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1. Patient Preferences Influencing Treatment Decision-Making in Early-Stage Breast Cancer in Germany, Italy, and Japan

Author

Flood E, McCutcheon S, Beusterien K, Mackie DS, Mokiou S, Guillaume X, and Mulvihill E

Subjects
breast cancer, patient perspective, patient priorities, shared decision-making, patient satisfaction, Medicine (General), R5-920
Abstract

Emuella Flood,1 Susan McCutcheon,2 Kathleen Beusterien,3 deMauri S Mackie,3 Stella Mokiou,1 Xavier Guillaume,3 Emily Mulvihill3 1Patient Centered Science, AstraZeneca, Gaithersburg, MD, USA; 2Global Medical Affairs, AstraZeneca, Cambridge, UK; 3Health Division, Cerner Enviza, an Oracle Company, Kansas City, MO, USACorrespondence: Emily Mulvihill, Health Division, Cerner Enviza, an Oracle Company, 2800 Rock Creek Parkway, Kansas, MO, USA, Tel +1 314-724-9386, Email emily.mulvihill@cernerenviza.comPurpose: Patients with early breast cancer (eBC) are increasingly provided with different options, which may involve a sequence of different treatments and treatment modalities, and eligibility for certain adjuvant treatments depending upon pre-surgical and surgical outcomes. This study examined patient preferences around aspects of treatment decision-making in eBC.Patients and Methods: A total of 452 patients with self-reported eBC in Germany (n=151), Italy (n=151), and Japan (n=150) completed an online survey about physician interactions and treatment side effects. The survey included best-worst scaling (BWS) to assess prioritization of 13 statements reflecting aspects of treatment decision-making. In a series of choice tasks, participants chose their most and least preferred options among subsets of 4 statements. Hierarchical Bayesian modeling was used to estimate BWS preference scores for each statement. BWS scores were based on the number of times a statement was chosen as most versus least preferred; scores total 100 for each patient.Results: The most preferred aspects of treatment decision-making were “treatment aggressiveness matches personal risk” (mean BWS score = 13.49), “being told about what is coming” (13.18), deciding based on “own surgical outcome” (11.90), “avoiding unnecessary treatment” (10.35), and “involving in treatment decisions” (9.44). The least preferred aspects were “not being asked about treatment decisions along the way” (3.27) and “receiving the same treatment as other patients” (3.41). Patients in Japan preferred “being told about what is coming”, “deciding based on own surgical outcome”, “avoiding unnecessary treatment”, and being “involved in decisions” more than patients in Italy and Germany. Patients in Germany were more satisfied with their physician interactions and care, although their outcomes were not always better than those in Italy and Japan.Conclusion: Patients value individualized treatment tailored to their risk of recurrence and tolerance of side effects, highlighting the need for focused patient education about options, to encourage their engagement.Plain Language Summary: New treatment pathways based on promising biomarkers are being studied in early breast cancer. This study aimed to understand the importance that patients may place on different features describing how decisions are made along potential treatment pathways for early breast cancer. Participants in Italy, Germany, and Japan were asked to compare various aspects of treatment decision-making and choose those that were most and least important to them. Among the aspects tested, the top 4 were similar across countries: the desire to receive treatment with a level of aggressiveness that matches their individual prognosis, the need to receive adequate and timely information about their upcoming treatment, the need to tailor treatment decisions based on their individual surgery outcomes, and a desire to avoid overtreatment. Not being involved in treatment decisions was the least preferred of the aspects. Patients in Germany and Italy most valued the ability to tailor the aggressiveness of their treatment based on their individual risk of recurrence, whereas patients in Japan prioritized being knowledgeable and prepared for their treatment journey. The results from this study emphasize patients’ desire to be adequately informed about available treatment choices for early breast cancer, to avoid unnecessary treatments, and to be involved in treatment decisions. Keywords: breast cancer, patient perspective, patient priorities, shared decision-making, patient satisfaction

Published
2024

6. Alleghanian faulting in the southern Gaspe Peninsula of Quebec

Author

Jutras, P., Prichonnet, G., and McCutcheon, S.

Subjects
Gaspé Peninsula -- Natural history, Faults (Geology) -- Research, Geology -- Research, Earth sciences
Abstract

ABSTRACT Transcurrent faults and associated compressional structures affecting post-Middle Devonian rocks are recognized for the first time in the southern Gaspe Peninsula (Quebec). This region was previously thought to have [...]

Published
2003

15. Haptic Exploratory Procedures of Children and Youth with and without Cerebral Palsy

Author

Taylor, S., Girdler, Sonya, McCutcheon, S., McLean, B., Parsons, R., Falkmer, Torbjorn, Jacoby, P., Carey, L., Elliott, Catherine, Taylor, S., Girdler, Sonya, McCutcheon, S., McLean, B., Parsons, R., Falkmer, Torbjorn, Jacoby, P., Carey, L., and Elliott, Catherine

Abstract

Aims: Compare haptic exploratory procedures (EPs) and exploratory movements (EMs) of children. This study also tested the interrater reliability of a novel digital recording method. Methods: Participants were 31 children with typical development (TD) (aged 6 years 1 month to 15 years 9 months; 14 male) and 23 children with spastic unilateral cerebral palsy (CP) (aged 6 years to 15 years 5 months; 13 males; right hemiplegia, n = 12). Results: There were no statistically significant differences between groups for expected EP (p = .15), additional EPs (p = .78), or EMs (p = .69) but there was for mean duration of exploration (p < .001) and accuracy (p < .001). This suggests that although children with CP performed similar haptic EPs for each object as children with TD, they took more time and were less accurate in their identification. There was substantial agreement between the two raters' observations of expected EP, κ = .64, p < .0005. Conclusion: Children with CP performed similar haptic EPs as their TD peers. However, despite similarities, the results indicate that for children with CP manual ability was not the primary determinant of accuracy or speed of identification. This study provides evidence for a reliable method of recording haptic EPs.

Published
2018

20. Times of Deformation in the Canadian Appalachians

Author

Keppie, J. D., St. Julien, P., Hubert, C., Beland, J., Skidmore, B., Fyffe, L. R., Ruitenberg, A. A., McCutcheon, S. R., Williams, H., Bursnall, J., Schenk, Paul E., editor, Haworth, R. T., editor, Keppie, J. D., editor, Trzcienski, W. E., editor, Williams, P. F., editor, and Kelling, G., editor

Published
1983
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22. The effect of season and monensin sodium on the digestive characteristics of autumn and spring pasture fed to sheep

Author

Maas, J. A., Wilson, G. F., McCutcheon, S. N., Lynch, G. A., Burnham, D. L., and Frances, J.

Subjects
Monensin -- Health aspects, Sheep -- Food and nutrition, Digestion -- Research, Pastures -- Health aspects, Seasons -- Environmental aspects, Zoology and wildlife conservation
Abstract

The effects of season of growth and monensin treatment on ruminal digestion of fresh-cut autumn and spring pasture were measured in a single group of ruminally fistulated castrated male sheep, housed indoors in metabolism crates. Responses were assessed in terms of ruminal volatile fatty acid molar proportions, ammonia concentration, pH, apparent digestibility of the pasture, and nitrogen balance of the animals. Blood plasma concentrations of insulin, glucose, [Beta]-hydroxybutyrate, urea, and NEFA were also evaluated. Autumn pasture contained significantly lower proportions of water-soluble carbohydrate (P [is less than] 0.05), cellulose (P [is less than] 0.05), and lignin (P [is less than] 0.05) and increased pectin (P [is less than] 0.05), hemicellulose (P [is less than] 0.05), and crude protein (P [is less than] 0.10) concentrations when compared with spring pasture. Voluntary DMI by sheep of autumn pasture was lower (P [is less than] 0.01) than that of spring pasture and was significantly (P [is less than] 0.05) reduced by monensin treatment. Monensin treatment significantly decreased the ruminal molar proportions of acetic acid (P [is less than] 0.10) and butyric acid (P [is less than] 0.001) and increased the molar proportions of propionic acid (P [is less than] 0.001) and minor VFA (P [is less than] 0.01). Nitrogen retention of the sheep was significantly (P [is less than] 0.05) reduced by monensin treatment. Plasma glucose levels were increased (P [is less than] 0.10) by monensin treatment during the fourth 5-d collection period in both seasons. Chemical analysis suggested that the composition of autumn pasture was different from that of spring pasture and that this was manifested in vivo by increased DMI and digestibility of spring vs autumn pasture. Ruminal fermentation of autumn pasture also had an increased acetate-to-propionate ratio compared with spring pasture. Monensin treatment acted consistently across seasons by increasing the proportion of propionate and decreasing the proportion of acetate in ruminal fluid. Key Words: Digestion, Monensin, Pastures, Rumen, Seasons, Sheep

Published
2001

24. Significant differences in incubation times in sheep infected with bovine spongiform encephalopathy result from variation at codon 141 in the PRNP gene

Author

Tan, B. C., Blanco, A. R. A., Houston, E.F., Stewart, P., Goldmann, W., Gill, A. C., de Wolf, C., Manson, J. C., and McCutcheon, S.

Subjects
animal diseases, nervous system diseases
Abstract

The susceptibility of sheep to prion infection is linked to variation in the PRNP gene, which\ud encodes the prion protein. Common polymorphisms occur at codons 136, 154 and 171. Sheep\ud which are homozygous for the A136R154Q171 allele are the most susceptible to bovine spongiform\ud encephalopathy (BSE). The effect of other polymorphisms on BSE susceptibility is unknown. We\ud orally infected ARQ/ARQ Cheviot sheep with equal amounts of BSE brain homogenate and a\ud range of incubation periods was observed. When we segregated sheep according to the amino\ud acid (L or F) encoded at codon 141 of the PRNP gene, the shortest incubation period was\ud observed in LL141 sheep, whilst incubation periods in FF141 and LF141 sheep were significantly\ud longer. No statistically significant differences existed in the expression of total prion protein or the\ud disease-associated isoform in BSE-infected sheep within each genotype subgroup. This\ud suggested that the amino acid encoded at codon 141 probably affects incubation times through\ud direct effects on protein misfolding rates.

Published
2012

25. All clinically-relevant blood components transmit prion disease following a single blood transfusion: a sheep model of vCJD

Author

McCutcheon, S., Alejo Blanco, A.R., Houston, E.F., de Wolf, C., Tan, B.C., Smith, A., Groschup, M.H., Hunter, N., Hornsey, V.S., MacGregor, I.R., Prowse, C. V., Turner, M., and Manson, J.C.

Subjects
mental disorders, nervous system diseases
Abstract

Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion.

Published
2011

28. Prion Protein-specific antibodies that detect multiple TSE Agents with high sensitivity

Author

McCutcheon, S., Langeveld, J.P.M., Tan, B.C., Gill, A.C., de Wolf, C.A., Martin, S., Gonzalez, L., Alibhai, J., Alejo Blanco, A.R., Campbell, L., Hunter, N., Houston, E.F., McCutcheon, S., Langeveld, J.P.M., Tan, B.C., Gill, A.C., de Wolf, C.A., Martin, S., Gonzalez, L., Alibhai, J., Alejo Blanco, A.R., Campbell, L., Hunter, N., and Houston, E.F.

Abstract

This paper describes the generation, characterisation and potential applications of a panel of novel anti-prion protein monoclonal antibodies (mAbs). The mAbs were generated by immunising PRNP null mice, using a variety of regimes, with a truncated form of recombinant ovine prion protein spanning residues 94–233. Epitopes of specific antibodies were mapped using solid-phase Pepscan analysis and clustered to four distinct regions within the PrP molecule. We have demonstrated the utility of these antibodies by use of Western blotting and immunohistochemistry in tissues from a range of different species affected by transmissible spongiform encephalopathy (TSE). In comparative tests against extensively-used and widely-published, commercially available antibodies, similar or improved results can be obtained using these new mAbs, specifically in terms of sensitivity of detection. Since many of these antibodies recognise native PrPC, they could also be applied to a broad range of immunoassays such as flow cytometry, DELFIA analysis or immunoprecipitation. We are using these reagents to increase our understanding of TSE pathogenesis and for use in potential diagnostic screening assays.

Published
2014

37. Proteinase K resistant material in ARR/VRQ sheep brain affected with classical scrapie is composed mainly of VRQ prion protein

Author

Jacobs, J.G., Bossers, A., Rezaei, H., Van Keulen, L., McCutcheon, S., Sklaviadis, T., Lantier, I., Berthon, P., Lantier, F., van Zijderveld, F.G., Langeveld, J.P.M., Jacobs, J.G., Bossers, A., Rezaei, H., Van Keulen, L., McCutcheon, S., Sklaviadis, T., Lantier, I., Berthon, P., Lantier, F., van Zijderveld, F.G., and Langeveld, J.P.M.

Abstract

Classical scrapie is a prion disease in sheep and goats. In sheep, susceptibility to disease is genetically influenced by single amino acid substitutions. Genetic breeding programs aimed at enrichment of arginine-171 (171R) prion protein (PrP), the so called ARR allele, in the sheep population have demonstrated to be effective in reducing the occurrence of classical scrapie in the field. Understanding the molecular basis for this reduced prevalence would serve the assessment of ARR-adaptation. The prion formation mechanism and conversion of PrP from the normal form (PrPC) to scrapie associated form (PrPSc) could play a key-role in this process. Therefore, we investigated whether the ARR allele substantially contributes to scrapie prion formation in naturally infected heterozygous 171Q/R animals. Two methods were applied to brain tissue of 171Q/R heterozygous sheep with natural scrapie to determine the relative amount of the 171R PrP fraction in PrPres, the proteinase K-resistant PrPSc core. An antibody test differentiating between 171Q and 171R PrP fragments showed that PrPres mostly was composed of the 171Q allelotype. Furthermore using a novel tool for prion research, endoproteinase Lys-C digested PrPres yielded substantial amounts of non-glycosylated and mono-glycosylated 114-188 PrP fragment. Following two-dimensional gel electrophoresis only marginal amounts (

Published
2011

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