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BOADICEA is a comprehensive risk prediction model for breast and/or ovarian cancer (BC/OC) and for carrying pathogenic variants (PVs) in cancer susceptibility genes. In addition to BRCA1 and BRCA2, BOADICEA version 6 includes PALB2, CHEK2, ATM, BARD1, RAD51C and RAD51D. To validate its predictions for these genes, we conducted a retrospective study including 2033 individuals counselled at clinical genetics departments in Denmark. All counselees underwent comprehensive genetic testing by next generation sequencing on suspicion of hereditary susceptibility to BC/OC. Likelihoods of PVs were predicted from information about diagnosis, family history and tumour pathology. Calibration was examined using the observed-to-expected ratio (O/E) and discrimination using the area under the receiver operating characteristics curve (AUC). The O/E was 1.11 (95% CI 0.97–1.26) for all genes combined. At sub-categories of predicted likelihood, the model performed well with limited misestimation at the extremes of predicted likelihood. Discrimination was acceptable with an AUC of 0.70 (95% CI 0.66–0.74), although discrimination was better for BRCA1 and BRCA2 than for the other genes in the model. This suggests that BOADICEA remains a valid decision-making aid for determining which individuals to offer comprehensive genetic testing for hereditary susceptibility to BC/OC despite suboptimal calibration for individual genes in this population. [ABSTRACT FROM AUTHOR]

This article shows how Barcoded Medication Administration technology institutionally organizes and rules the daily actions of nurses. Although it is widely assumed that Barcoded Medication Administration technology improves quality and safety by reducing the risk of human error, little research has been done on how this technology alters the work of nurses. Drawing on empirical and conceptual strategies of analysis, this qualitative study used certain tools of institutional ethnography to provide a view of how nurses negotiate Barcoded Medication Administration technology. The approach also uses elements from practice theory in order to discern how technology operates as a player on the field instead of being viewed as a 'mere' tool. A literature review preceded participant observation, whereby 17 nurses were followed and data on an orthopaedic ward were collected over a period of 9 months in 2011 and 2012. Barcoded Medication Administration technology relies on nurses' knowledge to mediate between the embedded logics of its design and the unpredictable needs of patients. Nurses negotiate their own professional logic of care in the form of moment-to-moment deliberations which subvert the ruling frame of the barcoded system and its objectified model of patient safety. The logic of Barcoded Medication Administration technology differs from the logic of nursing care, as this technology presumes medication distribution to be linear, even though nurses follow another line of actor-bound safety practices that we characterize as 'deliberations'. [ABSTRACT FROM AUTHOR]

Summary: We investigated the incidence trend in all major osteoporotic fractures for the whole country of Denmark between 1995 and 2010. Hip and other osteoporotic fractures declined for the general population and especially among women. But, we observed some increasing trend among men which needs more attention. Purpose: The trend in osteoporotic fractures is varied across the globe, and there is no updated information in the case of Denmark for all major osteoporotic fractures (MOF). Thus, we investigated the incidence rates (IRs) of MOF among 50+ adults in Denmark over the period 1995–2010. Methods: A series of cross-sectional analyses was done using the Danish National Health Service Register. Participants were 50+ adults in the full country Denmark with a MOF between 1995 and 2010. Gender- specific IRs of MOF per 10,000 person years (PYs) were estimated, in addition to IRs of individual fracture sites (hip, vertebrae, humerus, and radius/ulna), and women-to-men IR ratios for MOF. Results: A general decline was observed in IRs of MOF for the whole population (from 169.8 per 10,000 PYs in 1995, to 148.0 in 2010), which was more pronounced among women. Thirty-one and nineteen percent of decline was observed in hip fracture rates among women and men, respectively. The trend in clinical vertebral fracture was slightly decreasing for women and increasing for men. The women-to-men rate ratio of MOF decreased noticeably from 2.93 to 2.72 during study period. Conclusions: We observed declining trends in MOF and hip fracture for both sexes. However, a lower rate of decrease of hip fracture and an increasing trend in vertebral fracture was noticed among men. Considering our observations and the major economic burden that accompanies this devastating disease, more attention should be paid to MOF, especially in men. [ABSTRACT FROM AUTHOR]

Paget's Disease of Bone (PDB) is one of the most frequent metabolic bone diseases, affecting 1-5% of Western populations older than 55 years. Mutations in the sequestosome1 (SQSTM1) gene cause PDB in about one-third of familial PDB cases and in 2.4-9.3% of nonfamilial PDB cases, with the 1215C-->T (P392L) mutation being the most frequent one. We investigated whether a founder effect of the P392L SQSTM1 mutation was present in Belgian (n = 233), Dutch (n = 82), and Spanish (n = 64) patients without a PDB family history. First, direct sequencing analysis of exon 8 in these three populations showed that the P392L mutation occurred in 17 Belgian patients (7.3%), three Dutch patients without a family history (3.7%), and two Dutch patients with a family history. In the Spanish population, 15.6% of patients (n = 10) had the P392L mutation, including one homozygous mutant. This is by far the highest mutation frequency of all populations investigated so far. Next, we examined the genetic background of 33 mutated chromosomes by analyzing haplotypes. We genotyped four single-nucleotide polymorphisms (SNPs) in exon 6 and the 3'-untranslated region of SQSTM1 (rs4935C/T, rs4797G/A, rs10277T/C, and rs1065154G/T) and used software programs WHAP and PHASE to reconstruct haplotypes. Finally, allele-specific primers allowed us to assign the mutation to one of the two haplotypes from each individual. Sequencing results revealed that all 33 P392L mutations were on the CGTG (H2) haplotype. The chance to obtain this result due to 33 independent mutation events is 3.97 x 10(-14), providing strong evidence for a founder effect of the P392L SQSTM1 mutation in Belgian, Dutch, and Spanish patients with PDB. [ABSTRACT FROM AUTHOR]

Genetic conditions are often familial, but not all relatives receive counseling from the same institution. It is therefore necessary to ensure consistency in variant interpretation, counseling practices, and clinical follow up across health care providers. Furthermore, as new possibilities for gene-specific treatments emerge and whole genome sequencing becomes more widely available, efficient data handling and knowledge sharing between clinical laboratory geneticists and medical specialists in clinical genetics are increasingly important. In Denmark, these needs have been addressed through the establishment of collaborative national networks called Genetic Expert Networks or "GENets". These networks have enhanced patient and family care significantly by bringing together groups of experts in national collaborations. This promotes coordinated clinical care, the dissemination of best clinical practices, and facilitates the exchange of new knowledge. [ABSTRACT FROM AUTHOR]

Objectives: Clinical trials have shown a beneficial effect from biological disease-modifying antirheumatic drugs (bDMARDs) on hand or axial bone loss in patients with rheumatoid arthritis; however, it is unclear if this translates to a reduced fracture risk. We investigated the effect of bDMARDs on osteoporotic fracture risk compared to no biological treatment in rheumatoid arthritis.Methods: A cohort of patients with rheumatoid arthritis aged 18+ from DANBIO was linked to population-based health registries in Denmark (2006-2016). Adopting a prevalent new-user design, we matched bDMARD users to bDMARD-naïve patients using time-conditional propensity scores. The risk of incident osteoporotic fractures (including hip, vertebrae, humerus, and forearm) was estimated among the matched patients by Cox proportional hazards models.Results: Out of 24,678 patients with rheumatoid arthritis, 4265 bDMARD users were matched to the same number of bDMARD-naïve patients (mean age 56.2 years, 74% female). During follow-up, 229 osteoporotic fractures occurred among bDMARD users and 205 fractures among bDMARD-naïve patients (incidence rates 12.1 and 13.0 per 1000 person-years, respectively). The use of bDMARDs was not associated with a reduced risk of osteoporotic fractures among patients with rheumatoid arthritis (hazard ratio 0.97, 95% confidence interval 0.78-1.20), compared with no biological treatment. The risk estimates were similar for all osteoporotic fracture sites.Conclusion: We found no independent beneficial effect from using bDMARDs on reducing the risk of osteoporotic fractures in patients with rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

We investigated the incidence trend in all major osteoporotic fractures for the whole country of Denmark between 1995 and 2010. Hip and other osteoporotic fractures declined for the general population and especially among women. But, we observed some increasing trend among men which needs more attention., Purpose: The trend in osteoporotic fractures is varied across the globe, and there is no updated information in the case of Denmark for all major osteoporotic fractures (MOF). Thus, we investigated the incidence rates (IRs) of MOF among 50+ adults in Denmark over the period 1995-2010., Methods: A series of cross-sectional analyses was done using the Danish National Health Service Register. Participants were 50+ adults in the full country Denmark with a MOF between 1995 and 2010. Gender- specific IRs of MOF per 10,000 person years (PYs) were estimated, in addition to IRs of individual fracture sites (hip, vertebrae, humerus, and radius/ulna), and women-to-men IR ratios for MOF., Results: A general decline was observed in IRs of MOF for the whole population (from 169.8 per 10,000 PYs in 1995, to 148.0 in 2010), which was more pronounced among women. Thirty-one and nineteen percent of decline was observed in hip fracture rates among women and men, respectively. The trend in clinical vertebral fracture was slightly decreasing for women and increasing for men. The women-to-men rate ratio of MOF decreased noticeably from 2.93 to 2.72 during study period., Conclusions: We observed declining trends in MOF and hip fracture for both sexes. However, a lower rate of decrease of hip fracture and an increasing trend in vertebral fracture was noticed among men. Considering our observations and the major economic burden which accompanies this devastating disease, more attention should be paid to MOF, especially in men.