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

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

Resolving uncertainties in foraminifera-based relative sea-level reconstruction: a case study from southern New Zealand

Since the pioneering work of David Scott and others in the 1970s and 1980s, foraminifera have been used to develop precise sea-level reconstructions from salt marshes around the world. In New Zealand, reconstructions feature rapid rates of sea-level rise during the early to mid 20th century. Here, we test whether infaunality, taphonomy, and sediment compaction influence these reconstructions. We find that surface (0 – 1 cm) and subsurface (3 – 4 cm) foraminiferal assemblages show a high degree of similarity. A landward shift in assemblage zones is consistent with recent sea-level rise and transgression. Changes associated with infaunality and taphonomy do not affect transfer function-based sea-level reconstructions. Applying a geotechnical modelling approach to the core from which sea-level changes were reconstructed, we demonstrate compaction is also negligible, resulting in maximum post-depositional lowering of 2.5 mm. We conclude that salt-marsh foraminifera are indeed highly accurate and precise indicators of past sea levels

Contrasting records of sea-level change in the eastern and western North Atlantic during the last 300 years

We present a new 300-year sea-level reconstruction from a salt marsh on the Isle of Wight (central English Channel, UK) that we compare to other salt-marsh and long tide-gauge records to examine spatial and temporal variability in sea-level change in the North Atlantic. Our new reconstruction identifies an overall rise in relative sea level (RSL) of c. 0.30 m since the start of the eighteenth century at a rate of . Error-in-variables changepoint analysis indicates that there is no statistically significant deviation from a constant rate within the dataset. The reconstruction is broadly comparable to other tide-gauge and salt-marsh records from the European Atlantic, demonstrating coherence in sea level in this region over the last 150–300 years. In contrast, we identify significant differences in the rate and timing of RSL with records from the east coast of North America. The absence of a strong late 19th/early 20th century RSL acceleration contrasts with that recorded in salt marsh sediments along the eastern USA coastline, in particular in a well-dated and precise sea-level reconstruction from North Carolina. This suggests that this part of the North Carolina sea level record represents a regionally specific sea level acceleration. This is significant because the North Carolina record has been used as if it were globally representative within semi-empirical parameterisations of past and future sea-level change. We conclude that regional-scale differences of sea-level change highlight the value of using several, regionally representative RSL records when calibrating and testing semi-empirical models of sea level against palaeo-records. This is because by using records that potentially over-estimate sea-level rise in the past such models risk over-estimating sea-level rise in the future