While ICU health care workers consistently identify a number of patient factors as important in decisions to withdraw care, there is extreme variability, which may be explained in part by the values of individual health care providers.

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Background Osteogenesis Imperfecta (OI) is characterized by bone fragility, and secondary features such as blue sclerae, dentinogenesis imperfecta, hearing loss, ligamentous laxity and short stature. It was thought that health-related quality of life (Qol) in patients with OI mainly depends on the severity of the skeletal deformities. However, it has become clear that additional factors can affect the Qol in all OI patients. In this study, we compare dimensions of QoL in adults with OI with a control population. Methods The SF-36 questionnaire was distributed among 330 adult patients with different OI types. Results were compared with two control populations from the Netherlands. Age-matched comparisons were made with one of the two control populations. Results The results were summarized in 8 domains: General and Mental Health, Physical and Social Function, Bodily Pain, Vitality, Physical and Emotional Role. General health and physical function in all types of OI are low compared to controls, except OI type 4 patients aged 55+ years. Bodily pain in OI patients appeared significantly worse than in the control population. There was no significant difference between OI types regarding pain and vitality. Vitality was only in the OI type 1 group significantly lower compared to controls. Patients with OI type 1 had a significantly reduced mental health. Social functioning appeared most effective in type 3 around 20 years of age. Conclusion Qol in adult patients with OI should be an important outcome measure in every OI clinic but the amount of baseline data on this subject in adults is sparse. This baseline measurement study is the largest study to date investigating Qol in OI patients. The mean scores indicate that people with OI generally have a significantly lower Qol than the control population. Further qualitative evaluation of Qol and its influencers is important for future management.

Osteogenesis imperfecta (OI) is characterized primarily by susceptibility to fractures with or without bone deformation. OI is genetically heterogeneous: over 20 genetic causes are recognized. We identified bi-allelic pathogenic KDELR2 variants as a cause of OI in four families. KDELR2 encodes KDEL endoplasmic reticulum protein retention receptor 2, which recycles ER-resident proteins with a KDEL-like peptide from the cis-Golgi to the ER through COPI retrograde transport. Analysis of patient primary fibroblasts showed intracellular decrease of HSP47 and FKBP65 along with reduced procollagen type I in culture media. Electron microscopy identified an abnormal quality of secreted collagen fibrils with increased amount of HSP47 bound to monomeric and multimeric collagen molecules. Mapping the identified KDELR2 variants onto the crystal structure of G. gallus KDELR2 indicated that these lead to an inactive receptor resulting in impaired KDELR2-mediated Golgi-ER transport. Therefore, in KDELR2-deficient individuals, OI most likely occurs because of the inability of HSP47 to bind KDELR2 and dissociate from collagen type I. Instead, HSP47 remains bound to collagen molecules extracellularly, disrupting fiber formation. This highlights the importance of intracellular recycling of ER-resident molecular chaperones for collagen type I and bone metabolism and a crucial role of HSP47 in the KDELR2-associated pathogenic mechanism leading to OI.Osteogenesis imperfecta (OI) (MIM: PS166200) is a clinically and genetically heterogeneous connective tissue disorder characterized by liability to fractures with or without bone deformation. Secondary features include blue sclerae, dentinogenesis imperfecta (DI), progressive hearing loss, and joint hypermobility. OI is divided into five clinical types, and it has long been estimated that 90% of individuals with OI have dominant pathogenic variants in COL1A1 (MIM: 120150) or COL1A2 (MIM: 120160) encoding the a1 and a2 chains of collagen type I. However, there is growing evidence that autosomal-recessive forms of OI can be more common in consanguineous populations. 1,2 OI type 1 (MIM: 166200) is usually caused by pathogenic variants resulting in haploinsufficiency of COL1A1, and OI type 5 (MIM: 610967) is always caused by the dominant c.À14C>T variant in the 5 0 UTR of IFITM5. 1 To date,

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