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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/1.73m2in 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.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjmed.2005.10.049 Byline: Laura A. Schaap (a), Saskia M.F. Pluijm (a), Dorly J.H. Deeg (a), Marjolein Visser (a)(b) Keywords: Sarcopenia; Muscle strength; Interleukin-6; C-reactive protein; [alpha]1-Antichymotrypsin Abstract: The objective of this study was to investigate whether high levels of serum interleukin (IL)-6, C-reactive protein (CRP), and [alpha]1-antichymotrypsin (ACT) were associated with the loss of muscle strength or muscle mass (sarcopenia) in older persons. Author Affiliation: (a) Institute for Research in Extramural Medicine (EMGO Institute), VU University Medical Center (b) Institute of Health Sciences, Faculty of Earth and Life Sciences, Vrije Universiteit, Amsterdam, The Netherlands Article History: Received 25 February 2005; Accepted 14 October 2005 Article Note: (footnote) The Longitudinal Aging Study Amsterdam is financially supported by the Dutch Ministry of Public Health, Welfare and Sports.

A classification tree for predicting the risk of recurrent falling in community-dwelling older persons is invented using a tree-structured survival analysis. This tree can identify subjects that are eligible for preventive measures in public health strategies.

Research indicates that physical activity may curb mobility performance decline in older persons. Studies revealed a beneficial effect for both sports and nonsports physical activities regardless of whether chronic disease was present.

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Objective.Low-dose methotrexate (MTX) is the anchor drug in the treatment for rheumatoid arthritis (RA). Response to MTX is related to the intracellular MTX-polyglutamate (MTX-PG) levels and little is known about its determinants. We aimed to define the determinants of erythrocyte MTX-PG concentrations in 2 prospective cohorts of patients with RA.Methods.Patients with RA treated with MTX from 2 longitudinal cohorts were included: 93 from the MTX-R study (Rotterdam, the Netherlands derivation cohort), and 247 from the treatment in Rotterdam Early Arthritis Cohort study (validation cohort). MTX-PG concentrations were measured at 3 months of treatment using liquid chromatography/mass spectrometry. The MTX-PG were used as outcome measure. Various sociodemographic, clinical, biochemical, and genetic factors were assessed at baseline. Associations with MTX-PG levels were analyzed using multivariate regression analysis.Results.Age was positively associated with MTX-PG1 (stβ 0.23, p = 0.033) and total MTX-PG (stβ 0.23, p = 0.018) in the derivation cohort, and with all MTX-PG in the validation cohort (MTX-PG1: stβ 0.13, p = 0.04; MTX-PG2: stβ 0.21, p = 0.001; MTX-PG3: stβ 0.22, p < 0.001; MTX-PG4+5: stβ 0.25, p < 0.001; and total MTX-PG: stβ 0.32, p < 0.001). Erythrocyte folate levels were positively associated with MTX-PG3 (stβ 0.3, p = 0.021) and total MTX-PG levels (stβ 0.32, p = 0.022) in the derivation cohort, which was replicated for MTX-PG3 (stβ 0.15, p = 0.04) in the validation cohort. Patients with the folylpolyglutamate synthase (FPGS) rs4451422 wild-type genotype had higher concentrations of MTX-PG3 (p < 0.05), MTX-PG4+5 (p < 0.05), and total MTX-PG (p < 0.05) in both cohorts. In the combined cohort, MTX dose was positively associated with levels of MTX-PG3 (stβ 0.23, p < 0.001), MTX-PG4+5 (stβ 0.30, p < 0.001), and total MTX-PG (stβ 0.20, p = 0.002), but negatively associated with MTX-PG2 levels (stβ −0.22, p < 0.001).Conclusion.Our prospective study shows that higher age, higher MTX dose, higher erythrocyte folate status, and the FPGS rs4451422 wild-type genotype are associated with higher MTX-PG concentrations. While only up to 21% of interpatient variability can be explained by these determinants, this knowledge may aid in the development of personalized treatment in RA.

No relevant conflicts of interest to declare.

Background-Impaired bone mineral density (BMD) is a frequently reported side-effect of patients with childhood cancer. Vitamin D deficiency is suggested to be a risk factor for diminished BMD and fractures during and after cessation of treatment of childhood hematological malignancies.