Bone mineral density among long-term survivors of childhood acute lymphoblastic leukemia: results from the St. Jude Lifetime Cohort Study.

BACKGROUND: The prevalence of low bone mineral density (BMD) in adult survivors of childhood acute lymphoblastic leukemia (ALL), and the degree of recovery or decline, are not well elucidated. PROCEDURE: Study subjects (age ≥ 18 years and ≥10 years post-diagnosis) participated in an institutional follow-up protocol and risk-based clinical evaluation based on Children's Oncology Group guidelines. Trabecular volumetric BMD was ascertained using quantitative computed tomography, reported as age- and sex-specific Z-scores. RESULTS: At median age 31 years, 5.7% of 845 subjects had a BMD Z-score of ≤-2 and 23.8% had a Z-score of -1 to -2. Cranial radiation dose of ≥24 Gy, but not cumulative methotrexate or prednisone equivalence doses, was associated with a twofold elevated risk of a BMD Z-score of ≤-1. The cranial radiation effect was stronger in females than in males. In a subset of 400 subjects, 67% of those who previously had a BMD Z-score of ≤-2 improved by one or more categories a median of 8.5 years later. CONCLUSIONS: Very low BMD was relatively uncommon in this sample of adult survivors of childhood ALL, and BMD Z-scores tended to improve from adolescence to young adulthood. High-dose cranial or craniospinal radiation exposure was the primary predictor of suboptimal BMD in our study. Given that cranial radiation treatment for childhood ALL is used far more sparingly now than in earlier treatment eras, concerns about persistently low BMD among most current childhood ALL patients may be unwarranted.

Getting heavier, younger: trajectories of obesity over the life course.

CONTEXT: Although recent trends in obesity have been well documented, generational patterns of obesity from early childhood through adulthood across birth cohorts, which account for the recent epidemic of childhood obesity, have not been well described. Such trends may have implications for the prevalence of obesity-associated conditions among population subgroups, including type 2 diabetes. OBJECTIVE: Our objective was to evaluate trajectories of obesity over the life course for the US population, overall and by gender and race. DESIGN, SETTING AND PARTICIPANTS: We conducted an age, period and birth cohort analysis of obesity for US individuals who participated in the National Health and Nutrition Examination Surveys (NHANES) (1971-2006). MAIN OUTCOME MEASURES: Obesity was defined as a body mass index >or=95th percentile for individuals aged 2-16 years or >or=30 kg m(-2) among individuals older than 16 years. Age was represented by the age of the individual at each NHANES, period was defined by the year midpoint of each survey, and cohort was calculated by subtracting age from period. RESULTS: Recent birth cohorts are becoming obese in greater proportions for a given age, and are experiencing a greater duration of obesity over their lifetime. For example, although the 1966-1975 and 1976-1985 birth cohorts had reached an estimated obesity prevalence of at least 20% by 20-29 years of age, this level was only reached by 30-39 years for the 1946-1955 and 1956-1965 birth cohorts, by 40-49 years for the 1936-1945 birth cohort and by 50-59 years of age for the 1926-1935 birth cohort. Trends are particularly pronounced for female compared with male, and black compared with white cohorts. CONCLUSIONS: The increasing cumulative exposure to excess weight over the lifetime of recent birth cohorts will likely have profound implications for future rates of type 2 diabetes, and mortality within the US population.

Prevalence of conception and pregnancy outcomes after hematopoietic cell transplantation: report from the Bone Marrow Transplant Survivor Study.

We conducted a retrospective study to describe the magnitude of compromise in reproductive function and investigate pregnancy outcomes in 619 women and partners of men treated with autologous (n=241) or allogeneic (n=378) hematopoietic cell transplantation (HCT) between 21 and 45 years of age, and surviving 2 or more years. Median age at HCT was 33.3 years and median time since HCT 7.7 years. Mailed questionnaires captured pregnancies and their outcomes (live birth, stillbirth, miscarriage). Thirty-four patients reported 54 pregnancies after HCT (26 males, 40 pregnancies; eight females, 14 pregnancies), of which 46 resulted in live births. Factors associated with reporting no conception included older age at HCT (> or =30 years: odds ratio (OR)=4.8), female sex (OR=3.0), and total body irradiation (OR=3.3). Prevalence of conception and pregnancy outcomes in HCT survivors were compared to those of 301 nearest-age siblings. Although the risk for not reporting a conception was significantly increased among HCT survivors (OR=36), survivors were not significantly more likely than siblings to report miscarriage or stillbirth (OR=0.7). Although prevalence of conception is diminished after HCT, if pregnancy does occur, outcome is likely to be favorable. Patients should be counseled prior to transplant regarding strategies to preserve fertility.

Environmental exposure and cancer in children. A conceptual framework for the pediatrician.

Ultimately, after gathering and assessing all available evidence, pediatricians and health care policymakers must make informed decisions on whether exposure to a specific agent has the potential to cause cancer in children. In the case of DES, for which the results were clear, there was no question that the drug should be taken off the market; however, most cases of suspected carcinogens lack such clear evidence documenting cause and effect. An example of a murky topic is the suspected relationship between residential electromagnetic fields (EMFs) and childhood cancer. Epidemiologic and biologic researchers have tried for more than 2 decades to determine whether exposure to relatively high levels of EMFs poses health hazards, especially cancer in children. Although the preponderance of evidence favors a judgment that this ubiquitous environmental exposure is harmless, concerns remain in many public circles and some scientific ones. Any proposed intervention to remove a potentially carcinogenic agent must be weighed against the cost and inconvenience to the affected community. Pediatricians are placed in a vulnerable position when faced with questions of a carcinogenic potential because of the frequency of claims in the popular literature stating that exposure to a certain product or food is associated with an increased risk for cancer in adults and possibly children. When such studies are published or, more often, released to the press, the strength of the evidence for a causal association with cancer, coupled with the context of the study, should be considered as a reasonable starting point. Better communication models of disseminating cancer-risk information are needed so that the public understands the difference between a weak study that appeared on the local news with little evidence to support a cause-and-effect relationship versus a well-designed study that was published in a peer-reviewed journal and indicates a likely cause-and-effect association.

Brain and other central nervous system tumors: rates, trends, and epidemiology.

Reports that central nervous system (CNS) cancer rates are increasing have prompted debate on whether secular trends reflect environmental changes related to etiology or artifacts of case ascertainment. We present the most recent data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program on incidence rates and trends of CNS malignancies, including primary CNS lymphomas, and on survival probability. We discuss the new 2000 standard for adjusting rates; underreporting of CNS tumor rates resulting from the exclusion of nonmalignancies in most cancer registries; and information on CNS tumor risk factors, including concerns related to nonionizing electromagnetic fields and wireless mobile telephones.

Knowledge and preference for breast conservation therapy among women without breast cancer.

We interviewed 419 adult women in Minnesota, who were selected at random and without a history of breast cancer, to ascertain what percentage could correctly report that cure was the same for breast conservation therapy and mastectomy, what percentage would state a preference for breast conservation therapy rather than mastectomy, and characteristics associated with these outcomes. Nearly all women (n = 360; 86%) had heard of both mastectomy and breast conservation therapy; among these women, 37% correctly reported that the two treatments were equally efficacious. Given a scenario where they were diagnosed with breast cancer amenable to either treatment, 58% of participants stated a preference for breast conservation therapy. Older women were less likely than younger women to know that cure was the same for breast conservation therapy and mastectomy (adjusted OR = 0.5, 95% CI 0.2, 1.0), and women residing in urban areas were more likely to prefer breast conservation therapy over mastectomy compared to rural residents (adjusted OR = 2.2, 95% CI 1. 3, 3.8). Comparing these findings to women diagnosed with breast cancer in Minnesota, breast conservation therapy was found to be performed less frequently than preference for such therapy among women in our study would suggest. Educating women prior to diagnosis about breast cancer treatment options, and exploring reasons for the gap between actual utilization of breast conservation therapy and prediagnosis preference, may be indicated.

Mammography use among women as a function of age and patient involvement in decision-making.

OBJECTIVE: To assess the extent to which self-reported patient involvement in decision-making for initiation of mammography differs with age. DESIGN: Data from the 1992 National Health Interview Survey (NHIS) Cancer Control Supplement were evaluated. Prevalences were weighted and variances were adjusted using SUDAAN software to account for the complex, multistage sampling probability design of the NHIS. Logistic regression was used to evaluate the relative likelihood of self-reported involvement in the decision to have a mammogram within the preceding year as a function of age and other covariates. PARTICIPANTS: Mammography use was assessed among 3,863 NHIS female respondents 40 years of age or older. The analysis of decision-making was restricted to the subgroup of 1,064 women who reported a screening mammogram within the preceding year and who provided information on the other relevant variables. MEASUREMENTS AND MAIN RESULTS: The probability of reported mammography use within the preceding year declines among older groups of interviewees. Among women with a mammogram in the preceding year, the weighted percentage of women reporting active involvement in the decision (patient decision or decided jointly with a physician) declines from 51% among women 40 to 45 years of age to 19% among those aged 75 years or older. The adjusted odds ratio comparing the likelihood of participating in the decision to have a mammogram for the oldest women, compared with the youngest, was 0.31 (95% confidence interval 0.15 to 0.61). CONCLUSIONS: Older women are substantially less likely than younger women to report active involvement in the mammography decision-making process. Increased use of screening mammography among older women will require greater promotion by physicians. Other interventions, such as directed educational efforts, may also be needed to increase mammography demand among older women.

Evidence-based decision making in public health.

A stronger focus on evidence-based decision making in day-to-day public health practice is needed. This article describes the rationale for this need, including (1) the inter-relationships between evidence-based medicine and evidence-based public health (EBPH); (2) commonly used analytic tools and processes; (3) keys to when public health action is warranted; (4) a strategic, six-step approach to more analytic decision making; and (5) summary barriers and opportunities for widespread implementation of EBPH. The approach outlined is being tested through a series of courses for mid-level managers in the Missouri Department of Health--initial results from a pilot test are encouraging. It is hoped that the greater use of an evidence-based framework in public health will lead to more effective programs.

Seasonal variations in the diagnosis of childhood cancer in the United States.

Seasonal trends in month of diagnosis have been reported for childhood acute lymphoblastic leukaemia (ALL) and non-Hodgkin's lymphoma (NHL). This seasonal variation has been suggested to represent an underlying viral aetiology for these malignancies. Some studies have shown the highest frequency of diagnoses in the summer months, although this has been inconsistent. Data from the Children's Cancer Group and the Pediatric Oncology Group were analysed for seasonal incidence patterns. A total of 20,949 incident cancer cases diagnosed in the USA from 1 January 1989 through 31 December 1991 were available for analyses. Diagnosis-specific malignancies available for evaluation included ALL, acute myeloid leukaemia (AML), Hodgkin's disease, NHL, rhabdomyosarcoma, neuroblastoma, retinoblastoma, osteosarcoma, Wilms' tumour, retinoblastoma, Ewings' sarcoma, central nervous system (CNS) tumours and hepatoblastoma. Overall, there was no statistically significant seasonal variation in the month of diagnosis for all childhood cancers combined. For diagnosis-specific malignancies, there was a statistically significant seasonal variation for ALL (P = 0.01; peak in summer), rhabdomyosarcoma (P = 0.03; spring/summer) and hepatoblastoma (P = 0.01; summer); there was no seasonal variation in the diagnosis of NHL. When cases were restricted to latitudes greater than 40 degrees ('north'), seasonal patterns were apparent only for ALL and hepatoblastoma. Notably, 33% of hepatoblastoma cases were diagnosed in the summer months. In contrast, for latitudes less than 40 degrees ('south'), only CNS tumours demonstrated a seasonal pattern (P = 0.002; winter). Although these data provide modest support for a summer peak in the diagnosis of childhood ALL, any underlying biological mechanisms that account for these seasonal patterns are likely complex and in need of more definitive studies.

The risk of hospitalization for acute myocardial infarction among older adults.

BACKGROUND: The purpose of this study was to prospectively examine the risk of hospitalization for acute myocardial infarction (AMI) in a large, nationally representative sample of very old men and women. METHODS: We utilized secondary analysis of the Longitudinal Study of Aging. Baseline (1984) in-person interview data were linked to Medicare hospitalization records for 1984-1991. Subjects were 6,071 noninstitutionalized adults 70 years old or older at baseline. Hospitalization for AMI was defined as having primary discharge diagnoses containing ICD9-CM 410 codes. Multivariable proportional hazards regression was used to evaluate the epidemiologic risks for all persons, and separately for women, men, self-respondents, those with no previous AMIs, and those with no history of coronary heart disease. RESULTS: Of the sample, 357 persons (5.9%; 172 women and 185 men) had at least one primary discharge diagnosis of AMI. Significant (p<.05) risk factors for being hospitalized with an AMI (adjusted hazards ratios in parentheses) from the pooled analysis were male gender (1.86), having no more than a grade school education (1.35), atherosclerosis (1.43), hypertension (1.29), coronary heart disease (1.63), angina (1.60), previous AMI (1.52), diabetes (1.89), and four or more lower body limitations (1.43). The gender-specific analyses, however, revealed that hypertension, angina, diabetes, and lower body limitations were risk factors only for women, and that having no more than a grade school education was a risk factor only for men. CONCLUSION: Men, especially those with low education, women with diabetes, angina, hypertension, or lower body limitations, and either men or women with previous AMIs, coronary heart disease, or atherosclerosis have elevated risks for AMI resulting in hospitalization, and they should be considered for evaluation and monitoring. Current protocols for therapeutic management should be adopted, and compliance should be encouraged.

The contribution of nonmalignant tumors to CNS tumor incidence rates among children in the United States.

OBJECTIVES: According the U.S. National Cancer Institute (NCI), the incidence rate of primary malignant central nervous system (CNS) neoplasms among children is about 30 per million person-years. This rate, however, underestimates the true burden of CNS tumors because nonmalignancies are not included in the NCI case reporting system. Intracranial tumors, to an extent regardless of their histological behavior, can have a malignant clinical course and result in a high degree of morbidity and mortality. The purpose of this report is to estimate the contribution that nonmalignant tumors have on the overall incidence of CNS tumors in children. METHODS: Population-based data from the Central Brain Tumor Registry of the United States were analyzed. Included in the analysis were children aged 0-19 years who were diagnosed with a primary CNS tumor from 1990-93 (N = 1133). RESULTS: The inclusion of nonmalignancies increased the CNS tumor incidence rate by 28% from 29.4 to 37.6 per million person-years. The increases were 17% for children aged 0-4 years, 17% for children aged 5-9 years, 31% for children aged 10-14 years and 57% for adolescents aged 15-19 years. Differences in patterns between malignant and nonmalignant tumor occurrence by sex, histology, and location were also observed. CONCLUSION: Because of the potentially profound adverse health effects on children who experience CNS tumors, the systematic collection of both malignancies and nonmalignancies is consistent with the mission of public health surveillance. Without such population-based data, analytic epidemiologic studies to evaluate disease etiology and assess disease consequences are greatly hindered.

Gender differences in the sequelae of hospitalization for acute myocardial infarction among older adults.

OBJECTIVE: To examine the effect of gender differences among older adults hospitalized for an acute myocardial infarction (AMI) on subsequent health outcomes. DESIGN: Secondary analysis of the Longitudinal Study on Aging. Data from baseline interviews (1984) and three biennial (1986, 1988, and 1990) re-interviews were linked to Medicare hospitalization and National Death Index records for 1984-1991. PARTICIPANTS: A total of 6071 community-dwelling adults aged 70 years or older at baseline. METHODS: Pooled and stratified multivariable models were used to examine gender differences in the independent effects of being hospitalized for an AMI on all-cause mortality, the risk and volume of subsequent hospitalization, and increases in the number of functional limitations. Two comparison groups were used. RESULTS: Three hundred fifty-seven AMI cases (6%; 172 women and 185 men) were compared with 3976 hospitalized controls and 1738 nonhospitalized controls. The risk of all-cause mortality for AMI cases was greater than that for either hospitalized controls or nonhospitalized controls (referent), and this increased risk was significantly (P < .001) stronger for women (adjusted hazards ratio (AHR) = 14.24, 95%CI = 10.99, 18.46) than for men (AHR = 9.91, 95%CI = 7.75, 12.67). Overall, AMI cases were also more likely to be hospitalized subsequently than the hospitalized controls (referent; adjusted odds ratio (AOR) = 1.47, 95%CI = 1.17, 1.85), although in the stratified analysis this association held for men (AOR = 1.73, 95%CI = 1.25, 2.41) but not for women (AOR = 1.25, 95%CI = .90, 1.73). Among those subsequently hospitalized, both women and men AMI cases consumed more hospital resources than the hospitalized controls, and there were gender differences suggesting that the effects on total charges and length of stay were greater for women than for men with AMI. Finally, although the AMI cases had greater adjusted mean increases in the number of instrumental activities of daily living limitations and lower body limitations than the nonhospitalized controls, they were no worse off than the hospitalized controls, and there were no gender differences in those effects. CONCLUSION: Relative to the appropriate comparison groups, hospitalization for an AMI increases the risk of death and the total costs and lengths of stay of subsequent hospitalizations for women more than for men. Therefore, increased primary prevention, diagnosis, and treatment efforts should be directed toward women.

Extremely low frequency electromagnetic fields (EMF) and brain cancer in adults and children: review and comment.

Epidemiologic and experimental research on the potential carcinogenic effects of extremely low frequency electromagnetic fields (EMF) has now been conducted for over two decades. Cancer epidemiology studies in relation to EMF have focused primarily on brain cancer and leukemia, both from residential sources of exposure in children and adults and from occupational exposure in adult men. Because genotoxic effects of EMF have not been shown, most recent laboratory research has attempted to show biological effects that could be related to cancer promotion. In this report, we briefly review residential and occupational EMF studies on brain cancer. We also provide a general review of experimental studies as they relate both to the biological plausibility of an EMF-brain cancer relation and to the insufficiency of such research to help guide exposure assessment in epidemiologic studies. We conclude from our review that no recent research, either epidemiologic or experimental, has emerged to provide reasonable support for a causal role of EMF on brain cancer.

Health status and mammography use among older women.

OBJECTIVE: To assess the extent to which an age-associated reduction in mammography use can be explained by declining self-reported health status. DESIGN: We analyzed data from the 1992 National Health Interview Survey (NHIS) and Cancer Control Supplement. Logistic regression analysis was used to evaluate the association between age, health status (self-reported health and limitations in major activity), and other variables potentially related to mammography use within the past 1 year (recent mammography). PARTICIPANTS: Of 12,035 NHIS respondents we restricted our analysis to the 1,772 women aged 50 years or older who reported one or more lifetime mammograms. We excluded women without a mammogram (n = 937) because we were interested in factors related to recent use versus past use of mammography. MEASUREMENTS AND MAIN RESULTS: The percentage of women with a recent mammogram declined with increasing age, and the age association was independent of other factors including health status (adjusted odds ratio [OR] comparing women aged 75 years or older with those aged 50 to 64 years was 0.54; 95% confidence interval [CI] 0.41, 0.70). This age effect persisted in an analysis restricted to women reporting good or better health (adjusted OR was 0.60, 95% CI 0.44, 0.80). CONCLUSION: The observed decline in recent mammography use with advancing age was not explained by variation in health status. Because healthy elderly women may live long enough to realize the potential benefit of screening mammography, factors responsible for its reduced use should be identified. Doing so will allow for the selective promotion of screening mammography among those older women most likely to benefit.

The sequelae of hospitalization for ischemic stroke among older adults.

OBJECTIVES: To estimate the independent effect of hospitalization for ischemic stroke on change in functional status, subsequent hospitalization, and mortality. DESIGN: Secondary analysis of the nationally representative Longitudinal Study on Aging. Baseline (1984) interview data were linked to Medicare hospitalization and death records for 1984-1991 and to functional status reports at three biennial follow-ups. SETTING: In-person and telephone interviews were conducted. PARTICIPANTS: A total of 6071 noninstitutionalized respondents 70 years old or older at baseline. MEASUREMENTS: Hospitalization for ischemic stroke was defined as having one or more episodes with primary discharge ICD9-CM codes of 433.0-434.9, 436, and 437.0-437.1. Two reference groups were used: those who were hospitalized for something other than stroke, and those who were not hospitalized at all. The statistical methods employed were multivariable proportional hazards, logistic, and linear regression. RESULTS: The adjusted hazards ratio for having a primary hospital discharge diagnosis of ischemic stroke on mortality was 7.57 (CI95% = 6.47 to 8.85) versus 3.67 (CI95% = 3.28 to 4.10) for having been hospitalized for something other than stroke (both compared with the reference category of those not hospitalized at all). The adjusted odds ratio for having any subsequent hospitalization associated with having a primary hospital discharge diagnosis of ischemic stroke (compared with having been hospitalized for something other than stroke) was not significantly elevated (AOR = 1.16; CI95% = .94 to 1.42). However, the percent increases in the subsequent number of hospital episodes, total charges, and total length of stay for those who were hospitalized for ischemic stroke relative to those hospitalized for something other than stroke were significant (P < .001), and ranged from 16.3 to 39.0%. Hospitalization for ischemic stroke was also related significantly to greater increases in the regression-adjusted mean number of instrumental activities of daily living and lower body function limitations at follow-up. CONCLUSION: Hospitalization for ischemic stroke among older adults substantially increases the risk of subsequent mortality, the volume of hospital resource consumption, and greater functional decline, even when compared with hospitalization for something other than stroke. Therefore, greater attention to the prevention and management of ischemic stroke is needed.

The risk of hospitalization for ischemic stroke among older adults.

OBJECTIVES: The purpose of this study was to identify risk factors for stroke and to estimate their relative importance in a large, nationally representative sample of very old men and women. METHODS: The study was designed as a secondary analysis of the Longitudinal Study on Aging. Baseline (1984) in-person interview data were linked to Medicare hospitalization records for 1984 to 1991. Participants were 6,071 noninstitutionalized adults 70 years old or older at baseline. Hospitalization for ischemic stroke was defined as having one or more episodes with a primary discharge diagnosis containing ICD-9-CM codes of 433.0-434.9, 436, and 437.0-437.1. Multivariable proportional hazards regression was used to estimate the risks associated with previously identified epidemiologic factors. RESULTS: Five hundred and three persons (8.3%) had at least one primary discharge diagnosis of ischemic stroke. In descending order of importance-based on the partial r statistics associated with their adjusted hazards ratios (AHRs), the salient risk factors were having a previous history of stroke (AHR = 2.86), age (AHR = 1.04 per year), diabetes (AHR = 1.78), male gender (AHR = 1.42), lower body limitations (AHR = 1.09 per limitation), arthritis (AHR = 0.74), hypertension (AHR = 1.29), and poverty (AHR = 1.33). CONCLUSION: Patients presenting with the high risk factors identified in this study should be considered for further evaluation and monitoring. Current protocols for the therapeutic management of these higher risk patients should be considered, and compliance should be encouraged.