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8. Cost-effectiveness of routine measuring of serum drug concentrations and anti-drug antibodies in treatment of rheumatoid arthritis patients with TNF-α blockers

Author

Laine J, Jokiranta TS, Eklund KK, Väkeväinen M, and Puolakka K

Subjects
TNF blockers, anti-drug antibodies, drug concentration, Medicine (General), R5-920
Abstract

Juha Laine,1 T Sakari Jokiranta,2,3 Kari K Eklund,4,5 Merja Väkeväinen,1 Kari Puolakka6 1Pfizer Oy, Helsinki, 2United Medix Laboratories Ltd, Espoo, 3Research Programs Unit, Immunobiology, 4Department of Rheumatology, University of Helsinki, 5Helsinki University Central Hospital, Helsinki, 6Department of Medicine, South Karelia, Finland Abstract: Monitoring of anti-drug antibodies (ADAbs) or serum concentrations of biologicals in treatment of rheumatoid arthritis could provide an explanation for a loss of efficacy and help in the choice of subsequent medication. Current clinical practices do not generally include such monitoring of tumor necrosis factor (TNF)-α blockers on a routine basis. The main aims of this study were to estimate the probabilities of optimal and nonoptimal treatment decisions if infliximab or adalimumab drug trough level (DL) and ADAbs are tested or not in rheumatoid arthritis, and to model cost-effectiveness of performing such monitoring on a routine basis. Data on DLs and ADAbs concentrations were obtained in Finland from clinically requested monitoring analyses of 486 and 1,137 samples from patients on adalimumab and infliximab, respectively. DL was within the target range in 42% of samples from adalimumab- and 50.4% of infliximab-treated patients. ADAbs were detected in approximately 20% and 13.5% of samples from adalimumab- and infliximab-treated patients, respectively. ADAbs were found in 52.3% and 41.3% of those with low adalimumab or infliximab DLs, respectively. The monitoring data were incorporated into probabilities for making the optimal treatment decision. Economic impact of clinical decision-making was modeled in a short-term (3–6 months) scenario with 100 hypothetical patients. In the model, the combined measurement of DLs and ADAbs was cost-saving compared to the nontesting scenario when the monitoring results affected the treatment decision in at least 2–5 of 100 patients, a proportion which is easily exceeded in real-life clinical practice. This study indicates that routine monitoring of drug level and ADAbs is cost-beneficial in clinical practice, thereby improving the decision-making process in using TNF-α blockers. Keywords: anti-TNF drugs, anti-drug antibodies, trough level measurement

Published
2016

10. Determinants of Human Fixed-Interval Performance Following Varied Exposure to Reinforcement Schedules

Author

Torgrud, Laine J., Holborn, Stephen W., and Zak, Robert D.

Abstract

Undergraduates given accurate instructions pressed keys for token points under either a variety of reinforcement schedules (variety training) or under a single schedule. Response rates on a fixed-interval (FI) test schedule then were assessed. Experiment 1 compared variety training inclusive of FI-optimal rates (functional) to training excluding such rates (nonfunctional). Participants provided functional training showed low test rates relative to those provided nonfunctional and single-instruction training, implicating response-rate history as a determinant of subsequent FI performance. Experiment 2 manipulated functional and nonfunctional variety training, and the correspondence of FI test-phase point densities with those of high-, low-, or both high- and low-rate training components. Performances under FI were affected by density correspondence, suggesting discriminative control of response rate by point density. (Contains 4 tables and 5 figures.)

Published
2006

23. HSEQ at shared industrial workplaces:experiences from collaboration on supplier audits

Author

Jounila, H. (Henri), Reiman, A. (Arto), Laine, J. (Janne), and Kauppila, O. (Osmo)

Subjects
HSEQ, Supplier development, Shared workplace, Audit, Buyer, Collaboration
Abstract

The trend of outsourcing in industries has led to a situation in which various service providers are working at industrial sites. Managing such complex multi-employer worksites is a challenge. This study introduces a collaboration procedure for supplier audits in the context of integrated health, safety, environment, and quality management by large Finnish industrial buyers. A supplier-audit database is analyzed and supplemented by interviews with the buyers. Altogether, 456 audit observations are categorized in seven thematic areas to introduce what kinds of development areas suppliers have. With regard to the collaborative nature of the procedure, the benefits from the buyers’ side were identified from the interviews. Cluster collaboration has proven advantageous in financial savings, objective assessments, and supplier development.

Published
2020

39. Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: a multi-cohort analysis

Author

Fiorito, G., Mccrory, C., Robinson, O., Carmeli, C., Rosales, C. O., Zhang, Y., Colicino, E., Dugue, P. -A., Artaud, F., Mckay, G. J., Jeong, A., Mishra, P. P., Nost, T. H., Krogh, V., Panico, S., Sacerdote, C., Tumino, R., Palli, D., Matullo, G., Guarrera, S., Gandini, M., Bochud, M., Dermitzakis, E., Muka, T., Schwartz, J., Vokonas, P. S., Just, A., Hodge, A. M., Giles, G. G., Southey, M. C., Hurme, M. A., Young, I., Mcknight, A. J., Kunze, S., Waldenberger, M., Peters, A., Schwettmann, L., Lund, E., Baccarelli, A., Milne, R. L., Kenny, R. A., Elbaz, A., Brenner, H., Kee, F., Voortman, T., Probst-Hensch, N., Lehtimaki, T., Elliot, P., Stringhini, S., Vineis, P., Polidoro, S., Alberts, J., Alenius, H., Avendano, M., Baltar, V., Bartley, M., Barros, H., Bellone, M., Berger, E., Blane, D., Candiani, G., Carra, L., Castagne, R., Chadeau-Hyam, M., Cima, S., Clavel-Chapelon, F., Costa, G., Courtin, E., Delpierre, C., D'Errico, A., Dermitzakis, M., Elovainio, M., Elliott, P., Fagherazzi, G., Fraga, S., Gares, V., Gerbouin-Rerolle, P., Giles, G., Goldberg, M., Greco, D., Guessous, I., Haba-Rubio, J., Heinzer, R., Hodge, A., Joost, S., Karimi, M., Kelly-Irving, M., Kahonen, M., Karisola, P., Khenissi, L., Kivimaki, M., Laine, J., Lang, T., Laurent, A., Layte, R., Lepage, B., Lorsch, D., Macguire, F., Machell, G., Mackenbach, J., Marmot, M., de Mestral, C., Miller, C., Milne, R., Muennig, P., Nusselder, W., Petrovic, D., Pilapil, L., Preisig, M., Pulkki-Raback, L., Raitakari, O., Ribeiro, A. I., Ricceri, F., Recalcati, P., Reinhard, E., Valverde, J. R., Saba, S., Santegoets, F., Satolli, R., Simmons, T., Severi, G., Shipley, M. J., Tabak, A., Terhi, V., Tieulent, J., Vaccarella, S., Vigna-Taglianti, F., Vollenweider, P., Vuilleumier, N., Zins, M., Medical Research Council (MRC), Commission of the European Communities, BIOS Consortium, Lifepath consortium, Epidemiology, Dermitzakis, Emmanouil, and Stringhini, Silvia

Subjects
Male, Aging, Geriatrics & Gerontology, Disease, epigenetic clocks, Bioinformatics, 0601 Biochemistry and Cell Biology, DISEASE, Epigenesis, Genetic, Cohort Studies, 0302 clinical medicine, Risk Factors, DNA METHYLATION, media_common, 0303 health sciences, education, Lifepath consortium, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, CARDIOVASCULAR RISK, Aged, Aging/genetics, Aging/psychology, DNA Methylation, Educational Status, Female, Humans, Life Style, Mutation, Social Class, biological aging, socioeconomic position, Longevity, ASSOCIATION, Biological aging, Education, Epigenetic clocks, Socioeconomic position, 3. Good health, WIDE METHYLATION, Aging/genetics/psychology, DNA methylation, Biomarker (medicine), HEALTH, BIOS Consortium, Life Sciences & Biomedicine, Research Paper, Cohort study, VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714, media_common.quotation_subject, CANCER-RISK, 610 Medicine & health, VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical genetics: 714, Biology, PERIPHERAL-BLOOD, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genetic, 360 Social problems & social services, 1112 Oncology and Carcinogenesis, Epigenetics, ddc:613, 030304 developmental biology, Science & Technology, Mechanism (biology), MUTATIONS, dNaM, Socioeconomic Position, Biological Aging, Epigenetic Clocks, Cell Biology, 0606 Physiology, DRIFT, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, 030217 neurology & neurosurgery, Epigenesis
Abstract

Source at https://doi.org/10.18632/aging.101900. Differences in health status by socioeconomic position (SEP) tend to be more evident at older ages, suggesting the involvement of a biological mechanism responsive to the accumulation of deleterious exposures across the lifespan. DNA methylation (DNAm) has been proposed as a biomarker of biological aging that conserves memory of endogenous and exogenous stress during life. We examined the association of education level, as an indicator of SEP, and lifestyle-related variables with four biomarkers of age-dependent DNAm dysregulation: the total number of stochastic epigenetic mutations (SEMs) and three epigenetic clocks (Horvath, Hannum and Levine), in 18 cohorts spanning 12 countries. The four biological aging biomarkers were associated with education and different sets of risk factors independently, and the magnitude of the effects differed depending on the biomarker and the predictor. On average, the effect of low education on epigenetic aging was comparable with those of other lifestyle-related risk factors (obesity, alcohol intake), with the exception of smoking, which had a significantly stronger effect. Our study shows that low education is an independent predictor of accelerated biological (epigenetic) aging and that epigenetic clocks appear to be good candidates for disentangling the biological pathways underlying social inequalities in healthy aging and longevity.

Published
2019
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40. Maternal educational inequalities in measured body mass index trajectories in three European countries

Author

Mccrory, C., Leahy, S., Ribeiro, A. I., Fraga, S., Barros, H., Avendano, M., Vineis, P., Layte, R., Alenius, H., Baglietto, L., Bartley, M., Bellone, M., Berger, E., Bochud, M., Candiani, G., Carmeli, C., Carra, L., Castagne, R., Chadeau-Hyam, M., Cima, S., Costa, G., Courtin, E., Delpierre, C., D'Errico, A., Donkin, A., Dugue, P. -A., Elliott, P., Fagherazzi, G., Fiorito, G., Gandini, Martina, Gares, V., Gerbouin-Rerrolle, P., Giles, G., Goldberg, M., Greco, D., Guida, F., Hodge, A., Karimi, M., Karisola, P., Kelly, M., Kivimaki, M., Laine, J., Lang, T., Laurent, A., Lepage, B., Lorsch, D., Machell, G., Mackenbach, J., Marmot, M., Milne, David Robert, Muennig, P., Nusselder, W., Petrovic, D., Polidoro, S., Preisig, M., Recalcati, P., Reinhard, E., Ricceri, F., Robinson, O., Jose, R., Severi, PAULA GABRIELA, Simmons, T., Stringhini, S., Terhi, V., Than, J., Vergnaud, A. -C., Vigna-Taglianti, F., Vollenweider, P., Zins, M., Epidemiology, Public Health, HRB, and ERC

Subjects
Male, Pediatric Obesity, obesity, Adolescent, Inequality, Epidemiology, body mass index, children, cohort study, growth curves, overweight, social inequalities, media_common.quotation_subject, Social gradient, Mothers, Prospective data, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Prevalence, medicine, Humans, Social inequality, Prospective Studies, Child, media_common, 2. Zero hunger, 030219 obstetrics & reproductive medicine, Portugal, business.industry, 4. Education, Health Status Disparities, medicine.disease, Obesity, United Kingdom, Millennium Cohort Study (United States), Child, Preschool, Pediatrics, Perinatology and Child Health, Cohort, Educational Status, Female, business, Ireland, Body mass index, Demography
Abstract

BACKGROUND: Social inequalities in the prevalence of childhood overweight and obesity are well-established, but less is known about when the social gradient first emerges and how it evolves across childhood and adolescence.OBJECTIVE: This study examines maternal education differentials in children's body mass trajectories in infancy, childhood and adolescence using data from four contemporary European child cohorts.METHODS: Prospective data on children's body mass index (BMI) were obtained from four cohort studies-Generation XXI (G21-Portugal), Growing Up in Ireland (GUI) infant and child cohorts, and the Millennium Cohort Study (MCS-UK)-involving a total sample of 41,399 children and 120,140 observations. Children's BMI trajectories were modelled by maternal education level using mixed-effect models.RESULTS: Maternal educational inequalities in children's BMI were evident as early as three years of age. Children from lower maternal educational backgrounds were characterised by accelerated BMI growth, and the extent of the disparity was such that boys from primary-educated backgrounds measured 0.42 kg/m2 (95% CI 0.24, 0.60) heavier at 7 years of age in G21, 0.90 kg/m2 (95% CI 0.60, 1.19) heavier at 13 years of age in GUI and 0.75 kg/m2 (95% CI 0.52, 0.97) heavier in MCS at 14 years of age. The corresponding figures for girls were 0.71 kg/m2 (95% CI 0.50, 0.91), 1.31 kg/m2 (95% CI 1.00, 1.62) and 0.76 kg/m2 (95% CI 0.53, 1.00) in G21, GUI and MCS, respectively.CONCLUSIONS: Maternal education is a strong predictor of BMI across European nations. Socio-economic differentials emerge early and widen across childhood, highlighting the need for early intervention.

Published
2019
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