National Institute for Clinical Excellence and its value judgments

The National Institute for Clinical Excellence (NICE) offers health professionals in England and Wales advice on providing NHS patients with the highest attainable standards of care. NICE gives guidance on individual health technologies, the management of specific conditions, and the safety and efficacy of interventional diagnostic and therapeutic procedures. Guidance is based on the best available evidence. The evidence may not, however, be very good and is rarely complete. Those responsible for formulating the NICE’s advice therefore have to make judgments both about what is good and bad in the available science (scientific value judgments) and about what is good for society (social value judgments). In this article we focus on the scientific and social judgments forming the crux of the institute’s assessment of cost effectiveness. Scientific value judgments and those relating to clinical effectiveness are considered elsewhere

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

All-Arthroscopic Double-Bundle Coracoclavicular Ligament Reconstruction Using Autogenous Semitendinosus Graft: A New Technique

We present our novel arthroscopic anatomic double-bundle coracoclavicular ligament reconstruction technique using a semitendinosus tendon autograft. The dorsal limb of the graft is positioned around the dorsal edge of the clavicle, re-creating the conoid ligament. The anterior limb proceeds superiorly and re-creates the trapezoid ligament. The solution effectively stabilizes the acromioclavicular joint and prevents anterior posterior translation. This new arthroscopic double-bundle coracoclavicular joint reconstruction is an effective and reliable method in stabilizing the clavicle and neutralizing the anterior-posterior translation, and we find it to be technically practical for the surgeon