Ultrasound measurements for the prediction of osteoporotic fractures in elderly people

In this prospective study we investigated the predictive value of quantitative ultrasound (QUS) measurements and other potential predictors of osteoporotic fractures in the elderly. During a I-year period, 710 participants (132 men and 578 women), aged 70 years and older (mean age ± SD: 82.8 ± 5.9), were recruited from seven homes and apartment houses for the elderly. QUS measurements (broadband ultrasound attenuation (BUA) and speed of sound (SOS)) were assessed with a clinical bone densitometer. A structured questionnaire was used to collect information on other potential predictors. Follow-up of fractures was done each half year by telephone interviews. During the study period (median follow-up 2.8 years, maximum 3.7 years), 30 participants had a first hip fracture and 54 suffered from a first other nonspinal fracture. Cox regression analyses, adjusted for age and sex, showed that the relative risk (RR) of hip fracture for each standard deviation reduction was 2.3 (95% CI, 1.4-3.7) for BUA and 1.6 (95% CI, 1.1-2.3) for SOS. Slightly weaker relationships were found for any fracture (BUA: RR, 1.6; 95% CI, 1.2-2.1; SOS: RR, 1.3; 95% CI, 1.0-1.6). Multivariable analyses identified low BUA values and immobility as the strongest predictors for hip fractures and any fracture. Female gender proved to be the strongest predictor for other nonspinal fractures. It can be concluded that QUS measurements can predict the risk for hip fracture and any fracture in elderly people

Daily physical activity and the use of a walking aid in relation to falls in elderly people in a residential care setting

Physical activity is usually considered as an important com0ponent of a healthy lifestyle, including a preventive effect on the risk of falls in the elderly. The relationship between physical activity and falls is complex: physical activity is a prerequisite to maintain neuromuscular functioning, necessary to keep balance and to react to a fall, but a higher level of physical activity also implies a greater exposure to environmental threats, possibly leading to a fall. Related to this greater exposure to threats, the use of a walking aid may protect against falls in those who have impaired mobility. In this cross-sectional study we investigated the relationship between daily physical activity and falls and the use of a walking aid in elderly subjects. Participants were 131 men and 563 women, aged 70 years and over (mean age and standard deviation: 82 ± 6 years), living in homes for the elderly (n = 335) and apartment houses for elderly (n = 359). Data on baseline characteristics and falls in the previous year were obtained using a questionnaire. The level of daily physical activity in the previous year was obtained by means of a questionnaire regarding household and leisure activities. Subjects with a lower extremity fracture in the previous year were excluded from the analyses. Data were analysed using multiple logistic regression, adjusted for age, gender, and residence. In the past year, 40% of the participants fell at least one time, and 19% of the participants fell two times or more. Since falls and recurrent falls were nonlinearly related to the level of daily physical activity, the physical activity score was grouped into quartiles: the highest quartile corresponding to the highest activity level. Odds ratios (and 95% confidence intervals) for falls and recurrent falls for subjects in the highest quartile contrasted with those in the lowest quartile were 0.5 (0.3-0.9) and 0.3 (0.2-0.6), respectively. The risk of falls and recurrent falls was not lower for those with intermediate levels of daily physical activity. The use of a walking aid protected against falls in those with intermediate high activity levels (third quartile). It was suggested that the exposure to environmental hazards, due to some degree of physical activity may have been responsible for the nonlinear relationship between daily physical activity and falling. We conclude that a high activity level and the use of a walking aid may protect against falls

Functional limitations and poor physical performance as independent risk factors for self-reported fractures in older persons

Objective: This study examined whether three aspects of functioning (i.e., functional limitations, physical performance, and physical activity) were associated with fractures in older men and women. Design: A 3-year prospective cohort study. Participants and setting: A total of 715 men and 762 women, aged 65 years and older, of the population-based Longitudinal Aging Study Amsterdam. Measurements: During an interview at home, three aspects of functioning were assessed: functional limitations (what people say they can do), physical performance, i.e., three performance tests and handgrip strength (what people are able to do), and physical activity (what people actually do). Afterward, a follow-up on fractures was conducted for 3 years. Results: 77 patients (5.2%) suffered a fracture during 3-year follow-up. Most patients suffered a hip fracture (1.6%) or a wrist fracture (1.4%). The fracture rate per 1,000 person-years was 20.1. During 3-year follow-up, a fracture was reported by 12%, 10%, 12%, and 6% of the respondents with functional limitations, low performance test score, poor handgrip strength, and low physical activity, respectively. Using Cox proportional hazard analysis, functional limitations (RR = 3.5; 95%CI, 2.1 to 6.0), low performance test score (RR = 1.9; 95% CI, 1.1 to 3.3), low handgrip strength (RR = 2.5; 95% CI, 1.5 to 4.1), and low physical activity (RR = 1.9; 95% CI, 1.1 to 3.5) were significantly associated with fractures after adjustment for age and sex. Functional limitations (RR = 3.2; 95% CI, 1.8 to 5.5), low performance test score (RR = 1.8; 95% CI, 1.0 to 3.3) and low handgrip strength (RR = 2.0; 95% CI, 1.1 to 3.6) remained significantly associated with fractures after additional adjustment for body composition, chronic diseases, psychosocial factors, life style factors, and the other levels of functioning. No significant interaction terms were found. Conclusions: Functional limitations and poor physical performance were independent risk factors for fractures

Study protocol: DexaDays-2, hydrocortisone for treatment of dexamethasone-induced neurobehavioral side effects in pediatric leukemia patients: a double-blind placebo controlled randomized intervention study with cross-over design

Background: Dexamethasone, a highly effective drug in treating pediatric acute lymphoblastic leukemia (ALL), can induce serious neurobehavioral side effects. These side effects are experienced by patients and parents as detrimental with respect to health related quality of life (HRQoL). Based on previous studies, it has been suggested that neurobehavioral side effects are associated to cortisol depletion of the mineralocorticoid receptor in the brain. Our previously reported randomized controlled trial, the Dexadagen study (NTR3280), suggests that physiological hydrocortisone addition during dexamethasone treatment may overcome clinically relevant neurobehavioral problems in patients who experience these problems during dexamethasone treatment. With our current study, we aim to replicate these results in a targeted larger sample before further implementing this intervention into standard of care.Methods: In a national center setting, pediatric ALL patients between 3 and 18 years are enrolled in an Identification study, which identifies patients with clinically relevant dexamethasone-induced neurobehavioral side effects using the Strengths and Difficulties Questionnaire (SDQ). Contributing factors, such as genetic susceptibility, dexamethasone pharmacokinetics as well as psychosocial and family factors are studied to determine their influence in the inter-patient variability for developing dexamethasone-induced neurobehavioral side effects.Patients with clinically relevant problems (i.e. a rise of >= 5 points on the SDQ Total Difficulties Score after 5 days of dexamethasone) are subsequently included in a randomized double-blind placebo-controlled trial with a cross-over design. They receive two courses placebo followed by two courses hydrocortisone during dexamethasone treatment, or vice versa, each time at least 16 days without study medication in between. The primary endpoint is change in SDQ score. The secondary endpoints are sleep (measured with actigraphy and the Sleep Disturbance Scale for Children) and HRQoL (Pediatric Quality of Life Questionnaire).Discussion: The results of our current study may contribute to the management of future ALL patients who experience dexamethasone-induced neuropsychological problems as it may improve HRQoL for patients who suffer most from dexamethasone-induced neurobehavioral side effects. Furthermore, by investigating multiple risk factors that could be related to inter-patient variability in developing these side effects, we might be able to identify and treat patients who are at risk earlier during treatment.Analysis and Stochastic

Effect of post-consolidation regimen on symptomatic osteonecrosis in three DCOG acute lymphoblastic leukemia protocols

Development and application of statistical models for medical scientific researc

Prediction of Methotrexate Intolerance in Juvenile Idiopathic Arthritis: A prospective, observational cohort study

Background: Methotrexate (MTX) is an effective and safe drug in the treatment of juvenile idiopathic arthritis (JIA). Despite its safety, MTX-related gastrointestinal adverse effects before and after MTX administration, termed MTX intolerance, occur frequently, leading to non-compliance and potentially premature MTX termination. The aim of this study was to construct a risk model to predict MTX intolerance. Methods: In a prospective JIA cohort, clinical variables and single nucleotide polymorphisms were determined at MTX start. The Methotrexate Intolerance Severity Score was employed to measure MTX intolerance in the first year of treatment. MTX intolerance was most prevalent at 6 or 12months after MTX start, which was defined as the outcome for the prediction model. The model was developed in 152 patients using multivariable logistic regression analysis and subsequently internally validated using bootstrapping. Results: The prediction model included the following predictors: JIA category, antinuclear antibody, parent/patient assessment of pain, Juvenile Arthritis Disease Activity Score-27, thrombocytes, alanine aminotransferase and creatinine. The model classified 77.5% of patients correctly, and 66.7% of patients after internal validation by bootstrapping. The lowest predicted risk of MTX intolerance was 18.9% and the highest predicted risk was 85.9%. The prediction model was transformed into a risk score (range 0-17). At a cut-off of 6, sensitivity was 82.0%, specificity 56.1%, positive predictive value was 58.7% and negative predictive value 80.4%. Conclusions: This clinical prediction model showed moderate predictive power to detect MTX intolerance. To develop into a clinically usable tool, it should be validated in an independent cohort and updated with new predictors. Such an easy-to-use tool could then assist clinicians in identifying patients at risk to develop MTX intolerance, and in turn to monitor them closely and intervene timely in order to prevent the development of MTX intolerance

Hydrocortisone as an intervention for dexamethasone-induced adverse effects in pediatric patients with acute lymphoblastic leukemia: results of a double-blind, randomized controlled trial

Purpose Dexamethasone is a key component in the treatment of pediatric acute lymphoblastic leukemia (ALL), but can induce serious adverse effects. Recent studies have led to the hypothesis that neuropsychological adverse effects may be a result of cortisol depletion of the cerebral mineralocorticoid receptors. We examined whether including a physiologic dose of hydrocortisone in dexamethasone treatment can reduce neuropsychologic and metabolic adverse effects in children with ALL. Patients and Methods We performed a multicenter, double-blind, randomized controlled trial with a crossover design. Of 116 potentially eligible patients (age 3 to 16 years), 50 were enrolled and were treated with two consecutive courses of dexamethas

Homocysteine levels and the risk of osteoporotic fracture

BACKGROUND: Very high plasma homocysteine levels are characteristic of homocystinuria, a rare autosomal recessive disease accompanied by the early onset of generalized osteoporosis. We therefore hypothesized that mildly elevated homocysteine levels might be related to age-related osteoporotic fractures. METHODS: We studied the association between circulating homocysteine levels and the risk of incident osteoporotic fracture in 2406 subjects, 55 years of age or older, who participated in two separate prospective, population-based studies. In the Rotterdam Study, there were two independent cohorts: 562 subjects in cohort 1, with a mean follow-up period of 8.1 years; and 553 subjects in cohort 2, with a mean follow-up period of 5.7 years. In the Longitudinal Aging Study Amsterdam, there was a single cohort of 1291 subjects, with a mean follow-up period of 2.7 years. Multivariate Cox proportional-hazards regression mode

Development and validation of a prognostic multivariable model to predict insufficient clinical response to methotrexate in rheumatoid arthritis

Objective The objective was to predict insufficient response to 3 months methotrexate (MTX) in DMARD naïve rheumatoid arthritis patients. Methods A Multivariable logistic regression model of rheumatoid arthritis patients starting MTX was developed in a derivation cohort with 285 patients starting MTX in a clinical multicentre, stratified single-blinded trial, performed in seven secondary care clinics and a tertiary care clinic. The model was validated in a validation cohort with 102 patients starting MTX at a tertiary care clinic. Outcome was insufficient response (disease activity score (DAS)28 >3.2) after 3 months of MTX treatment. Clinical characteristics, lifestyle variables, genetic and metabolic biomarkers were determined at baseline in both cohorts. These variables were dichotomized and used to construct a multivariable prediction model with backward logistic regression analysis. Results The prediction model for insufficient response in the derivation cohort, included: DAS28>5.1, Health Assessment Questionnaire>0.6, current smoking, BMI>25 kg/m2, ABCB1 rs1045642 genotype, ABCC3 rs4793665 genotype, and erythrocyte-folate<750 nmol/L. In the derivation cohort, AUC of ROC curve was 0.80 (95%CI: 0.73–0.86), and 0.80 (95%CI: 0.69–0.91) in the validation cohort. Betas of the prediction model were transformed into total risk score (range 0–8). At cutoff of 4, probability for insufficient response was 44%. Sensitivity was 71%, specificity 72%, with positive and negative predictive value of 72% and 71%. Conclusions A prognostics prediction model for insufficient response to MTX in 2 prospective RA cohorts by combining genetic, metabolic, clinical and lifestyle variables was developed and validated. This model satisfactorily identified RA patients with high risk of insufficient response to MTX