Description: Objective To identify existing prognostic delirium prediction models and evaluate their validity and statistical methodology in the older adult (≥60 years) acute hospital population. Design Systematic review. Data sources and methods PubMed, CINAHL, PsychINFO, SocINFO, Cochrane, Web of Science and Embase were searched from 1 January 1990 to 31 December 2016. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses and CHARMS Statement guided protocol development. Inclusion criteria: age 〉60 years, inpatient, developed/validated a prognostic delirium prediction model. Exclusion criteria: alcohol-related delirium, sample size ≤50. The primary performance measures were calibration and discrimination statistics. Two authors independently conducted search and extracted data. The synthesis of data was done by the first author. Disagreement was resolved by the mentoring author. Results The initial search resulted in 7,502 studies. Following full-text review of 192 studies, 33 were excluded based on age criteria (〈60 years) and 27 met the defined criteria. Twenty-three delirium prediction models were identified, 14 were externally validated and 3 were internally validated. The following populations were represented: 11 medical, 3 medical/surgical and 13 surgical. The assessment of delirium was often non-systematic, resulting in varied incidence. Fourteen models were externally validated with an area under the receiver operating curve range from 0.52 to 0.94. Limitations in design, data collection methods and model metric reporting statistics were identified. Conclusions Delirium prediction models for older adults show variable and typically inadequate predictive capabilities. Our review highlights the need for development of robust models to predict delirium in older inpatients. We provide recommendations for the development of such models.

Description: Recombinant soluble HIV-1 envelope glycoprotein (Env) SOSIP trimers are a design platform for inducing broadly neutralizing antibodies (bNAbs) by vaccination. To date, these and alternative designs of native-like trimers, given singly or in pairs, have not induced bNAbs in test animals such as rabbits or macaques. Here, we have evaluated whether trivalent and tetravalent combinations of SOSIP trimers from clades A, B, and C, delivered simultaneously or sequentially, induce better neutralizing antibody responses in rabbits than when given alone. None of the tested formulations led to the induction of bNAbs. We found that BG505 clade A trimers dominated the autologous NAb responses induced by combinations, which probably relates to the presence of immunodominant glycan holes on the BG505 trimer. Furthermore, autologous NAb responses to all individual trimers were reduced when they were delivered in combinations compared with when delivered alone, suggesting that immunogen interference had occurred. Finally, in a sequential regimen, a heterologous clade C trimer cross-boosted NAb responses that were primed by earlier immunizations with clade A and B trimers. Taken together, these findings should allow us to improve the design of immunization regimens based on native-like HIV-1 Env trimers. IMPORTANCE A successful HIV-1 vaccine most probably requires a trimeric envelope glycoprotein (Env) component, as Env is the only viral protein on the surface of the virus and therefore the only target for neutralizing antibodies. Native-like Env trimers can induce strain-specific neutralizing antibodies but not yet broadly neutralizing antibodies. To try to broaden the antibody response, we immunized rabbits with soluble native-like Env trimers from three different clades using monovalent, multivalent, and sequential regimens. We found that the neutralizing antibody response against each immunogen was reduced when the immunogens were delivered in combination or sequentially compared to the monovalent regimen. In contrast, when the Env trimers from different clades were delivered sequentially, the neutralizing antibody response could be cross-boosted. Although the combination of native-like Env trimers from different clades did not induce broadly neutralizing antibodies, the results provide clues on how to use native-like trimers in vaccination experiments.