The burden of cardiovascular disease and risk for subsequent major adverse cardiovascular events in survivors of childhood cancer: a prospective, longitudinal analysis from the St Jude Lifetime Cohort Study.

BACKGROUND: The effect of the increasing lifetime burden of non-major cardiovascular conditions on risk for a subsequent major adverse cardiovascular event among survivors of childhood cancer has not been assessed. We aimed to characterise the prevalence of major adverse cardiovascular events and their association with the cumulative burden of non-major adverse cardiovascular events in childhood cancer survivors. METHODS: This is a longitudinal cohort study with participant data obtained from an ongoing cohort study at St Jude Children's Research Hospital: the St Jude Lifetime Cohort Study (SJLIFE). Prospective clinical follow-up was of 5-year survivors of childhood cancer who were diagnosed when aged younger than 25 years from 1962 to 2012. Age-frequency, sex-frequency, and race-frequency matched community-control participants completed a similar one-time clinical assessment. 22 cardiovascular events were graded using a St Jude Children's Research Hospital-modified version of the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03). Cumulative incidence and burden of the primary outcome of major adverse cardiovascular events (cardiomyopathy, myocardial infarction, stroke, and other cardiovascular-related mortality) were estimated. Rate ratios (RR) of the association of major adverse cardiovascular events with 22 non-major adverse cardiovascular events were estimated using multivariable piecewise-exponential regression adjusting for attained age, age at diagnosis, sex, race and ethnicity, treatment era, diagnosis of diabetes, and exposure to cardiotoxic cancer therapies. The St Jude Lifetime Cohort study is registered with ClinicalTrials.gov, NCT00760656, and is ongoing. FINDINGS: 9602 5-year survivors of childhood cancer, and 737 community controls were included in the longitudinal follow-up (from Sept 13, 2007, to Dec 17, 2021). The median follow-up was 20·3 years (IQR 12·0-31·4) from the date of primary cancer diagnosis (4311 [44.9%] were females). By the age of 50 years (analysis stopped at age 50 years due to the low number of participants older than that age), the cumulative incidence of major adverse cardiovascular events among survivors was 17·7% (95% CI 15·9-19·5) compared with 0·9% (0·0-2·1) in the community controls. The cumulative burden of major adverse cardiovascular events in survivors was 0·26 (95% CI 0·23-0·29) events per survivor compared with 0·009 (0·000-0·021) events per community control participant. Increasing cumulative burden of grade 1-4 non-major adverse cardiovascular events was associated with an increased future risk of major adverse cardiovascular events (one condition: RR 4·3, 95% CI 3·1-6·0; p<0·0001; two conditions: 6·6, 4·6-9·5; p<0·0001; and three conditions: 7·7, 5·1-11·4; p<0·0001). Increased risk for major adverse cardiovascular events was observed with specific subclinical conditions (eg, grade 1 arrhythmias [RR 1·5, 95% CI 1·2-2·0; p=0·0017]), grade 2 left ventricular systolic dysfunction (2·2, 1·6-3·1; p<0·0001), grade 2 valvular disorders (2·2, 1·2-4·0; p=0·013), but not grade 1 hypercholesterolaemia, grade 1-2 hypertriglyceridaemia, or grade 1-2 vascular stenosis. INTERPRETATION: Among an ageing cohort of survivors of childhood cancer, the accumulation of non-major adverse cardiovascular events, including subclinical conditions, increased the risk of major adverse cardiovascular events and should be the focus of interventions for early detection and prevention of major adverse cardiovascular events. FUNDING: The US National Cancer Institute and the American Lebanese Syrian Associated Charities.

Financial hardship among siblings of long-term survivors of childhood cancer: A Childhood Cancer Survivor Study report.

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.

Sugar and sugar-sweetened beverages in relation to premature aging in adult survivors of childhood cancer.

BACKGROUND: Premature aging is a significant concern in adult survivors of childhood cancer as they develop aging-related conditions at a younger age than their peers with no history of childhood cancer. Although modifiable lifestyle factors, such as diet, are postulated to affect aging process, supporting evidence is sparse. METHODS: We examined if the consumption of sugar and sugar-sweetened beverages was related to premature aging in 3322 adult survivors of childhood cancer in the St. Jude Lifetime Cohort. Premature aging was assessed using the Deficit Accumulation Index (DAI) that was a ratio of the number of age-related chronic health conditions each survivor had out of 44 conditions total. Multinomial logistic regressions adjusting for confounders were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: There were 46% of childhood cancer survivors consumed SSBs once or more times per day. High intake of sugar, especially sugars added to foods during preparation or processing, and habitual consumption of sugar-sweetened beverage were associated with an increased risk of premature aging. DISCUSSION: Our findings support a need to include strategies to reduce sugar and sugar-sweetened beverages consumption in lifestyle interventions to promote healthy aging in adult survivors of childhood cancer.

Job lock among survivors of childhood cancer and their spouses post Affordable Care Act implementation: A Childhood Cancer Survivor Study brief report.

It is unknown how common job lock (i.e., staying at job to maintain health insurance) remains among childhood cancer survivors after Affordable Care Act (ACA) implementation in 2010. We examined prevalence of and factors associated with job lock using a cross-sectional survey from the Childhood Cancer Survivor Study (3503 survivors; 942 siblings). Survivor, spousal, and any survivor/spouse job lock were more frequently reported by survivors than siblings. Survivor job lock/any job lock was associated with older age, low income, severe chronic conditions, and debt/inability to pay debt. Job lock remains more common among survivors than siblings after ACA implementation.

Uncovering the story within the story: a scoping review of response shift in qualitative research.

PURPOSE: The role of qualitative research in response-shift research has not been well characterized. This scoping review summarizes the status of qualitative studies on response shift. METHODS: A scoping review of the medical literature was done using the keywords "response shift" and "qualitative" or "interview." After excluding ineligible works, each retained article was rated by two independent raters according to the modified Critical Appraisal Skill Program (CASP) criteria. A synthesis of adjudicated review results further characterized the articles. RESULTS: The search yielded 50 unique articles published from 1991 to 2023, 39 of which were retained after applying exclusion criteria. Most (69%) had the highest possible CASP score. Studies involved a broad range of patients by diagnosis or therapeutic context, caregivers, and healthcare professionals. While studies were often purely descriptive, many addressed components of response-shift theory or assumptions of response-shift methods. Study goals varied by design, time-focus (i.e., retrospective, present-focus or prospective), and by whether response-shift hypotheses were planned or post-hoc. The theoretical value added by the qualitative process involved examining the cognitive/emotional processes underlying quality-of-life ratings and response shifts. The methodological value added by the qualitative process facilitates understanding measurement error and non-responsiveness, and whether the methods used reflect the researchers' presumptions. CONCLUSION: The use of qualitative methods in response-shift research yields a nuanced understanding of what response-shift "looks like" in different patient populations, thereby helping to translate results more directly to clinical experience. Studies contributed to response-shift theory or methods in ways not easily captured by purely quantitative research.

Financial hardship in families of children or adolescents with cancer: a systematic literature review.

Financial hardship in childhood cancer contributes to poor health outcomes and global disparities in survival, but the extent of the financial burden on families is not yet fully understood. We systematically reviewed financial hardship prevalence and individual components characterising financial hardship across six domains (medical, non-medical, and indirect costs, financial strategies, psychosocial responses, and behavioural responses) and compared characteristics across country income levels using an established theory of human needs. We included 123 studies with data spanning 47 countries. Extensive heterogeneity in study methodologies and measures resulted in incomparable prevalence estimates and limited analysis. Components characterising financial hardship spanned the six domains and showed variation across country income contexts, yet a synthesis of existing literature cannot establish whether these are true differences in characterisation or burden. Our findings emphasise a crucial need to implement a data-driven methodological framework with validated measures to inform effective policies and interventions to address financial hardship in childhood cancer.

Dietary supplement use among adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort Study.

BACKGROUND: Adult survivors of childhood cancer have poor adherence to nutrition guidelines and inadequate intake of dietary vitamins D and E, potassium, fiber, magnesium, and calcium. The contribution of vitamin and mineral supplement use to total nutrient intake in this population is unclear. METHODS: We examined the prevalence and dose of nutrient intake among 2570 adult survivors of childhood cancer participating in the St. Jude Lifetime Cohort Study, and the association of dietary supplement use with treatment exposures, symptom burden, and quality of life. RESULTS: Nearly 40% of the adult survivors of cancer survivors reported regular use of dietary supplements. Although cancer survivors who used dietary supplements were less likely to have inadequate intake of several nutrients, they were also more likely to have excessive intake (total nutrient intake ≥ tolerable upper intake levels) of folate (15.4% vs. 1.3%), vitamin A (12.2% vs. 0.2%), iron (27.8% vs. 1.2%), zinc (18.6% vs. 1%), and calcium (5.1% vs. 0.9%) compared with survivors who did not use dietary supplements (all p < 0.05). Treatment exposures, symptom burden, and physical functioning were not associated with supplement use, whereas emotional well-being and vitality were positively associated with supplement use among childhood cancer survivors. CONCLUSIONS: Supplement use is associated with both inadequate and excessive intake of specific nutrients, but positively impacts aspects of quality of life among childhood cancer survivors.

Emotional, behavioral, and physical health consequences of loneliness in young adult survivors of childhood cancer: Results from the Childhood Cancer Survivor Study.

BACKGROUND: Young adults in the general population are at risk of experiencing loneliness, which has been associated with physical and mental health morbidities. The prevalence and consequences of loneliness in young adult survivors of childhood cancer remain unknown. METHODS: A total of 9664 young adult survivors of childhood cancer (median age at diagnosis 10.5 years [interquartile range (IQR), 5-15], 27.1 years at baseline [IQR, 23-32]) and 2221 siblings enrolled in the Childhood Cancer Survivor Study completed a self-reported survey question assessing loneliness on the Brief Symptom Inventory-18 at baseline and follow-up (median follow-up, 6.6 years). Multivariable models evaluated the prevalence of loneliness at baseline only, follow-up only, and baseline + follow-up, and its associations with emotional distress, health behaviors, and chronic conditions at follow-up. RESULTS: Survivors were more likely than siblings to report loneliness at baseline + follow-up (prevalence ratio [PR] 2.2; 95% confidence interval [CI], 1.7-3.0) and at follow-up only (PR, 1.4; 95% CI, 1.1-1.7). Loneliness at baseline + follow-up was associated with elevated risk of anxiety (relative risk [RR], 9.8; 95% CI, 7.5-12.7), depression (RR, 17.9; 95% CI, 14.1-22.7), and current smoking (odds ratio [OR], 1.7; 95% CI, 1.3-2.3) at follow-up. Loneliness at follow-up only was associated with suicidal ideation (RR, 1.5; 95% CI, 1.1-2.1), heavy/risky alcohol consumption (RR, 1.3; 95% CI, 1.1-1.5), and new-onset grade 2-4 chronic conditions (RR, 1.3; 95% CI, 1.0-1.7). CONCLUSIONS: Young adult survivors of childhood cancer have elevated risk of experiencing loneliness, which is associated with future emotional distress, risky health behaviors, and new-onset chronic conditions.

Response-shift effects in childhood cancer survivors: A prospective study.

BACKGROUND: Treatment-related late effects can worsen over time among cancer survivors. Such worsening health states may trigger changes in internal standards, values, or conceptualization of quality-of-life (QOL). This "response-shift" phenomenon can jeopardize the validity of QOL assessment, and misrepresent QOL comparisons over time. This study tested response-shift effects in reporting future-health concerns among childhood cancer survivors who experienced progression in chronic health conditions (CHCs). METHODS: 2310 adult survivors of childhood cancer from St. Jude Lifetime Cohort Study completed a survey and clinical assessment at two or more timepoints. Based on 190 individual CHCs graded for adverse-event severity, global CHC burden was classified as "progression" or "non-progression". QOL was assessed using the SF-36TM eight domains and physical- and mental-component summary scores (PCS, MCS). A single global item measured concerns about future health. Random-effects models comparing survivors with and without progressive global CHC burden (progressors vs. non-progressors) evaluated response-shift effects (recalibration, reprioritization, reconceptualization) in reporting future-health concerns. RESULTS: Compared with non-progressors, progressors were more likely to de-emphasize (or downplay) overall physical and mental health in evaluating future-health concerns (p-values<0.05), indicating recalibration response-shift, and more likely to de-emphasize physical health earlier rather than later in follow-up (p-value<0.05), indicating reprioritization response-shift. There was evidence for a reconceptualization response-shift with progressor classification associated with worse-than-expected future-health concerns and physical health, and better-than-expected pain and role-emotional functioning (p-values<0.05). CONCLUSION: We identified three types of response-shift phenomena in reporting concerns about future health among childhood cancer survivors. Survivorship care or research should consider response-shift effects when interpreting changes in QOL over time.

Health-related quality of life profiles in adolescents and young adults with chronic conditions.

PURPOSE: To assess health-related quality of life (HRQOL) among adolescents and young adults (AYAs) with chronic conditions. METHODS: AYAs (N = 872) aged 14-20 years completed NIH's Patient-Reported Outcomes Measurement Information System® (PROMIS®) measures of physical function, pain interference, fatigue, social health, depression, anxiety, and anger. Latent profile analysis (LPA) was used to group AYAs into HRQOL profiles using PROMIS T-scores. The optimal number of profiles was determined by model fit statistics, likelihood ratio test, and entropy. Multinomial logistic regression models were used to examine how LPA's HRQOL profile membership was associated with patient demographic and chronic conditions. The model prediction accuracy on profile membership was evaluated using Huberty's I index with a threshold of 0.35 for good effect. RESULTS: A 4-profile LPA model was selected. A total of 161 (18.5%), 256 (29.4%), 364 (41.7%), and 91 (10.4%) AYAs were classified into Minimal, Mild, Moderate, and Severe HRQOL Impact profiles. AYAs in each profile had distinctive mean scores with over a half standard deviation (5-points in PROMIS T-scores) of difference between profiles across most HRQOL domains. AYAs who were female or had conditions such as mental health condition, hypertension, and self-reported chronic pain were more likely to be in the Severe HRQOL Impact profile. The Huberty's I index was 0.36. CONCLUSIONS: Approximately half of AYAs with a chronic condition experience moderate to severe HRQOL impact. The availability of risk prediction models for HRQOL impact will help to identify AYAs who are in greatest need of closer clinical care follow-up.

Applying latent profile analysis to identify adolescents and young adults with chronic conditions at risk for poor health-related quality of life.

The impact of chronic diseases on health-related quality of life (HRQOL) in adolescents and young adults (AYAs) is understudied. Latent profile analysis (LPA) can identify profiles of AYAs based on their HRQOL scores reflecting physical, mental, and social well-being. This paper will (1) demonstrate how to use LPA to identify profiles of AYAs based on their scores on multiple HRQOL indicators; (2) explore associations of demographic and clinical factors with LPA-identified HRQOL profiles of AYAs; and (3) provide guidance on the selection of adult or pediatric versions of Patient-Reported Outcomes Measurement Information System® (PROMIS®) in AYAs. A total of 872 AYAs with chronic conditions completed the adult and pediatric versions of PROMIS measures of anger, anxiety, depression, fatigue, pain interference, social health, and physical function. The optimal number of LPA profiles was determined by model fit statistics and clinical interpretability. Multinomial regression models examined clinical and demographic factors associated with profile membership. As a result of the LPA, AYAs were categorized into 3 profiles: Minimal, Moderate, and Severe HRQOL Impact profiles. Comparing LPA results using either the pediatric or adult PROMIS T-scores found approximately 71% of patients were placed in the same HRQOL profiles. AYAs who were female, had hypertension, mental health conditions, chronic pain, and those on medication were more likely to be placed in the Severe HRQOL Impact Profile. Our findings may facilitate clinicians to screen AYAs who may have low HRQOL due to diseases or treatments with the identified risk factors without implementing the HRQOL assessment.

Self-Reported Health Outcomes of Children and Youth with 10 Chronic Diseases.

OBJECTIVES: To identify pediatric patient-reported outcomes (PROs) that are associated with chronic conditions and to evaluate the effects of chronic disease activity on PROs. STUDY DESIGN: Participants (8-24 years old) and their parents were enrolled into 14 studies that evaluated Patient-Reported Outcome Measurement Information System PROs across 10 chronic conditions-asthma, atopic dermatitis, cancer, cancer survivors, chronic kidney disease, Crohn's disease, juvenile idiopathic arthritis, lupus, sickle cell disease, and type 1 diabetes mellitus. PRO scores were contrasted with the US general population of children using nationally representative percentiles. PRO-specific coefficients of variation were computed to illustrate the degree of variation in scores within vs between conditions. Condition-specific measures of disease severity and Cohen d effect sizes were used to examine PRO scores by disease activity. RESULTS: Participants included 2975 child respondents and 2392 parent respondents who provided data for 3409 unique children: 52% were 5-12 years old, 52% female, 25% African American/Black, and 14% Hispanic. Across all 10 chronic conditions, children reported more anxiety, fatigue, pain, and mobility restrictions than the general pediatric population. Variation in PRO scores within chronic disease cohorts was equivalent to variation within the general population, exceeding between-cohort variation by factors of 1.9 (mobility) to 5.7 (anxiety). Disease activity was consistently associated with poorer self-reported health, and these effects were weakest for peer relationships. CONCLUSIONS: Chronic conditions are associated with symptoms and functional status in children and adolescents across 10 different disorders. These findings highlight the need to complement conventional clinical evaluations with those obtained directly from patients themselves using PROs.

Childhood Neurotoxicity and Brain Resilience to Adverse Events during Adulthood.

OBJECTIVE: This study used childhood cancer survivors as a novel model to study whether children who experience central nervous system (CNS) injury are at higher risk for neurocognitive impairment associated with subsequent late onset chronic health conditions (CHCs). METHODS: Adult survivors of childhood cancer (n = 2,859, ≥10 years from diagnosis, ≥18 years old) completed a comprehensive neurocognitive battery and clinical examination. Neurocognitive impairment was defined as age-adjusted z score < 10th percentile. Participants impaired on ≥3 tests had global impairment. CHCs were graded using the Common Terminology Criteria for Adverse Events v4.3 (grade 1, mild; 2, moderate; 3, severe/disabling; 4, life-threatening) and were combined into a severity/burden score by frequency and grade (none/low, medium, high, and very high). A total of 1,598 survivors received CNS-directed therapy including cranial radiation, intrathecal methotrexate, or neurosurgery. Logistic regression estimated the odds of neurocognitive impairment associated with severity/burden score and grade 2 to 4 conditions, stratified by CNS treatment. RESULTS: CNS-treated survivors performed worse than non-CNS-treated survivors on all neurocognitive tests and were more likely to have global neurocognitive impairment (46.9% vs 35.3%, p < 0.001). After adjusting for demographic and treatment factors, there was a dose-response association between severity/burden score and global neurocognitive impairment, but only among CNS-treated survivors (high odds ratio [OR] = 2.24, 95% confidence interval [CI] = 1.42-3.53; very high OR = 4.07, 95% CI = 2.30-7.17). Cardiovascular and pulmonary conditions were associated with processing speed, executive function, and memory impairments in CNS-treated but not non-CNS-treated survivors who were impacted by neurologic conditions. INTERPRETATION: Reduced cognitive/brain reserve associated with CNS-directed therapy during childhood may make survivors vulnerable to adverse cognitive effects of cardiopulmonary conditions during adulthood. ANN NEUROL 2021;89:534-545.

Patient-reported outcomes in survivors of childhood hematologic malignancies with hematopoietic stem cell transplant.

Patient-reported outcomes among survivors of pediatric hematopoietic stem cell transplant (HSCT) are understudied. We compared symptom prevalence, health-related quality of life (HRQOL), and risk factors in adult survivors of childhood hematologic malignancies treated with HSCT to those treated with conventional therapy and noncancer controls. Survivors of childhood hematologic malignancies (HSCT N = 112 [70% allogeneic, 30% autologous]; conventionally treated N = 1106) and noncancer controls (N = 242) from the St. Jude Lifetime Cohort Study completed surveys assessing 10 symptom domains and SF-36 HRQOL summary scores. Chronic health conditions (CHCs) were validated by clinical assessment. Multivariable logistic regression reveals that compared with noncancer controls, HSCT survivors endorsed a significantly higher symptom prevalence in sensation (OR = 4.7, 95% confidence interval [CI], 2.6-8.4), motor/movement (OR = 4.3, 95% CI, 1.6-11.0), pulmonary (OR = 4.6, 95% CI, 1.8-11.8), and memory domains (OR = 4.8, 95% CI, 2.5-9.2), and poorer physical HRQOL (OR = 6.9, 95% CI, 2.8-17.0). HSCT and conventionally treated survivors had a similar prevalence of all symptom domains and HRQOL (all P > .05); however, HSCT survivors had a significantly higher cumulative prevalence for specific symptoms: double vision (P = .04), very dry eyes (P < .0001), and trouble seeing when wearing glasses (P < .0001). Occurrence of organ-specific CHCs, instead of transplant receipt, was significantly associated with a higher prevalence of all symptom domains (all P < .05) in adult survivors of childhood cancer, except for pain and anxiety domains. This study found that patient-reported outcomes were equally impaired between HSCT and conventionally treated survivors, but poorer in both groups compared with noncancer controls. Poor patient-reported outcomes in all survivors of childhood hematologic malignancies correlated with the presence of CHCs, whether treated with conventional therapy or HSCT.

Health utilities in pediatric cancer patients and survivors: a systematic review and meta-analysis for clinical implementation.

PURPOSE: Health utility (HU) is a useful metric for evaluating cost and utility of cancer therapies or prioritizing healthcare resources. We conducted a meta-analysis to compare HUs in association with clinical parameters and identify missing cancer-related themes from the extant HU measures for pediatric cancer patients and survivors. METHODS: Studies published in the PubMed, Embase, Web of Science, and Cochrane Library were identified. Meta-analyses were performed to estimate weighted means of HUs assessed by self- and proxy-responses. Mixed-effects meta-regressions were applied to compare HUs between cancer patients/survivors and general populations. Missing themes in the extant measures were identified based on established patient-reported outcomes frameworks. RESULTS: Of 123 selected studies included pediatric cancer populations, 44% used the Health Utilities Index version 2 (HUI2), and 48% used version 3 (HUI3). Compared to general populations, cancer patients undergoing therapies for acute lymphoblastic leukemia (ALL) had 0.129 (95% CI - 0.183 to - 0.075) and brain tumor had 0.257 (95% CI - 0.354 to - 0.160) lower HUs per proxy-reported HUI3, whereas survivors of ALL had 0.028 (95% CI - 0.062 to 0.007) and brain tumor had 0.188 (95% CI - 0.237 to - 0.140) lower HUs per proxy-reported HUI3. Compared to general populations, cancer patients treated with multimodality therapy and survivors off therapy 2-5 years had significantly poorer HUs (p's < 0.05). Missing cancer-specific contents from the HU measures were identified. CONCLUSION: Pediatric cancer patients and survivors had poorer HUs than general populations. It is important to select appropriate HUs for economic evaluations, and offer interventions to minimize HU deficits for particular cancer populations.

If it's information, it's not "bias": a scoping review and proposed nomenclature for future response-shift research.

BACKGROUND: The growth in response-shift methods has enabled a stronger empirical foundation to investigate response-shift phenomena in quality-of-life (QOL) research; but many of these methods utilize certain language in framing the research question(s) and interpreting results that treats response-shift effects as "bias," "noise," "nuisance," or otherwise warranting removal from the results rather than as information that matters. The present project will describe the various ways in which researchers have framed the questions for investigating response-shift issues and interpreted the findings, and will develop a nomenclature for such that highlights the important information about resilience reflected by response-shift findings. METHODS: A scoping review was done of the QOL and response-shift literature (n = 1100 articles) from 1963 to 2020. After culling only empirical response-shift articles, raters characterized how investigators framed and interpreted study research questions (n = 164 articles). RESULTS: Of 10 methods used, papers using four of them utilized terms like "bias" and aimed to remove response-shift effects to reveal "true change." Yet, the investigators' reflections on their own conclusions suggested that they do not truly believe that response shift is error to be removed. A structured nomenclature is proposed for discussing response-shift results in a range of research contexts and response-shift detection methods. CONCLUSIONS: It is time for a concerted and focused effort to change the nomenclature of those methods that demonstrated this misinterpretation. Only by framing and interpreting response shift as information, not bias, can we improve our understanding and methods to help to distill outcomes with and without response-shift effects.

Transforming challenges into opportunities: conducting health preference research during the COVID-19 pandemic and beyond.

The disruptions to health research during the COVID-19 pandemic are being recognized globally, and there is a growing need for understanding the pandemic's impact on the health and health preferences of patients, caregivers, and the general public. Ongoing and planned health preference research (HPR) has been affected due to problems associated with recruitment, data collection, and data interpretation. While there are no "one size fits all" solutions, this commentary summarizes the key challenges in HPR within the context of the pandemic and offers pragmatic solutions and directions for future research. We recommend recruitment of a diverse, typically under-represented population in HPR using online, quota-based crowdsourcing platforms, and community partnerships. We foresee emerging evidence on remote, and telephone-based HPR modes of administration, with further studies on the shifts in preferences related to health and healthcare services as a result of the pandemic. We believe that the recalibration of HPR, due to what one would hope is an impermanent change, will permanently change how we conduct HPR in the future.

Cardiometabolic factors explaining the association between physical activity and quality of life: U.S. National Health and Nutrition Examination Survey.

Purpose: To test the Clustered Cardiometabolic Risk (CCMR) factor explaining the relationship between physical activity and physical quality of life (QOL). Methods: Using the U.S. National Health and Nutrition Examination Survey 2003-2006, 2,445 adults completed the CDC Healthy Days Questionnaire for measuring QOL, wore the accelerometer for assessing physical activity pattern (PAP), and completed triglyceride, glucose, serum insulin, waist circumference, blood pressure, and HDL-cholesterol tests from which the CCMR factor was created. Physical QOL was classified as poor (≥14 days with poor physical health within past 30 days) vs. good (<14 days). We classified PAP by moderate-to-vigorous physical activity (MVPA), light-intensity physical activity (LIPA), and sedentary behavior (SB). We defined MVPA, LIPA, and SB as ≥2020 counts/minute, 100-2019 counts/minute, and ≤99 counts/minute, respectively. We further classified PAP status as unhealthy (MVPA <150 min/week & SB>LIPA) or healthy (MVPA <150 min/week & SBLIPA or SB

Association of co-morbidities with financial hardship in survivors of adult cancer.

PURPOSE: To evaluate the impact of co-morbidities on financial hardship in adult cancer survivors and the role of health insurance and a usual source of care (i.e., a particular doctor's office/health center/other place that the person usually goes if he/she is sick or needs advice) in relieving this impact. METHODS: Using the Medical Expenditure Panel Survey, we estimated prevalence of two financial hardships, out-of-pocket (OOP) burden and financial worry, among 1196 adult cancer survivors. A modified Charlson co-morbidity index (CCI) assessed co-morbidities, which represent a medical event (e.g., a doctor's appointment) associated with co-morbid conditions within the past 1 year. Multivariable logistic regression tested the influence of health insurance and a usual source of care on associations of co-morbidities with financial hardship by middle/high vs. low-income families and by working vs. retirement-age individuals. RESULTS: Years since cancer diagnosis ranged from 0 to 76 years (mean: 10.3, SD: 9.8), 10 and 25% of survivors experienced OOP burden and financial worry. For OOP burden, increased CCI was a risk factor among survivors of low-income families, ORs: 1.91 (95% CI: 1.06, 3.46) for a CCI 1-2 and 3.37 (95% CI: 1.72, 6.61) for a CCI ≥ 3 vs. CCI of 0. For financial worry, increased CCI was a risk factor among working-age survivors, ORs: 1.58 (95% CI: 1.02, 2.47) for a CCI 1-2 and 2.15 (95% CI: 1.19, 3.87) for a CCI ≥ 3 vs. CCI of 0. However, having health insurance and a usual source of care did not mitigate impact of co-morbidities on financial hardship (P values > 0.05). CONCLUSIONS: Impact of co-morbidities on OOP and financial worry burden was greatest in survivors of low-income families and working-age, respectively. Health insurance and a usual source of care did not relieve the impact of co-morbidities on financial hardship. IMPLICATIONS: Effective strategies are warranted to mitigate financial hardship for survivors.

Natural Language Processing and Machine Learning Methods to Characterize Unstructured Patient-Reported Outcomes: Validation Study.

BACKGROUND: Assessing patient-reported outcomes (PROs) through interviews or conversations during clinical encounters provides insightful information about survivorship. OBJECTIVE: This study aims to test the validity of natural language processing (NLP) and machine learning (ML) algorithms in identifying different attributes of pain interference and fatigue symptoms experienced by child and adolescent survivors of cancer versus the judgment by PRO content experts as the gold standard to validate NLP/ML algorithms. METHODS: This cross-sectional study focused on child and adolescent survivors of cancer, aged 8 to 17 years, and caregivers, from whom 391 meaning units in the pain interference domain and 423 in the fatigue domain were generated for analyses. Data were collected from the After Completion of Therapy Clinic at St. Jude Children's Research Hospital. Experienced pain interference and fatigue symptoms were reported through in-depth interviews. After verbatim transcription, analyzable sentences (ie, meaning units) were semantically labeled by 2 content experts for each attribute (physical, cognitive, social, or unclassified). Two NLP/ML methods were used to extract and validate the semantic features: bidirectional encoder representations from transformers (BERT) and Word2vec plus one of the ML methods, the support vector machine or extreme gradient boosting. Receiver operating characteristic and precision-recall curves were used to evaluate the accuracy and validity of the NLP/ML methods. RESULTS: Compared with Word2vec/support vector machine and Word2vec/extreme gradient boosting, BERT demonstrated higher accuracy in both symptom domains, with 0.931 (95% CI 0.905-0.957) and 0.916 (95% CI 0.887-0.941) for problems with cognitive and social attributes on pain interference, respectively, and 0.929 (95% CI 0.903-0.953) and 0.917 (95% CI 0.891-0.943) for problems with cognitive and social attributes on fatigue, respectively. In addition, BERT yielded superior areas under the receiver operating characteristic curve for cognitive attributes on pain interference and fatigue domains (0.923, 95% CI 0.879-0.997; 0.948, 95% CI 0.922-0.979) and superior areas under the precision-recall curve for cognitive attributes on pain interference and fatigue domains (0.818, 95% CI 0.735-0.917; 0.855, 95% CI 0.791-0.930). CONCLUSIONS: The BERT method performed better than the other methods. As an alternative to using standard PRO surveys, collecting unstructured PROs via interviews or conversations during clinical encounters and applying NLP/ML methods can facilitate PRO assessment in child and adolescent cancer survivors.