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107 results on '"Nair, N."'

3. Genome-wide association study of methotrexate-induced liver injury in rheumatoid arthritis patients

Author

Eektimmerman, F., Swen, J.J., Broeder, A.A. den, Hazes, J.M.W., Kurreeman, F.S., Verstappen, S.M.M., Nair, N., Pawlik, A., Nurmohamed, M.T., Dolzan, V., Bohringer, S., Allaart, C.F., and Guchelaar, H.J.

Abstract

Hepatotoxicity is a serious adverse drug reaction related to methotrexate (MTX). However, the cause of drug-induced liver injury (DILI) is still unclear and unpredictable. Genetic risk factors may predispose for MTX-DILI. Therefore, we conducted a nested case-control genome-wide association study to explore genetic risk factors associated with MTX-DILI. Seven international groups contributed blood samples and data of patients with rheumatoid arthritis who used MTX. MTX-DILI was defined as an alanine aminotransferase (ALT) level of at least three times the upper limit of normal (ULN), to increase contrast controls ALT levels did not raise above two times the ULN. Per study site, control subjects and patients with MTX-DILI (ratio 3:1) were matched for age, gender, and duration of MTX use. Patients were genotyped using Illumina GSA MD-24v1-0 and data were imputed using the 1000 Genomes reference panel. Single-nucleotide polymorphisms (SNPs) were analyzed using an additive genetic model, corrected for sex, country, and age. A P-value of

Published
2023

6. Latent class trajectory modelling of 2‐components‐DAS28 identifies multiple rheumatoid arthritis phenotypes of response to biologic disease modifying anti‐rheumatic drugs

Author

Dagliati, A, Plant, D, Nair, N, Jani, M, Amico, B, Peek, N, Morgan, AW, Isaacs, J, Wilson, AG, Hyrich, KL, Geifman, N, Barton, A, and BRAGGSS

Subjects
musculoskeletal diseases, immune system diseases, skin and connective tissue diseases
Abstract

Objectives: To determine whether using a re‐weighted disease activity score that better reflects joint synovitis, the 2‐component DAS28 (2C‐DAS28), based on 28‐swollen joint count and C‐reactive protein, produces more clinically relevant treatment outcome trajectories compared with the standard 4 component DAS28 (4C‐DAS28). Methods: Latent class mixed modelling (LCMM) of response to biologic treatment was applied to 2,991 patients with RA about to commence bDMARD treatment from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS) cohort using both 4C‐DAS28 and 2C‐DAS28 as outcomes. Identified patient groups with similar trajectories were compared in terms of pre‐treatment baseline characteristics – including disability, comorbidities ‐ and follow‐up characteristics – including anti‐drug antibody (ADAb) events, adherence to treatments and blood drug levels, We compared the trajectories obtained using the 4C and 2C scores to determine which characteristics were better captured by the 2CDAS28 compared with the 4C‐DAS28 trajectories. Results: Using the 4C‐DAS28 we identified 3 trajectory groups, which is consistent with previous reports. We show that the 4C‐DAS28 captures information relating to depression. Using the 2C‐DAS28, 7 trajectory groups were identified; among them, distinct groups of non‐responders had a higher incidence of respiratory comorbidities and a higher proportion of ADAb events. We also identified a group of participants for which the 2C‐DAS28 disease activity score remained relatively low and which was enriched for patients who were non‐adherent to treatment. This highlights the utility of both the 4C and 2C‐DAS28 for monitoring different components of disease activity. Conclusions: Here we show that the 2C‐DAS28 modified disease activity score defines important biological and clinical phenotypes associated with treatment outcome in RA and characterizes important underlying response mechanisms to biologic drugs.

Published
2020

7. Variation in the practice of tracheal intubation in Europe after traumatic brain injury : a prospective cohort study

Author

Gravesteijn, BY, Sewalt, CA, Ercole, A, Lecky, F, Menon, D, Steyerberg, EW, Maas, AIR, Lingsma, HF, Klimek, M, Åkerlund, C, Adams, H, Amrein, K, Andelic, N, Andreassen, L, Anke, A, Audibert, G, Azouvi, P, Azzolini, M, Bartels, R, Beer, R, Bellander, B, Benali, H, Berardino, M, Beretta, L, Blaabjerg, M, Borgen, L, Brorsson, C, Buki, A, Cabeleira, M, Caccioppola, A, Calappi, E, Calvi, M, Cameron, P, Carbayo, L, Carbonara, M, León, A, Chevallard, G, Chieregato, A, Citerio, G, Coburn, M, Coles, J, Cooper, J, Correia, M, Cnossen, M, Czeiter, E, Czosnyka, M, Fizelier, C, De Keyser, V, Degos, V, Della Corte, F, Boogert, H, Depreitere, B, Dilvesi, D, Dixit, A, Donoghue, E, Dreier, J, Dulière, G, Ercole Ari, A, Ezer, E, Fabricius, M, Foks, K, Frisvold, S, Furmanov, A, Galanaud, D, Gantner, D, Ghuysen, A, Giga, L, Golubovic, J, Gomez, P, Grossi, F, Gupta, D, Haitsma, I, Helbok, R, Helseth, E, Hutchinson, P, Jankowski, S, Karan, M, Kolias, A, Kondziella, D, Koskinen, L, Kovács, N, Lagares, A, Laureys, S, Lightfoot, R, Lingsma, H, Maas, A, Manara, A, Martino, C, Maréchal, H, Mattern, J, McFadyen, C, McMahon, C, Menovsky, T, Mulazzi, D, Muraleedharan, V, Murray, L, Nair, N, Negru, A, Nelson, D, Newcombe, V, Noirhomme, Q, Nyirádi, J, Ortolano, F, Payen, J, Perlbarg, V, Persona, P, Peul, W, Piippo‐Karjalainen, A, Ples, H, Pomposo, I, Posti, J, Puybasset, L, Radoi, A, Ragauskas, A, Raj, R, Rhodes, J, Richter, S, Rocka, S, Roe, C, Roise, O, Rosenfeld, J, Rosenlund, C, Rosenthal, G, Rossaint, R, Rossi, S, Sahuquillo, J, Sandro, O, Sakowitz, O, Porras, R, Schirmer‐Mikalsen, K, Schou Rico, F, Smielewski, P, Sorinola, A, Stamatakis, E, Kowalk, A, Steyerberg, E, Stocchetti, N, Sundström, N, Takala, R, Tamás, V, Tamosuitis, T, Tenovuo, O, Thomas, M, Tibboel, D, Tolias, C, Trapani, T, Tudora, C, Vajkoczy, P, Vallance, S, Valeinis, E, Vámos, Z, Van der Steen, G, van Dijck, J, Essen, T, Vanhaudenhuyse, A, Wijk, R, Vargiolu, A, Vega, E, Vik, A, Vilcinis, R, Volovici, V, Voormolen, D, Vulekovic, P, Williams, G, Wolf, S, Younsi, A, Zeiler, F, Ziverte, A, and Zoerle, T

Abstract

Traumatic brain injury patients frequently undergo tracheal intubation. We aimed to assess current intubationpractice in Europe and identify variation in practice. We analysed data from patients with traumatic brain injuryincluded in the prospective cohort study collaborative European neurotrauma effectiveness research intraumatic brain injury (CENTER-TBI) in 45 centres in 16 European countries. We included patients who weretransported to hospital by emergency medical services. We used mixed-effects multinomial regression toquantify the effects on pre-hospital or in-hospital tracheal intubation of the following: patient characteristics;injury characteristics; centre; and trauma system characteristics. A total of 3843 patients were included. Ofthese, 1322 (34%) had their tracheas intubated; 839 (22%) pre-hospital and 483 (13%) in-hospital. Thefit of themodel with only patient characteristics predicting intubation was good (Nagelkerke R2 64%). The probability oftracheal intubation increased with the following: younger age; lower pre-hospital or emergency departmentGCS; higher abbreviated injury scale scores (head and neck, thorax and chest, face or abdomen abbreviatedinjury score); and one or more unreactive pupils. The adjusted median odds ratio for intubation between tworandomly chosen centres was 3.1 (95%CI 2.1–4.3) for pre-hospital intubation, and 2.7 (95%CI 1.9–3.5) for in-hospital intubation. Furthermore, the presence of an anaesthetist was independently associated with more pre-hospital intubation (OR 2.9, 95%CI 1.3–6.6), in contrast to the presence of ambulance personnel who areallowed to intubate (OR 0.5, 95%CI 0.3–0.8). In conclusion, patient and injury characteristics are key drivers oftracheal intubation. Between-centre differences were also substantial. Further studies are needed to improvethe evidence base supporting recommendations for tracheal intubation.

Published
2019

13. Economic evaluation of single-fraction versus multiple-fraction palliative radiotherapy for painful bone metastases in breast, lung and prostate cancer

Author

Collinson, L, Kvizhinadze, G, Nair, N, McLeod, M, Blakely, T, Collinson, L, Kvizhinadze, G, Nair, N, McLeod, M, and Blakely, T

Abstract

INTRODUCTION: Single- and multiple-fraction external beam radiotherapy (SFX-EBRT and MFX-EBRT) are palliative treatment options for localized metastatic bone pain. MFX is the preferred choice in many developed countries. Evidence shows little difference in how effectively SFX and MFX reduce pain. However, SFX is associated with higher retreatment and (in one meta-analysis) pathological fracture rates. MFX is, however, more time-consuming and expensive. We estimated the cost-effectiveness of SFX versus MFX for metastatic bone pain in breast, prostate and lung cancer in New Zealand. METHODS: We constructed a Markov microsimulation model to estimate health gain (in quality-adjusted life-years or QALYs), health system costs (in real 2011 NZ dollars) and cost-effectiveness. The model was populated using effect estimates from randomized controlled trials and other studies, and New Zealand cancer and cost data. Disability weights from the 2010 Global Burden of Disease study were used in estimating QALYs. RESULTS: Across all three cancers, QALY gains were similar for SFX compared to MFX, and per patient costs were less for SFX than MFX, with a difference of NZ$1469 (95% uncertainty interval $1112 to $1886) for lung cancer, $1316 ($810 to $1854) for prostate cancer and $1344 ($855 to $1846) for breast cancer. Accordingly, from a cost-effectiveness perspective, SFX was the preferable treatment option. Various sensitivity analyses did not overturn the clear preference for SFX. CONCLUSION: For all three cancers, SFX was clearly more cost-effective than MFX. This adds to the case for desisting from offering MFX to patients with metastatic bone pain, from a cost-effectiveness angle.

Published
2016

40. A controlled dose‐ranging study of remoxipride and haloperidol in schizophrenia ‐ a Canadian multicentre trial

Author

Lapierre, Y. D., primary, Nair, N. P. V., additional, Chouinard, G., additional, Awad, A. G., additional, Saxena, B., additional, Jones, B., additional, McClure, D. J., additional, Bakish, D., additional, Max, P., additional, Manchanda, R., additional, Beaudry, P., additional, BIoom, D., additional, Rotstein, E., additional, Ancill, R., additional, Sandor, P., additional, Sladen‐Dew, N., additional, Durand, C., additional, Chandrasena, R., additional, Horn, E., additional, Elliot, D., additional, Das, M., additional, Ravindran, A., additional, and Matsos, G., additional

Published
1990
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