Health status and health-related quality of life in adolescent survivors of cancer in childhood

PurposeAdolescent survivors of cancer in childhood face particular challenges due to their maturational trajectory, including psychosocial adjustments, self-help skills, intellectual functioning and socialization. To better understand these, we assessed the health status and health-related quality of life (HRQL) in a 20-year cohort of such survivors in a single institution.MethodsHealth status and HRQL were measured with a self-complete questionnaire from the Health Utilities Index (HUI) family of multi-attribute, preference-based instruments that provide utility scores for single attributes and overall HRQL.ResultsEighty-four (42 males, 42 females) of 129 eligible subjects (65%) participated. More than 80% of the respondents reported some form of morbidity. Overall HRQL utility scores were lower for both the males and females than for corresponding members of the Canadian general population. Female survivors self-reported a significantly greater burden of morbidity (mean overall HUI2/HUI3 scores: .83/.73 vs. .90/.84 for males, p < .02), which was most evident in the attributes of emotion and cognition.ConclusionsThe majority of adolescent survivors of cancer in childhood carry a morbidity burden into their teen and young adult years. These findings may guide the support required by this population.     

Translation and cultural adaptation of Health Utilities Index (HUI) Mark 2 (HUI2) and Mark 3 (HUI3) with application to survivors of childhood cancer in Brazil

Introduction: There are few publications reporting health-related quality of life (HRQL) in developing nations. Most instruments measuring HRQL have been developed in English-speaking countries. These instruments need to be culturally adapted for use in non-English-speaking countries. The HUI2 and HUI3 are generic, preference-based systems for describing health status and HRQL. Developed in Canada, the systems have been translated into more than a dozen languages and used worldwide in hundreds of studies of clinical and general populations. Methods: The Brazilian–Portuguese translation of the HUI systems was supervised by senior HUInc staff having experience with both the HUI systems and translations. The process included two independent forward translations of the multi-attribute health status classification systems and related questionnaires, consensus between translators on a forward translation, back-translation by two independent translators of the forward translation, and review of the back-translations by original developers of the HUI. The final questionnaires were tested by surveying a sample of convenience of 50 patients recruited at the Centro de Tratamento e Pesquisa–Hospital do Câncer in São Paulo, Brazil. Results: Fifty patients were enrolled in the study. No assessor, patient or nurse or physician, reported problems answering the HUI questionnaires. No significant differences were found in mean overall HUI2 or HUI3 utility scores among types of assessors. Variability in scores are similar to those from other studies in Latin America and Canada. Conclusion: Test results provide preliminary evidence that the Brazilian–Portuguese translation is acceptable, understandable, reliable and valid for assessing health-status and HRQL among survivors of cancer in childhood in Brazil.     

The feasibility and responsiveness of the health utilities index in patients with early-stage breast cancer: A prospective longitudinal study

Background The health utilities index (HUI3) is a health measurement instrument based on individuals’ preferences for different health states. Breast cancer (BC) is common, with a high proportion of long-term survivors, making evaluation of treatment effects important. Feasibility and responsiveness of HUI3 was compared to the short-form 36 (SF-36) in patients with BC. Methods HUI3 and SF-36 were administered eight times: at initial surgical consultation, 1 week before surgery; 1 week, 3, 6, 12, 18, and 24 months after surgery. Effect size, analysis of variance, and Pearson product moment correlations were calculated. BC data were compared to normative values. Results Eighty-five patients were enrolled. Ninety-one percent of planned assessments were completed. HUI3 showed significant responsiveness (P < 0.01) after surgery and during recovery. HUI3 scores correlated with SF-36 scores. Comparison to normative data demonstrated the significant detrimental effect of BC diagnosis. Results showed long-term effects of treatment on physical health and positive effects on mental/emotional health in BC survivors. Conclusion(s) HUI3 was found to be feasible and responsive in our cohort of BC patients. Changes in HUI3 values over time, and compared to normative data, paralleled SF-36 scores. HUI3 is a valuable tool in health-related quality of life and cost-utility studies in patients with BC.     

Cross-cultural comparisons of health status in Canada using the Health Utilities Index

Objective. The purpose of this study was to examine the differences in health status, as measured by the Health Utilities Index (HUI), among seven cultural groups in Canada defined by place of birth and language. Design. The study analysed cross-sectional data from the National Population Health Survey conducted by Statistics Canada in 1994-95. Results. Age-standardized prevalence of dysfunction, defined as HUI < 0.83, varied from 12.7% in English-speaking immigrants to 17.8% in French-speaking Canadians. Considerable differences between the groups were found in the reporting of pain, emotional function, and cognitive function. The variation in HUI scores across the cultural groups could not be explained by differences in socioeconomic status and self-reported chronic conditions. Conclusions. Although the healthy immigrant effect is probably responsible for some of the variation in health status among cultural groups in Canada, considerable differences exist within the immigrant and Canadian-born populations. Cultural factors may have a substantial effect on the reporting of pain and mental health problems. Further studies are needed to determine the cross-cultural validity of the HUI.     

Areas of decrement in health-related quality of life (HRQL): Comparing the SF-12, EQ-5D,and HUI 3

Background: Different measures of health status and health-related quality of life (HRQL) have been advocated for different purposes at the clinical and population level. Relatively little is known about how these measures function in relationship to one another. We examined the relationship between the Short-Form 12 (SF-12), EQ-5D, and Health Utilities Index (HUI) Mark 3 for overall scores and in analogous domains of health. A convenience sample was obtained through surveying patients at an inner-city community health center. Measurements and main results: The sample was comprised primarily of low-income racial/ethnic minorities; 393 patients were approached and 301 patients (77%) participated. The three measures had correlations between overall scores that ranged from 0.41 to 0.69 and correlations between similar domains from different measures that ranged from 0.42 to 0.59. For the HUI 3, any impairment most frequently was noted with pain, vision, cognition, and emotion. For the EQ-5D, pain/discomfort and anxiety/depression were reported as impaired most often. Compared to published population scores, participants reported impairments with increased frequency and at a greater level. Conclusions: Participants demonstrated consistency with responses to similar types of items and correlations between related aspects of health were moderate to strong. Domains of health most often reported as impaired resembled those noted in national surveys. Despite differences in the structure of the measures, all three instruments capture information about decrements in broadly analogous domains of health.     

Genetic effects of radiotherapy for childhood cancer

Radiation-induced heritable diseases have not been demonstrated in humans and estimates of genetic risks for protection purposes are based on mouse experiments. The most comprehensive epidemiologic study is of the Japanese atomic bomb survivors and their children, which found little evidence for inherited defects attributable to parental radiation. Studies of workers exposed to occupational radiation or of populations exposed to environmental radiation appear too small and exposures too low to convincingly detect inherited genetic damage. In contrast, survivors of childhood cancer form the largest group of people exposed to high doses of ionizing radiation before reproduction and offer unique advantages for studying trans-generation effects. A wide range of gonadal doses are possible, several comparison groups are readily available (including siblings), and there is a strong willingness among cancer survivors to participate in health studies. Cancer patients also have detailed medical records that facilitate both the accurate estimation of gonadal doses and the assessment of potentially confounding factors, such as intercurrent illness, personal and family medical histories, lifestyle characteristics such as tobacco use, and circumstances at delivery. An international study is nearing completion of over 25,000 survivors of childhood cancer in the United States and Denmark who gave birth to or fathered over 6,000 children. Doses to gonads are being reconstructed from radiotherapy records with 46% over 100 mSv and 16% over 1,000 mSv. Adverse pregnancy outcomes being evaluated include major congenital malformations, cytogenetic abnormalities, stillbirths, miscarriages, neonatal deaths, total deaths, leukemia and childhood cancers, altered sex ratio, and birth weight. The main analyses are based on dose-response evaluations. Blood studies of trios (cancer survivor, spouse or partner and offspring) have been initiated to evaluate mechanistic evidence for the transmission of any radiation-induced genetic damage such as minisatellite mutations. Markers of cancer susceptibility such as chromosomal radiosensitivity and genotype profile will also be examined. In the United States series to date, 4,214 children were born to cancer survivors among whom 157 (3.7%) genetic diseases were reported in contrast to 95 (4.1%) reported conditions among 2,339 children born to sibling controls. In the Denmark series the comparable figures were 82 (6.1%) birth defects among 1,345 children of cancer survivors and 211 (5.0%) among 4,225 children of sibling controls. Coupled with prior studies, these preliminary findings, if sustained by ongoing dose-response analyses, provide reassurance that cancer treatments including radiotherapy do not carry much if any risk for inherited genetic disease in offspring conceived after exposure.     

Quality of life in adult survivors of childhood cancer.

Sixty-four adult survivors of childhood cancer, recruited via Israel's largest pediatric cancer treatment center, participated in a multi-dimensional assessment of long-term adjustment and quality of life in the domains of educational achievement, employment status, military service, family status, health, and psychological well-being. Subjects had been diagnosed with cancer prior to age 18, were three years or more off therapy with no evidence of disease, and over 18 years old at the time of the study. Data from structured interviews were compared to responses on similar items from a control group with no history of serious illness during childhood, matched for age, sex, and parental education levels. Results indicated an overall pattern of integration into the social mainstream, with similar objective levels of achievement for survivors and controls for most measures of education, employment, significant relationships, and psychological well-being. Results also indicated certain areas of disadvantage, such as military recruitment difficulties, lower income levels, and higher rates of workplace rejection. Significantly, almost half of the survivor sample reported subjective feelings that their illness experience had impaired their achievement in several domains. Quality of life is considered an important outcome parameter in terms of clinical decision making as well as in guiding preventive and supportive intervention efforts.     

Measuring health status and decline in at-risk seniors residing in the community using the Health Utilities Index Mark 2

Purpose The purpose of this study was to assess the responsiveness of one measure of HRQL, the HUI Mark 2 (HUI2), to changes in health status over time in an older community-based population.Methods The sample consisted of 192 individuals age 65 and over residing in their homes and receiving health and support services in Calgary, Canada. Subjects received three assessments at 6-month intervals using the HUI2, to measure health-related quality of life (HRQL), and the Minimum Data Set for Home Care (MDS-HC) for demographic and health status information. Change scores were calculated as the difference between scores at the second and third assessments. The relationship between the HUI2 and other measures of health status were examined using t-tests and ANOVA. Associations between the magnitude of decline in HUI2 and declines on other measures were examined using multiple linear regression.Results Lower HUI2 scores were significantly associated with the presence of depressive symptoms, impairment in activities of daily living (ADL), and clinical instability at baseline. Over 6 months of follow-up, HUI2 decline was associated with worsening depressive symptoms, increase in the number of chronic conditions, and age 85 and over.Conclusion The HUI2 measure of HRQL in older persons at risk for institutionalization appears to reflect health status at a point in time and to be responsive to changes in health status over time.     

微波作业人员健康的动态观察

目的 接触微波辐射两年半对健康影响的动态观察。方法 以微波作业者接触前、后及对照组进行测询以及晶体、微核、免疫球蛋白等观察剂量－效应关系。结果 接触微波作业人员神经系统,血心管、晶体、微核等与对照组有一定差别。结论 从事微波作业对健康有一定影响。     

Comparing directly measured standard gamble scores to HUI2 and HUI3 utility scores: group- and individual-level comparisons

Directly measured standard gamble (SG) utility scores reflect the respondent's assessment and valuation of their own health status. Scores from the health utilities index (HUI) are based on self-assessed health status but valued using community preferences obtained using the SG. Our objectives were to find if mean directly measured utility scores agree with mean HUI mark 2 (HUI2) and mean HUI mark 3 (HUI3) scores. Also, if individual directly measured utility scores agree with HUI2 and HUI3 scores, and whether HUI2 and HUI3 scores agree. Questionnaires based on the HUI2 and HUI3 health-status classification systems were administered by interviewers to 140 teenage survivors of extremely low birthweight (ELBW) and 124 control group teens. Respondents were asked to think about their own usual health states using six dimensions from HUI2 and value that state using the SG. Mean SG scores are compared with mean HUI2 and mean HUI3 scores using paired sample t-tests. Mean HUI2 scores are compared with mean HUI3 scores. Agreement among scores is assessed using intra-class correlation coefficient (ICC). The effect of severity of health-state morbidity on agreement was assessed using three approaches. ELBW cohort mean (standard deviation) SG, HUI2, and HUI3 scores were 0.90 (0.20), 0.89 (0.14), and 0.80 (0.22). Results for controls were 0.93 (0.11), 0.95 (0.09), and 0.89 (0.13). Mean SG and HUI2 scores did not differ; mean SG and HUI3 did differ; mean HUI2 and HUI3 also differed. At the individual level for ELBW, the ICCs between SG and HUI2, SG and HUI3, and HUI2 and HUI3 scores were 0.13, 0.28, and 0.64. For controls the ICCs were 0.14, 0.24, and 0.56. HUI2 scores appear to match directly measured utility scores reasonably well at the group level. HUI2 and HUI3 scores differ systematically. At the individual level, however, HUI2 and HUI3 scores are poor substitutes for directly measured scores.     

Risk of second malignant neoplasms among childhood cancer survivors treated with radiotherapy: meta-analysis of nine epidemiological studies

In the light of notable advances made in childhood cancer therapies, an understanding of the late effects of treatment is important for continued medical care. We conducted a meta-analysis of studies on the excess relative risk (ERR) of second malignant neoplasm (SMN) among childhood cancer survivors treated with radiotherapy. Relevant studies were retrieved by searching the PubMed database, supplemented by hand-searching of reference lists of already retrieved papers. Nine studies were identified and overall ERR estimates were calculated using a fixed effects model and a random effects model.
The overall ERR per Gy (absorbed dose of ionising radiation) estimates of radiotherapy by a fixed effect model and a random effects model were 0.50 [95% CI 0.20, 1.21] and 0.53 [95% CI 0.22, 1.31] respectively. Heterogeneity among studies was suggested by Cochran's Q statistic (Q = 40.4, d.f. = 8, P  < 0.001). The estimate obtained using a random effects model was far smaller than the corresponding estimate of 1.7 [95% CI 1.1, 2.5] from the study on atomic bomb survivors exposed as young children, suggesting underestimation of ERR estimates among the nine studies compared with the estimates from the study of atomic bomb survivors. In view of the heterogeneity and underestimation in ERR estimates, more studies concerning the risk of SMN among childhood cancer survivors are still needed for further understanding of the carcinogenic effects of radiotherapy on children.     

Radiation and cancer risk in atomic-bomb survivors

With the aim of accurately assessing the effects of radiation exposure in the Japanese atomic-bomb survivors, the Radiation Effects Research Foundation has, over several decades, conducted studies of the Life Span Study (LSS) cohort, comprising 93?000 atomic-bomb survivors and 27?000 controls. Solid cancer: the recent report on solid cancer incidence found that at age 70 years following exposure at age 30 years, solid cancer rates increase by about 35% Gy(-1) for men and 58%?Gy(-1) for women. Age-at-exposure is an important risk modifier. In the case of lung cancer, cigarette smoking has been found to be an important risk modifier. Radiation has similar effects on first-primary and second-primary cancer risks. Finally, radiation-associated increases in cancer rates appear to persist throughout life. Leukaemia: the recent report on leukaemia mortality suggests that radiation effects on leukaemia mortality persisted for more than 50 years. Moreover, significant dose-response for myelodysplastic syndrome was observed in Nagasaki LSS members even 40-60 years after radiation exposure. Future perspective: given the continuing solid cancer increase in the survivor population, the LSS will likely continue to provide important new information on radiation exposure and solid cancer risks for another 15-20 years, especially for those exposed at a young age.     

Health status prediction in critically ill children: A pilot study introducing Standardized Health Ratios

Performance of intensive care is usually quantified by means of standardized mortality rates, where standardization is directed towards the severity of illness on admission. However, as more critically ill patients survive, functional outcome and quality of life of these patients becomes more important. In a prospective study in a 10-bed tertiary paediatric intensive care unit (ICU), admission and follow-up health status were collected for 209 surviving patients. For this cohort of patients, health status 1 year after admission was also predicted, using the quantified health-utility-index (HUI), as a value between 0 and 1. For this purpose, two alternative multiple regression models were constructed. The most important predictors of 1-year health status were the level of sensation, mobility and cognition on admission to which self-care, systolic blood pressure, oxygen, Glascow Coma Scale, glucose and age may be added. The two alternative predictive models performed equally well (R2=0.83 and 0.84 respectively), indicating that health status could be predicted to a significant degree. The concept of relating expected future health status (based on base-line health status), with actual (observed) health status is denoted with the Standardized Health Ratio (SHR). In combination with the Standardized Mortality Ratios (SMR), such a ratio may become a new comprehensive indicator of performance in intensive care medicine.     

Health-Related Quality of Life in Children With Low Language or Congenital Hearing Loss,as Measured by the PedsQL and Health Utility Index Mark 3

ObjectivesTo examine health-related quality of life (HRQoL) in young children with low language or congenital hearing loss and to explore the value of assessing HRQoL by concurrently administering 2 HRQoL instruments in populations of children.MethodsData were from 2 Australian community-based studies: Language for Learning (children with typical and low language at age 4 years, n = 1012) and the Statewide Comparison of Outcomes study (children with hearing loss, n = 108). HRQoL was measured using the parent-reported Health Utilities Index Mark 3 (HUI3) and the Pediatrics Quality of Life Inventory 4.0 (PedsQL) generic core scale. Agreement between the HRQoL instruments was assessed using intraclass correlation and Bland-Altman plots.ResultsChildren with low language and with hearing loss had lower HRQoL than children with normal language; the worst HRQoL was experienced by children with both. The lower HRQoL was mainly due to impaired school functioning (PedsQL) and speech and cognition (HUI3). Children with hearing loss also had impaired physical and social functioning (PedsQL), vision, hearing, dexterity, and ambulation (HUI3). Correlations between instruments were poor to moderate, with low agreement.ConclusionsChildren with low language and congenital hearing loss might benefit from interventions targeting overall health and well-being, not just their impairments. The HUI3 and PedsQL each seemed to provide unique information and thus may supplement each other in assessing HRQoL of young children, including those with low language or congenital hearing loss.     

Relationship between health status and utility measures in older claudicants

The purpose of this study was to examine the relationship between health status and health utility measures in 34 older claudicants and to determine which attributes of health status were significant predictors of health state valuation/preference. The MOS SF-36 was used to assess health status and the rating scale and multiattribute Health Utility Index (HUI) were used to assess utility scores. With regard to health status, the bodily pain and physical functioning subscales contributed the most to reductions in quality of life (QoL) with mean subscale scores substantially lower than reported population norms. Patients rated their health status approximately one-third below a state of perfect health on both utility measures. Moderate correlations were observed between the MOS SF-36 subscale scores and the HUI and rating scale scores. In multivariable regression models, physical functioning and mental health were the best predictors of HUI scores, whereas general health and vitality were the best predictors of rating scale scores. Approximately 50% of the variance in utility scores was explained by these attributes. This study provides further documentation that bodily pain and reductions in physical function contribute to reductions in QoL in older patients with intermittent claudication. Other attributes of health status, however, notably psychological distress, were predictive of patients' preference for health states. Recognized constructs of physical and mental health explained the substantial variation in the utility/preference assessment in this population. Furthermore, these data are consistent with those reported in the Dutch Iliac Stent Trial.     

Do the determinants of health differ between people living in the community and in institutions?

Determinants of health studies have mainly dealt with samples of community-dwelling subjects. We utilized the 1996/97 Canadian National Population Health Survey community and institutional surveys to identify factors associated with the selection of individuals to institutions. We also assessed whether the same determinants of health variables explain variations in health in those living in the community and those living in institutions. Logistic regression analysis was used to investigate factors associated with selection to institutions. Results showed that health status, age, chronic conditions, education, race, marital status, smoking and alcohol were associated with the probability of being in an institution. Multiple linear regression analyses (dependent variable: Health Utilities Index Mark 3 [HUI3] score) with individual characteristics, socio-economic status, and health risk factors were also estimated. Results showed that advanced age, higher number of chronic conditions, lower education, smoking and being an alcohol non-drinker were negatively and significantly associated with HUI3 scores for the community sample. Except for age, chronic conditions and being an alcohol non-drinker, none of these factors were significantly associated with HUI3 for the institutional sample. Moreover, the association between age and HUI3 was weaker for the institutional sample in comparison to the community sample. Implications are that, for those who are institutionalized, the usual determinants of health factors are less important. In conclusion, there appears to be important heterogeneity in determinants of health between persons living in the institution and community.     

Adjusting distributions of the Health Utilities Index Mark 3 utility scores of health-related quality of life

The Health Utilities Index Mark 3 (HUI3) is a multi-dimensional, preference-based measure of health status and health-related quality of life (HRQoL). HUI3 scores correlate strongly with self-ratings of health status and functional disability and vary according to age, gender and occupation. In comparative studies relating to HRQoL, it is necessary to carry out adjusted comparison of the health status of the different groups, taking into account unbalanced distribution of confounding variables. This paper describes a stratification method to adjust the distributions of HUI3 scores. This method provides a graphical representation of adjusted distribution of HUI3, which can also be used to adjust other HRQoL scores. Cross-sectional data from the 1998/1999 National Population Health Survey (NPHS) in Canada were used to verify the proposed method. Male agriculture workers and male construction workers in Canada had quite different age distributions but similar HUI3 distributions. After adjusting the age distribution of the construction group to match the distribution of agriculture group, the mean HUI3 score of the former significantly decreased.     

Second neoplasms in survivors of childhood and adolescent cancer are often treatable.

PURPOSE: To estimate the incidence and types of second neoplasms in survivors of childhood and adolescent cancer, as well as the characteristics of those who developed second neoplasms. METHODS: Survivors who were under age 21 years at initial diagnosis, off therapy, and in remission for 2 years are referred to the Long Term Survivors' Clinic (LTSC) at Children's National Medical Center (CNMC). This review includes patients entered in the clinic database from January 1, 1997 to August 30, 2002. RESULTS: Twenty-three (2.3%) of 987 childhood cancer survivors followed in the LTSC had 26 (2.6%) second and third neoplasms. The mean age was 6.7 years at initial diagnosis, 20.3 years at diagnosis of the second neoplasm, and 20.5 years at diagnosis of the third neoplasm. Of 10 female and 13 male patients, 15 were white, six black, one Hispanic, and one Asian. All but two of the patients received radiation. Nineteen neoplasms, including seven thyroid carcinomas, six central nervous system tumors (three meningiomas), three basal cell carcinomas, two breast cancers, and one soft tissue sarcoma, occurred at sites within or contiguous to radiation sites. Five patients died, but the majority of neoplasms were treatable and most patients had good outcomes. CONCLUSION: Indefinite follow-up in a long-term survivors' clinic is indicated for adolescent and adult survivors of childhood cancer, with routine examination and screening for recurrence of the initial cancer as well as late effects, including second neoplasms.     

Telomere length in Chernobyl accident recovery workers in the late period after the disaster

The outcome of the Chernobyl nuclear power plant (CNPP) accident was that a huge number of people were exposed to ionizing radiation. Previous studies of CNPP clean-up workers from Latvia revealed a high occurrence of age-associated degenerative diseases and cancer in young adults, as well as a high mortality as a result of cardiovascular disorders at age 45–54 years. DNA tandem repeats that cap chromosome ends, known as telomeres, are sensitive to oxidative damage and exposure to ionizing radiation. Telomeres are important in aging processes and carcinogenesis. The aim of this study was to investigate the long-term effect of protracted ionizing radiation exposure on telomere length in CNPP clean-up workers. Relative telomere length (RTL) was measured in peripheral blood leukocytes of 595 CNPP clean-up workers and 236 gender- and age-matched controls using real-time quantitative polymerase chain reaction (q-PCR). Close attention was paid to participation year and tasks performed during the worker''s stay in Chernobyl, health status, and RTL differences between subgroups. Telomere shortening was not found in CNPP clean-up workers; on the contrary, their RTL was slightly greater than in controls (P = 0.001). Longer telomeres were found in people who worked during 1986, in those undertaking ‘dirty’ tasks (digging and deactivation), and in people with cancer. Shorter telomeres appeared frequently in those with cataract, osteoporosis, atherosclerosis, or coronary heart disease. We conclude that the longer telomeres revealed in people more heavily exposed to ionizing radiation probably indicate activation of telomerase as a chromosome healing mechanism following damage, and reflect defects in telomerase regulation that could potentiate carcinogenesis.