Five short screening tests in the detection of prevalent delirium: diagnostic accuracy and performance in different neurocognitive subgroups.

BACKGROUND: Delirium is prevalent and serious, yet remains under-recognised. Systematic screening could improve detection; however, consensus is lacking as to the best approach. Our aim was to assess the diagnostic accuracy of five simple cognitive tests in delirium screening: six-item cognitive impairment test (6-CIT), clock-drawing test, spatial span forwards, months of the year backwards (MOTYB) and intersecting pentagons (IPT). METHODS: A cross-sectional study was conducted. Within 36 h of admission, older medical patients were assessed for delirium using the Revised Delirium Rating Scale. They also underwent testing using the five cognitive tests outlined above. Sensitivity, specificity, positive and negative predictive values (PPV; NPV) were calculated for each method. Where appropriate, area under the receiver operating characteristic curve (AUC) was also calculated. RESULTS: Four hundred seventy patients were included, and 184 had delirium. Of the tests scored on a scale, the 6-CIT had the highest AUC (0.876), the optimum cut-off for delirium screening being 8/9 (sensitivity 89.9%, specificity 62.7%, NPV 91.2%, PPV 59.2%). The MOTYB, scored in a binary fashion, also performed well (sensitivity 84.6%, specificity 58.4%, NPV 87.4%, PPV 52.8). On discriminant analysis, 6-CIT was the only test to discriminate between patients with delirium and those with dementia (without delirium), Wilks' Lambda = 0.748, p < 0.001. CONCLUSION: The 6-CIT measures attention, temporal orientation and short-term memory and shows promise as a delirium screening test. This study suggests that it may also have potential in distinguishing the cognitive impairment of delirium from that of dementia in older patients. Copyright © 2016 John Wiley & Sons, Ltd.

X-ray crystal structure of a monoclonal antibody that binds to a major autoantigenic epitope on thyroid peroxidase.

Thyroid peroxidase (TPO) catalyzes the production of thyroid hormones and is a major autoantigen in autoimmune thyroid disease (AITD). It is believed that the majority of TPO autoantibodies bind to an immunodominant region consisting of two overlapping domains. Precise location of these domains would help our understanding of the interaction between TPO and TPO autoantibodies. 4F5 is a mouse monoclonal antibody (IgG1, kappa) that reacts with high affinity (2.6 x 10(10) mol/L(-1)) with one of the major autoantigenic regions on TPO. Heavy chain genes of 4F5 were from the VH1 germline gene family, germline genes for the D region could not be assigned and the J region was from the JH2 germline. Light chain genes were from Vkappa4/5 and Jkappa2, germline gene families. The Fab fragment of 4F5 was prepared by papain digestion, purified, crystallized, and the structure solved to 1.9 A using molecular replacement. The refined structure had an R factor of 19.5% and a free R factor of 23.9%. Deduced amino acid sequence and amino acid sequence obtained from diffraction analysis were compared and used to finalize the 4F5 Fab model. Structural analysis indicated that the structure of 4F5 is that of a standard Fab and its combining site is flat and is rich in tyrosine residues. Comparison of the structure of 4F5 with that of a TPO autoantibody Fab, TR1.9 suggests that the two antibodies are unlikely to recognise the same structures on TPO.