Decision-analytic evaluation of the comparative effectiveness and cost-effectiveness of strategies to prevent breast and ovarian cancer in German women with BRCA-1/2 mutations

Abstract Background Women with inherited mutations in the BRCA1 or BRCA2 genes have increased lifetime risks for developing breast and/or ovarian cancer and may develop these cancers around the age of 30 years. Therefore, prevention of breast and ovarian cancer in these women may need to start relatively early in life. In this study we systematically evaluate the long-term effectiveness and cost effectiveness of different prevention strategies for breast and ovarian cancer in women with BRCA-1/2 mutation in Germany. Methods A decision-analytic Markov model simulating lifetime breast and ovarian cancer development in BRCA-1/2 carriers was developed. Different strategies including intensified surveillance (IS), prophylactic bilateral mastectomy (PBM), and prophylactic bilateral salpingo-oophorectomy (PBSO) alone or in combination at different ages were evaluated. German clinical, epidemiological, and economic (in 2022 Euro) data were used. Outcomes included cancer incidences, mortality, life years (LYs), quality-adjusted life years (QALYs), and discounted incremental cost-effectiveness ratios (ICER). We adopted the German health-care system perspective and discounted costs and health effects with 3% annually. Results All intervention strategies are more effective and less costly than IS alone. Prevention with PBM plus PBSO at age 30 maximizes life expectancy with 6.3 LYs gained, whereas PBM at age 30 with delayed PBSO at age 35 improves quality of life with 11.1 QALYs gained, when compared to IS alone. A further delay of PBSO was associated with lower effectiveness. Both strategies are cost effective with ICERs significantly below 10,000 EUR/LYG or QALY. Conclusion Based on our results, PBM at age 30 plus PBSO between age 30 and 40 prolongs life and is cost effective in women with BRCA-1/2 mutations in Germany. Serial preventive surgeries with delayed PBSO potentially improve quality of life for women. However, delaying PBM and/or PBSO further may lead to increased mortality and reduced QALYs

A Systematic Review On Cost-effectiveness Studies Evaluating Ovarian Cancer Early Detection And Prevention Strategies

Ovarian cancer imposes a substantial health and economic burden. We systematically reviewed current health-economic evidence for ovarian cancer early-detection or prevention strategies. Accordingly, we searched relevant databases for cost-effectiveness studies evaluating ovarian cancer early-detection or prevention strategies. Study characteristics and results including quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICERs) were summarized in standardized evidence tables. Economic results were transformed into 2017 Euros. The included studies (N=33) evaluated ovarian cancer screening, risk-reducing interventions in women with heterogeneous cancer risks and genetic testing followed by risk-reducing interventions for mutation carriers. Multimodal screening with a risk-adjusted algorithm in postmenopausal women achieved ICERs of 9,800-81,400 Euros/QALY, depending on assumptions on mortality data extrapolation, costs, test performance and screening frequency. Cost-effectiveness of risk-reducing surgery in mutation carriers ranged from cost-saving to 59,000 Euros/QALY. Genetic testing plus risk-reducing interventions for mutation carriers ranged from cost-saving to 54,000 Euros/QALY in women at increased mutation risk. Our findings suggest that preventive surgery and genetic testing plus preventive surgery in women at high risk for ovarian cancer can be considered effective and cost-effective. In postmenopausal women from the general population, multimodal screening using a risk-adjusted algorithm may be cost-effective

Sexing Viking Age horses from burial and non-burial sites in Iceland using ancient DNA

© 2018 The Authors Horses are the most common grave goods found in Icelandic Viking Age graves. Horse skeletons have previously been sexed based on pelvis shape and the presence of canine teeth in male horses over 4–5 years of age. Morphological data has shown that all horses from Icelandic burials that were amenable to sexing were male. Yet the use of morphological methods to determine sex is problematic since they rely on finding a well-preserved pelvis and/or robust canine teeth. Furthermore, quantitative data underlying the features of the horse pelvis used for sexing is lacking and canine teeth have been reported to occur in mares. In this study we build upon and extend recently developed methodologies to make use of shotgun sequencing of ancient DNA (aDNA) for molecular sexing of Viking Age horse remains. With minimal sequencing effort we identified the sex of the largest collection (n = 22) of Viking Age Icelandic horses studied to date, sourced from both burial (n = 19) and non-burial (n = 3) sites. Our results revealed a male to female sex bias ratio of 18:1 in burial sites, versus 0:3 in non-burial sites. These findings support the significant over-representation of male horses in Viking Age graves in Iceland, yet show that –albeit rare– mares could also be selected for ritual burial in Viking Age Iceland. This cost-effective method provides statistical confidence to allow for sexing of highly fragmented archaeological specimens with low endogenous DNA content

Not a limitless resource: Ethics and guidelines for destructive sampling of archaeofaunal remains

With the advent of ancient DNA, as well as other methods such as isotope analysis, destructive sampling of archaeofaunal remains has increased much faster than the effort to collect and curate them. While there has been considerable discussion regarding the ethics of destructive sampling and analysis of human remains, this dialogue has not extended to archaeofaunal material. Here we address this gap and discuss the ethical challenges surrounding destructive sampling of materials from archaeofaunal collections. We suggest ways of mitigating the negative aspects of destructive sampling and present step-by-step guidelines aimed at relevant stakeholders, including scientists, holding institutions and scientific journals. Our suggestions are in most cases easily implemented without significant increases in project costs, but with clear long-term benefits in the preservation and use of zooarchaeological material.</p

Odour-mediated orientation of beetles is influenced by age, sex and morph

The behaviour of insects is dictated by a combination of factors and may vary considerably between individuals, but small insects are often considered en masse and thus these differences can be overlooked. For example, the cowpea bruchid Callosobruchus maculatus F. exists naturally in two adult forms: the active (flight) form for dispersal, and the inactive (flightless), more fecund but shorter-lived form. Given that these morphs show dissimilar biology, it is possible that they differ in odour-mediated orientation and yet studies of this species frequently neglect to distinguish morph type, or are carried out only on the inactive morph. Along with sex and age of individual, adult morph could be an important variable determining the biology of this and similar species, informing studies on evolution, ecology and pest management. We used an olfactometer with motion-tracking to investigate whether the olfactory behaviour and orientation of C. maculatus towards infested and uninfested cowpeas and a plant-derived repellent compound, methyl salicylate, differed between morphs or sexes. We found significant differences between the behaviour of male and female beetles and beetles of different ages, as well as interactive effects of sex, morph and age, in response to both host and repellent odours. This study demonstrates that behavioural experiments on insects should control for sex and age, while also considering differences between adult morphs where present in insect species. This finding has broad implications for fundamental entomological research, particularly when exploring the relationships between physiology, behaviour and evolutionary biology, and the application of crop protection strategies

Upstream Statin Therapy and Long-Term Recurrence of Atrial Fibrillation after Cardioversion: A Propensity-Matched Analysis

The relationship of statin therapy with recurrence of atrial fibrillation (AF) after cardioversion (CV) has been evaluated by several investigations, which provided conflicting results and particularly long-term data is scarce. We sought to examine whether upstream statin therapy is associated with long-term recurrence of AF after CV. This was a single-center registry study including consecutive AF patients (n = 454) undergoing CV. Cox regression models were performed to estimate AF recurrence comparing patients with and without statins. In addition, we performed a propensity score matched analysis with a 1:1 ratio. Statins were prescribed to 183 (40.3%) patients. After a median follow-up period of 373 (207–805) days, recurrence of AF was present in 150 (33.0%) patients. Patients receiving statins had a significantly lower rate of AF recurrence (log-rank p < 0.001). In univariate analysis, statin therapy was associated with a significantly reduced rate of AF recurrence (HR 0.333 (95% CI 0.225–0.493), p = 0.001), which remained significant after adjustment (HR 0.238 (95% CI 0.151–0.375), p < 0.001). After propensity score matching treatment with statins resulted in an absolute risk reduction of 27.5% for recurrent AF (21 (18.1%) vs. 53 (45.7%); p < 0.001). Statin therapy was associated with a reduced risk of long-term AF recurrence after successful cardioversion

Patterns of homozygosity in insular and continental goat breeds

Background: Genetic isolation of breeds may result in a significant loss of diversity and have consequences on health and performance. In this study, we examined the effect of geographic isolation on caprine genetic diversity patterns by genotyping 480 individuals from 25 European and African breeds with the Goat SNP50 BeadChip and comparing patterns of homozygosity of insular and nearby continental breeds. Results: Among the breeds analysed, number and total length of ROH varied considerably and depending on breeds, ROH could cover a substantial fraction of the genome (up to 1.6 Gb in Icelandic goats). When compared with their continental counterparts, goats from Iceland, Madagascar, La Palma and Ireland (Bilberry and Arran) displayed a significant increase in ROH coverage, ROH number and F ROH values (P value &lt; 0.05). Goats from Mediterranean islands represent a more complex case because certain populations displayed a significantly increased level of homozygosity (e.g. Girgentana) and others did not (e.g. Corse and Sarda). Correlations of number and total length of ROH for insular goat populations with the distance between islands and the nearest continental locations revealed an effect of extremely long distances on the patterns of homozygosity. Conclusions: These results indicate that the effects of insularization on the patterns of homozygosity are variable. Goats raised in Madagascar, Iceland, Ireland (Bilberry and Arran) and La Palma, show high levels of homozygosity, whereas those bred in Mediterranean islands display patterns of homozygosity that are similar to those found in continental populations. These results indicate that the diversity of insular goat populations is modulated by multiple factors such as geographic distribution, population size, demographic history, trading and breed management

Genome-Wide Association Analyses Highlight the Potential for Different Genetic Mechanisms for Litter Size Among Sheep Breeds

201