Making Medical Treatment Decisions for Unrepresented Patients in the ICU. An Official American Thoracic Society/American Geriatrics Society Policy Statement.

Background and Rationale: ICU clinicians regularly care for patients who lack capacity, an applicable advance directive, and an available surrogate decision-maker. Although there is no consensus on terminology, we refer to these patients as "unrepresented." There is considerable controversy about how to make treatment decisions for these patients, and there is significant variability in both law and clinical practice.Purpose and Objectives: This multisociety statement provides clinicians and hospital administrators with recommendations for decision-making on behalf of unrepresented patients in the critical care setting.Methods: An interprofessional, multidisciplinary expert committee developed this policy statement by using an iterative consensus process with a diverse working group representing critical care medicine, palliative care, pediatric medicine, nursing, social work, gerontology, geriatrics, patient advocacy, bioethics, philosophy, elder law, and health law.Main Results: The committee designed its policy recommendations to promote five ethical goals: 1) to protect highly vulnerable patients, 2) to demonstrate respect for persons, 3) to provide appropriate medical care, 4) to safeguard against unacceptable discrimination, and 5) to avoid undue influence of competing obligations and conflicting interests. These recommendations also are intended to strike an appropriate balance between excessive and insufficient procedural safeguards. The committee makes the following recommendations: 1) institutions should offer advance care planning to prevent patients at high risk for becoming unrepresented from meeting this definition; 2) institutions should implement strategies to determine whether seemingly unrepresented patients are actually unrepresented, including careful capacity assessments and diligent searches for potential surrogates; 3) institutions should manage decision-making for unrepresented patients using input from a diverse interprofessional, multidisciplinary committee rather than ad hoc by treating clinicians; 4) institutions should use all available information on the patient's preferences and values to guide treatment decisions; 5) institutions should manage decision-making for unrepresented patients using a fair process that comports with procedural due process; 6) institutions should employ this fair process even when state law authorizes procedures with less oversight.Conclusions: This multisociety statement provides guidance for clinicians and hospital administrators on medical decision-making for unrepresented patients in the critical care setting

Robin Hood: There Will Be Tights (A Medieval Drama Production)

Through the staging of this production, the English 312 (Medieval Drama) class developed an academic understanding of the original spirit of five Robin Hood plays & ballads and translated these in a lively manner into contemporary idiom for a modern audience. Students in this course have translated and staged ten very different productions since 1999, and this was our first attempt at popular folk theater. Robin Hood was a wildly popular figure during the late Middle Ages and the early Renaissance, and was often the May King in spring celebrations that combined mumming, music, dance, games, and action-packed improvisational theatrics; in our production, we tried to add some of that festive flavor in in between various scenes. These plays are slapstick and involve broad burlesque humor we might recognize from Monty Python or Benny Hill or modern British pantomime, and involve a certain level of audience participation; our actors performed in front, behind, to the side, and within the audience, and active spectator engagement was encouraged. During the Middle Ages, performances like these might include an opportunity to give alms to the poor, thus manifesting the type of generosity often attributed to Robin Hood. In our production, we invited charitable donations of cash, clothing, and non-perishable food stuffs for our local soup kitchen, and we gathered a substantial volume of such donations. Although we tend to think of Robin Hood as the Outlaw with a Heart of Gold who robs from the rich to give to the poor, this is a fairly late understanding of this figure; during the Middle Ages, on the other hand, Robin Hood provided a mischievous protagonist who inverted the power structure; our plays reflected this theme. In mythological terms, Robin is a Trickster: Like all Tricksters, he is impish and he inverts authority. Tricksters are also associated with fecundity and the rebirth of the natural world and growing season, and are sometimes androgynous. Thus Robin’s role as the May King underscores his identity as a Trickster. In our production, this ambiguity was manifested both by men in tights and by women cast as men: “Robin” is, after all, a gender-neutral name, and so we had two men and one woman playing Robin Hood. Indeed, the “Men in Tights” aspect of the Robin Hood tradition lends itself so readily to humor in our culture precisely because gender-bending and cross-dressing in slapstick comedy both reflects and subverts common perceptions and stereotypes regarding gender; the reason the Monty Python boys are so quick to put a lad in a skirt for a quick laugh is that such humor exposes in a non-threatening way basic tensions in our culture regarding gender roles. The humor in our play stemmed in part from exploiting such tensions

Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis.

BACKGROUND: Rare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes. METHODS: We did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11 744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses. FINDINGS: A locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55-2·08], p=5·13 × 10-15) and a second locus in HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 [1·42-1·71], p=7·65 × 10-20) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25-1·48], p=1·69 × 10-12; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-mediated inhibition of the enhancer reduced SOX17 expression. The HLA-DPA1/DPB1 rs2856830 genotype was strongly associated with survival. Median survival from diagnosis in patients with pulmonary arterial hypertension with the C/C homozygous genotype was double (13·50 years [95% CI 12·07 to >13·50]) that of those with the T/T genotype (6·97 years [6·02-8·05]), despite similar baseline disease severity. INTERPRETATION: This is the first study to report that common genetic variation at loci in an enhancer near SOX17 and in HLA-DPA1/DPB1 is associated with pulmonary arterial hypertension. Impairment of SOX17 function might be more common in pulmonary arterial hypertension than suggested by rare mutations in SOX17. Further studies are needed to confirm the association between HLA typing or rs2856830 genotyping and survival, and to determine whether HLA typing or rs2856830 genotyping improves risk stratification in clinical practice or trials. FUNDING: UK NIHR, BHF, UK MRC, Dinosaur Trust, NIH/NHLBI, ERS, EMBO, Wellcome Trust, EU, AHA, ACClinPharm, Netherlands CVRI, Dutch Heart Foundation, Dutch Federation of UMC, Netherlands OHRD and RNAS, German DFG, German BMBF, APH Paris, INSERM, Université Paris-Sud, and French ANR