Physical frailty deteriorates after a 5-day dexamethasone course in children with acute lymphoblastic leukemia, results of a national prospective study

Background: Dexamethasone is important in the treatment for pediatric acute lymphoblastic leukemia (ALL) but induces muscle atrophy with negative consequences for muscle mass, muscle strength, and functional abilities. The aim of this study was to establish the effect of a dexamethasone course on sarcopenia and physical frailty in children with ALL, and to explore prognostic factors. Methods: Patients with ALL aged 3–18 years were included during maintenance therapy. Patients had a sarcopenia/frailty assessment on the first day of (T1) and on the day after (T2) a 5-day dexamethasone course. Sarcopenia was defined as low muscle strength in combination with low muscle mass. Prefrailty and frailty were defined as having two or ≥three of the following components, respectively: low muscle mass, low muscle strength, fatigue, slow walking speed, and low physical activity. Chi-squared and paired t-tests were used to assess differences between T1 and T2. Logistic regression models were estimated to explore patient- and therapy-related prognostic factors for frailty on T2. Results: We included 105 patients, 61% were boys. Median age was 5.3 years (range: 3–18.8). At T1, sarcopenia, prefrailty, and frailty were observed in respectively 2.8%, 23.5%, and 4.2% of patients. At T2, the amount of patients with frailty had increased to 17.7% (p = 0.002), whereas the number of patients with sarcopenia and prefrailty remained similar. Higher ASMM (odds ratio [OR]: 0.49, 95% CI: 0.28–0.83), stronger handgrip strength (OR: 0.41, 95% CI: 0.22–0.77) and more physical activity minutes per day (OR: 0.98, 95% CI: 0.96–0.99) decreased the risk of frailty at T2. Slower walking performance (OR: 2, 95% CI: 1.2–3.39) increased the risk. Fatigue levels at T1 were not associated with frailty at T2. Conclusion: Physical frailty increased strikingly after a 5-days dexamethasone course in children with ALL. Children with poor physical state at start of the dexamethasone course were more likely to be frail after the course.</p

The Dutch Childhood Cancer Survivor Study (DCCSS)-LATER 2 kidney analysis examined long-term glomerular dysfunction in childhood cancer survivors

This investigation aimed to evaluate glomerular dysfunction among childhood cancer survivors in comparison with matched controls from the general population. In the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER 2 kidney analysis, a nationwide cross-sectional cohort study, 1024 survivors five or more years after diagnosis, aged 18 or more years at study, treated between 1963-2001 with nephrectomy, abdominal radiotherapy, total body irradiation, cisplatin, carboplatin, ifosfamide, high-dose cyclophosphamide or hematopoietic stem cell transplantation participated. In addition, 500 age- and sex-matched controls from Lifelines, a prospective population-based cohort study in the Netherlands, participated. At a median age of 32.0 years (interquartile range 26.6-37.4), the glomerular filtration rate was under 60 ml/min/1.73m2 in 3.7% of survivors and in none of the controls. Ten survivors had kidney failure. Chronic kidney disease according to age-thresholds (glomerular filtration rate respectively under 75 for age under 40, under 60 for ages 40-65, and under 40 for age over 65) was 6.6% in survivors vs. 0.2% in controls. Albuminuria (albumin-to-creatinine ratio over3 mg/mmol) was found in 16.2% of survivors and 1.2% of controls. Risk factors for chronic kidney disease, based on multivariable analyses, were nephrectomy (odds ratio 3.7 (95% Confidence interval 2.1-6.4)), abdominal radiotherapy (1.8 (1.1-2.9)), ifosfamide (2.9 (1.9-4.4)) and cisplatin over 500 mg/m2 (7.2 (3.4-15.2)). For albuminuria, risk factors were total body irradiation (2.3 (1.2-4.4)), abdominal radiotherapy over 30 Gy (2.6 (1.4- 5.0)) and ifosfamide (1.6 (1.0-2.4)). Hypertension and follow-up 30 or more years increased the risk for glomerular dysfunction. Thus, lifetime monitoring of glomerular function in survivors exposed to these identified high risk factors is warranted.</p

Assessing fatigue in childhood cancer survivors:Psychometric properties of the Checklist Individual Strength and the Short Fatigue Questionnaire––a DCCSS LATER study

BACKGROUND: Fatigue is often reported by patients with childhood cancer both during and after cancer treatment. Several instruments to measure fatigue exist, although none are specifically validated for use in childhood cancer survivors (CCS). The aim of the current study was to present norm values and psychometric properties of the Checklist Individual Strength (CIS) and Short Fatigue Questionnaire (SFQ) in a nationwide cohort of CCS. METHODS: In total, 2073 participants were included from the Dutch Childhood Cancer Survivor Study (DCCSS) LATER cohort. Normative data, construct validity, structural validity, and internal consistency were calculated for the CIS and SFQ. In addition, reliability and a cutoff score to indicate severe fatigue were determined for the SFQ. RESULTS: Correlations between CIS/SFQ and vitality measures asking about fatigue were high (>0.8). Correlations between CIS/SFQ and measures of different constructs (sleep, depressive emotions, and role functioning emotional) were moderate (0.4–0.6). Confirmatory factor analysis resulted in a four‐factor solution for the CIS and a one‐factor solution for the SFQ with Cronbach's alpha for each (sub)scale showing good to excellent values (>0.8). Test–retest reliability of the SFQ was adequate (Pearson's correlation = 0.88; ICC = 0.946; weighted Cohen's kappa item scores ranged 0.31–0.50) and a cut‐off score of 18 showed good sensitivity and specificity scores (92.6% and 91.3%, respectively). CONCLUSION: The current study shows that the SFQ is a good instrument to screen for severe fatigue in CCS. The CIS can be used as a tool to assess the multiple fatigue dimensions in CCS

Hypertension in long-term childhood cancer survivors after treatment with potentially nephrotoxic therapy; DCCSS-LATER 2:Renal study

Purpose: To evaluate the prevalence of and risk factors for hypertension in childhood cancer survivors (CCSs) who were treated with potentially nephrotoxic therapies. Methods: In the Dutch Childhood Cancer Survivor Study LATER cohort part 2 renal study, 1024 CCS ≥5 years after diagnosis, aged ≥18 years at study participation, treated between 1963 and 2001 with nephrectomy, abdominal radiotherapy, total body irradiation (TBI), cisplatin, carboplatin, ifosfamide, high-dose cyclophosphamide (≥1 g/m2 per single dose or ≥10 g/m2 total) or haematopoietic stem cell transplantation participated and 500 controls from Lifelines. Hypertension was defined as blood pressure (BP) (mmHg) systolic ≥140 and/or diastolic ≥90 or receiving medication for diagnosed hypertension. At the study visit, the CKD-EPI 2012 equation including creatinine and cystatin C was used to estimate the glomerular filtration rate (GFR). Multivariable regression analyses were used. For ambulatory BP monitoring (ABPM), hypertension was defined as BP daytime: systolic ≥135 and/or diastolic ≥85, night time: systolic ≥120 and/or diastolic ≥70, 24-h: systolic ≥130 and/or diastolic ≥80. Outcomes were masked hypertension (MH), white coat hypertension and abnormal nocturnal dipping (aND). Results: Median age at cancer diagnosis was 4.7 years (interquartile range, IQR 2.4–9.2), at study 32.5 years (IQR 27.7–38.0) and follow-up 25.5 years (IQR 21.4–30.3). The prevalence of hypertension was comparable in CCS (16.3%) and controls (18.2%). In 12% of CCS and 17.8% of controls, hypertension was undiagnosed. A decreased GFR (<60 ml/min/1.73 m2) was associated with hypertension in CCS (OR 3.4, 95% CI 1.4–8.5). Risk factors were abdominal radiotherapy ≥20 Gy and TBI. The ABPM-pilot study (n = 77) showed 7.8% MH, 2.6% white coat hypertension and 20.8% aND. Conclusion: The prevalence of hypertension was comparable among CCS who were treated with potentially nephrotoxic therapies compared to controls, some of which were undiagnosed. Risk factors were abdominal radiotherapy ≥20 Gy and TBI. Hypertension and decreased GFR were associated with CCS. ABPM identified MH and a ND

The Impact of Cancer-Related Fatigue on HRQOL in Survivors of Childhood Cancer:A DCCSS LATER Study

Simple Summary Survivors of childhood cancer have an increased risk to experience symptoms of severe and persistent fatigue. We studied how fatigue might affect the health-related quality of life of these survivors. Questionnaire items asking about a broad range of daily life aspects were compared between fatigued survivors, survivors without fatigue and the general Dutch population. A total of eleven aspects were studied which were all negatively affected by fatigue, with the largest impact seen for Vitality (how much energy does a person have), General Health (perception of current and future health) and Role Limitations (work-related activities). Results show the negative impact fatigue can have on the daily lives of survivors and why it is important to treat fatigue adequately. Background: Early detection and management of late effects of treatment and their impact on health-related quality of life (HRQOL) has become a key goal of childhood cancer survivorship care. One of the most prevalent late effects is chronic fatigue (CF). The current study aimed to investigate the association between CF and HRQOL in a nationwide cohort of CCS. Methods: Participants were included from the Dutch Childhood Cancer Survivor Study (DCCSS) LATER cohort, a nationwide cohort of CCS. Participants completed the Checklist Individual Strength (CIS) to indicate CF (CIS fatigue severity subscale >= 35 and duration of symptoms >= 6 months) and the Short Form-36 (SF-36) and TNO (Netherlands Organization for Applied Scientific Research) and AZL (Leiden University Medical Centre) Adult's Health-Related Quality of Life questionnaire (TAAQOL) as measures for HRQOL. Differences in mean HRQOL domain scores between CF and non-CF participants were investigated using independent samples t-tests and ANCOVA to adjust for age and sex. The association between CF and impaired HRQOL (scoring >= 2 SD below the population norm) was investigated using logistic regression analyses, adjusting for confounders. Results: A total of 1695 participants were included in the study. Mean HRQOL domain scores were significantly lower in participants with CF. In addition, CF was associated with impaired HRQOL on all of the domains (except physical functioning) with adjusted odds ratios ranging from 2.1 (95% CI 1.3-3.4; sexuality domain) to 30.4 (95% CI 16.4-56.2; vitality domain). Conclusions: CF is associated with impaired HRQOL, urging for the screening and regular monitoring of fatigue, and developing possible preventative programs and interventions

Balance and mobility performance as treatable risk factors for recurrent falling in older persons

Background and Objectives: The purpose of this study was to examine whether easily measurable measures for balance and muscle strength predicted recurrent falling as well as sophisticated measurements, and to examine which of the modifiable risk factors were strongest associated with recurrent falling. Methods: The study was performed in a subsample (n = 439, aged 69-92 years) of the Longitudinal Aging Study Amsterdam (LASA). Balance, muscle strength, physical activity, and performance tests were assessed. Falls were recorded during 1 year. The outcome measure was recurrent falls (≥2 falls within 1 year). Results: The area under the curve (AUC) of mediolateral sway (AUC = 0.67; 95% CI:0.57-0.77), tandem stand (AUC = 0.61; 95% CI:0.49-0.73), leg extension strength (AUC = 0.58; 95% CI:0.51-0.64), and handgrip strength (AUC = 0.57; 95% CI:0.51-0.64) for recurrent falling were not significantly different. In a multivariate model, mediolateral sway (OR = 2.8; 95% CI:1.1-6.9), tandem stand (OR = 2.1; 95% CI:1.1-3.8), and walking test (OR = 2.2; 95% CI:1.1-4.1) were significantly associated with recurrent falling. Conclusions: The easily measurable tandem stand and handgrip strength predicted recurrent falling as well as the sophisticated measures. Mediolateral sway was strongest associated with recurrent falling

Consequences of falling in older men and women and risk factors for health service use and functional decline

Objectives: (1) to examine consequences of falls in older men and women and (2) to examine risk factors for health service use and functional decline among older fallers. Methods: The study was performed within the Longitudinal Aging Study Amsterdam. In 1998/1999, potential risk factors were assessed during the third data collection. In 1999/2000, 204 community-dwelling persons (≥65 years) who reported at least one fall in the year before the interview, were asked about consequences of their last fall, including physical injury, health service use, treatment and functional decline (i.e. decline in functional status, social and physical activities). Results: As a consequence of falling, respondents reported physical injury (68.1%), major injury (5.9%), health service use (23.5%), treatment (17.2%), and decline in functional status (35.3%), and social (16.7%) and physical activities (15.2%). Using multivariate logistic regression, specific risk factors for health service use after falling could not be identified. Female gender (OR = 2.8, 95% CI = 1.5-5.1), higher medication use (OR = 1.5, 95% CI = 1.0-2.2) and depressive symptoms (OR = 1.9, 95% CI = 1.3-2.8) were independently associated with functional decline after falling. Depressive symptoms (OR = 2.0, 95% CI = 1.2-3.3) and falls inside (OR = 2.6, 95% CI = 1.1-6.5) were risk factors for decline in social activities, while female gender (OR = 2.7, 95% CI = 1.1-7.0) and depressive symptoms (OR = 1.9, 95% CI = 1.2-3.0) were risk factors for decline in physical activities after falling. Conclusions: Almost 70% of the respondents suffered physical injury, almost one-quarter used health services and more than one-third suffered functional decline after falling. No risk factors were found for health service use needed after falling. Female gender, higher medication use, depressive symptoms and falls inside were risk factors for functional decline after falling

Different cognitive functions in relation to falls among older persons: Immediate memory as an independent risk factor for falls

It is not clear which specific cognitive function is strongest related to falls. To investigate this, not only "general cognitive functioning," but also "nonverbal and abstract reasoning," "information processing speed," and "immediate memory" were related to falls. Furthermore, relevant effect modifiers, confounders, and mediators were identified. This study was performed within the Longitudinal Aging Study Amsterdam (LASA), a multidisciplinary, prospective cohort study. In this study (n = 1437), an interaction between "immediate memory" and age was found. In persons aged 75 years and over, "immediate memory," as measured by the 15 Words Test, showed to be an independent risk factor for falls. Part of this relationship was explained by the mediating effects of activity, mobility, and grip strength. The association between the other cognitive functions and falls was only statistically significant in univariate analysis. We conclude that "immediate memory" is an independent risk factor for recurrent falls in persons aged 75 years and older

Validation of the LASA fall risk profile for recurrent falling in older recent fallers

Objectives: The fall risk profile developed in the Longitudinal Aging Study Amsterdam (LASA) identifies community-dwelling elderly at high risk for recurrent falling. This study assessed the predictive validity of this profile in older persons seeking care after a fall. Study Design and Setting: The LASA fall risk profile was completed for 408 persons of 65 years and older who consulted the emergency department or general practitioner after a fall. Falls were prospectively reported with a calendar during 1 year. Recurrent falling was defined as ≥2 falls within a period of 6 months. Results: During 1 year of followup, 76 (18.6%) participants became recurrent fallers. The area under the receiver operating characteristic curve was 0.65 (95% confidence interval [95% CI]: 0.58-0.72). At a cutoff value of 8, the sensitivity was 56.6% (CI: 51.8-61.4), the specificity was 71.4% (CI: 67.0-75.8), the positive predictive value was 34.1% (CI: 29.5-38.7), and the negative predictive value was 85.6% (CI: 82.2-89.0). Conclusion: The discriminative ability of the LASA fall risk profile was moderate. The predictive validity of the LASA fall risk profile to identify recurrent fallers is limited among older persons who consulted the emergency department or general practitioner after a fall

Vitamin D status in relation to one-year risk of recurrent falling in older men and women

Background: Falls frequently occur in the elderly and are a major cause of morbidity and mortality. Objective: The objective of the study was to prospectively investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and risk of recurrent falling in older men and women. Design: This was a prospective cohort study. Setting: An age- and sex-stratified random sample of the Dutch older population was determined. Subjects: Subjects included 1231 men and women (aged 65 yr and older) participating in the Longitudinal Aging Study Amsterdam. Measurements: Baseline serum 25(OH)D was determined by a competitive protein binding assay. During 1 yr, falls were prospectively recorded by means of a fall calendar. Results: Low 25(OH)D (<10 ng/ml) was associated with an increased risk of falling. After adjustment for age, sex, education level, region, season, physical activity, smoking, and alcohol intake, the odds ratios (95% confidence interval) were 1.78 (1.06-2.99) for subjects who experienced two falls or more as compared with those who did not fall or fell once and 2.23 (1.17-4.25) for subjects who fell three or more times as compared with those who fell two times or less. There was a statistically significant effect modification by age, and stratified analyses (<75 and ≥ 75 yr) showed that the associations were particularly strong in the younger age group; the odds ratios (95% confidence interval) were 5.21 (2.03-13.40) for two falls or more and 4.96 (1.52-16.23) for three falls or more. Conclusions: Poor vitamin D status is independently associated with an increased risk of falling in the elderly, particularly in those aged 65-75 yr