for unilateral Wilms tumor (WT) diagnosed during childhood on pregnancy complications, birth weight, and the frequency of congenital malformations in live-born offspring. Patients and Methods We reviewed pregnancy outcomes among female survivors and partners of male survivors of WT treated on National Wilms Tumor Studies 1, 2, 3, and 4 by using a maternal questionnaire and a review of both maternal and offspring medical records. Results We received reports of 1,021 pregnancies with duration of 20 weeks or longer, including 955 live-born singletons, for whom 700 sets of maternal and offspring medical records were reviewed. Rates of hypertension complicating pregnancy (International Classification of Diseases [ICD] code 642), early or threatened labor (ICD-644) and malposition of the fetus (ICD-652) increased with increasing radiation dose in female patients. The percentages of offspring weighing less than 2,500 g at birth and of those having less than 37 weeks of gestation also increased with dose. There was no significant trend with radiation dose in the number of congenital anomalies recorded in offspring of female patients. Conclusion Women who receive flank radiation therapy as part of the treatment for unilateral WT are at increased risk of hypertension complicating pregnancy, fetal malposition, and premature labor. The offspring of these women are at risk for low birth weight and premature (ie, < 37 weeks gestation) birth. These risks must be considered in the obstetrical management of female survivors of WT.

Objective: This study examined the extent to which stigma-related concerns about mental health care account for the underuse of mental health services among low-income immigrant and U.S.-born black and Latina women. Methods: Participants included 15,383 low-income women screened for depression in county entitlement services who were asked about barriers to care, stigma-related concerns, and whether they wanted or were getting mental health care. Results: Among those who were depressed, compared with U.S.-born white women, each of the black groups were more likely to report stigma concerns (African immigrants, odds ratio [OR]=3.28, p=.004; Caribbean immigrants, OR=6.17, p=.005; U.S.-born blacks, OR=6.17, p=.06). Compared with U.S.-born white women, immigrant African women (OR=.18, p

The standard treatment of pulmonary metastases in patients with Wilms tumor (WT) includes 12-gray radiotherapy (RT) to the entire chest. To the authors' knowledge, the risk of breast cancer (BC) in a large cohort of female survivors of WT has not previously been reported.A total of 2492 female participants in National Wilms Tumor Studies 1 through 4 (1969-1995) were followed from age 15 years through the middle of 2013 for incident BC. The median age at the time of last contact was 27.3 years. The authors calculated cumulative risk at age 40 years (CR40), hazard ratios (HR) by Cox regression, standardized incidence ratios (SIRs) relative to US population rates, and 95% confidence intervals (95% CIs).The numbers of survivors with invasive BC divided by the numbers at risk were 16 of 369 (CR40, 14.8% [95% CI, 8.7-24.5]) for women who received chest RT for metastatic WT, 10 of 894 (CR40, 3.1% [95% CI, 1.3-7.41]) for those who received only abdominal RT, and 2 of 1229 (CR40, 0.3% [95% CI, 0.0-2.3]) for those who received no RT. The SIRs for these 3 groups were 27.6 (95% CI, 16.1-44.2) based on 5010 person-years (PY) of follow-up, 6.0 (95% CI, 2.9-11.0) based on 13,185 PY of follow-up, and 2.2 (95% CI, 0.3-7.8) based on 13,560 PY of follow-up, respectively. The risk was high regardless of the use of chest RT among women diagnosed with WT at age ≥10 years, with 9 of 90 women developing BC (CR40, 13.5% [95% CI, 5.6-30.6]; SIR, 23.6 [95% CI, 10.8-44.8] [PY, 1463]).Female survivors of WT who were treated with chest RT had a high risk of developing early BC, with nearly 15% developing invasive disease by age 40 years. Current guidelines that recommend screening only those survivors who received ≥20 Gy of RT to the chest might be reevaluated.

Multistate models are used to characterize individuals’ natural histories through diseases with discrete states. Observational data resources based on electronic medical records pose new opportunities for studying such diseases. However, these data consist of observations of the process at discrete sampling times, which may either be pre-scheduled and non-informative, or symptom-driven and informative about an individual’s underlying disease status. We have developed a novel joint observation and disease transition model for this setting. The disease process is modeled according to a latent continuous-time Markov chain; and the observation process, according to a Markov-modulated Poisson process with observation rates that depend on the individual’s underlying disease status. The disease process is observed at a combination of informative and non-informative sampling times, with possible misclassification error. We demonstrate that the model is computationally tractable and devise an expectation-maximization algorithm for parameter estimation. Using simulated data, we show how estimates from our joint observation and disease transition model lead to less biased and more precise estimates of the disease rate parameters. We apply the model to a study of secondary breast cancer events, utilizing mammography and biopsy records from a sample of women with a history of primary breast cancer.

textabstractBackground: Estimates of risk for radiation-induced breast cancer from mammography screening have not considered variation in dose exposure or diagnostic work-up after abnormal screening results. Objective: To estimate distributions of radiation-induced breast cancer incidence and mortality from digital mammography screening while considering exposure from screening and diagnostic mammography and dose variation among women. Design: 2 simulation-modeling approaches. Setting: U.S. population. Patients: Women aged 40 to 74 years. Intervention: Annual or biennial digital mammography screening from age 40, 45, or 50 years until age 74 years. Measurements: Lifetime breast cancer deaths averted (bene-fits) and radiation-induced breast cancer incidence and mortality (harms) per 100 000 women screened. Results: Annual screening of 100 000 women aged 40 to 74 years was projected to induce 125 breast cancer cases (95% CI, 88 to 178) leading to 16 deaths (CI, 11 to 23), relative to 968 breast cancer deaths averted by early detection from screening. Women exposed at the 95th percentile were projected to develop 246 cases of radiation-induced breast cancer leading to 32 deaths per 100 000 women. Women with large breasts requiring extra views for complete examination (8% of population) were projected to have greater radiation-induced breast cancer risk (266 cancer cases and 35 deaths per 100 000 women) than other women (113 cancer cases and 15 deaths per 100 000 women). Biennial screening starting at age 50 years reduced risk for radiation-induced cancer 5-fold. Limitation: Life-years lost from radiation-induced breast cancer could not be estimated. Conclusion: Radiation-induced breast cancer incidence and mortality from digital mammography screening are affected by dose variability from screening, resultant diagnostic work-up, initiation age, and screening frequency. Women with large breasts may have a greater risk for radiation-induced breast cancer. Primary Funding Source: Agency for Healthcare Research and Quality, U.S. Preventive Services Task Force, National Cancer Institute.

Lernen durch Beobachtung kann die Entwicklung schmerzassoziierter Uberzeugungen und Verhaltensweisen beeinflussen. Trost et al. von der University of North Texas untersuchten diesen Zusammenhang in einem experimentellen Ansatz an gesunden Versuchspersonen.

A combined cohort of 8,884 North American, 2,893 British and 1,574 Nordic subjects with Wilms tumor (WT) diagnosed before 15 years of age during 1960–2004 was established to determine the risk of secondary malignant neoplasms (SMN). After 169,641 person-years (PY) of observation through 2005, 174 solid tumors (exclusive of basal cell carcinomas) and 28 leukemias were ascertained in 195 subjects. Median survival time following a solid SMN diagnosis 5 years or more from WT was 11 years; it was 10 months for all leukemia. Age-specific incidence of secondary solid tumors increased from approximately 1 case per 1,000 PY at age 15 to 5 cases per 1,000 PY at age 40. The cumulative incidence of solid tumors at age 40 for subjects who survived free of SMNs to age 15 was 6.7%. Leukemia risk, by contrast, was highest during the first 5 years following WT diagnosis. Standardized incidence ratios (SIRs) for solid tumors and leukemias were 5.1 and 5.0, respectively. Results for solid tumors for the 3 geographic areas were remarkably consistent; statistical tests for differences in incidence rates and SIRs were all negative. Age-specific incidence rates and SIRs for solid tumors were lower for patients whose WT was diagnosed after 1980, though the trends with decade of diagnosis were not statistically significant. Incidence rates and SIRs for leukemia were highest among those diagnosed after 1990 (p-trend =0.003). These trends may reflect the decreasing use of radiation therapy and increasing intensity of chemotherapy in modern protocols for treatment of WT.

Racial-ethnic diversity among children in the United States is increasing. In 2000 children from minority groups accounted for 39% of the population under 18 (1), and the proportion is projected to rise to 48% in the next quarter century (2). Increasingly, evidence-based mental health interventions have been found effective for youths from ethnic minority groups (3,4). Nevertheless, these children are less likely than white youths to receive high-quality mental health services (5,6) and more likely to leave treatment prematurely (7). Strategies for addressing mental health disparities among youths are needed, because untreated depression in this population is associated with suicide, school dropout, pregnancy, substance abuse, and depression in adulthood (8-14). A promising approach to address health disparities has been to improve the quality of mental health services provided in primary care settings (15-18), because primary care is a gateway to mental health care for individuals from racial-ethnic minority groups. Quality improvement interventions in primary care settings aimed at improving access to evidence-based depression treatments have been found to be more effective than usual care for diverse groups of depressed adults (16,17,19), elderly persons (20), and adolescents from diverse backgrounds (21). In the Partners in Care study of adults, intervention effects on clinical outcomes were greatest for blacks and Latinos (22). The quality improvement interventions significantly decreased the likelihood of participant reports of probable depression at six- and 12-month follow-ups for blacks and Latinos in the study, whereas their white counterparts showed no such difference (22). In the IMPACT study of elderly adults, all racial-ethnic groups (blacks, Latinos, and whites) in the quality improvement condition showed greater rates of depression care, lower depression severity, and less health-related functional impairments than patients in the usual care group (23). No study has examined racial-ethnic differences in the impact of quality improvement interventions in an adolescent population. Youth Partners in Care is the first and largest study to evaluate a quality improvement intervention for depression among youths that was delivered in primary care settings. Results indicated that quality improvement aimed at increasing rates of evidence-based depression care (primarily cognitive-behavior therapy [CBT] and medication) was associated with improved depression and quality-of-life outcomes, satisfaction with care, and increased rates of care—primarily counseling (21). The study reported here examined the differential impact of the quality improvement intervention among racial-ethnic groups, with the overall goal of informing efforts to decrease mental health disparities and improve outcomes for youths from minority groups. We hypothesized that racial-ethnic differences similar to those found in studies of adults would result from the quality improvement intervention, such that black and Latino youths would report greater improvement in depression symptoms than their white counterparts six months after the intervention.

To examine perceived need for care for mental health problems as a possible contributor to ethnic disparities in receiving care among low-income depressed women.The role of ethnicity, somatization, and stigma as they relate to perceived need for care is examined. Participants were 1577 low-income women who met criteria for depression.Compared with U.S.-born depressed white women, most depressed ethnic minority women were less likely to perceive a need for mental health care (black immigrants: OR 0.30, p0.001; U.S.-born blacks: OR 0.43, p0.001; immigrant Latinas: OR 0.52, p0.01). Stigma-related concerns decreased the likelihood of perceiving a need for mental health care (OR 0.80, p0.05). Having multiple somatic symptoms (OR 1.57, p0.001) increased the likelihood of endorsing perceived need.Findings suggest that there are ethnic differences in perceived need for mental healthcare that may partially account for the low rates of care for depression among low-income and minority women. The relations among stigma, somatization, and perceived need were strikingly similar across ethnic groups.

Mental health care preferences are examined among 1,893 low-income immigrant and U.S.-born women with an acknowledged emotional problem (mean age = 29.1, SD = 89.6). Ethnicity, depression, somatization, and stigma are examined as they relate to mental health care preferences (medication, individual and group counseling, faith, family/friends). Seventy-eight percent of participants counseling would be helpful; 55%; group counseling; and 32% medication. Faith was cited by 81%; family and friends were endorsed by 65%. Minorities had lower odds than Whites of endorsing medication (Black immigrants: OR = 0.27, p < 0.001, U.S.-born Blacks: OR = 0.30, p < 0.001, immigrant Latinas: OR = 0.50, p < 0.01). Most minorities also had higher odds of endorsing faith compared to Whites (Black immigrants: OR = 3.62, p < 0.001; U.S.-born Blacks, OR = 3.85, p < 0.001; immigrant Latinas: OR = 9.76, p < 0.001). Being depressed was positively associated with endorsing medication (OR = 1.93, p < 0.001), individual counseling (OR = 2.66, p < 0.001), and group counseling (OR = 1.35, p < 0.01). Somatization was positively associated with endorsing medication (OR = 1.29, p < 0.05) and faith (OR = 1.37, p < 0.05). Stigma-concerns reduced the odds of endorsing group counseling (OR = 0.58, p < 0.001). Finally, being in mental health treatment was related to increased odds of endorsing medication (OR = 3.88, p < 0.001) and individual counseling (OR = 2.29, p = 0.001).

Low-risk elective surgical procedures are common, but there are no clear guidelines for when preoperative consultations are required. Such consultations may therefore represent a substantial discretionary service.To assess temporal trends, explanatory factors, and geographic variation for preoperative consultation in Medicare beneficiaries undergoing cataract surgery, a common low-risk elective procedure.Cohort study using a 5% national random sample of Medicare part B claims data including a cohort of 556,637 patients 66 years or older who underwent cataract surgery from 1995 to 2006. Temporal trends in consultations were evaluated within this entire cohort, whereas explanatory factors and geographic variation were evaluated within the 89,817 individuals who underwent surgery from 2005 to 2006.Separately billed preoperative consultations (performed by family practitioners, general internists, pulmonologists, endocrinologists, cardiologists, nurse practitioners, or anesthesiologists) within 42 days before index surgery.The frequency of preoperative consultations increased from 11.3% in 1998 to 18.4% in 2006. Among individuals who underwent surgery in 2005 to 2006, hierarchical logistic regression modeling found several factors to be associated with preoperative consultation, including increased age (75-84 years vs 66-74 years: adjusted odds ratio [AOR], 1.09 [95% CI, 1.04-1.13]), race (African American race vs other: AOR, 0.71 [95% CI, 0.65-0.78]), urban residence (urban residence vs isolated rural town: AOR, 1.64 [95% CI, 1.49-1.81]), facility type (outpatient hospital vs ambulatory surgical facility: AOR, 1.10 [95% CI, 1.05-1.15]), anesthesia provider (anesthesiologist vs non-medically directed nurse anesthetist: AOR, 1.16 [95% CI, 1.10-1.24), and geographic region (Northeast vs South: AOR, 3.09 [95% CI, 2.33-4.10]). The burden of comorbidity was associated with consultation, but the effect size was small (10%). Variation in frequency of consultation across hospital referral regions was substantial (median [range], 12% [0-69%]), even after accounting for differences in patient-level, anesthesia provider-level, and facility-level characteristics.Between 1995 and 2006, the frequency of preoperative consultation for cataract surgery increased substantially. Referrals for consultation seem to be primarily driven by nonmedical factors, with substantial geographic variation.