| 1. |
- Sakornsakolpat, Phuwanat, et al.
(författare)
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Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 494-505
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 x 10-8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.
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| 2. |
- Keogan, Katharine, et al.
(författare)
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Global phenological insensitivity to shifting ocean temperatures among seabirds
- 2018
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Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 8:4, s. 313-318
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Tidskriftsartikel (refereegranskat)abstract
- Reproductive timing in many taxa plays a key role in determining breeding productivity(1), and is often sensitive to climatic conditions(2). Current climate change may alter the timing of breeding at different rates across trophic levels, potentially resulting in temporal mismatch between the resource requirements of predators and their prey(3). This is of particular concern for higher-trophic-level organisms, whose longer generation times confer a lower rate of evolutionary rescue than primary producers or consumers(4). However, the disconnection between studies of ecological change in marine systems makes it difficult to detect general changes in the timing of reproduction(5). Here, we use a comprehensive meta-analysis of 209 phenological time series from 145 breeding populations to show that, on average, seabird populations worldwide have not adjusted their breeding seasons over time (-0.020 days yr(-1)) or in response to sea surface temperature (SST) (-0.272 days degrees C-1) between 1952 and 2015. However, marked between-year variation in timing observed in resident species and some Pelecaniformes and Suliformes (cormorants, gannets and boobies) may imply that timing, in some cases, is affected by unmeasured environmental conditions. This limited temperature-mediated plasticity of reproductive timing in seabirds potentially makes these top predators highly vulnerable to future mismatch with lower-trophic-level resources(2).
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| 3. |
- Anscombe, Elizabeth, et al.
(författare)
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Identification and Characterization of an Irreversible Inhibitor of CDK2
- 2015
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Ingår i: Chemistry and Biology. - : Elsevier BV. - 1074-5521 .- 1879-1301. ; 22:9, s. 1159-1164
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Tidskriftsartikel (refereegranskat)abstract
- Irreversible inhibitors that modify cysteine or lysine residues within a protein kinase ATP binding site offer, through their distinctive mode of action, an alternative to ATP-competitive agents. 4-((6-(Cyclo-hexylmethoxy)-9H-purin-2-yl) amino) benzenesulfonamide (NU6102) is a potent and selective ATP-competitive inhibitor of CDK2 in which the sulfonamide moiety is positioned close to a pair of lysine residues. Guided by the CDK2/NU6102 structure, we designed 6-(cyclohexylmethoxy)-N-(4-(vinylsulfonyl) phenyl)-9H- purin-2-amine (NU6300), which binds covalently to CDK2 as shown by a co-complex crystal structure. Acute incubation with NU6300 produced a durable inhibition of Rb phosphorylation in SKUT-1B cells, consistent with it acting as an irreversible CDK2 inhibitor. NU6300 is the first covalent CDK2 inhibitor to be described, and illustrates the potential of vinyl sulfones for the design of more potent and selective compounds.
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| 4. |
- Hohenschurz-Schmidt, David, et al.
(författare)
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Recommendations for the development, implementation, and reporting of control interventions in efficacy and mechanistic trials of physical, psychological, and self-management therapies : the CoPPS Statement
- 2023
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Ingår i: BMJ. British Medical Journal. - : BMJ Publishing Group Ltd. - 0959-8146 .- 0959-535X. ; 381, s. e072108-
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Tidskriftsartikel (refereegranskat)abstract
- Control interventions (often called "sham," "placebo," or "attention controls") are essential for studying the efficacy or mechanism of physical, psychological, and self-management interventions in clinical trials. This article presents core recommendations for designing, conducting, and reporting control interventions to establish a quality standard in non-pharmacological intervention research. A framework of additional considerations supports researchers' decision making in this context. We also provide a reporting checklist for control interventions to enhance research transparency, usefulness, and rigour.
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| 5. |
- ODonnell, Michael, et al.
(författare)
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Registered Replication Report: Dijksterhuis and van Knippenberg (1998)
- 2018
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Ingår i: Perspectives on Psychological Science. - : SAGE PUBLICATIONS LTD. - 1745-6916 .- 1745-6924. ; 13:2, s. 268-294
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Tidskriftsartikel (refereegranskat)abstract
- Dijksterhuis and van Knippenberg (1998) reported that participants primed with a category associated with intelligence (professor) subsequently performed 13% better on a trivia test than participants primed with a category associated with a lack of intelligence (soccer hooligans). In two unpublished replications of this study designed to verify the appropriate testing procedures, Dijksterhuis, van Knippenberg, and Holland observed a smaller difference between conditions (2%-3%) as well as a gender difference: Men showed the effect (9.3% and 7.6%), but women did not (0.3% and -0.3%). The procedure used in those replications served as the basis for this multilab Registered Replication Report. A total of 40 laboratories collected data for this project, and 23 of these laboratories met all inclusion criteria. Here we report the meta-analytic results for those 23 direct replications (total N = 4,493), which tested whether performance on a 30-item general-knowledge trivia task differed between these two priming conditions (results of supplementary analyses of the data from all 40 labs, N = 6,454, are also reported). We observed no overall difference in trivia performance between participants primed with the professor category and those primed with the hooligan category (0.14%) and no moderation by gender.
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| 6. |
- Sumaila, U. Rashid, et al.
(författare)
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WTO must ban harmful fisheries subsidies
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6567, s. 544-544
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Williams, David J., et al.
(författare)
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Comparability : Manufacturing, characterization and controls, report of a UK Regenerative Medicine Platform Pluripotent Stem Cell Platform Workshop, Trinity Hall, Cambridge, 14-15 September 2015
- 2016
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Ingår i: Regenerative Medicine. - : Future Medicine Ltd. - 1746-0751 .- 1746-076X. ; 11:5, s. 483-492
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Tidskriftsartikel (refereegranskat)abstract
- This paper summarizes the proceedings of a workshop held at Trinity Hall, Cambridge to discuss comparability and includes additional information and references to related information added subsequently to the workshop. Comparability is the need to demonstrate equivalence of product after a process change; a recent publication states that this 'may be difficult for cell-based medicinal products'. Therefore a well-managed change process is required which needs access to good science and regulatory advice and developers are encouraged to seek help early. The workshop shared current thinking and best practice and allowed the definition of key research questions. The intent of this report is to summarize the key issues and the consensus reached on each of these by the expert delegates.
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| 8. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 9. |
- Aczel, Balazs, et al.
(författare)
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Consensus-based guidance for conducting and reporting multi-analyst studies
- 2021
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Ingår i: eLIFE. - : eLife Sciences Publications. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Any large dataset can be analyzed in a number of ways, and it is possible that the use of different analysis strategies will lead to different results and conclusions. One way to assess whether the results obtained depend on the analysis strategy chosen is to employ multiple analysts and leave each of them free to follow their own approach. Here, we present consensus-based guidance for conducting and reporting such multi-analyst studies, and we discuss how broader adoption of the multi-analyst approach has the potential to strengthen the robustness of results and conclusions obtained from analyses of datasets in basic and applied research.
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| 10. |
- Bulkeley, Harriet, et al.
(författare)
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Governing climate change transnationally: assessing the evidence from a database of sixty initiatives
- 2012
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Ingår i: Environment and Planning C: Government and Policy. - : SAGE Publications. - 1472-3425 .- 0263-774X. ; 30:4, s. 591-612
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Tidskriftsartikel (refereegranskat)abstract
- With this paper we present an analysis of sixty transnational governance initiatives and assess the implications for our understanding of the roles of public and private actors, the legitimacy of governance 'beyond' the state, and the North-South dimensions of governing climate change. In the first part of the paper we examine the notion of transnational governance and its applicability in the climate change arena, reflecting on the history and emergence of transnational governance initiatives in this issue area and key areas of debate. In the second part of the paper we present the findings from the database and its analysis. Focusing on three core issues, the roles of public and private actors in governing transnationally, the functions that such initiatives perform, and the ways in which accountability for governing global environmental issues might be achieved, we suggest that significant distinctions are emerging in the universe of transnational climate governance which may have considerable implications for the governing of global environmental issues. In conclusion, we reflect on these findings and the subsequent consequences for the governance of climate change.
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| 11. |
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| 12. |
- Garg, Manik, et al.
(författare)
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Tumour gene expression signature in primary melanoma predicts long-term outcomes
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Adjuvant systemic therapies are now routinely used following resection of stage III melanoma, however accurate prognostic information is needed to better stratify patients. We use differential expression analyses of primary tumours from 204 RNA-sequenced melanomas within a large adjuvant trial, identifying a 121 metastasis-associated gene signature. This signature strongly associated with progression-free (HR = 1.63, p = 5.24 × 10−5) and overall survival (HR = 1.61, p = 1.67 × 10−4), was validated in 175 regional lymph nodes metastasis as well as two externally ascertained datasets. The machine learning classification models trained using the signature genes performed significantly better in predicting metastases than models trained with clinical covariates (pAUROC = 7.03 × 10−4), or published prognostic signatures (pAUROC < 0.05). The signature score negatively correlated with measures of immune cell infiltration (ρ = −0.75, p < 2.2 × 10−16), with a higher score representing reduced lymphocyte infiltration and a higher 5-year risk of death in stage II melanoma. Our expression signature identifies melanoma patients at higher risk of metastases and warrants further evaluation in adjuvant clinical trials.
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| 13. |
- Lewycka, Sonia, et al.
(författare)
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Effect of women's groups and volunteer peer counselling on rates of mortality, morbidity, and health behaviours in mothers and children in rural Malawi (MaiMwana) : a factorial, cluster-randomised controlled trial
- 2013
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 381:9879, s. 1721-35
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Women's groups and health education by peer counsellors can improve the health of mothers and children. We assessed their effects on mortality and breastfeeding rates in rural Malawi.METHODS: We did a 2×2 factorial, cluster-randomised trial in 185,888 people in Mchinji district. 48 equal-sized clusters were randomly allocated to four groups with a computer-generated number sequence. 24 facilitators guided groups through a community action cycle to tackle maternal and child health problems. 72 trained volunteer peer counsellors made home visits at five timepoints during pregnancy and after birth to support breastfeeding and infant care. Primary outcomes for the women's group intervention were maternal, perinatal, neonatal, and infant mortality rates (MMR, PMR, NMR, and IMR, respectively); and for the peer counselling were IMR and exclusive breastfeeding (EBF) rates. Analysis was by intention to treat. The trial is registered as ISRCTN06477126.FINDINGS: We monitored outcomes of 26,262 births between 2005 and 2009. In a factorial model adjusted only for clustering and the volunteer peer counselling intervention, in women's group areas, for years 2 and 3, we noted non-significant decreases in NMR (odds ratio 0.93, 0.64-1.35) and MMR (0.54, 0.28-1.04). After adjustment for parity, socioeconomic quintile, and baseline measures, effects were larger for NMR (0.85, 0.59-1.22) and MMR (0.48, 0.26-0.91). Because of the interaction between the two interventions, a stratified analysis was done. For women's groups, in adjusted analyses, MMR fell by 74% (0.26, 0.10-0.70), and NMR by 41% (0.59, 0.40-0.86) in areas with no peer counsellors, but there was no effect in areas with counsellors (1.09, 0.40-2.98, and 1.38, 0.75-2.54). Factorial analysis for the peer counselling intervention for years 1-3 showed a fall in IMR of 18% (0.82, 0.67-1.00) and an improvement in EBF rates (2.42, 1.48-3.96). The results of the stratified, adjusted analysis showed a 36% reduction in IMR (0.64, 0.48-0.85) but no effect on EBF (1.18, 0.63-2.25) in areas without women's groups, and in areas with women's groups there was no effect on IMR (1.05, 0.82-1.36) and an increase in EBF (5.02, 2.67-9.44). The cost of women's groups was US$114 per year of life lost (YLL) averted and that of peer counsellors was $33 per YLL averted, using stratified data from single intervention comparisons.INTERPRETATION: Community mobilisation through women's groups and volunteer peer counsellor health education are methods to improve maternal and child health outcomes in poor rural populations in Africa.
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| 14. |
- Matti, Simon, et al.
(författare)
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Values, beliefs and elite decision-making : The case of the Markbygden wind power development
- 2017
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Ingår i: Environmental Policy and Governance. - 1756-932X .- 1756-9338.
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Tidskriftsartikel (refereegranskat)abstract
- The outputs of political processes, i.e. policy, reflect rational cost-benefit calculations and power relationships, but are also shaped by the values and beliefs of policy actors, i.e. sovereigns, involved in the decision-making process. Values and beliefs affect how rational analyses and power relationships are understood and valued by sovereigns. This article suggests that understanding sovereigns’ values and beliefs is, however, necessary but insufficient for understanding concrete policy outputs, particularly in complex policy processes characterized by conflicting interests and values. In such cases, sovereigns are forced to prioritize among their values and beliefs. This article proposes a framework for studying how sovereigns prioritize among their values and beliefs. This framework is then used to study a complex policy process ridden with conflicts of interest and value-conflicts, which highlights the value and necessity of studying sovereigns, their values and beliefs, as well as the prioritizations they make among those values and beliefs.
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| 15. |
- Newell, David
(författare)
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Implementing Wind Power Policy : Institutional Frameworks and The Beliefs of Sovereigns
- 2018
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Ingår i: Land use policy. - : Elsevier. - 0264-8377 .- 1873-5754. ; 72, s. 16-26
-
Tidskriftsartikel (refereegranskat)abstract
- As the development of renewable energy remains prominent on the global policy agenda, international organizations and states have created policies intended to foster renewable energy development. With wind power projected to make the largest contribution to Europe’s renewable energy mix, the EU and EU member-states have attempted to create institutional frameworks favoring the development of wind power. In many cases, however, this has proven to be a necessary, but insufficient, condition for wind power development, making wind power policy an interesting case of policy implementation. Because of the inherently local nature of wind power development, the influence of local actors and institutions on the policy process must also be considered. This article suggests how a proposed theoretical development in the Advocacy Coalition Framework can be used to explain how concerns exogenous to local policy subsystems can affect local political decision-making and policy implementation. This approach is then used to examine the case of wind power development in Markbygden, Sweden and finds partial support for the effect of exogenous concerns on local political decision-making.
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| 16. |
- Newell, David
(författare)
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Locating Wind Power Policy : The Mechanics of Policy Subsystem Interactions
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation investigates the drivers behind political decision-making and the policy outcomes resulting from political decisions. It is proposed that in policy processes where political decisions are made at multiple levels or across multiple policy subsystems, policy outcomes can be understood in terms of the mechanisms (i.e. the processes or means) of interaction between multiple policy subsystems within which political decisions are made,resulting in more or less policy alignment between political decisions and policy outcomes. Policy network theory and policy subsystem theory are used separately as the basis forderiving two potential explanations for the mechanics of policy subsystem interactions. Because political decision-making authority in the wind power policy process in most Western democratic countries is spread across multiple policy subsystems, and because there has been significant variation between wind power policy outcomes between these countries, wind power policy processes in European Union countries are used as an empirical point-of-departure for exploring and illustrating the mechanics of policy subsystem interaction. A survey of the research on wind power development is used to illustrate and explore preliminary empirical indications of support for a framework derived from policy network theory. The case of political decisions made in Sweden over the past twenty years related to wind power development and production is used to illustrate and explore preliminary empirical indications of support for an explanation of policy subsystem interactions derived from the Advocacy Coalition Framework proposed here, as well as to explore the drivers of political decisions. This dissertation therefore contributes to understanding how policy subsystems interact. The dissertation contributes theoretically to the literature on policy processes generally, as well as to network/network management theory, and to the Advocacy Coalition Framework/policy subsystem theory. It also contributes to understanding two strategically chosen, embedded cases within the broader case study of political decision-making in the wind power policy process in Sweden.
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| 17. |
- Newell, David, et al.
(författare)
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Network management and renewable energy development : An analytical framework with empirical illustrations
- 2017
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Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 23, s. 199-210
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Tidskriftsartikel (refereegranskat)abstract
- The promotion of renewable energy is an essential component of energy and climate policies, but it is increasingly recognized that the transition toward an increased use of renewable energy sources constitutes a complex socio-political process. Policy is manifested in multi-actor networks beyond formal hierarchies and must therefore build on a comprehensive empirical understanding of the local collaboration processes that make investments in renewable energy projects possible. The objectives of this article are to: (a) propose an analytical framework within which the local development processes leading to renewable energy investments can be understood, in particular emphasizing the management of the relevant actor networks; and (b) provide empirical illustrations of the framework based on existing research. The article argues that, based on network management theory, some network structures can be expected to be more successful than others in facilitating renewable energy development, and we recognize the ways in which networks and their structure tend to be placed within certain institutional contexts of rules. By consulting selected research on wind power development at the local level we illustrate the added value of the proposed framework, and outline the seeds of a future research agenda.
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| 18. |
- Newell, David
(författare)
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Wind Power Policy Implementation : The Beliefs of Sovereigns, Policy Outputs and Policy Impacts
- 2017
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Ingår i: Environmental Politics. - 0964-4016 .- 1743-8934.
-
Tidskriftsartikel (refereegranskat)abstract
- As energy security, climate change and other environmental concerns remain prominent on the global agenda, international organizations and states have created policies intended to foster the development of renewable energy. With wind power projected to make the largest contribution to Europe’s renewable energy mix, the EU and EU member-states have created an institutional framework designed to that favor the development of wind power. While some states have been successful in reaching their renewable energy goals, others have been less so. This article seeks to understand the reasons why states are successful in achieving their intended policy outcomes despite the inherent difficulties in implementing policy. Using the Advocacy Coalition Framework as a point-of-departure, this article will explore the relationship between the beliefs of national lawmakers, policy outputs and policy impacts, as well as how these relationships can help explain wind power policy implementation.
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| 19. |
- Newell, Felicity, et al.
(författare)
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Whole-genome landscape of mucosal melanoma reveals diverse drivers and therapeutic targets
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Knowledge of key drivers and therapeutic targets in mucosal melanoma is limited due to the paucity of comprehensive mutation data on this rare tumor type. To better understand the genomic landscape of mucosal melanoma, here we describe whole genome sequencing analysis of 67 tumors and validation of driver gene mutations by exome sequencing of 45 tumors. Tumors have a low point mutation burden and high numbers of structural variants, including recurrent structural rearrangements targeting TERT, CDK4 and MDM2. Significantly mutated genes are NRAS, BRAF, NF1, KIT, SF3B1, TP53, SPRED1, ATRX, HLA-A and CHD8. SF3B1 mutations occur more commonly in female genital and anorectal melanomas and CTNNB1 mutations implicate a role for WNT signaling defects in the genesis of some mucosal melanomas. TERT aberrations and ATRX mutations are associated with alterations in telomere length. Mutation profiles of the majority of mucosal melanomas suggest potential susceptibility to CDK4/6 and/or MEK inhibitors.
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| 20. |
- Newell, Marie-Louise, et al.
(författare)
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Detection of virus in vertically exposed HIV-antibody-negative children
- 1996
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Ingår i: The Lancet. - 1474-547X. ; 347:8996, s. 213-215
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Tidskriftsartikel (refereegranskat)abstract
- Background. HIV-infected mothers can transmit their infection to their children in utero or at delivery (vertical transmission). There have been cases of children who were reported as acquiring infection vertically and later clearing the infection. We report the frequency of this phenomenon in a European cohort study. Methods. In four centres of the European Collaborative Study of children born to HIV-infected mothers, 299 children became HIV-antibody-negative and 264 of these had been followed up with virus culture and PCR for viral DNA at least once. Findings. Nine of the 264 children were positive by virus culture or PCR, and subsequently seroreverted. Two of the nine tested virus-positive after they became antibody negative. Six cases were virus-positive early in life and became negative thereafter, which is consistent with clearance of infection. The pattern was less clear in the other three. The nine cases had had their last virus test at age 16-101 months. All nine children had been bottlefed only. Eight had been delivered vaginally. The children had no HIV-related symptoms and received no anti-HIV treatments. Based on only those children who had two or more positive virological tests, we estimate that 2.7% (6/219) cleared or 'tolerated' the virus. Interpretation. The detection of virus or viral DNA in 'uninfected' children born to HIV-infected mothers was rare and was not associated with clinical disease or immunological abnormalities. The timing of samples will affect the documentation of clearance since, in uninfected children of HIV-positive mothers who cleared the virus, viraemia was intermittent. Current paediatric opinion is to inform parents of children who serorevert that the child is not HIV-infected.
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| 21. |
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| 22. |
- Sosnoff, Jacob J., et al.
(författare)
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Coherence of EMG activity and single motor unit discharge patterns in human rhythmical force production.
- 2005
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 158:2, s. 301-310
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to examine the modulation of the motor neuronal pool as a function of task dynamics. Specifically, we investigated the effects of task frequency on the single motor unit discharge pattern, electromyogram (EMG) activity and effector force output. Myoelectric activity and effector force were recorded while young adults isometrically abducted their first dorsal interosseus at five sinusoidal targets (0.5 Hz, 1 Hz, 2 Hz, 3Hz and 4 Hz) and at two force levels (5% and 25% maximum voluntary contraction (MVC)). Individual motor unit spike trains were isolated from the EMG. Auto-spectral and coherence analyses were performed on the force output, EMG and motor unit spike trains. The frequency of maximal coherence between the EMG and force output closely corresponded to the target frequency in all conditions. There was a broadband distribution of power with multiple peaks in the EMG and motor unit spectrums in the 0.5 Hz and 1Hz targets. However, the EMG and motor unit spectrums in the 2 Hz, 3Hz and 4Hz targets were characterized by an increasingly narrower band of activity with one dominant peak that closely corresponded to the target. There is high coherence between EMG output and target force frequency, but the relative contribution of the fast and slow neuromuscular bands are differentially influenced by the task frequency. The rhythmical organization of neuromuscular output in the 0.5 Hz task is relatively broadband and similar to that shown previously for constant level force output. The frequency structure of neuromuscular organization becomes increasingly more narrowband as the frequency of the target increases (2–4 Hz). The modulation of the motor neuronal pool is adaptive and depends on the relative contribution of feedback and feedforward control processes, which are driven by the task demands.
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| 23. |
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| 24. |
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| 25. |
- Wolin, Edward M., et al.
(författare)
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Phase III study of pasireotide long-acting release in patients with metastatic neuroendocrine tumors and carcinoid symptoms refractory to available somatostatin analogues
- 2015
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Ingår i: Drug Design, Development and Therapy. - 1177-8881. ; 9, s. 5075-5086
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Tidskriftsartikel (refereegranskat)abstract
- In a randomized, double-blind, Phase III study, we compared pasireotide long-acting release (pasireotide LAR) with octreotide long-acting repeatable (octreotide LAR) in managing carcinoid symptoms refractory to first-generation somatostatin analogues. Adults with carcinoid tumors of the digestive tract were randomly assigned (1:1) to receive pasireotide LAR (60 mg) or octreotide LAR (40 mg) every 28 days. Primary outcome was symptom control based on frequency of bowel movements and flushing episodes. Objective tumor response was a secondary outcome. Progression-free survival (PFS) was calculated in a post hoc analysis. Adverse events were recorded. At the time of a planned interim analysis, the data monitoring committee recommended halting the study because of a low predictive probability of showing superiority of pasireotide over octreotide for symptom control (n=43 pasireotide LAR, 20.9%; n=45 octreotide LAR, 26.7%; odds ratio, 0.73; 95% confidence interval [CI], 0.27-1.97; P=0.53). Tumor control rate at month 6 was 62.7% with pasireotide and 46.2% with octreotide (odds ratio, 1.96; 95% CI, 0.89-4.32; P=0.09). Median (95% CI) PFS was 11.8 months (11.0 - not reached) with pasireotide versus 6.8 months (5.6 - not reached) with octreotide (hazard ratio, 0.46; 95% CI, 0.20-0.98; P=0.045). The most frequent drug-related adverse events (pasireotide vs octreotide) included hyperglycemia (28.3% vs 5.3%), fatigue (11.3% vs 3.5%), and nausea (9.4% vs 0%). We conclude that, among patients with carcinoid symptoms refractory to available somatostatin analogues, similar proportions of patients receiving pasireotide LAR or octreotide LAR achieved symptom control at month 6. Pasireotide LAR showed a trend toward higher tumor control rate at month 6, although it was statistically not significant, and was associated with a longer PFS than octreotide LAR.
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| 26. |
- Kanai, M, et al.
(författare)
-
- 2023
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swepub:Mat__t
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