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Background: Multiple nutritional screening tools are available for older people; however, few screening tools include specific eating behaviours as risk factors that could lead to poor food intake. The 24-item mealtime observation checklist (MOCL), developed by the Japanese Ministry of Health, Labour and Welfare in 2015, comprises signs, symptoms and conditions during mealtime that reflect eating and swallowing functions and oral conditions., Objectives: To examine factors associated with malnutrition among the MOCL items in older people., Methods: A cross-sectional study was conducted using data from a retrospective cohort study conducted at four long-term care facilities in Japan. Among the older people residing in the facilities, 198 who received oral intake support were included in the analyses. Nutritional status was assessed using the Mini Nutritional Assessment-Short Form (MNA ® -SF), and comparisons were made between 'malnutrition' and 'at-risk or well-nourished'. The association between each MOCL item and malnutrition was assessed using multivariable logistic regression analysis., Results: Of the 198 participants, 98 (49.5%) were classified as 'malnutrition', 98 (49.5%) as 'at-risk' and 2 (1%) as 'well-nourished' by MNA ® -SF. After adjusting for participant characteristics such as age and sex, significant associations with malnutrition were observed for four items from the 24-item MOCL: 'Has fatigue due to extended mealtime (odds ratio [OR] = 3.20, 95% confidence interval [CI]: 1.36-7.53)', 'Food residues in the oral cavity are conspicuous (OR = 2.77, 95% CI: 1.38-5.52)', 'Has difficulty swallowing food and takes time to swallow (OR = 3.78, 95% CI: 1.45-9.84)' and 'Assisted feeding is required (OR = 3.70, 95% CI: 1.73-7.91)'., Conclusions: The four signs, symptoms and conditions during mealtime identified in this study may be associated with malnutrition in older people., Implications for Practice: These may indicate the potential eating problems that can lead to malnutrition. By incorporating them into early intervention and prevention measures, health care providers may help prevent malnutrition and improve the nutritional status of older people., (© 2024 John Wiley & Sons Ltd.)

Background: Siblings of children with cancer may experience adverse household economic consequences, but their financial outcomes in adulthood are unknown., Methods: A total of 880 siblings (aged 18-64 years) of adult-aged childhood cancer survivors were surveyed to estimate the prevalence of financial hardship by three established domains (behavioral, material, and psychological). For individual financial hardship items matching the contemporaneous National Health Interview Survey or Behavioral Risk Factor Surveillance System, siblings were compared with the general population by calculating adjusted prevalence odds ratios (ORs) to sample-weighted responses. Multivariable logistic regression models examined associations between sibling characteristics and each hardship domain and between sibling hardship and survivors' cancer/treatment characteristics., Results: Behavioral, material, and psychological hardship was reported by 24%, 35%, and 28%, respectively. Compared with national survey respondents, siblings were more likely to report worries about medical bills (OR, 1.14; 95% confidence interval [CI], 1.06-1.22), difficulty affording nutritious foods (OR, 1.79; 95% CI, 1.54-2.07), and forgoing needed medical care (OR, 1.38; 95% CI, 1.10-1.73), prescription medications (OR, 2.52; 95% CI, 1.99-3.20), and dental care (OR, 1.34; 95% CI, 1.15-1.57) because of cost. Sibling characteristics associated with reporting financial hardship in one or more domains included female sex, older age, chronic health conditions, lower income, not having health insurance, high out-of-pocket medical expenditures, and nonmedical/nonhome debt. No survivor cancer/treatment characteristics were associated with sibling financial hardship., Conclusions: Adult siblings of childhood cancer survivors were more likely to experience financial hardship compared with the general population. Childhood cancer may adversely affect entire households, with potentially lasting implications., (© 2023 American Cancer Society.)

In health-science research, outcomes ascertained through surveys and interviews are subject to potential bias with respect to the true outcome status, which is only ascertainable with clinical and laboratory assessment. This measurement error may lead to biased inference when evaluating associations between exposures and outcomes of interest. Here, we consider a cohort study in which the outcome of interest is ascertained via questionnaire, subject to imperfect ascertainment, but where a subset of participants also have a clinically assessed, validated outcome available. This presents a methodological opportunity to address potential bias. Specifically, we constructed the likelihood in two parts, one using the validated subset and the other using a subset without validation. This work expands on that proposed by Pepe and enables inference with standard statistical software. Weighted generalized linear model estimates for our method and maximum likelihood estimates (MLE) for Pepe's method were computed, and the statistical inference was based on the standard large-sample likelihood theory. We compare the finite sample performance of two approaches through Monte Carlo simulations. This methodological work was motivated by a large cohort study of long-term childhood cancer survivors, allowing us to provide a relevant application example where we examined the association between clinical factors and chronic health conditions., (© 2023 John Wiley & Sons Ltd.)

Background: Treatment exposures for childhood cancer reduce ovarian reserve. However, the success of assisted reproductive technology (ART) among female survivors is not well established., Methods: Five-year survivors of childhood cancer in the Childhood Cancer Survivor Study were linked to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System, which captures national ART outcomes. The authors assessed the live birth rate, the relative risk (RR) with 95% confidence intervals (95% CIs), and associations with treatment exposure using generalized estimating equations to account for multiple ovarian stimulations per individual. Siblings from a random sample of survivors were recruited to serve as a comparison group., Results: Among 9885 female survivors, 137 (1.4%; median age at diagnosis, 10 years [range, 0-20 years]; median years of follow-up after age 18 years, 11 years [range, 2-11 years]) underwent 224 ovarian stimulations using autologous or donor eggs and/or gestational carriers (157 autologous ovarian stimulation cycles, 67 donor ovarian stimulation cycles). In siblings, 33 (1.4%) underwent 51 autologous or donor ovarian stimulations. Of those who used embryos from autologous eggs without using gestational carriers, 97 survivors underwent 155 stimulations, resulting in 49 live births, for a 31.6% chance of live birth per ovarian stimulation (vs. 38.3% for siblings; p = .39) and a 43.9% chance of live birth per transfer (vs. 50.0%; p = .33). Prior treatment with cranial radiation therapy (RR, 0.44; 95% CI, 0.20-0.97) and pelvic radiation therapy (RR, 0.33; 95% CI, 0.15-0.73) resulted in a reduced chance of live birth compared with siblings. The likelihood of live birth after ART treatment in survivors was not affected by alkylator exposure (cyclophosphamide-equivalent dose, ≥8000 mg/m 2 vs. none; RR, 1.04; 95% CI, 0.52-2.05)., Conclusions: Childhood cancer survivors are as likely to undergo treatment using ART as sibling controls. The success of ART treatment was not reduced after alkylator exposure. The results from the current study provide needed guidance on the use of ART in this population., (© 2023 American Cancer Society.)

Background: For the lack of standardized activated partial thromboplastin time (APTT), it has been pointed out that there are differences in values among several reagents. Recently, we have performed a parallel measurement on two reagents, Thrombocheck APTT-SLA and Coagpia APTT-n, and resulted with some dissociated samples. The purpose of this study is to clarify the possible factors related to ΔAPTT, the difference in measured values between the two reagents., Materials and Methods: In order to clarify the factors related to ΔAPTT, multiple regression analysis was performed on 8324 samples, using clinical laboratory data of all test items requested simultaneously with APTT. To confirm the items extracted from the multiple regression analysis, the target substance was spiked to pooled plasma and measured with two APTT reagents. Additionally, by spiking phospholipids, the effect on APTT measurement system was assessed., Result: Multiple regression analysis detected albumin-globulin ratio (AGR), C-reactive protein (CRP), hematocrit, and prothrombin time as factors related to ΔAPTT (p < 0.001). Results revealed no significant differences when albumin was added to change the AGR. Whereas with the addition of CRP, prolongation of APTT was observed in Coagpia APTT-n compared to Thrombocheck APTT-SLA (p < 0.001). This prolongation was canceled by the addition of phospholipids, suggesting the interaction of CRP with phospholipids leads to the pseudo-prolongation., Conclusion: It is considered that the pseudo-prolongation of APTT is triggered by the interaction of CRP on the phospholipid in Coagpia APTT-n, which contributed to the APTT dissociation., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: Treatment characteristics such as cranial radiation therapy (CRT) do not fully explain adiposity risk in childhood acute lymphoblastic leukemia (ALL) survivors. This study was aimed at characterizing genetic variation related to adult body mass index (BMI) among survivors of childhood ALL., Methods: Genetic associations of BMI among 1458 adult survivors of childhood ALL (median time from diagnosis, 20 years) were analyzed by multiple approaches. A 2-stage genome-wide association study in the Childhood Cancer Survivor Study (CCSS) and the St. Jude Lifetime Cohort Study (SJLIFE) was performed. BMI was a highly polygenic trait in the general population. Within the known loci, the BMI percent variance explained was estimated, and additive interactions (chi-square test) with CRT in the CCSS were evaluated. The role of DNA methylation in CRT interaction was further evaluated in a subsample of ALL survivors., Results: In a meta-analysis of the CCSS and SJLIFE, 2 novel loci associated with adult BMI among survivors of childhood ALL (LINC00856 rs575792008 and EMR1 rs62123082; P Meta < 5E-8) were identified. It was estimated that the more than 700 known loci explained 6.2% of the variation in adult BMI in childhood ALL survivors. Within the known loci, significant main effects for 23 loci and statistical interactions with CRT at 9 loci (P < 7.0E-5) were further identified. At 2 CRT-interacting loci, DNA methylation patterns may have differed by age., Conclusions: Adult survivors of childhood ALL have genetic heritability for BMI similar to that observed in the general population. This study provides evidence that treatment with CRT can modify the effect of genetic variants on adult BMI in childhood ALL survivors., (© 2020 American Cancer Society.)

Background: The dietary variety score (DVS), a simple dietary survey method for older adults, investigates the weekly frequency of consumption of the 10 food groups in Japan. The DVS is also associated with nutritional status. The original scoring method applied only to community-dwelling older adults, not to older patients receiving home care, who have little dietary variety., Aim: Using three different scoring methods for the DVS, we examined which method was most likely to reflect the nutritional status of older patients receiving home care., Methods: This cross-sectional study was carried out on older patients receiving home care. Participant characteristics, the DVS (evaluated using three different scoring methods), and the Mini Nutritional Assessment-Short Form (MNA ® -SF) survey were researched. A receiver operating characteristic (ROC) analysis was performed to find the cut-off value for the DVS. Multivariate analysis was performed, with malnutrition as the outcome, to investigate the extent to which the DVS is associated with malnutrition., Results: We studied 317 participants. The DVS could produce significant ROC curves using modified scoring methods A and B (p = .028 and .042) with nutritional status as the outcome. Cut-off value, sensitivity and specificity were 30 points, 60.9% and 55.9% in modified scoring method A and 5 points, 79.1%, and 35.6% in modified scoring method B. Results of the multivariate logistic regression analysis, in Model 1 dysphagia (odds ratio [95% confidence interval]: 3.85 [1.70-8.71]) and the DVS of modified scoring method A (2.00 [1.11-3.62]) were significant independent factors. In Model 2, dysphagia (3.57 [1.58-8.07]) and the DVS based on modified scoring method B (2.36 [1.24-4.47]) were significant independent factors., Conclusions: Modified scoring method B was found to be most suitable for the dietary assessment of older patients receiving home care., Implications for Practice: Even in the absence of registered dietitians, any care staff member who is involved in providing nursing services during home-visits is capable of administering a dietary survey, when using the easy DVS scoring method., (© 2019 John Wiley & Sons Ltd.)

Background: Poor socioeconomic and health-related quality of life (HRQOL) outcomes in survivors of childhood cancer can lead to distress and overall negatively impact the lives of these individuals. The current report has highlighted the impact of stroke and stroke recurrence on mortality, psychological HRQOL, and socioeconomic outcomes within the Childhood Cancer Survivor Study (CCSS)., Methods: The CCSS is a retrospective cohort study with longitudinal follow-up concerning survivors of pediatric cancer who were diagnosed between 1970 and 1986. Mortality rates per 100 person-years were calculated across 3 periods: 1) prior to stroke; 2) after first stroke and before recurrent stroke; and 3) after recurrent stroke. Socioeconomic outcomes, the standardized Brief Symptoms Inventory-18, the Medical Outcomes Study 36-Item Short Form Health Survey, and the CCSS-Neurocognitive Questionnaire also were assessed., Results: Among 14,358 participants (median age, 39.7 years), 224 had a stroke after their cancer diagnosis (single stroke in 161 patients and recurrent stroke in 63 patients). Based on 2636 deaths, all-cause late mortality rates were 0.70 (95% CI, 0.68-0.73) prior to stroke, 1.03 (95% CI, 0.73-1.46) after the first stroke, and 2.42 (95% CI, 1.48-3.94) after the recurrent stroke. Among 7304 survivors, those with stroke were more likely to live with a caregiver (single stroke odds ratio [OR], 2.3 [95% CI, 1.4-3.8]; and recurrent stroke OR, 5.3 [95% CI, 1.7-16.8]) compared with stroke-free survivors. Stroke negatively impacted task efficiency (single stroke OR, 2.4 [95% CI, 1.4-4.1] and recurrent stroke OR, 3.3 [95% CI, 1.1-10.3]) and memory (single stroke OR, 2.1 [95% CI, 1.2-3.7]; and recurrent stroke OR, 3.5 [95% CI, 1.1-10.5])., Conclusions: Stroke and stroke recurrence are associated with increased mortality and negatively impact HRQOL measures in survivors of pediatric cancer., (© 2019 American Cancer Society.)

Background: The prevalence and associated psychosocial morbidity of late-onset anorectal disease after surgery and radiotherapy for the treatment of childhood cancer are not known., Methods: A total of 25,530 survivors diagnosed between 1970 and 1999 (median age at cancer diagnosis, 6.1 years; age at survey, 30.2 years) and 5036 siblings were evaluated for late-onset anorectal disease, which was defined as a self-reported fistula-in-ano, self-reported anorectal stricture, or pathology- or medical record-confirmed anorectal subsequent malignant neoplasm (SMN) 5 or more years after the primary cancer diagnosis. Piecewise exponential models compared the survivors and siblings and examined associations between cancer treatments and late-onset anorectal disease. Multiple logistic regression with generalized estimating equations was used to evaluate associations between late-onset anorectal disease and emotional distress, as defined by the Brief Symptom Inventory 18 (BSI-18), and health-related quality of life, as defined by the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36)., Results: By 45 years after the diagnosis, 394 survivors (fistula, n = 291; stricture, n = 116; anorectal SMN, n = 26) and 84 siblings (fistula, n = 73; stricture, n = 23; anorectal neoplasm, n = 1) had developed late-onset anorectal disease (adjusted rate ratio [RR] for survivors vs siblings, 1.2; 95% confidence interval [CI], 1.0-1.5). Among survivors, pelvic radiotherapy with ≥30 Gy within 5 years of the cancer diagnosis was associated with late-onset anorectal disease (adjusted RR for 30-49.9 Gy vs none, 1.6; 95% CI, 1.1-2.3; adjusted RR for ≥50 Gy vs none, 5.4; 95% CI, 3.1-9.2). Late-onset anorectal disease was associated with psychosocial impairment in all BSI-18 and SF-36 domains., Conclusions: Late-onset anorectal disease was more common among childhood cancer survivors who received higher doses of pelvic radiotherapy and was associated with substantial psychosocial morbidity., (© 2019 American Cancer Society.)

Background: Survivors of childhood cancer are at risk of neurocognitive impairment, emotional distress, and poor health-related quality of life (HRQOL); however, the effect of race/ethnicity is understudied. The objective of this study was to identify race/ethnicity-based disparities in neurocognitive, emotional, and HRQOL outcomes among survivors of childhood cancer., Methods: Self-reported measures of neurocognitive function, emotional distress (the Brief Symptom Inventory-18), and HRQOL (the Medical Outcomes Study Short Form-36 health survey) were compared between minority (Hispanic, n = 821; non-Hispanic black [NHB], n = 600) and non-Hispanic white (NHW) (n = 12,287) survivors from the Childhood Cancer Survivor Study (median age, 30.9 years; range, 16.0-54.1 years). By using a sample of 3055 siblings, the magnitude of same-race/same-ethnicity survivor-sibling differences was compared between racial/ethnic groups, adjusting for demographic and treatment characteristics and current socioeconomic status (SES)., Results: No clear pattern of disparity in neurocognitive outcomes by race/ethnicity was observed. The magnitude of the survivor-sibling difference in the mean score for depression was greater in Hispanics than in NHWs (3.59 vs 1.09; P = .004). NHBs and Hispanics had greater survivor-sibling differences in HRQOL than NHWs for mental health (NHBs: -5.78 vs -0.69; P = .001; Hispanics: -3.87 vs -0.69; P = .03), and social function (NHBs: -7.11 vs -1.47; P < .001; Hispanics: -5.33 vs -1.47; P = .001). NHBs had greater survivor-sibling differences in physical subscale scores for HRQOL than NHWs. In general, the findings were not attenuated by current SES., Conclusions: Although no pattern of disparity in neurocognitive outcomes was observed, differences across many HRQOL outcomes among minorities compared with NHWs, not attenuated by current SES, were identified. This suggests that further research into environmental and sociocultural factors during and immediately after treatment is needed., (© 2019 American Cancer Society.)

Background: Childhood cancer survivors are at risk for adverse psychological outcomes. Whether exercise can attenuate this risk is unknown., Methods: In total, 6199 participants in the Childhood Cancer Survivor Study (median age, 34.3 years [range, 22.0-54.0 years]; median age at diagnosis, 10.0 years [range, 0-21.0 years]) completed a questionnaire assessing vigorous exercise and medical/psychological conditions. Outcomes were evaluated a median of 7.8 years (range, 0.1-10.0 years) later and were defined as: symptom level above the 90th percentile of population norms for depression, anxiety, or somatization on the Brief Symptom Inventory-18; cancer-related pain; cognitive impairment using a validated self-report neurocognitive questionnaire; or poor health-related quality of life. Log-binomial regression estimated associations between exercise (metabolic equivalent [MET]-hours per week -1 ) and outcomes adjusting for cancer diagnosis, treatment, demographics, and baseline conditions., Results: The prevalence of depression at follow-up was 11.4% (95% CI, 10.6%-12.3%), anxiety 7.4% (95% CI, 6.7%-8.2%) and somatization 13.9% (95% CI, 13.0%-14.9%). Vigorous exercise was associated with lower prevalence of depression and somatization. The adjusted prevalence ratio for depression was 0.87 (95% CI, 0.72-1.05) for 3 to 6 MET hours per week -1 , 0.76 (95% CI, 0.62-0.94) for 9 to 12 MET-hours per week -1 , and 0.74 (95% CI, 0.58-0.95) for 15 to 21 MET-hours per week -1 . Compared with 0 MET hours per week -1 , 15 to 21 MET-hours per week -1 were associated with an adjusted prevalence ratio of 0.79 (95% CI, 0.62-1.00) for somatization. Vigorous exercise also was associated with less impairment in the physical functioning, general health and vitality (P trend  < .001), emotional role limitations (P trend  = .02), and mental health (P trend  = .02) domains as well as higher cognitive function in the domains of task completion, organization, and working memory (P < .05 for all), but not in the domain of cancer pain., Conclusions: Vigorous exercise is associated with less psychological burden and cognitive impairment in childhood cancer survivors., (© 2019 American Cancer Society.)

Background: Neuroblastoma survivors may be at elevated risk for psychological impairments because of their young age at diagnosis and neurotoxic treatment, but this is not well described., Methods: A total of 859 ≥5-year survivors of neuroblastoma younger than 18 years (diagnosed in 1970-1999), who had a median age at diagnosis of 0.8 years (range: 0.0-7.3 years) and a median follow-up of 13.3 years (range: 8.0-17.9 years), were compared with 872 siblings of childhood cancer survivors who were younger than 18 years with the parent-reported Behavior Problem Index (BPI) for psychological functioning. Age- and sex-adjusted multivariate log-binomial models were used to identify factors associated with impairment in BPI domains (scores worse than the sibling 10th percentile). The impact of psychological impairment on educational outcomes was examined among survivors., Results: Compared with siblings, neuroblastoma survivors had an increased prevalence of impairment in the domains of anxiety/depression (19% vs 14%; P = .003), headstrong behavior (19% vs 13%; P < .001), attention deficits (21% vs 13%; P < .001), peer conflict/social withdrawal (26% vs 17%; P < .001), and antisocial behavior (16% vs 12%; P = .01). Common treatment exposures (vincristine, cisplatin, and retinoic acid) were not associated with impairment. Having 2 or more chronic health conditions predicted impairment in 4 domains (P < .001). Specifically, pulmonary disease predicted impairment in all 5 domains (P ≤ .004). Endocrine disease (P ≤ .004) and peripheral neuropathy (P ≤ .02) each predicted impairment in 3 domains. Psychological impairment was associated with special education service usage and educational attainment less than college., Conclusions: Neuroblastoma survivors are at elevated risk for psychological impairment, which is associated with special education service usage and lower adult educational attainment. Those with chronic health conditions may represent a high-risk group for targeted screening and intervention. Cancer 2018. © 2018 American Cancer Society., (© 2018 American Cancer Society.)

The population of adult survivors of childhood cancer continues to grow as survival rates improve. Although it is well established that these survivors experience various complications and comorbidities related to their malignancy and treatment, this risk is modified by many factors that are not directly linked to their cancer history. Research evaluating the influence of patient-specific demographic and genetic factors, premorbid and comorbid conditions, health behaviors, and aging has identified additional risk factors that influence cancer treatment-related toxicity and possible targets for intervention in this population. Furthermore, although current long-term follow-up guidelines comprehensively address specific therapy-related risks and provide screening recommendations, the risk profile of the population continues to evolve with ongoing modification of treatment strategies and the emergence of novel therapeutics. To address the multifactorial modifiers of cancer treatment-related health risk and evolving treatment approaches, a patient-centered and risk-adapted approach to care that often requires a multidisciplinary team approach, including medical and behavioral providers, is necessary for this population. CA Cancer J Clin 2018;68:133-152. © 2018 American Cancer Society., (© 2018 American Cancer Society.)

Background: Ewing sarcoma survivors (ESSs) are at increased risk for treatment-related complications. The incidence of treatment-related morbidity and late mortality with aging is unknown., Methods: This study reports survival probabilities, estimated with the Kaplan-Meier method, and the cumulative incidence of cause-specific mortality and chronic conditions among ESSs in the Childhood Cancer Survivor Study who were treated between 1970 and 1986. Piecewise exponential models were used to estimate relative rates (RRs) and 95% confidence intervals (CIs) for these outcomes. Chronic conditions were graded with the Common Terminology Criteria for Adverse Events (version 4.03)., Results: Among 404 5-year ESSs (median age at last follow-up, 34.8 years; range, 9.1-54.8 years), the 35-year survival rate was 70% (95% CI, 66%-74%). Late recurrence (cumulative incidence at 35 years, 15.1%) was the most common cause of death, and it was followed by treatment-related causes (11.2%). There were 53 patients with subsequent neoplasms (SNs; cumulative incidence at 35 years, 24.0%), and 38 were malignant (14.3% at 35 years). The standardized incidence ratios were 377.1 (95% CI, 172.1-715.9) for osteosarcoma, 28.9 (95% CI, 3.2-104.2) for acute myeloid leukemia, 14.9 (95% CI, 7.9-25.5) for breast cancer, and 13.1 (95% CI, 4.8-28.5) for thyroid cancer. Rates of chronic conditions were highest for musculoskeletal (RR, 18.1; 95% CI, 12.8-25.7) and cardiac complications (RR, 1.8; 95% CI, 1.4-2.3). Thirty-five years after the diagnosis, the cumulative incidences of any chronic conditions and 2 or more chronic conditions were 84.6% (95% CI, 80.4%-88.8%) and 73.8% (95% CI, 67.8%-79.9%), respectively., Conclusions: With extended follow-up, ESSs' risk for late mortality and SNs does not plateau. Treatment-related chronic conditions develop years after therapy, and this supports the need for lifelong follow-up. Cancer 2017;123:2551-60. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Background: Emergency department (ED) visit volumes can be especially high during the Christmas-New Year holidays, a period occurring during the influenza season in Canada., Methods: Using daily data, we examined the relationship between ED visits for the chief complaint "cough" (for Edmonton, Alberta residents) and laboratory detections for influenza A and respiratory syncytial virus (RSV) (for Edmonton and surrounding areas), lagged 0-5 days ahead, for non-pandemic years (2004-2008 and 2010-2014) using multivariable linear regression adjusting for temporal variables. We defined these cough-related visits as influenza-like illness (ILI)-related ED visits and, for 2004-2014, compared Christmas-New Year holiday (December 24-January 3) and non-holiday volumes during the influenza season (October-April)., Results: Adjusting for temporal variables, ILI-related ED visits were significantly associated with laboratory detections for influenza A and RSV. During non-pandemic years, the highest peak in ILI-related visit volumes always occurred during the holidays. The median number of holiday ILI-related visits/day (42.5) was almost twice the non-holiday median (24) and was even higher in 2012-2013 (80) and 2013-2014 (86). Holiday ILI-related ED visit volumes/100 000 population ranged from 56.0 (2010-2011) to 117.4 (2012-2013). In contrast, lower visit volumes occurred during the holidays of pandemic-affected years (2008-2010)., Conclusions: During non-pandemic years, ILI-related ED visit volumes were associated with variations in detections for influenza A and RSV and always peaked during the Christmas-New Year holidays. This predictability should be used to prepare for, and possibly prevent, this increase in healthcare use; however, interventions beyond disease prevention strategies are likely needed., (© 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Background: Pulmonary complications after cancer therapy are varied. This study describes pulmonary outcomes among childhood cancer survivors and evaluates their impact on daily activities., Methods: The incidence of pulmonary outcomes (asthma, chronic cough, emphysema, lung fibrosis, oxygen need, and recurrent pneumonia) reported among 5-year cancer survivors (n = 14,316) and the incidence of death due to pulmonary causes among all eligible survivors (n = 20,690) in the Childhood Cancer Survivor Study were compared with those for sibling controls (n = 4027) with cumulative incidence, standardized mortality ratio (SMR), and piecewise exponential models. Logistic regression with random effects was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for activity limitations with pulmonary complications., Results: By the age of 45 years, the cumulative incidence of any pulmonary condition was 29.6% (95% CI, 29.1%-30.0%) for cancer survivors and 26.5% (95% CI, 24.9%-28.0%) for siblings. Fewer survivors reported ever smoking (23.6% vs 36.4%, P < .001), but survivors were more likely to report chronic cough (rate ratio [RR], 1.6; 95% CI, 1.4-1.9), oxygen need (RR, 1.8; 95% CI, 1.5-2.2), lung fibrosis (RR, 3.5; 95% CI, 2.3-5.4), and recurrent pneumonia (RR, 2.0; 95% CI, 1.4-3.0). The SMR for death due to pulmonary causes was 5.9 (95% CI, 4.2-8.1), and it was associated with platinum exposure and lung radiation (P < .01). The impact of chronic cough on daily activities for survivors (OR vs survivors without chronic cough, 2.7) was greater than that for siblings (OR, 2.0; P = .04)., Conclusions: Pulmonary complications are substantial among adult survivors of childhood cancer and can affect daily activities. Cancer 2016;122:3687-96. © 2016 American Cancer Society., Competing Interests: Authors indicate no conflicts of interest, (© 2016 American Cancer Society.)

By the middle of this century, racial/ethnic minority populations will collectively constitute 50% of the US population. This temporal shift in the racial/ethnic composition of the US population demands a close look at the race/ethnicity-specific burden of morbidity and premature mortality among survivors of childhood cancer. To optimize targeted long-term follow-up care, it is essential to understand whether the burden of morbidity borne by survivors of childhood cancer differs by race/ethnicity. This is challenging because the number of minority participants is often limited in current childhood cancer survivorship research, resulting in a paucity of race/ethnicity-specific recommendations and/or interventions. Although the overall childhood cancer incidence increased between 1973 and 2003, the mortality rate declined; however, these changes did not differ appreciably by race/ethnicity. The authors speculated that any racial/ethnic differences in outcome are likely to be multifactorial, and drew on data from the Childhood Cancer Survivor Study to illustrate the various contributors (socioeconomic characteristics, health behaviors, and comorbidities) that could explain any observed differences in key treatment-related complications. Finally, the authors outlined challenges in conducting race/ethnicity-specific childhood cancer survivorship research, demonstrating that there are limited absolute numbers of children who are diagnosed and survive cancer in any one racial/ethnic minority population, thereby precluding a rigorous evaluation of adverse events among specific primary cancer diagnoses and treatment exposure groups. Cancer 2016;122:2426-2439. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Background: Long-term survivors of pediatric cancer are at risk of life-threatening late effects of their cancer. Previous studies have shown excesses in long-term mortality within high-risk groups defined by demographic and treatment characteristics., Methods: To investigate conditional survival in a pediatric cancer population, the authors performed an analysis of conditional survival in the original Childhood Cancer Survivor Study (CCSS) cohort and the Surveillance, Epidemiology, and End Results (SEER) database registry. The overall probability of death for patients at 5 years and 10 years after they survived 5, 10, 15, and 20 years since cancer diagnosis and cause-specific death in 10 years for 5-year survivors were estimated using the cumulative incidence method., Results: Among patients in the CCSS and SEER cohorts who were alive 5 years after their cancer diagnosis, within each diagnosis group at least 92% were alive in the subsequent 5 years, except for patients with leukemia, of whom only 88% of 5-year survivors remained alive in the subsequent 5 years. The probability of all-cause mortality in the next 10 years among patients who survived at least 5 years after diagnosis was 8.8% in CCSS and 10.6% in SEER, approximately 75% of which was due to neoplasms as the cause of death., Conclusions: The risk of death among survivors of pediatric cancer in 10 years can vary between diagnosis groups by at most 12%, even up to 20 years after diagnosis. This information is clinically significant when counseling patients regarding their conditional survival, particularly when survivors are seen in long-term follow-up., (© 2014 American Cancer Society.)

Background: Little is known about infections among adult survivors of childhood cancer. The authors report the occurrence of infections and risk factors for infections in a large cohort of survivors of childhood cancer., Methods: The Childhood Cancer Survivor Study cohort was used to compare incidence rates of infections among 12,360 5-year survivors of childhood cancer with the rates of 4023 siblings. Infection-related mortality of survivors was compared with that of the US population. Demographic and treatment variables were analyzed using Poisson regression to determine the rate ratios (RRs) and corresponding 95% confidence intervals (CIs) for associations with infectious complications., Results: Compared with the US population, survivors were at an increased risk of death from infectious causes (standardized mortality ratio [SMR], 4.2; 95% CI, 3.2-5.4), with the greatest risk observed among females (SMR, 3.2; 95% CI, 1.5-6.9) and among those who had been exposed to total body irradiation (SMR, 7.8; 95% CI, 1.8-33.0). Survivors also reported higher rates than siblings of overall infectious complications (RR, 1.3; 95% CI, 1.2-1.4) and higher rates of all categories of infection., Conclusions: Survivors of childhood cancer remain at elevated risk for developing infectious-related complications, and they have a higher risk of infection-related mortality years after therapy. Further investigation is needed to provide insight into the mechanisms for the observed excess risks., (© 2014 American Cancer Society.)

Background: Interest in citizens' juries for eliciting the views of the public to inform coverage decisions on new health technologies has grown. However, evaluative information, particularly regarding their short- and/or longer-term impact on participants' views is limited. As citizens' juries can be resource intensive, such information is required to make 'evidence-based' decisions about their use., Objectives: To assess the impact of citizens' juries on participants' preferences for the distribution of health care across populations over time., Setting and Participants: Two citizens' juries, involving a different representative sample of the public, were held. Participants completed identical questionnaires before (T1), directly after (T2) and 6 weeks following the jury (T3). Questionnaires comprised rating, ranking and choice-based questions related to four characteristics of competing patient populations (age, current health, life expectancy without treatment and health gain resulting from an intervention). Semi-structured telephone interviews were also conducted to explore the impact of the jury on participants' distributive preferences. Changes in responses to the self-administered survey over the three time points were assessed quantitatively, while interview questions were analysed using qualitative techniques., Results: No significant differences in responses to rating questions were observed. Pre/post-jury changes in the rankings of two factors were statistically significant in one of the juries. However, in both juries, T1-T2 changes in responses to several of the choice-based questions reached statistical significance. The number was lower between T2 and T3, suggesting that jurors retained their views. According to findings from the interviews, jurors' views changed or were clarified through participation in the jury., Conclusions: There appears to be evidence suggesting that the views of individuals who participate in citizens' juries change as a result of the experience, and those 'informed' views are sustained., (© 2012 John Wiley & Sons Ltd.)

Background: A new predictive biomarker for determining prognosis in patients with hepatocellular carcinoma (HCC) who receive sorafenib is required, because achieving a reduction in tumor size with sorafenib is rare, even in patients who have a favorable prognosis. Vascular endothelial growth factor (VEGF) receptor is a sorafenib target. In the current study, the authors examined changes in plasma VEGF concentrations during sorafenib treatment and determined the clinical significance of VEGF as a prognostic indicator in patients with HCC., Methods: Plasma VEGF concentrations were serially measured in 63 patients with advanced HCC before and during sorafenib treatment. A plasma VEGF concentration that decreased >5% from the pretreatment level at 8 weeks was defined as a "VEGF decrease." An objective tumor response was determined using modified Response Evaluation Criteria in Solid Tumors 1 month after the initiation of therapy and every 3 months thereafter., Results: Patients who had a VEGF decrease at week 8 (n=14) had a longer median survival than those who did not have a VEGF decrease (n=49; 30.9 months vs 14.4 months; P=.038). All patients who had a VEGF decrease survived for >6 months, and the patients who had both a VEGF decrease and an α-fetoprotein response (n=6) survived during the observation period (median, 19.7 months; range, 6.5-31.0 months). In univariate analyses, a VEGF decrease, radiologic findings classified as progressive disease, and major vascular invasion were associated significantly with 1-year survival; and, in multivariate analysis, a VEGF decrease was identified as an independent factor associated significantly with survival., Conclusions: A plasma VEGF concentration decrease at 8 weeks after starting sorafenib treatment may predict favorable overall survival in patients with advanced HCC., (© 2013 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.)

Objective: Investigations examining psychosocial adjustment among childhood cancer survivors have focused primarily on negative effects and psychopathology. Emergent literature suggests the existence of positive impact or adjustment experienced after cancer, as well. The purpose of this study is to examine the distribution of Perceived Positive Impact (PPI) and its correlates in young adult survivors of childhood cancer., Methods: 6425 survivors and 360 siblings completed a comprehensive health survey, inclusive of a modified version of the Post-traumatic Growth Inventory (PTGI) as a measure of PPI. Linear regression models were used to examine demographic, disease and treatment characteristics associated with PPI., Results: Survivors were significantly more likely than siblings to report PPI. Endorsement of PPI was significantly greater among female and non-white survivors, and among survivors exposed to at least one intense therapy, a second malignancy or cancer recurrence. Survivors diagnosed at older ages and fewer years since diagnosis were more likely to report PPI. Income, education and marital/relationship status appeared to have varied relationships to PPI depending upon the subscale being evaluated., Conclusions: The existence and variability of PPI in survivors in this study suggest that individual characteristics, inclusive of race, gender, cancer type, intensity of treatment, age at diagnosis and time since diagnosis, have unique and specific associations with different aspects of perceived positive outcomes of childhood cancer., (Copyright © 2011 John Wiley & Sons, Ltd.)

This paper compares three different methods for performing cancer incidence prediction in an area without a cancer registry under a Bayesian framework, using linear and log-linear age-period models with either age-specific slopes or a common slope across age groups. The three methods assume that a nearby area with a cancer registration has similar incidence and mortality patterns as the area of interest without a cancer registry where the cancer incidence prediction is carried out. The three methods differ in modeling strategies: (i) modeling the incidence rate directly; (ii) modeling the ratio of the number of incident cases to that of mortality cases; and (iii) modeling the difference between the incidence rate and the mortality rate. Strategy (iii) is a new approach in this type of projection. Empirical assessment is made using real data from the cancer registry of Tarragona, Spain, to predict cancer incidence in Girona, Spain, and vice versa. Predictions of short-term (3-4 years) incidence were made for 2001 in Tarragona using observed cancer incidence and mortality data for 1994-1998 from Girona. Short-term predictions were made for 2002 in Girona using Tarragona's 1994-1998 data. Additionally, long-term (10 years) incidence rate predictions were made for 2002 in Girona using data from Tarragona for the period 1985-1992. Our results suggest that extrapolating time-trends of incidence rates minus mortality rates may have the best predictive performance overall. These methods of population-level disease-incidence prediction are highly relevant to health care planning and policy decisions., (Copyright © 2012 John Wiley & Sons, Ltd.)

Background: Surgery followed by adjuvant chemotherapy has been standard treatment for stage III colon cancer since 1990. However, to date, clinical trials have not been conducted to determine the definitive outer time limit by which adjuvant chemotherapy should be received for optimal survival benefit. The objective of the current study was to assess the association between the receipt/timing of adjuvant chemotherapy and patient survival in clinical practice., Methods: Residents of Alberta who were diagnosed with stage III colon adenocarcinoma in years 2000 to 2005 who underwent surgery were included in the study. Patients were identified from the Alberta Cancer Registry and were linked to hospital data and neighborhood-level socioeconomic data from the 2001 Canadian Census. Cox proportional hazards models were used to estimate hazard ratios of death according to the timing of chemotherapy., Results: There were 1053 patients in the study; 648 (61%) initiated adjuvant chemotherapy within 16 weeks of surgery. There was no difference in overall survival or colon cancer-specific survival between those who received adjuvant chemotherapy from 8 to 12 weeks postsurgery compared with those who received it within 8 weeks. However, those who received chemotherapy 12 to 16 weeks after surgery and those who either received it >16 weeks after surgery or received no treatment had a 43% and 107% greater risk of dying, respectively, than those who received chemotherapy within 8 weeks of surgery (hazard ratio, 1.43 [95% confidence interval, 0.96-2.13] and hazard ratio, 2.07 [95% confidence interval, 1.56-2.76], respectively). Analyses were controlled for age, year, and region of residence at diagnosis; sex; neighborhood-level socioeconomic factors; and number of comorbidities., Conclusions: The results from this study were consistent with current guideline recommendations in Alberta that patients with stage III adenocarcinoma should receive chemotherapy within 12 weeks of surgery., (Copyright © 2011 American Cancer Society.)

Background: Lack of health insurance is a key barrier to accessing care for chronic conditions and cancer screening. The influence of insurance type (private, public, none) on survivor-focused and general preventive health care in adult survivors of childhood cancer was examined., Methods: The Childhood Cancer Survivor Study is a retrospective cohort study of childhood cancer survivors diagnosed between 1970 and 1986. Among 8425 adult survivors, the relative risk (RR) and 95% confidence interval (CI) of receiving survivor-focused and general preventive health care were estimated for uninsured (n = 1390) and publicly insured (n = 640), compared with for the privately insured (n = 6395), Results: Uninsured survivors were less likely than those privately insured to report a cancer-related visit (adjusted RR, 0.83; 95% CI, 0.75-0.91) or a cancer center visit (adjusted RR, 0.83; 95% CI, 0.71-0.98). Uninsured survivors had lower levels of utilization in all measures of care in comparison with privately insured. In contrast, publicly insured survivors were more likely to report a cancer-related visit (adjusted RR, 1.22; 95% CI, 1.11-1.35) or a cancer center visit (adjusted RR, 1.41; 95% CI, 1.18-1.70) than were privately insured survivors. Although publicly insured survivors had similar utilization of general health examinations, they were less likely to report a Papanicolaou test or a dental examinations, Conclusions: Among this large, socioeconomically diverse cohort, publicly insured survivors utilize survivor-focused health care at rates at least as high as survivors with private insurance. Uninsured survivors have lower utilization of both survivor-focused and general preventive health care., (Copyright © 2010 American Cancer Society.)

Background: Osteosarcoma survivors have received significant chemotherapy and have undergone substantial surgeries. Their very long-term outcomes (20 year) are reported here., Methods: The authors assessed the long-term outcomes of 733 5-year survivors of childhood osteosarcoma diagnosed from 1970 to 1986 to provide a comprehensive evaluation of medical and psychosocial outcomes for survivors enrolled in the Childhood Cancer Survivor Study (CCSS). Outcomes evaluated included overall survival, second malignant neoplasms (SMNs), recurrent osteosarcoma, chronic health conditions, health status (general and mental health and functional limitations), and psychosocial factors. Outcomes of osteosarcoma survivors were compared with general-population statistics, other CCSS survivors, and CCSS siblings., Results: Survivors had a mean follow-up of 21.6 years. The overall survival of children diagnosed with osteosarcoma who survived 5 years at 20 years from original diagnosis was 88.6% (95% confidence interval [CI], 86.6%-90.5%). The cumulative incidence of SMNs at 25 years was 5.4%, with a standardized incidence ratio of 4.79 (95% CI, 3.54-6.33; P<.01). Overall, 86.9% of osteosarcoma survivors experienced at least 1 chronic medical condition, and >50% experienced ≥2 conditions. Compared with survivors of other cancers, osteosarcoma survivors did not differ in their reported general health status (odds ratio [OR], 0.9; 95% CI, 0.7-1.2), but were more likely to report an adverse health status in at least 1 domain (OR, 1.9; 95% CI, 1.6-2.2), with activity limitations (29.1%) being the most common., Conclusions: Childhood osteosarcoma survivors in this cohort did relatively well, considering their extensive treatment, but are at risk of experiencing chronic medical conditions and adverse health status. Survivors warrant life-long follow-up., (Copyright © 2010 American Cancer Society.)

Background: Many patients with stage III colon adenocarcinoma do not receive adjuvant chemotherapy despite the proven survival advantage it offers. To enhance the provision of optimal cancer care, patient characteristics associated with not receiving guideline-adherent treatment must be identified among patients with operable, stage III colon adenocarcinoma., Methods: This was a population-based, retrospective study of all patients who underwent surgery for stage III colon adenocarcinoma diagnosed from 2002 through 2005 in Alberta, Canada. Demographic and treatment information captured in the Alberta Cancer Registry were linked to: 1) hospital discharge data to determine comorbidities, 2) electronic medical records to identify consults with oncologists, and 3) the 2001 Canadian census for neighborhood-level socioeconomic data. Multivariate log-binomial regression models were used to identify patient characteristics that were associated with not having a consultation with a medical oncologist and not receiving adjuvant chemotherapy., Results: Of the 772 patients who underwent surgery for stage III colon adenocarcinoma and met the eligibility criteria, 618 patients (80%) had a consultation with an oncologist. Of those, 388 patients (63%) initiated adjuvant chemotherapy within 84 days of their surgery. Patient characteristics that were associated with not having a consultation with an oncologist were neighborhood income, geography, age, and comorbidities. Of those patients who had a consultation, after adjusting for comorbidities, only older age was related to not receiving adjuvant chemotherapy., Conclusions: The current results indicated that the proportion of patients with stage III colon adenocarcinoma who did not receive treatment according to evidence-based guidelines was appreciable. The authors concluded that the association of this failure with patient age, geography, and income is concerning and that evaluation of referral patterns and interventions are needed., (© 2010 American Cancer Society.)

Relative risks (RRs) and prevalence ratios (PRs) are measures of association that are more intuitively interpretable than odds ratios (ORs). Many health science studies report OR estimates, however, even when their designs permit and study questions target RRs and/or PRs. This is, partially, attributable to the popularity and technical advantage (i.e. no restriction on the parameter space) of logistic regression for estimating ORs. To improve this practice, several biostatistical approaches for estimating RR/PR, adjusting for potential confounders, have been proposed. In this paper, we consider two RR/PR estimating methods: (1) the modification of log-binomial regression with the COPY method; and (2) an inverse-probability-of-treatment-weighted (IPTW) log-binomial regression we newly propose. For the COPY method, we rigorously establish the existence and uniqueness of the maximum-likelihood estimator, provided certain degeneracies in the data do not occur. Moreover, the global maximum of the COPY-modified likelihood is shown to occur at an interior point of the restricted parameter space. This result explains why the COPY method avoids convergence problems of log-binomial models frequently. For the IPTW estimator, we show that its simple procedure results in standardized estimates of RR/PR, and discuss its potential challenges, extensions, and an improvement through propensity-score-based grouping of observations. Furthermore, we compare the performances of four RR/PR estimation methods, including the COPY method and IPTW log-binomial regression, on simulated data. We demonstrate a lack of robustness of the COPY method against misspecification of the true relationship between binary outcome and explanatory variables, and show robustness of the IPTW approach in this regard.

Background: Limited data exist on the comprehensive assessment of late medical and social effects experienced by survivors of childhood and young adult acute myeloid leukemia (AML)., Methods: This analysis included 272 5-year AML survivors who participated in the Childhood Cancer Survivor Study (CCSS). All patients were diagnosed at age < or =21 years between the years 1970 and 1986, and none underwent stem cell transplantation. Rates of survival, relapse, and late outcomes were analyzed., Results: The average follow-up was 20.5 years (range, 5-33 years). The overall survival rate was 97% at 10 years (95% confidence interval [95%CI], 94%-98%) and 94% at 20 years (95% CI, 90%-96%). Six survivors reported 8 recurrences. The cumulative incidence of recurrent AML was 6.6% at 10 years (95% CI, 3.7%-9.6%) and 8.6% at 20 years (95% CI, 5.1%-12.1%). Ten subsequent malignant neoplasms (SMN) were reported, including 4 with a history of radiation therapy, for a 20-year cumulative incidence of 1.7% (95% CI, 0.02%-3.4%). Six cardiac events were reported, for a 20-year cumulative incidence 4.7% (95% CI, 2.1%-7.3%). Half of the survivors reported a chronic medical condition and, compared with siblings, were at increased risk for severe or life-threatening chronic medical conditions (16% vs 5.8%; P < .001). Among those aged > or =25 years, the age-adjusted marriage rates were similar among survivors and the general United States population (57% for both) and lower compared with siblings (67%; P < .01). Survivors' college graduation rates were lower compared with siblings but higher than the general population (40% vs 52% vs 34%, respectively; P < .01). Employment rates were similar between survivors, siblings, and the general population (93%, 97.6%, and 95.8%, respectively)., Conclusions: Long-term survival from childhood AML > or =5-years after diagnosis was favorable. Late-occurring medical events remained a concern with socioeconomic achievement lower than expected within the individual family unit, although it was not different from the general United States population.

Background: Exercise training improves supportive care outcomes in patients with breast cancer who are receiving adjuvant therapy, but the responses are heterogeneous. In this study, the authors examined personal and clinical factors that may predict exercise training responses., Methods: Breast cancer patients who were initiating adjuvant chemotherapy (N=242) were assigned randomly to receive usual care (UC) (n=82), resistance exercise training (RET) (n=82), or aerobic exercise training (AET) (n=78) for the duration of chemotherapy. Endpoints were quality of life (QoL), aerobic fitness, muscular strength, lean body mass, and body fat. Moderators were patient preference for group assignment, marital status, age, disease stage, and chemotherapy regimen., Results: Adjusted linear mixed-model analyses demonstrated that patient preference moderated QoL response (P= .005). Patients who preferred RET improved QoL when they were assigned to receive RET compared with UC (mean difference, 16.5; 95% confidence interval [95% CI], 4.3-28.7; P= .008) or AET (mean difference, 11; 95% CI, -1.1-23.4; P= .076). Patients who had no preference had improved QoL when they were assigned to receive AET compared with RET (mean difference, 23; 95% CI, 4.9-41; P= .014). Marital status also moderated QoL response (P= .026), age moderated aerobic fitness response (P= .029), chemotherapy regimen moderated strength gain (P= .009), and disease stage moderated both lean body mass gain (P< .001) and fat loss (P= .059). Unmarried, younger patients who were receiving nontaxane-based therapies and had more advanced disease stage experienced better outcomes. The findings were not explained by differences in adherence., Conclusions: Patient preference, demographic variables, and medical variables moderated the effects of exercise training in breast cancer patients who were receiving chemotherapy. If replicated, these results may inform clinical practice.

Toward concise access to functionalized amides and lactams, palladium-catalyzed amidations of alkynes and alkenes with formamide derivatives were developed. Cyanoformamides having an alkynyl group were found to undergo intermolecular cyanoamidation in the presence of palladium catalyst to afford alpha-alkylidene lactams. Whereas, when cyanoformamides that possess a 1,1-disubstituted alkenyl group were used as starting materials, alpha,alpha-disubstituted lactams were obtained. The latter reaction was extended to enantioselective transformation by utilizing optically active phosphoramidites as ligand. Furthermore, chloroformamides having a 1,1,2-trisubsituted alkenyl group were found to give alpha-vinyl-lactams in the presence of palladium catalyst, base and silver salt. Additionally, formal intermolecular hydroamidation of alkenes was performed through one-pot hydroboration-carbamoylation sequence., (2008 The Japan Chemical Journal Forum and Wiley Periodicals, Inc.)

Background: Colorectal cancer (CRC) is a leading cause of cancer mortality in the US. Surveys reveal low CRC screening levels among Asians in the US, including Chinese Americans., Methods: A randomized controlled trial was conducted with Chinese patients to evaluate a clinic-based, culturally and linguistically appropriate intervention promoting fecal occult blood test (FOBT) screening. The multifaceted intervention included a trilingual and bicultural health educator, bilingual materials (a video, a motivational pamphlet, an informational pamphlet, and FOBT instructions), and three FOBT cards. Patients in the control arm received usual care. Our primary outcome measure was FOBT screening within 6 months after randomization. The proportion of FOBT completion in the intervention and control arms was compared by using a chi-square test, and logistic regression analysis was performed to adjust for the effects of sociodemographic variables and prior screening history. Potential effect modifications were also tested by using logistic regression models., Results: Our intervention had a strong effect on FOBT completion (intervention group, 69.5%; control group, 27.6%), and the adjusted odds of FOBT slightly increased to over 6-fold greater in the intervention arm compared with the control arm. No effect modification by age, gender, language, insurance, or prior FOBT was found., Conclusions: The authors' multifaceted, culturally appropriate intervention significantly increased FOBT screening in a group of low-income and less-acculturated minority patients. Given the large effect size, future research should determine the effective core component(s) that can increase CRC screening in both the general and minority populations.

During the past 30 years, changes in the treatment of children and adolescents with cancer have led to substantial improvements in survival. Although treatment-related factors have been shown to impact subsequent health status and quality of life, there is limited information on survivors who are now two or more decades after treatment. The Childhood Cancer Survivor Study (CCSS) was established as a resource for investigating the long-term outcomes of a cohort of 5-year survivors of childhood and adolescent cancer, diagnosed between 1970-1986. The CCSS cohort has more than 14,000 active participants, including survivors of leukemia, brain tumors, Hodgkin disease, non-Hodgkin lymphoma, Wilms tumor, neuroblastoma, soft-tissue sarcoma, and bone tumors. Study participants, extensively characterized by their cancer therapy, have provided self-reported sociodemographic- and health-related information. Although the survivor population has been found to be at significantly increased risk of several adverse outcomes, such as late mortality, second cancers, pulmonary complications, pregnancy loss, low birth weight of offspring, and decreased education, the overall proportion of survivors affected is relatively small. Subgroups at high risk of adverse outcomes, defined by treatment-related, demographic, or medical factors, can be identified. The ongoing evaluation of large and diverse cohorts of cancer survivors will aid in further identifying individuals who should be the target of innovative intervention strategies.

Background: One of the most serious late effects of treatment for childhood cancer is the occurrence of subsequent malignancy. Survivors of Hodgkin disease (HD), in particular, have been shown to be at high risk of subsequent malignancy, the occurrence of which has been associated strongly with exposure to radiotherapy., Methods: In the current study, the authors investigated the association between polymorphisms in 3 genes--glutathione-S-transferase M1 (GSTM1), glutathione-S-transferase T1 (GSTT1), and XRCC1, with roles in protection from a variety of DNA-damaging agents-and the risk of subsequent malignancy in 650 survivors of HD enrolled in the Childhood Cancer Survivor Study who had received radiotherapy., Results: Individuals lacking GSTM1 but not GSTT1 were at increased risk of any subsequent malignancy (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.0-2.3), and for subsequent cancer within the radiation field (OR, 1.4; 95% CI, 0.9-2.1). A nonsignificant increased risk of thyroid carcinoma was observed in individuals lacking either GSTM1 (OR, 2.9; 95% CI, 0.8-10.9) or GSTT1 (OR, 3.7; 95% CI, 0.6-23.5). Individuals having the genotype of the arginine/glutamine polymorphism at codon 399 in the XRCC1 gene (R399) showed a nonsignificant increased risk of breast carcinoma compared with those without (OR, 1.4; 95% CI, 0.7-2.7), and a nonsignificant decreased risk against a subsequent thyroid carcinoma (OR, 0.6; 95% CI, 0.2-1.6). No differences in genotype frequencies were observed between survivors with basal cell carcinoma when compared with survivors without a subsequent cancer., Conclusions: These data illustrated the potential value of incorporating the collection of genomic DNA in longitudinal cohort studies of populations with well defined, potentially carcinogenic exposures. Evaluation of additional genetic polymorphisms in this cohort may help define genes that influence individual sensitivity to radiotherapy., (Copyright 2004 American Cancer Society.)

Background: With increasing numbers of childhood cancer survivors, direct sequelae of cancer therapy and psychosocial outcomes are becoming more important. The authors described psychosocial outcomes (education, employment, health insurance, and marriage) for survivors of pediatric lower extremity bone tumors., Methods: The long-term follow-up study of the Childhood Cancer Survivor Study is a multiinstitutional cohort study comprising 14,054 individuals who have survived for 5 or more years after treatment for cancer diagnosed during childhood or adolescence. Baseline demographic and medical information were obtained. Six hundred ninety-four survivors had osteosarcoma or Ewing sarcoma of the lower extremity or pelvis and were classified by amputation status and by age at diagnosis. The median age at diagnosis was 14 years old with a median of 16 years of follow up since diagnosis. Demographic characteristics were used to analyze the rates of psychosocial outcomes., Results: Amputation status and age at diagnosis did not significantly influence any of the measured psychosocial outcomes. Education was a significant positive predictor of employment, having health insurance, and being currently in their first marriage. Male gender predicted ever being employed and female gender predicted having health insurance and marriage. When compared with siblings, amputees had significant deficits in education, employment, and health insurance., Conclusions: Overall, no differences between amputees and nonamputees were found. However, gender and education play a prominent role. When compared with siblings, amputees in this cohort may benefit from additional supports., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11363)

Background: Breast carcinoma is the most common major malignancy among several Asian-American populations. This study surveyed mammography screening knowledge and practices among Chinese-American women., Methods: In 1999, the authors conducted a cross-sectional, community-based survey in Seattle, Washington. Bilingual and bicultural interviewers administered surveys in Mandarin, Cantonese, or English at participants' homes., Results: The survey cooperation rate (responses among reachable and eligible households) was 72% with 350 eligible women (age >or= 40 years with no prior history of breast carcinoma or double mastectomy). Seventy-four percent of women reported prior mammography screening, and 61% of women reported screening in the last 2 years. In multivariate analysis, a strong association was found between mammography screening and recommendations by physicians and nurses (prior screening: odds ratio [OR], 16.0; 95% confidence interval [95% CI], 7.8-35.0; recent screening: OR, 7.0; 95% CI, 3.8-13.6). This finding applied to both recent immigrants (< 15 years in the U.S.) and earlier immigrants (>or= 15 years in the U.S.). Thirty-two percent of women reported that the best way to detect breast carcinoma was a modality other than mammogram., Conclusions: The authors recommend a multifaceted approach to increase mammography screening by Chinese-American women: recommendations from the provider plus targeted education to address the effectiveness of screening mammography compared with breast self examination and clinical breast examination., (Copyright 2003 American Cancer Society.)

We investigated the phylogenetic and biogeographic relationships of natural populations of diploid and tetraploid Fagopyrum cymosum (Polygonaceae). Intraspecific variation of chloroplast DNA sequences was detected in three regions approximately 5 kb long in total: the 3' end of rbcL, accD and associated intergenic spacer region, the trnC (GCA)-rpoB spacer region, the trnK (UUU) intron, and the matK region. The accessions of F. cymosum were divided into two major groups, a Tibet-Himalayan clade and a Yunnan-Sichuan clade, with a high bootstrap probability. It was estimated that these two clades diverged about 0.7 million years ago. The geographical and climatic interruption by the Hengduanshan mountains might have caused the genetic divergence in F. cymosum. Autotetraploid populations of F. cymosum have arisen allopatrically from a diploid progenitor at least twice, once in the Tibet-Himalayan area and once in the Yunnan-Sichuan area. This conclusion reinforces a previous study based on allozyme variation. We also found that F. tataricum, a close relative of F. cymosum, was completely included within the Tibet-Himalayan clade in the phylogenetic tree. This suggests that F. tataricum speciated from F. cymosum in the Tibet-Himalayan area.

Background: Survivors of childhood brain tumors (CBTs) are at high risk for a variety of late adverse effects. Most research on long-term effects of CBTs has been comprised of single-institution case series without comparison groups. Research on CBT late effects often is focused on neurologic and sensory outcomes, with less emphasis on other potential targets such as the endocrine and circulatory systems. The current study was conducted to contrast the incidence of endocrine and cardiovascular conditions among CBT survivors as a function of treatment and to determine the risk of occurrence of these conditions relative to a sibling comparison group., Methods: As part of the Childhood Cancer Survivor Study (CCSS), treatment data were collected from medical records and self-reported late effects were ascertained from a survey questionnaire of 1,607 CBT patients who survived their disease for 5 or more years. For comparison purposes, questionnaire data were also collected from 3418 randomly selected siblings of participants in CCSS., Results: One or more endocrine conditions were reported by 43% of CBT survivors. Compared with siblings, CBT survivors had a significantly increased risk of late-onset (>/= 5 years postdiagnosis) hypothyroidism (relative risk [RR] = 14.3; 95% confidence interval [95% CI] 9.7-21.0), growth hormone deficiency (RR = 277.8; 95% CI 111.1-694.9), the need for medications to induce puberty (RR = 86.1; 95% CI 31.1-238.2), and osteoporosis (RR = 24.7; 95% CI 9.9-61.4). One or more cardiovascular conditions were reported by 18% of CBT survivors, with an elevated late-onset risk for stroke (RR = 42.8; 95% CI 16.7-109.8), blood clots (RR = 5.7; 95% CI 3.2-10.0), and angina-like symptoms (RR = 2.0; 95% CI 1.5-2.7). Very few late effects were evident among those treated with surgery only, but risks were consistently elevated for those treated with radiation and surgery, and higher still for those who also received adjuvant chemotherapy., Conclusions: Childhood brain tumor survivors are at a significantly increased risk for several adverse endocrine and cardiovascular late effects, particularly if they were treated with radiation and chemotherapy. Lifetime medical surveillance and follow-up for potential toxicities are necessary because treatment-related complications may occur many years after therapy., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11095)

Background: The Childhood Cancer Survivor Study is a resource that was designed to investigate long-term effects among 5-year survivors of childhood and adolescent malignancies. Previous studies have shown that exposure to chemotherapy and/or radiation can compromise pulmonary function in these survivors of childhood cancer., Methods: Using information obtained from questionnaires from 12,390 childhood cancer survivors and 3546 randomly selected siblings, the authors evaluated the rate of first occurrence of 15 selected pulmonary conditions in three periods: during therapy, from the end of therapy to 5 years postdiagnosis, and >/= 5 years postdiagnosis. Multivariate analyses were used to determine the relative risks with 95% confidence intervals of reported pulmonary conditions by exposure to the following treatment variables: radiation therapy to the chest, bleomycin, cyclophosphamide, busulfan, lomustine (CCNU), and/or carmustine (BCNU)., Results: Compared with siblings, survivors had a statistically significant increased relative risk (RR) of lung fibrosis, recurrent pneumonia, chronic cough, pleurisy, use of supplemental oxygen, abnormal chest wall, exercise-induced shortness of breath, bronchitis, recurrent sinus infection, and tonsillitis for all three periods. During the period of >or= 5 years postdiagnosis, statistically significant associations were present for lung fibrosis and chest radiation (RR, 4.3; P = 0 001); for supplemental oxygen use and chest radiation (RR, 1.8; P < 0.001), BCNU (RR, 1.4; P = 0.05), bleomycin (RR, 1.7; P = 0.001), busulfan (RR, 3.2; P = 0.002), CCNU (RR, 2.1; P < 0.001), and cyclophosphamide (RR, 1.5; P = 0.01); for recurrent pneumonia and chest radiation (RR, 2.2; P = 0.001) and cyclophosphamide (RR, 1.6; P = 0.04); for chronic cough and chest radiation (RR, 2.0; P < 0.001), bleomycin (RR, 1.9; P < 0.001), and cyclophosphamide (RR, 1.3; P = 0.004); and for pleurisy and chest radiation (RR, 1.4; P = 0.02) and busulfan (RR, 5.1; P = 0.02). Chest radiation was associated with a 3.5% cumulative incidence of lung fibrosis at 20 years after diagnosis., Conclusions: For self-report of pulmonary conditions, treatment-related factors that continue to manifest > 5 years after diagnosis and treatment are important determinants of risk. Continued follow-up of childhood cancer survivors is needed to evaluate the impact of pulmonary conditions on quality of life., (Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10978)

Background: The association between method of detection and breast carcinoma histopathology has not been assessed adequately in a population-based setting., Methods: Among women who were included in a population-based, case-control study of breast cancer, patients who were newly diagnosed with invasive breast carcinoma were identified from Wisconsin's statewide tumor registry. Only women age > or = 50 years were analyzed, because screening by mammography was not recommended before age 50 years at the time of the study. The breast tumors among these women (n = 2341 tumors) included the following histopathologies: lobular carcinoma (n = 206 tumors); ductal carcinoma, not otherwise specified (n = 1920 tumors); papillary carcinoma (n = 15 tumors); medullary carcinoma (n = 36 tumors); mucinous adenocarcinoma (n = 56 tumors); tubular adenocarcinoma (n = 41 tumors); invasive comedocarcinoma (n = 24 tumors); scirrhous adenocarcinoma (n = 15 tumors); and mixed ductal/lobular carcinoma (n = 28 tumors)., Results: Overall, women reported that 41% of tumors were detected by mammography, 48% of tumors were self detected, and 11% of tumors were detected by clinical breast examination (CBE). Detection by mammography was significantly more likely for women who had tubular carcinoma (83%; P < 0.001) and invasive comedocarcinoma (67%; P = 0.23) compared with women who had ductal carcinoma (40%). Mammography was significantly less likely to detect medullary carcinoma (17%) than ductal carcinoma (40%; P = 0.01). Lobular carcinoma was the only histopathology that, compared with ductal carcinoma, was detected significantly more often by CBE than by self detection. Mammography detected lobular carcinoma (42%) as frequently as ductal carcinoma (40%). However, the use of postmenopausal hormones may have modified these detection patterns: Among current users, mammography discovered a greater percentage of ductal carcinomas (51%) and fewer lobular carcinomas (36%) than nonusers., Conclusions: Among women age > or = 50 years, breast cancer detection by mammography, self detection, and CBE varied according to tumor histopathology., (Copyright 2002 American Cancer Society.)

Empirical and fully Bayes estimation of small area disease risks places a prior distribution on area-specific risks. Several forms of priors have been used for this purpose including gamma, log-normal and non-parametric priors. Spatial correlation among area-specific risks can be incorporated in log-normal priors using Gaussian Markov random fields or other models of spatial dependence. However, the criterion for choosing one prior over others has been mostly logical reasoning. In this paper, we evaluate empirically the various priors used in the empirical Bayes estimation of small area disease risks. We utilize a Spanish mortality data set of a 12-year period to give the underlying true risks, and estimate the true risks using only a 3-year portion of the data set. Empirical Bayes estimates are shown to have substantially smaller mean squared errors than Poisson likelihood-based estimates. However, relative performances of various priors differ across a variety of mortality outcomes considered. In general, the non-parametric prior provides good estimates for lower-risk areas, while spatial priors provide good estimates for higher-risk areas. Ad hoc composite estimates averaging the estimates from the non-parametric prior and those from a spatial log-normal prior appear to perform well overall. This suggests that an empirical Bayes prior that strikes a balance between these two priors, if one can construct such a prior, may prove to be useful for the estimation of small area disease risks., (Copyright 2000 John Wiley & Sons, Ltd.)

Between-community variance or community-by-time variance is one of the key factors driving the cost of conducting group randomized trials, which are often very expensive. We investigated empirically whether between-community variance could be reduced by controlling individual- and/or community-level covariates and identified these covariates from four large community-based group randomized trials or surveys: the Working Well Trial; Kaiser Adolescent Survey; Kaiser Adults Survey; and the Eating Patterns Study. We found that adjusting for covariates will often substantially reduce the between-community variance component. Therefore investigators could block the communities according to these covariates, or adjust for these covariates to improve the power of community trials. We found that the community-by-time variance components are always near zero in these data sets, especially for the surveys where a cohort was followed over time. The covariate adjustment had less impact on reducing the community-by-time variance for the cohort samples than for the cross-sectional samples. This suggests that blocking may not be necessary for the design of the group randomized trials where the change from baseline is of primary interest. The Working Well Trial data were used to illustrate this point.

DNA sequences of the rbcL and accD 5' coding regions and their intergenic region (IGR) were determined in 20 taxa of 12 species of Fagopyrum. By comparing the sequence data and constructing phylogenetic trees, phylogenetic relationships among Fagopyrum species were investigated. The accD 5' coding region and the IGR have evolved about five times faster than the rcbL coding region; hence the phylogenetic trees based on the data of the accD 5' coding region, the IGR, and these data combined, had higher resolution than the trees based on rcbL alone. The classification of Fagopyrum based on the DNA sequences was almost perfectly consistent with the classification by Ohnishi and Matsuoka (1996, Genes & Genetic Systems 71: 383-390). New facts and minor differences are (1) polyploidization in F. cymosum might have occurred more than once, (2) F. lineare may not be a sister species of F. leptopodum, and (3) F. pleioramosum rather than F. capillatum may be a sister species of F. gracilipes.