Reasons for physician-related variability in end-of-life decision-making in intensive care.

BACKGROUND: There is increasing evidence that the individual physician is the main factor influencing variability in end-of-life decision-making in intensive care units. End-of-life decisions are complex and should be adapted to each patient. Physician-related variability is problematic as it may result in unequal assessments that affect patient outcomes. The primary aim of this study was to investigate factors contributing to physician-related variability in end-of-life decision-making. METHOD: This is a qualitative substudy of a previously conducted study. In-depth thematic analysis of semistructured interviews with 19 critical care specialists from five different Swedish intensive care units was performed. Interviews took place between 1 February 2017 and 31 May 2017. RESULTS: Factors influencing physician-related variability consisted of different assessment of patient preferences, as well as intensivists' personality and values. Personality was expressed mainly through pace and determination in the decision-making process. Personal prejudices appeared in decisions, but few respondents had personally witnessed this. Avoidance of criticism and conflicts as well as individual strategies for emotional coping were other factors that influenced physician-related variability. Many respondents feared criticism for making their assessments, and the challenging nature of end-of-life decision-making lead to avoidance as well as emotional stress. CONCLUSION: Variability in end-of-life decision-making is an important topic that needs further investigation. It is imperative that such variability be acknowledged and addressed in a more formal and transparent manner. The ethical issues faced by intensivists have recently been compounded by the devastating impact of the COVID-19 pandemic, demonstrating in profound terms the importance of the topic.

Swedish intensivists' experiences and attitudes regarding end-of-life decisions.

BACKGROUND: To make end-of-life (EOL) decisions is a complex and challenging task for intensive care physicians and a substantial variability in this process has been previously reported. However, a deeper understanding of intensivists' experiences and attitudes regarding the decision-making process is still, to a large extent, lacking. The primary aim of this study was to address Swedish intensivists' experiences, beliefs and attitudes regarding decision-making pertaining to EOL decisions. Second, we aimed to identify underlying factors that may contribute to variability in the decision-making process. METHOD: This is a descriptive, qualitative study. Semi-structured interviews with nineteen intensivists from five different Swedish hospitals, with different ICU levels, were performed from 1 February 2017 to 31 May 2017. RESULTS: Intensivists strive to make end-of-life decisions that are well-grounded, based on sufficient information. Consensus with the patient, family and other physicians is important. Concurrently, decisions that are made with scarce information or uncertain medical prognosis, decisions made during on-call hours and without support from senior consultants cause concern for many intensivists. Underlying factors that contribute to the variability in decision-making are lack of continuity among senior intensivists, lack of needed support during on-call hours and disagreements with physicians from other specialties. There is also an individual variability primarily depending on the intensivist's personality. CONCLUSION: Swedish intensivists' wish to make end-of-life decisions based on sufficient information, medically certain prognosis and consensus with the patient, family, staff and other physicians. Swedish intensivists' experience a variability in end-of-life decisions, which is generally accepted and not questioned.

The Discovery of a LEMD2-Associated Nuclear Envelopathy with Early Progeroid Appearance Suggests Advanced Applications for AI-Driven Facial Phenotyping.

Over a relatively short period of time, the clinical geneticist's "toolbox" has been expanded by machine-learning algorithms for image analysis, which can be applied to the task of syndrome identification on the basis of facial photographs, but these technologies harbor potential beyond the recognition of established phenotypes. Here, we comprehensively characterized two individuals with a hitherto unknown genetic disorder caused by the same de novo mutation in LEMD2 (c.1436C>T;p.Ser479Phe), the gene which encodes the nuclear envelope protein LEM domain-containing protein 2 (LEMD2). Despite different ages and ethnic backgrounds, both individuals share a progeria-like facial phenotype and a distinct combination of physical and neurologic anomalies, such as growth retardation; hypoplastic jaws crowded with multiple supernumerary, yet unerupted, teeth; and cerebellar intention tremor. Immunofluorescence analyses of patient fibroblasts revealed mutation-induced disturbance of nuclear architecture, recapitulating previously published data in LEMD2-deficient cell lines, and additional experiments suggested mislocalization of mutant LEMD2 protein within the nuclear lamina. Computational analysis of facial features with two different deep neural networks showed phenotypic proximity to other nuclear envelopathies. One of the algorithms, when trained to recognize syndromic similarity (rather than specific syndromes) in an unsupervised approach, clustered both individuals closely together, providing hypothesis-free hints for a common genetic etiology. We show that a recurrent de novo mutation in LEMD2 causes a nuclear envelopathy whose prognosis in adolescence is relatively good in comparison to that of classical Hutchinson-Gilford progeria syndrome, and we suggest that the application of artificial intelligence to the analysis of patient images can facilitate the discovery of new genetic disorders.

Characterization of a Norwegian cherubism cohort; molecular genetic findings, oral manifestations and quality of life.

Bilateral multilocular radiolucencies of the mandible are the main feature of cherubism (OMIM #118400), a rare autosomal dominant disorder primarily affecting the jaw. Typically, symmetrical swelling of the lower face is evident from around three years of age and increases until puberty. The underlying radiolucent lesions consist of vascular fibrotic stroma with scattered multinuclear giant cells. By age 30 years the facial contours are often unremarkable. Missing and displaced teeth as well as premature tooth loss are characteristic. Diagnosis rests upon a combination of clinical, radiographic, histological and molecular findings. SH3BP2 is currently the only gene known to be associated with cherubism. This cross-sectional study describes oral manifestations, quality of life and results of mutation analysis of SH3BP2 in 11 females and 13 males ages five to 84 years with cherubism. One individual with molecularly confirmed Noonan syndrome was excluded from the cohort. Standard statistical tools were used to analyze quality of life data. Mutation analysis was positive in all 22 familial and negative in both sporadic cases. Disease manifestations in mutation carriers varied from none to severe. Although intra-familial variability was marked, we found no evidence of non-penetrance, and females were on average more severely affected than males. Dental sequelae were pronounced; adults lacked a mean of 13 teeth (range 2-28), 13 of 17 individuals aged 16 years and older had removable or fixed dentures and five had dental implants; implant survival rate was 79%. In spite of pronounced disease manifestations and dental sequelae, adult quality of life was good.