Cost of providing cell-free DNA screening for Down syndrome in Finland using different strategies

Introduction A financial analysis is carried out to assess costs and benefits of providing cell-free DNA screening in Finland, using different strategies. Materials and methods Three cell-free DNA screening strategies are considered: Primary, all women; Secondary, those with positive Combined test; and Contingent, the 10-30% with the highest Combined test risks. Three costs are estimated: additional cost for 10,000 pregnancies compared with the Combined test; 'marginal' cost of avoiding a Down syndrome birth which occurs in a pregnancy that would have been false-negative using the Combined test; and marginal cost of preventing the iatrogenic loss of a non-Down syndrome birth which occurs in a pregnancy that would have been false-positive. Results Primary cell-free DNA will require additional funds of euro250,000. The marginal cost per Down syndrome birth avoided is considerably less than the lifetime medical and indirect cost; the marginal cost per unaffected iatrogenic fetal loss prevented is higher than one benefit measure but lower than another. If the ultrasound component of the Combined test is retained, as would be in Finland, the additional funds required rise to euro992,000. Secondary cell-free DNA is cost-saving as is a Contingent strategy with 10% selected but whilst when 20-30% costs rise they are much less than for the Primary strategy and are cost-beneficial. Conclusions When considering the place of cell-free DNA screening it is important to make explicit the additional and marginal costs of different screening strategies and the associated benefits. Under most assumptions the balance is favorable for Contingent screening.Peer reviewe

Effect of mammographic screening from age 40 years on breast cancer mortality (UK Age trial):final results of a randomised, controlled trial

Background: The appropriate age range for breast cancer screening remains a matter of debate. We aimed to estimate the effect of mammographic screening at ages 40-48 years on breast cancer mortality.Methods: We did a randomised, controlled trial involving 23 breast screening units across Great Britain. We randomly assigned women aged 39-41 years, using individual randomisation, stratified by general practice, in a 1:2 ratio, to yearly mammographic screening from the year of inclusion in the trial up to and including the calendar year that they reached age 48 years (intervention group), or to standard care of no screening until the invitation to their first National Health Service Breast Screening Programme (NHSBSP) screen at approximately age 50 years (control group). Women in the intervention group were recruited by postal invitation. Women in the control group were unaware of the study. The primary endpoint was mortality from breast cancers (with breast cancer coded as the underlying cause of death) diagnosed during the intervention period, before the participant's first NHSBSP screen. To study the timing of the mortality effect, we analysed the results in different follow-up periods. Women were included in the primary comparison regardless of compliance with randomisation status (intention-to-treat analysis). This Article reports on long-term follow-up analysis. The trial is registered with the ISRCTN registry, ISRCTN24647151.Findings: 160 921 women were recruited between Oct 14, 1990, and Sept 24, 1997. 53 883 women (33·5%) were randomly assigned to the intervention group and 106 953 (66·5%) to the control group. Between randomisation and Feb 28, 2017, women were followed up for a median of 22·8 years (IQR 21·8-24·0). We observed a significant reduction in breast cancer mortality at 10 years of follow-up, with 83 breast cancer deaths in the intervention group versus 219 in the control group (relative rate [RR] 0·75 [95% CI 0·58-0·97]; p=0·029). No significant reduction was observed thereafter, with 126 deaths versus 255 deaths occurring after more than 10 years of follow-up (RR 0·98 [0·79-1·22]; p=0·86).Interpretation: Yearly mammography before age 50 years, commencing at age 40 or 41 years, was associated with a relative reduction in breast cancer mortality, which was attenuated after 10 years, although the absolute reduction remained constant. Reducing the lower age limit for screening from 50 to 40 years could potentially reduce breast cancer mortality.</p

Role of Second-Trimester Genetic Sonography After Down Syndrome Screening

To estimate the effectiveness of second-trimester genetic sonography in modifying Down syndrome screening test results

Models for intuitionistic logic

In this work I develop a formalization (M-L) of Martin-Löf type theory, the main concern being an accurate definition of what it is to be a model of M-L. Using this definition, I proceed with actual models of M-L (mainly realizability models) to establish the relative consistency of many intuitionistic principles. In addition to their consistency I investigate their interrelationship. The strongest principles which are shown to be consistent with M-L are Church's Thesis and the Fan Theorem. The expressive power of M-L is used to formalize certain theories. The Theory of Real Numbers, an Intuitionistic Set Theory and Category Theory are all formalizable. The constructions of the latter are used to describe Kripke Models of M-L. Finally, I prove that the subsystem of M-L obtained by dropping the rules for cartesian products of types and without rules for universes of types has proof theoretic ordinal ωω.</p

Models for intuitionistic logic: (with special reference to 'Martin-Löf Type Theory')

In this work I develop a formalization (M-L) of Martin-Löf type theory, the main concern being an accurate definition of what it is to be a model of M-L. Using this definition, I proceed with actual models of M-L (mainly realizability models) to establish the relative consistency of many intuitionistic principles. In addition to their consistency I investigate their interrelationship. The strongest principles which are shown to be consistent with M-L are Church's Thesis and the Fan Theorem. The expressive power of M-L is used to formalize certain theories. The Theory of Real Numbers, an Intuitionistic Set Theory and Category Theory are all formalizable. The constructions of the latter are used to describe Kripke Models of M-L. Finally, I prove that the subsystem of M-L obtained by dropping the rules for cartesian products of types and without rules for universes of types has proof theoretic ordinal ωω