Positive Scores on the 4AT Delirium Assessment Tool at Hospital Admission are Linked to Mortality, Length of Stay, and Home Time:Two-Centre Study of 82,770 Emergency Admissions

BACKGROUND: Studies investigating outcomes of delirium using large-scale routine data are rare. We performed a two-centre study using the 4 ‘A’s Test (4AT) delirium detection tool to analyse relationships between delirium and 30-day mortality, length of stay and home time (days at home in the year following admission). METHODS: The 4AT was performed as part of usual care. Data from emergency admissions in patients ≥65 years in Lothian, UK (n = 43,946) and Salford, UK (n = 38,824) over a period of [Formula: see text] 3 years were analysed using logistic regression models adjusted for age and sex. RESULTS: 4AT completion rates were 77% in Lothian and 49% in Salford. 4AT scores indicating delirium (≥4/12) were present in 18% of patients in Lothian, and 25% of patients in Salford. Thirty-day mortality with 4AT ≥4 was 5.5-fold greater than the 4AT 0/12 group in Lothian (adjusted odds ratio (aOR) 5.53, 95% confidence interval [CI] 4.99–6.13) and 3.4-fold greater in Salford (aOR 3.39, 95% CI 2.98–3.87). Length of stay was more than double in patients with 4AT scores of 1–3/12 (indicating cognitive impairment) or ≥ 4/12 compared with 4AT 0/12. Median home time at 1 year was reduced by 112 days (Lothian) and 61 days (Salford) in the 4AT ≥4 group (P < 0.001). CONCLUSIONS: Scores on the 4AT used at scale in practice are strongly linked with 30-day mortality, length of hospital stay and home time. The findings highlight the need for better understanding of why delirium is linked with poor outcomes and also the need to improve delirium detection and treatment

Delirium is under-reported in discharge summaries and in hospital administrative systems: a systematic review

Background Accurate recording of delirium in discharge summaries (DS) and hospital administrative systems (HAS) is critical for patient care. Objective To systematically review studies reporting the frequency of delirium documentation and coding in DS and HAS, respectively. Method We searched Medline, Embase, PsycINFO and Web of Science databases from inception to 23 June 2021. Eligibility criteria included requiring the term delirium in DS or HAS. Screening and full-text reviews were performed independently by two reviewers. Risk of bias (RoB) was assessed using the Effective Public Health Practice Project tool. Results The search yielded 7,910 results; 24 studies were included. The studies were heterogeneous in design and size (N=25 to 809,512). Mean age ranged from 57 to 84 years. Four studies reported only overall DS documentation and HAS coding in whole hospital or healthcare databases. Twenty studies used additional delirium ascertainment methods (e.g. chart review) in smaller patient subsets. Studies reported either DS figures only (N=8), HAS figures only (N=11), or both (N=5). Documentation rates in DS ranged from 0.1% to 64%. Coding rates in HAS ranged from 1.5% to 49%. Some studies explored the impact of race, and nurse versus physician practice. No significant differences were reported for race; one study reported that nurses showed higher documentation rates in DS relative to physicians. Most studies (N=22) had medium to high RoB. Conclusion Delirium is a common and serious medical emergency, yet studies show considerable under-documentation and under-coding in healthcare systems. This has important implications for patient care and service planning. Healthcare systems need to take action to reach satisfactory delirium documentation and coding rates

Teacher–researcher partnership in the translation and implementing of PALS (Peer‐Assisted Learning Strategies): An international perspective

Funding Information: We would like to thank the schools, teachers and students who have alongside us developed PALS for each international context outlined. Publisher Copyright: © 2022 The Authors. Journal of Research in Reading published by John Wiley & Sons Ltd on behalf of United Kingdom Literacy Association.Peer-Assisted Learning Strategies (PALS) is a class-wide structured supplementary paired reading programme to support learners with their reading (Fuchs et al., 1997). What remains at the core of implementing PALS in any given location is the co-creation with teachers to ensure PALS fits with that educational context. This paper discusses the involvement of teachers as co-creators in the process of adapting PALS in England, United Arab Emirates (UAE), Taiwan and Iceland. The aim is to demonstrate the importance of careful adaptation when implementing a programme adopted from another country. Each adaption used a different methodological approach to co-creation. For example, in England, field notes, informal conversations and interviews were utilised for co-creation. In Iceland, preschool and elementary teachers were instrumental in translating and adapting the PALS materials to the Icelandic context. From each adaption, the teachers supported the development of a literacy programme that was suitable for classroom use. In England, teachers' involvement resulted in the removal of the motivational point system. For the UAE context, PALS began in English to support second language learning, but the instructional routines were a good ‘fit’ for the school culture and were developed in Arabic. For the Taiwan context, PALS provided an empirical basis for a model of differentiated instruction to enhance the reading literacy of Chinese-speaking elementary students. In Iceland, teachers trained other teachers in PALS as a research-based and efficient approach to meeting diverse learning needs of students, especially those with Icelandic as an additional language. Careful adaptation, piloting and the involvement of key stakeholders is important for the successful implementation of a reading programme.Peer reviewe

Delirium is under-reported in discharge summaries and in hospital administrative systems: a systematic review

Background Accurate recording of delirium in discharge summaries (DS) and hospital administrative systems (HAS) is critical for patient care. Objective To systematically review studies reporting the frequency of delirium documentation and coding in DS and HAS, respectively. Method We searched Medline, Embase, PsycINFO and Web of Science databases from inception to 23 June 2021. Eligibility criteria included requiring the term delirium in DS or HAS. Screening and full-text reviews were performed independently by two reviewers. Risk of bias (RoB) was assessed using the Effective Public Health Practice Project tool. Results The search yielded 7,910 results; 24 studies were included. The studies were heterogeneous in design and size (N=25 to 809,512). Mean age ranged from 57 to 84 years. Four studies reported only overall DS documentation and HAS coding in whole hospital or healthcare databases. Twenty studies used additional delirium ascertainment methods (e.g. chart review) in smaller patient subsets. Studies reported either DS figures only (N=8), HAS figures only (N=11), or both (N=5). Documentation rates in DS ranged from 0.1% to 64%. Coding rates in HAS ranged from 1.5% to 49%. Some studies explored the impact of race, and nurse versus physician practice. No significant differences were reported for race; one study reported that nurses showed higher documentation rates in DS relative to physicians. Most studies (N=22) had medium to high RoB. Conclusion Delirium is a common and serious medical emergency, yet studies show considerable under-documentation and under-coding in healthcare systems. This has important implications for patient care and service planning. Healthcare systems need to take action to reach satisfactory delirium documentation and coding rates

The Delphi Delirium Management Algorithms. A practical tool for clinicians, the result of a modified Delphi expert consensus approach

Delirium is common in hospitalised patients, and there is currently no specific treatment. Identifying and treating underlying somatic causes of delirium is the first priority once delirium is diagnosed. Several international guidelines provide clinicians with an evidence-based approach to screening, diagnosis and symptomatic treatment. However, current guidelines do not offer a structured approach to identification of underlying causes. A panel of 37 internationally recognised delirium experts from diverse medical backgrounds worked together in a modified Delphi approach via an online platform. Consensus was reached after five voting rounds. The final product of this project is a set of three delirium management algorithms (the Delirium Delphi Algorithms), one for ward patients, one for patients after cardiac surgery and one for patients in the intensive care unit.</p

The Delphi Delirium Management Algorithms: A practical tool for clinicians, the result of a modified Delphi expert consensus approach

Delirium is common in hospitalised patients, and there is currently no specific treatment. Identifying and treating underlying somatic causes of delirium is the first priority once delirium is diagnosed. Several international guidelines provide clinicians with an evidence-based approach to screening, diagnosis and symptomatic treatment. However, current guidelines do not offer a structured approach to identification of underlying causes. A panel of 37 internationally recognised delirium experts from diverse medical backgrounds worked together in a modified Delphi approach via an online platform. Consensus was reached after five voting rounds. The final product of this project is a set of three delirium management algorithms (the Delirium Delphi Algorithms), one for ward patients, one for patients after cardiac surgery and one for patients in the intensive care unit

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10−5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10−17; including ADGC data, meta P = 5.0 × 10−21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10−14; including ADGC data, meta P = 1.2 × 10−16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10−4; including ADGC data, meta P = 8.6 × 10−9), CD33 (GERAD+, P = 2.2 × 10−4; including ADGC data, meta P = 1.6 × 10−9) and EPHA1 (GERAD+, P = 3.4 × 10−4; including ADGC data, meta P = 6.0 × 10−10)

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

Polygenic risk score in postmortem diagnosed sporadic early-onset Alzheimer’s disease

Sporadic early onset Alzheimer’s disease (sEOAD) exhibits the symptoms of late onset Alzheimer’s disease (LOAD) but lacks the familial aspect of the early onset familial form. The genetics of Alzheimer’s disease (AD) identifies APOEε4 to be the greatest risk factor; however, it is a complex disease involving both environmental risk factors and multiple genetic loci. Polygenic risk scores (PRS) accumulate the total risk of a phenotype in an individual based on variants present in their genome. We determined whether sEOAD cases had a higher PRS compared to controls. A cohort of sEOAD cases were genotyped on the NeuroX array and PRS were generated using PRSice. The target dataset consisted of 408 sEOAD cases and 436 controls. The base dataset was collated by the IGAP consortium, with association data from 17,008 LOAD cases and 37,154 controls, which can be used for identifying sEOAD cases due to having shared phenotype. PRS were generated using all common SNPs between the base and target dataset, PRS were also generated using only SNPs within a 500kb region surrounding the APOE gene. Sex and number of APOE ε2 or ε4 alleles were used as variables for logistic regression and combined with PRS. The results show that PRS is higher on average in sEOAD cases than controls, although there is still overlap amongst the whole cohort. Predictive ability of identifying cases and controls using PRSice was calculated with 72.9% accuracy, greater than the APOE locus alone (65.2%). Predictive ability was further improved with logistic regression, identifying cases and controls with 75.5% accuracy

A novel Alzheimer disease locus located near the gene encoding tau protein

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordAPOE ε4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ε4+ (10 352 cases and 9207 controls) and APOE ε4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ε4 status. Suggestive associations (P<1 × 10-4) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ε4+: 1250 cases and 536 controls; APOE ε4-: 718 cases and 1699 controls). Among APOE ε4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10-9). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ε4+ subjects (CR1 and CLU) or APOE ε4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10-7) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P≤1.3 × 10-8), frontal cortex (P≤1.3 × 10-9) and temporal cortex (P≤1.2 × 10-11). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10-6) and temporal cortex (P=2.6 × 10-6). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ε4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted