Purpose To investigate the validity of comparisons across patients with different musculoskeletal disorders and persons from the general population by evaluating differential item functioning (DIF)... Show morePurpose To investigate the validity of comparisons across patients with different musculoskeletal disorders and persons from the general population by evaluating differential item functioning (DIF) for the PROMIS physical function (PROMIS-PF), pain interference (PROMIS-PI), and pain behavior (PROMIS-PB) item banks.Methods Patients with chronic pain, rheumatoid arthritis (RA), or osteoarthritis (OA); patients receiving physiotherapy (PT); and persons from the Dutch general population completed the full Dutch-Flemish PROMIS-PF (121-items), PROMIS-PI (40-items), or PROMIS-PB (39-items) banks. DIF was assessed with ordinal logistic regression models and McFadden's pseudo R-2-change of >= 2% as critical value. The impact of DIF on item scores and the T-scores per bank was examined by inspecting item characteristic curves (ICCs) and test characteristic curves (TCCs).Results 2762 patients with chronic pain, 2029 with RA, 1247 with OA, 805 receiving PT, and 1310 healthy persons participated. For the PROMIS-PF, 25 out of 121 items were flagged for DIF, of which 10 items were flagged in multiple comparisons. For the PROMIS-PI, only 2 out of 40 items were flagged for DIF and for the PROMIS-PB, only 3 out of 39 items. Most DIF items had R-2 values just above the critical value of 2% and all showed uniform DIF. The ICCs and TCCs showed that the magnitude and impact of DIF on the item and T-scores were negligible.Conclusions This study supports the universal applicability of PROMIS across (patient) populations. Comparisons across patients with different musculoskeletal disorders and persons from the general population are valid, when applying the PROMIS-PF, PROMIS-PI, and PROMIS-PB banks. Show less
Jongen, E.L.W.; Deelen, A.; Euwals, R.; Graaf-Zijl, M. de; Hoekstra, K.; Boer, H-W. de; ... ; Huizen, T. van 2015
The offspring of nonagenarian siblings suffer less from age related conditions and have a lower risk of mortality compared to their partners. Fibroblast strains derived from such offspring in... Show moreThe offspring of nonagenarian siblings suffer less from age related conditions and have a lower risk of mortality compared to their partners. Fibroblast strains derived from such offspring in middle age show different in vitro responses to stress, more stress-induced apoptosis and less senescence when compared to strains of their partners. Aiming to find differences in cellular metabolism in vitro between these fibroblast strains, cell culture supernatants collected at 24 hours and five days were analysed using (1)H nuclear magnetic resonance (NMR)-based metabolic footprinting. Between 24 hours and five days of incubation, supernatants of all fibroblast strains showed decreased levels of glucose, pyruvate, alanine-glutamine (ala-gln), valine, leucine, isoleucine, serine and lysine and increased levels of glutamine, alanine, lactate and pyroglutamic acid. Strains from offspring and their partners were compared using a partial least squares-discriminant analysis (PLS-DA) model based on the data of the five-day time point. The ala-gln and glucose consumption were higher for fibroblast strains derived from offspring when compared to strains of their partners. Also, production of glutamine, alanine, lactate and pyroglutamic acid was found to be higher for fibroblast strains derived from offspring. In conclusion, differences in NMR-based metabolic profiles of human cells in vitro reflect the propensity for human longevity of the subjects from whom these were derived. Show less
With the ever-increasing life expectancies of people, the prevalence of aging-related diseases is also increasing. We studied a unique cohort of people; offspring of nonagenarian siblings with the... Show moreWith the ever-increasing life expectancies of people, the prevalence of aging-related diseases is also increasing. We studied a unique cohort of people; offspring of nonagenarian siblings with the propensity for longevity were also recruited and compared to their partners, representing the general population. The offspring (~60 year old) already show lower prevalence of cardiovascular disease and diabetes. In the thesis __Cellular stress in vitro and longevity on vivo__ it is reported how cells (dermal fibroblasts) derived from these offspring were compared with cells from their partners. It was shown that they react differenly in vitro under both non stressed and under conditions of oxidative stress. Future research is warranted to further elucidate the genes involved in these differences. Show less
Respiratory chain function becomes less efficient with age resulting in increased levels of damaging reactive oxygen species. We compared rotenone-exposed fibroblast strains from young and old... Show moreRespiratory chain function becomes less efficient with age resulting in increased levels of damaging reactive oxygen species. We compared rotenone-exposed fibroblast strains from young and old subjects and from offspring of nonagenarian siblings and the partners of the offspring. Rotenone increased reactive oxygen species levels, inhibited growth rate, and increased telomere shortening (all p < .05). Non-stressed strains from young subjects showed lower reactive oxygen species levels (p = .031) and higher growth rates (p = .002) than strains from old subjects. Stressed strains from young subjects showed smaller increases in reactive oxygen species levels (p = .014) and larger decreases in growth rate (p < .001) than strains from old subjects. Telomere-shortening rates were not different between groups. Stress-induced decreases in growth rate were larger in strains from offspring than from partners (p = .05). Strains from young and old subjects are differentially affected by chronic inhibition of the respiratory chain. Changed growth rates in strains from offspring resemble those from strains from young subjects. Show less
Cellular senescence, an important factor in ageing phenotypes, can be induced by replicative exhaustion or by stress. We investigated the relation between maximum replicative capacity, telomere... Show moreCellular senescence, an important factor in ageing phenotypes, can be induced by replicative exhaustion or by stress. We investigated the relation between maximum replicative capacity, telomere length, stress-induced cellular senescence, and apoptosis/cell death in human primary fibroblast strains obtained from nonagenarians of the Leiden 85-plus Study. Fibroblast strains were cultured until replicative senescence and stressed with rotenone at low passage. Telomere length, senescence-associated-β-galactosidase activity, sub-G1 content, and Annexin-V/PI positivity were measured in nonstressed and stressed conditions. Fibroblast strains with a higher replicative capacity had longer telomeres (p = .054). In nonstressed conditions, replicative capacity was not associated with β-gal activity (p = .07) and negatively with sub-G1 (p = .008). In rotenone-stressed conditions, replicative capacity was negatively associated with β-gal activity (p = .034) and positively with sub-G1 (p = .07). Summarizing, fibroblast strains with a higher maximum replicative capacity have longer telomeres, are less prone to go into stress-induced cellular senescence, and more prone to die after stress. Show less
