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5. Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease: Results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study

Author

Chanchlani, N, Lin, S, Auth, MK, Lee, CL, Robbins, H, Looi, S, Murugesan, SV, Riley, T, Preston, C, Stephenson, S, Cardozo, W, Sonwalkar, SA, Allah-Ditta, M, Mansfield, L, Durai, D, Baker, M, London, I, London, E, Gupta, S, Di Mambro, A, Murphy, A, Gaynor, E, Jones, KDJ, Claridge, A, Sebastian, S, Ramachandran, S, Selinger, CP, Borg-Bartolo, SP, Knight, P, Sprakes, MB, Burton, J, Kane, P, Lupton, S, Fletcher, A, Gaya, DR, Colbert, R, Seenan, JP, MacDonald, J, Lynch, L, McLachlan, I, Shields, S, Hansen, R, Gervais, L, Jere, M, Akhtar, M, Black, K, Henderson, P, Russell, RK, Lees, CW, Derikx, LAAP, Lockett, M, Betteridge, F, De Silva, A, Hussenbux, A, Beckly, J, Bendall, O, Hart, JW, Thomas, A, Hamilton, B, Gordon, C, Chee, D, McDonald, TJ, Nice, R, Parkinson, M, Gardner-Thorpe, H, Butterworth, JR, Javed, A, Al-Shakhshir, S, Yadagiri, R, Maher, S, Pollok, RCG, Ng, T, Appiahene, P, Donovan, F, Lok, J, Chandy, R, Jagdish, R, Baig, D, Mahmood, Z, Marsh, L, Moss, A, Abdulgader, A, Kitchin, A, Walker, GJ, George, B, Lim, Y-H, Gulliver, J, Bloom, S, Theaker, H, Carlson, S, Cummings, JRF, Livingstone, R, Beale, A, Carter, JO, Bell, A, Coulter, A, Snook, J, Stone, H, Kennedy, NA, Goodhand, JR, Ahmad, T, and IMSAT study investigators

Abstract

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD). AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to their second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF drug, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab. RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p

Published
2022

6. Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease: results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study.

Author

Chanchlani, N., Lin, S., Auth, M.K., Lee, C.L., Robbins, H., Looi, S., Murugesan, S.V., Riley, T., Preston, C., Stephenson, S., Cardozo, W., Sonwalkar, S.A., Allah-Ditta, M., Mansfield, L., Durai, D., Baker, M., London, I., London, E., Gupta, S., Mambro, A. Di, Murphy, A., Gaynor, E., Jones, K.D.J., Claridge, A., Sebastian, S., Ramachandran, S., Selinger, C.P., Borg-Bartolo, S.P., Knight, P., Sprakes, M.B., Burton, J., Kane, P., Lupton, S., Fletcher, A., Gaya, D.R., Colbert, R., Seenan, J.P., Macdonald, J., Lynch, L., McLachlan, I., Shields, S., Hansen, R., Gervais, L., Jere, M., Akhtar, M., Black, K., Henderson, P., Russell, R.K., Lees, C.W., Derikx, L.A.A.P., Lockett, M., Betteridge, F., Silva, Aminda de, Hussenbux, A., Beckly, J., Bendall, O., Hart, J.W., Thomas, A., Hamilton, B., Gordon, C., Chee, D., McDonald, T.J., Nice, R., Parkinson, M., Gardner-Thorpe, H., Butterworth, J.R., Javed, A., Al-Shakhshir, S., Yadagiri, R., Maher, S., Pollok, R.C.G., Ng, T., Appiahene, P., Donovan, F., Lok, James, Chandy, R., Jagdish, R., Baig, D., Mahmood, Z., Marsh, L., Moss, A., Abdulgader, A., Kitchin, A., Walker, G.J.A., George, B., Lim, Y.H., Gulliver, J., Bloom, S., Theaker, H., Carlson, S., Cummings, J.R.F., Livingstone, R., Beale, A., Carter, Jodi M., Bell, A., Coulter, A., Snook, J., Stone, H., Kennedy, N.A., Goodhand, J.R., Ahmad, T., Chanchlani, N., Lin, S., Auth, M.K., Lee, C.L., Robbins, H., Looi, S., Murugesan, S.V., Riley, T., Preston, C., Stephenson, S., Cardozo, W., Sonwalkar, S.A., Allah-Ditta, M., Mansfield, L., Durai, D., Baker, M., London, I., London, E., Gupta, S., Mambro, A. Di, Murphy, A., Gaynor, E., Jones, K.D.J., Claridge, A., Sebastian, S., Ramachandran, S., Selinger, C.P., Borg-Bartolo, S.P., Knight, P., Sprakes, M.B., Burton, J., Kane, P., Lupton, S., Fletcher, A., Gaya, D.R., Colbert, R., Seenan, J.P., Macdonald, J., Lynch, L., McLachlan, I., Shields, S., Hansen, R., Gervais, L., Jere, M., Akhtar, M., Black, K., Henderson, P., Russell, R.K., Lees, C.W., Derikx, L.A.A.P., Lockett, M., Betteridge, F., Silva, Aminda de, Hussenbux, A., Beckly, J., Bendall, O., Hart, J.W., Thomas, A., Hamilton, B., Gordon, C., Chee, D., McDonald, T.J., Nice, R., Parkinson, M., Gardner-Thorpe, H., Butterworth, J.R., Javed, A., Al-Shakhshir, S., Yadagiri, R., Maher, S., Pollok, R.C.G., Ng, T., Appiahene, P., Donovan, F., Lok, James, Chandy, R., Jagdish, R., Baig, D., Mahmood, Z., Marsh, L., Moss, A., Abdulgader, A., Kitchin, A., Walker, G.J.A., George, B., Lim, Y.H., Gulliver, J., Bloom, S., Theaker, H., Carlson, S., Cummings, J.R.F., Livingstone, R., Beale, A., Carter, Jodi M., Bell, A., Coulter, A., Snook, J., Stone, H., Kennedy, N.A., Goodhand, J.R., and Ahmad, T.

Abstract

Item does not contain fulltext, BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD). AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab. RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure. CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the seco

Published
2022

7. Repeated out-of-Africa expansions of Helicobacter pylori driven by replacement of deleterious mutations

Author

Thorpe, H. A. (Harry A.), Tourrette, E. (Elise), Yahara, K. (Koji), Vale, F. F. (Filipa F.), Liu, S. (Siqi), Oleastro, M. (Mónica), Alarcon, T. (Teresa), Perets, T.-T. (Tsachi-Tsadok), Latifi-Navid, S. (Saeid), Yamaoka, Y. (Yoshio), Martinez-Gonzalez, B. (Beatriz), Karayiannis, I. (Ioannis), Karamitros, T. (Timokratis), Sgouras, D. N. (Dionyssios N.), Elamin, W. (Wael), Pascoe, B. (Ben), Sheppard, S. K. (Samuel K.), Ronkainen, J. (Jukka), Aro, P. (Pertti), Engstrand, L. (Lars), Agreus, L. (Lars), Suerbaum, S. (Sebastian), Thorell, K. (Kaisa), Falush, D. (Daniel), Thorpe, H. A. (Harry A.), Tourrette, E. (Elise), Yahara, K. (Koji), Vale, F. F. (Filipa F.), Liu, S. (Siqi), Oleastro, M. (Mónica), Alarcon, T. (Teresa), Perets, T.-T. (Tsachi-Tsadok), Latifi-Navid, S. (Saeid), Yamaoka, Y. (Yoshio), Martinez-Gonzalez, B. (Beatriz), Karayiannis, I. (Ioannis), Karamitros, T. (Timokratis), Sgouras, D. N. (Dionyssios N.), Elamin, W. (Wael), Pascoe, B. (Ben), Sheppard, S. K. (Samuel K.), Ronkainen, J. (Jukka), Aro, P. (Pertti), Engstrand, L. (Lars), Agreus, L. (Lars), Suerbaum, S. (Sebastian), Thorell, K. (Kaisa), and Falush, D. (Daniel)

Abstract

Helicobacter pylori lives in the human stomach and has a population structure resembling that of its host. However, H. pylori from Europe and the Middle East trace substantially more ancestry from modern African populations than the humans that carry them. Here, we use a collection of Afro-Eurasian H. pylori genomes to show that this African ancestry is due to at least three distinct admixture events. H. pylori from East Asia, which have undergone little admixture, have accumulated many more non-synonymous mutations than African strains. European and Middle Eastern bacteria have elevated African ancestry at the sites of these mutations, implying selection to remove them during admixture. Simulations show that population fitness can be restored after bottlenecks by migration and subsequent admixture of small numbers of bacteria from non-bottlenecked populations. We conclude that recent spread of African DNA has been driven by deleterious mutations accumulated during the original out-of-Africa bottleneck.

Published
2022

19. Towards diffractive ways of knowing women's moving bodies: A baradian experiment with the fitbit-motherhood entanglement

Author

Clark, MI, Thorpe, H, Clark, MI, and Thorpe, H

Abstract

This article presents a diffractive experiment in thinking about mothers' engagements with self-tracking technologies as materially and discursively produced phenomena. Inspired by St. Pierre's claim that any empirical adventure with new materialisms must begin by living with theory, we share our feminist, collaborative journey with Fitbits and Karen Barad's agential realism to consider what might emerge when we begin thinking and living with concepts such as diffraction, entanglement, and intra-action. Unfolding within the uncertain intersections of theory, method, and data, our diffractive methodology prompted understandings of maternal, moving bodies as entangled agencies in continuous states of becoming and fostered generative feminist relationships that allowed us to embrace new ways of thinking, knowing, and being.

Published
2020

39. Kinematic cell model of macropore flow from intermittent irrigation pulses

Author

Bidwell, V. J. and Thorpe, H. R.

Subjects
Soil moisture -- Measurement -- Environmental aspects -- Analysis -- Models, Soil research -- Analysis -- Models -- Environmental aspects -- Measurement, Streamflow -- Models -- Analysis -- Environmental aspects -- Measurement, Irrigation farming -- Environmental aspects -- Analysis -- Measurement -- Models, Agricultural industry, Earth sciences, Analysis, Models, Measurement, Environmental aspects
Abstract

Abstract Significant fluctuations in soil water flux were observed in the drainage hydrographs from lysimeters (1220 mm diam., 900 mm deep) of undisturbed field soil, recorded at 5-min intervals, in [...]

Published
2001

40. The effects of adding zoledronic acid to neoadjuvant chemotherapy on tumour response: exploratory evidence for direct anti-tumour activity in breast cancer

Author

Coleman, R.E., Winter, M.C., Cameron, D., Bell, R., Dodwell, D., Keane, M.M., Gil, M., Ritchie, D., Passos-Coelho, J.L., Wheatley, D., Burkinshaw, R., Marshall, S.J., Thorpe, H., and AZURE (BIG01 04) , Investigators

Abstract

Background: Pre-clinical studies have demonstrated synergistic anti-tumour effects of chemotherapy (CT) and zoledronic acid (ZOL). Within the AZURE trial, designed to determine whether the addition of ZOL to neoadjuvant therapy improves disease outcomes, a subgroup received neoadjuvant CT. We report a retrospective evaluation comparing pathological response in the primary tumour between treatment groups.\ud \ud Methods: In total, 205 patients received neoadjuvant CT±ZOL (CT+ZOL, n=102; CT, n=103). The primary end point was pathologically assessed residual invasive tumour size (RITS) at surgery. Secondary end points were pathological complete response (pCR) rate and axillary nodal involvement. Following review of surgical pathology reports (n=195), outcome differences between groups were assessed adjusting for potential response modifiers.\ud \ud Results: Baseline characteristics and CT treatments were similar. In multivariate analysis, allowing for biological and clinical factors known to influence tumour response, the adjusted mean RITS in CT and CT+ZOL groups were 27.4 and 15.5 mm, respectively, giving a difference in means of 12 mm (95% confidence interval: 3.5–20.4 mm; P=0.006). The pCR rate was 6.9% in the CT group and 11.7% in the CT+ZOL group (P=0.146). There was no difference in axillary nodal involvement (P=0.6315).\ud \ud Conclusion: These data suggest a possible direct anti-tumour effect of ZOL in combination with CT, warranting formal evaluation in prospective studies.

Published
2010

41. Spirituality

Author

Meira, T. J., Booth, D., Thorpe, H., Meaning of life, and Levensbeschouwing ihb de humanistische (LB)

Published
2007

42. Short term costs of conventional versus laparoscopic assisted surgery in patients with colorectal cancer (MRC CLASSIC Trial)

Author

Guillou, PJ, Franks, PJ, Bosanquet, N, Thorpe, H, Brown, JM, Copeland, J, Smith, AMH, and Quirke, P

Subjects
digestive, oral, and skin physiology
Abstract

The short-term clinical results of the CLASICC trial indicated that clinical outcomes were similar between laparoscopic and open approaches. This study presents the short-term (3 month) cost analysis undertaken on a subset of patients entered into the CLASICC trial (682 of 794 patients). As expected the costs associated with the operation were higher in the 452 patients randomised to laparoscopic surgery (lap) compared with the 230 randomised to open procedure (open), £1703 vs £1386. This was partially offset by the other hospital (nontheatre) costs, which were lower in the lap group (£2930 vs £3176). The average cost to individuals for reoperations was higher in the lap group (£762 vs £553). Overall costs were slightly higher in the lap group (£6899 vs £6631), with mean difference of £268 (95%CI −689 to 1457). Sensitivity analysis made little difference to these results. The cost of rectal surgery was higher than for colon, for lap (£8259 vs £5586) and open procedures (£7820 vs £5503). The short-term cost analysis for the CLASICC trial indicates that the costs of either laparoscopic or open procedure were similar, lap surgery costing marginally more on average than open surgery.

Published
2006

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