| 511. |
- Holmes, G. R., et al.
(författare)
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Cost-Effectiveness Modeling of Surgery Plus Adjuvant Endocrine Therapy Versus Primary Endocrine Therapy Alone in UK Women Aged 70 and Over With Early Breast Cancer
- 2021
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Ingår i: Value in Health. - : Elsevier BV. - 1098-3015. ; 24:6, s. 770-779
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Approximately 20% of UK women aged 70+ with early breast cancer receive primary endocrine therapy (PET) instead of surgery. PET reduces surgical morbidity but with some survival decrement. To complement and utilize a treatment dependent prognostic model, we investigated the cost-effectiveness of surgery plus adjuvant therapies versus PET for women with varying health and fitness, identifying subgroups for which each treatment is cost-effective. Methods: Survival outcomes from a statistical model, and published data on recurrence, were combined with data from a large, multicenter, prospective cohort study of over 3400 UK women aged 70+ with early breast cancer and median 52-month follow-up, to populate a probabilistic economic model. This model evaluated the cost-effectiveness of surgery plus adjuvant therapies relative to PET for 24 illustrative subgroups: Age {70, 80, 90} × Nodal status {FALSE (F), TRUE (T)} × Comorbidity score {0, 1, 2, 3+}. Results: For a 70-year-old with no lymph node involvement and no comorbidities (70, F, 0), surgery plus adjuvant therapies was cheaper and more effective than PET. For other subgroups, surgery plus adjuvant therapies was more effective but more expensive. Surgery plus adjuvant therapies was not cost-effective for 4 of the 24 subgroups: (90, F, 2), (90, F, 3), (90, T, 2), (90, T, 3). Conclusion: From a UK perspective, surgery plus adjuvant therapies is clinically effective and cost-effective for most women aged 70+ with early breast cancer. Cost-effectiveness reduces with age and comorbidities, and for women over 90 with multiple comorbidities, there is little cost benefit and a negative impact on quality of life. © 2021 ISPOR–The Professional Society for Health Economics and Outcomes Research
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| 512. |
- MacDonald, Amy M., et al.
(författare)
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Maternal and child biomonitoring strategies and levels of exposure in western Canada during the past seventeen years : The Alberta Biomonitoring Program
- 2022
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Ingår i: International journal of hygiene and environmental health. - : Elsevier BV. - 1438-4639 .- 1618-131X. ; 244
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Tidskriftsartikel (refereegranskat)abstract
- The Alberta Biomonitoring Program (ABP) was created in 2005 with the initial goal of establishing baseline levels of exposure to environmental chemicals in specific populations in the province of Alberta, Canada, and was later expanded to include multiple phases. The first two phases focused on evaluating exposure in pregnant women (Phase One, 2005) and children (Phase Two, 2004–2006) by analyzing residual serum specimens. Phase Three (2013–2016) employed active recruitment techniques to evaluate environmental exposures using a revised list of chemicals in paired serum pools from pregnant women and umbilical cord blood. These three phases of the program monitored a total of 226 chemicals in 285 pooled serum samples representing 31,529 individuals. Phase Four (2017–2020) of the ABP has taken a more targeted approach, focusing on the impact of the federal legalization of cannabis on the exposure of pregnant women in Alberta to cannabis, as well as tobacco and alcohol using residual prenatal screening serum specimens. Chemicals monitored in the first three phases include herbicides, neutral pesticides, metals, metalloids, and micronutrients, methylmercury, organochlorine pesticides, organophosphate pesticides, parabens, phthalate metabolites, perfluoroalkyl substances (PFAS), phenols, phytoestrogens, polybrominated compounds, polychlorinated biphenyls (PCBs), dioxins and furans, polycyclic aromatic hydrocarbons (PAHs), and tobacco biomarkers. Phase Four monitored six biomarkers of tobacco, alcohol, and cannabis. All serum samples were pooled. Mean concentrations and 95% confidence intervals (CIs) were calculated for the chemicals detected in ≥25% of the sample pools. cross the first three phases, the data from the ABP has provided baseline exposure levels for the chemicals in pregnant women, children, and newborns across the province. Comparison within and among the phases has highlighted differences in exposure levels with age, geography, seasonality, sample type, and time. The strategies employed throughout the program phases have been demonstrated to provide effective models for population biomonitoring.
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| 513. |
- Morgan, J. L., et al.
(författare)
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Breast cancer surgery in older women: outcomes of the Bridging Age Gap in Breast Cancer study
- 2020
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 107:11, s. 1468-1479
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Tidskriftsartikel (refereegranskat)abstract
- Background: Breast cancer surgery in older women is variable and sometimes non-standard owing to concerns about morbidity. Bridging the Age Gap in Breast Cancer is a prospective multicentre cohort study aiming to determine factors influencing treatment selection and outcomes from surgery for older patients with breast cancer. Methods: Women aged at least 70 years with operable breast cancer were recruited from 57 UK breast units between 2013 and 2018. Associations between patient and tumour characteristics and type of surgery in the breast and axilla were evaluated using univariable and multivariable analyses. Oncological outcomes, adverse events and quality-of-life (QoL) outcomes were monitored for 2 years. Results: Among 3375 women recruited, surgery was performed in 2816 patients, of whom 24 with inadequate data were excluded. Sixty-two women had bilateral tumours, giving a total of 2854 surgical events. Median age was 76 (range 70–95) years. Breast surgery comprised mastectomy in 1138 and breast-conserving surgery in 1716 procedures. Axillary surgery comprised axillary lymph node dissection in 575 and sentinel node biopsy in 2203; 76 had no axillary surgery. Age, frailty, dementia and co-morbidities were predictors of mastectomy (multivariable odds ratio (OR) for age 1·06, 95 per cent c.i. 1·05 to 1·08). Age, frailty and co-morbidity were significant predictors of no axillary surgery (OR for age 0·91, 0·87 to 0·96). The rate of adverse events was moderate (551 of 2854, 19·3 per cent), with no 30-day mortality. Long-term QoL and functional independence were adversely affected by surgery. Conclusion: Breast cancer surgery is safe in women aged 70 years or more, with serious adverse events being rare and no mortality. Age, ill health and frailty all influence surgical decision-making. Surgery has a negative impact on QoL and independence, which must be considered when counselling patients about choices. © 2020 The Authors. British Journal of Surgery published by John Wiley & Sons Ltd on behalf of BJS Society Ltd
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| 514. |
- Musuamba, F. T., et al.
(författare)
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Advanced Methods for Dose and Regimen Finding During Drug Development : Summary of the EMA/EFPIA Workshop on Dose Finding (London 4-5 December 2014)
- 2017
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Ingår i: CPT. - : Wiley. - 2163-8306. ; 6:7, s. 418-429
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Tidskriftsartikel (refereegranskat)abstract
- Inadequate dose selection for confirmatory trials is currently still one of the most challenging issues in drug development, as illustrated by high rates of late-stage attritions in clinical development and postmarketing commitments required by regulatory institutions. In an effort to shift the current paradigm in dose and regimen selection and highlight the availability and usefulness of well-established and regulatory-acceptable methods, the European Medicines Agency (EMA) in collaboration with the European Federation of Pharmaceutical Industries Association (EFPIA) hosted a multistakeholder workshop on dose finding (London 4-5 December 2014). Some methodologies that could constitute a toolkit for drug developers and regulators were presented. These methods are described in the present report: they include five advanced methods for data analysis (empirical regression models, pharmacometrics models, quantitative systems pharmacology models, MCP-Mod, and model averaging) and three methods for study design optimization (Fisher information matrix (FIM)-based methods, clinical trial simulations, and adaptive studies). Pairwise comparisons were also discussed during the workshop; however, mostly for historical reasons. This paper discusses the added value and limitations of these methods as well as challenges for their implementation. Some applications in different therapeutic areas are also summarized, in line with the discussions at the workshop. There was agreement at the workshop on the fact that selection of dose for phase III is an estimation problem and should not be addressed via hypothesis testing. Dose selection for phase III trials should be informed by well-designed dosefinding studies; however, the specific choice of method(s) will depend on several aspects and it is not possible to recommend a generalized decision tree. There are many valuable methods available, the methods are not mutually exclusive, and they should be used in conjunction to ensure a scientifically rigorous understanding of the dosing rationale.
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| 515. |
- Paz Duran, América, et al.
(författare)
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Bringing the Nature Futures Framework to life : creating a set of illustrative narratives of nature futures
- 2023
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Ingår i: Sustainability Science. - 1862-4065 .- 1862-4057.
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Tidskriftsartikel (refereegranskat)abstract
- To halt further destruction of the biosphere, most people and societies around the globe need to transform their relationships with nature. The internationally agreed vision under the Convention of Biological Diversity—Living in harmony with nature—is that “By 2050, biodiversity is valued, conserved, restored and wisely used, maintaining ecosystem services, sustaining a healthy planet and delivering benefits essential for all people”. In this context, there are a variety of debates between alternative perspectives on how to achieve this vision. Yet, scenarios and models that are able to explore these debates in the context of “living in harmony with nature” have not been widely developed. To address this gap, the Nature Futures Framework has been developed to catalyse the development of new scenarios and models that embrace a plurality of perspectives on desirable futures for nature and people. In this paper, members of the IPBES task force on scenarios and models provide an example of how the Nature Futures Framework can be implemented for the development of illustrative narratives representing a diversity of desirable nature futures: information that can be used to assess and develop scenarios and models whilst acknowledging the underpinning value perspectives on nature. Here, the term illustrative reflects the multiple ways in which desired nature futures can be captured by these narratives. In addition, to explore the interdependence between narratives, and therefore their potential to be translated into scenarios and models, the six narratives developed here were assessed around three areas of the transformative change debate, specifically, (1) land sparing vs. land sharing, (2) Half Earth vs. Whole Earth conservation, and (3) green growth vs. post-growth economic development. The paper concludes with an assessment of how the Nature Futures Framework could be used to assist in developing and articulating transformative pathways towards desirable nature futures.
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| 516. |
- Pereira, Henrique M., et al.
(författare)
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Scenarios for Global Biodiversity in the 21st Century
- 2010
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 330:6010, s. 1496-1501
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Forskningsöversikt (refereegranskat)abstract
- Quantitative scenarios are coming of age as a tool for evaluating the impact of future socioeconomic development pathways on biodiversity and ecosystem services. We analyze global terrestrial, freshwater, and marine biodiversity scenarios using a range of measures including extinctions, changes in species abundance, habitat loss, and distribution shifts, as well as comparing model projections to observations. Scenarios consistently indicate that biodiversity will continue to decline over the 21st century. However, the range of projected changes is much broader than most studies suggest, partly because there are major opportunities to intervene through better policies, but also because of large uncertainties in projections.
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| 517. |
- Pereira, Laura, 1985-, et al.
(författare)
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The living infinite : Envisioning futures for transformed human-nature relationships on the high seas
- 2023
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Ingår i: Marine Policy. - 0308-597X .- 1872-9460. ; 153
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Tidskriftsartikel (refereegranskat)abstract
- We find ourselves at a critical crossroads for the future governance of the high seas, but the perceived remoteness of the global ocean creates a psychological barrier for people to engage with it. Given challenges of over-exploitation, inequitable access and other sustainability and equity concerns, current ocean governance mech-anisms are not fit-for-purpose. This decade offers opportunities for direct impact on ocean governance, however, triggering a global transformation on how we use and protect the half of our planet requires a concerted effort that is guided by shared values and principles across regions and sectors. The aim of the series of workshops outlined in this paper, was to undertake a futures thinking process that could use the Nature Futures Framework as a mechanism to bring more transformative energy into how humans conceptualise the high seas and therefore how we aim to govern the ocean. We found that engaging with the future through science fiction narratives allowed a more radical appreciation of what could be and infusing science with artistic elements can inspire audiences beyond academia. Thus, creative endeavours of co-production that promote and encourage imagi-nation to address current challenges should be considered as important tools in the science-policy interface, also as a way to elicit empathetic responses. This workshop series was a first, and hopefully promising, step towards generating a more creative praxis in how we imagine and then act for a better future for the high seas.
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| 518. |
- Scherer, SW, et al.
(författare)
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Human chromosome 7: DNA sequence and biology
- 2003
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 300:5620, s. 767-772
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Tidskriftsartikel (refereegranskat)abstract
- DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate genes for developmental diseases including autism.
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| 519. |
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| 520. |
- Simmons, David, et al.
(författare)
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Effect of treatment for early gestational diabetes mellitus on neonatal respiratory distress : A secondary analysis of the TOBOGM study
- 2024
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Ingår i: British Journal of Obstetrics and Gynecology. - : John Wiley & Sons. - 1470-0328 .- 1471-0528.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To identify factors associated with neonatal respiratory distress (NRD) in early Gestational diabetes mellitus (eGDM).DESIGN: Nested case-control analysis of the TOBOGM trial.SETTING: Seventeen hospitals: Australia, Sweden, Austria and India. POPULATION: Pregnant women, <20 weeks' gestation, singleton, GDM risk factors.METHODS: Women with GDM risk factors completed an oral glucose tolerance test (OGTT) before 20 weeks: those with eGDM (WHO-2013 criteria) were randomised to immediate or deferred GDM treatment. Logistic regression compared pregnancies with/without NRD, and in pregnancies with NRD, those with/without high-dependency nursery admission for ≤24 h with those admitted for >24 h. Comparisons were adjusted for age, pre-pregnancy body mass index, ethnicity, smoking, primigravity, education and site. Adjusted odds ratios (95% CI) are reported.MAIN OUTCOME MEASURES: NRD definition: ≥4 h of respiratory support (supplemental oxygen or supported ventilation) postpartum. Respiratory distress syndrome (RDS): Supported ventilation and ≥24 h nursery stay.RESULTS: Ninety-nine (12.5%) of 793 infants had NRD; incidence halved (0.50, 0.31-0.79) if GDM treatment was started early. NRD was associated with Caesarean section (2.31, 1.42-3.76), large for gestational age (LGA) (1.83, 1.09-3.08) and shorter gestation (0.95, 0.93-0.97 per day longer). Among NRD infants, >24 h nursery-stay was associated with higher OGTT 1-h glucose (1.38, 1.08-1.76 per mmol/L). Fifteen (2.0%) infants had RDS.CONCLUSIONS: Identifying and treating eGDM reduces NRD risk. NRD is more likely with Caesarean section, LGA and shorter gestation. Further studies are needed to understand the mechanisms behind this eGDM complication and any long-term effects.
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