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| 2. |
- Abrahamsson, L, et al.
(författare)
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Continuous tumour growth models, lead time estimation and length bias in breast cancer screening studies
- 2020
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Ingår i: Statistical methods in medical research. - : SAGE Publications. - 1477-0334 .- 0962-2802. ; 29:2, s. 374-395
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Tidskriftsartikel (refereegranskat)abstract
- Comparisons of survival times between screen-detected and symptomatically detected breast cancer cases are subject to lead time and length biases. Whilst the existence of these biases is well known, correction procedures for these are not always clear, as are not the interpretation of these biases. In this paper we derive, based on a recently developed continuous tumour growth model, conditional lead time distributions, using information on each individual's tumour size, screening history and percent mammographic density. We show how these distributions can be used to obtain an individual-based (conditional) procedure for correcting survival comparisons. In stratified analyses, our correction procedure works markedly better than a previously used unconditional lead time correction, based on multi-state Markov modelling. In a study of postmenopausal invasive breast cancer patients, we estimate that, in large (>12 mm) tumours, the multi-state Markov model correction over-corrects five-year survival by 2–3 percentage points. The traditional view of length bias is that tumours being present in a woman's breast for a long time, due to being slow-growing, have a greater chance of being screen-detected. This gives a survival advantage for screening cases which is not due to the earlier detection by screening. We use simulated data to share the new insight that, not only the tumour growth rate but also the symptomatic tumour size will affect the sampling procedure, and thus be a part of the length bias through any link between tumour size and survival. We explain how this has a bearing on how observable breast cancer-specific survival curves should be interpreted. We also propose an approach for correcting survival comparisons for the length bias.
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| 3. |
- Degli Esposti, M., et al.
(författare)
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Can synthetic controls improve causal inference in interrupted time series evaluations of public health interventions?
- 2020
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Ingår i: International journal of epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 49:6, s. 2010-2020
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Tidskriftsartikel (refereegranskat)abstract
- Interrupted time series designs are a valuable quasi-experimental approach for evaluating public health interventions. Interrupted time series extends a single group pre-post comparison by using multiple time points to control for underlying trends. But history bias-confounding by unexpected events occurring at the same time of the intervention-threatens the validity of this design and limits causal inference. Synthetic control methodology, a popular data-driven technique for deriving a control series from a pool of unexposed populations, is increasingly recommended. In this paper, we evaluate if and when synthetic controls can strengthen an interrupted time series design. First, we summarize the main observational study designs used in evaluative research, highlighting their respective uses, strengths, biases and design extensions for addressing these biases. Second, we outline when the use of synthetic controls can strengthen interrupted time series studies and when their combined use may be problematic. Third, we provide recommendations for using synthetic controls in interrupted time series and, using a real-world example, we illustrate the potential pitfalls of using a data-driven approach to identify a suitable control series. Finally, we emphasize the importance of theoretical approaches for informing study design and argue that synthetic control methods are not always well suited for generating a counterfactual that minimizes critical threats to interrupted time series studies. Advances in synthetic control methods bring new opportunities to conduct rigorous research in evaluating public health interventions. However, incorporating synthetic controls in interrupted time series studies may not always nullify important threats to validity nor improve causal inference.
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| 4. |
- Randall, S. K., et al.
(författare)
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Discovery of a complex spiral-shell structure around the oxygen-rich AGB star GX Monocerotis
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 636
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Tidskriftsartikel (refereegranskat)abstract
- The circumstellar envelopes of asymptotic giant branch (AGB) stars exhibit a wide range of morphologies and chemical compositions that can be exploited to unravel their mass-loss history as well as binary status. Here, we present ALMA Band 6 observations centred upon the oxygen-rich, high mass-loss rate AGB star GX Mon. The resulting CO (2-1) map reveals an intricate, complex circumstellar spiral-arc structure consistent with hydrodynamical models for an AGB experiencing mass loss in a highly eccentric, close binary system with an orbital period of around 140 years. Several other transitions (including SiO, SiS, SO2, and CS) are detected in the data, however only the SO (5-4) map shows a similar - although much weaker - distribution as imaged for the CO.
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| 5. |
- Stepniewska, Kasia, et al.
(författare)
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Efficacy of single dose primaquine with artemisinin combination therapy on P. falciparum gametocytes and transmission : A WWARN individual patient meta-analysis.
- 2020
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 225:7, s. 1215-1226
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Since the World Health Organization recommended single low-dose (0.25mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant P. falciparum, several single-site studies have been conducted to assess its efficacy.METHODS: An individual patient meta-analysis to assess the gametocytocidal and transmission-blocking efficacy of PQ used in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (i) gametocyte carriage in the first two weeks post-treatment; (ii) the probability of infecting at least one mosquito or of a mosquito becoming infected.RESULTS: In 2,574 participants from fourteen studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytaemia on day 0 (Odds Ratio (OR)=0.22; 95%CI 0.17-0.28 and OR=0.12; 95%CI 0.08-0.16, respectively). The rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (p=0.010 for day 7). Addition of 0.25mg/kg PQ was associated with near complete prevention of transmission to mosquitoes.CONCLUSION: Primaquine's transmission-blocking effects are achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP.
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