Improving the Detection, Assessment, Management, and Prevention of Delirium in Hospices (the DAMPen-D study): Feasibility Study of a flexible and scalable implementation strategy to deliver guideline-adherent delirium care

BackgroundDelirium is a complex condition, stressful for all involved. Although highly prevalent in palliative care settings, it remains underdiagnosed and associated with poor outcomes. Guideline-adherent delirium care may improve its detection, assessment, and management. AimTo inform a future definitive study that tests whether an implementation strategy designed to improve guideline-adherent delirium care in palliative care settings improves patient outcomes (reduced proportion of in-patient days with delirium).DesignWith Patient Involvement members, we conducted a feasibility study to assess the acceptability of and engagement with the implementation strategy by hospice staff (intervention), and whether clinical record data collection of process (e.g., guideline-adherent delirium care) and clinical outcomes (evidence of delirium using a validated chart-based instrument;) pre- and 12-weeks post-implementation of the intervention would be possible.Setting/participantsIn-patient admissions in three English hospices.Results Between June 2021-December 2022, clinical record data were extracted from 300 consecutive admissions. Despite data collection during COVID-19, target clinical record data collection (n=300) was achieved. Approximately two-thirds of patients had a delirium episode during in-patient stay at both timepoints. A 6% absolute reduction in proportion of delirium days in those with a delirium episode was observed. Post-implementation improvements in guideline-adherent metrics include: clinical delirium diagnosis 15% to 28%; delirium risk assessment 0% to 16%; screening on admission 7% to 35%.Conclusions Collection of data on delirium outcomes and guideline-adherence from clinical records is feasible. The signal of patient benefit supports formal evaluation in a large-scale study

A new state in 6He following the 7Li(γ,p)6He reaction

A broad excited state was observed in 6He with energy Ex=5+-1 MeV and width Gamma=3+-1 MeV, following the reaction 7Li(γ,p)6He. The state is consistent with a number of broad resonances predicted by recent cluster model calculations. The well-established reaction mechanism, combined with a simple and transparent analysis procedure confers considerable validity to this observation

Near-threshold measurement of the 4He(g,n) reaction

A near-threshold 4He(g,n) cross-section measurement has been performed at MAX-lab. Tagged photons from 23 < Eg < 42 MeV were directed toward a liquid 4He target, and neutrons were detected by time-of-flight in two liquid-scintillator arrays. Seven-point angular distributions were measured for eight photon energies. The results are compared to experimental data measured at comparable energies and Recoil-Corrected Continuum Shell Model, Resonating Group Method, and recent Hyperspherical-Harmonic Expansion calculations. The angle-integrated cross-section data is peaked at a photon energy of about 28 MeV, in disagreement with the value recommended by Calarco, Berman, and Donnelly in 1983.Comment: 10 pages, 3 figures, some revisions, submitted to Physics Letters

Prediction of fatal or near-fatal cardiac arrhythmia events in patients with depressed left ventricular function after an acute myocardial infarction†

To determine whether risk stratification tests can predict serious arrhythmic events after acute myocardial infarction (AMI) in patients with reduced left ventricular ejection fraction (LVEF <= 0.40). A total of 5869 consecutive patients were screened in 10 European centres, and 312 patients (age 65 +/- 11 years) with a mean LVEF of 31 +/- 6% were included in the study. Heart rate variability/turbulence, ambient arrhythmias, signal-averaged electrocardiogram (SAECG), T-wave alternans, and programmed electrical stimulation (PES) were performed 6 weeks after AMI. The primary endpoint was ECG-documented ventricular fibrillation or symptomatic sustained ventricular tachycardia (VT). To document these arrhythmic events, the patients received an implantable ECG loop-recorder. There were 25 primary endpoints (8.0%) during the follow-up of 2 years. The strongest predictors of primary endpoint were measures of heart rate variability, e.g. hazard ratio (HR) for reduced very-low frequency component ( <5.7 ln ms(2)) adjusted for clinical variables was 7.0 (95% CI: 2.4-20.3, P <0.001). Induction of sustained monomorphic VT during PES (adjusted HR = 4.8, 95% CI, 1.7-13.4, P = 0.003) also predicted the primary endpoint. Fatal or near-fatal arrhythmias can be predicted by many risk stratification methods, especially by heart rate variability, in patients with reduced LVEF after AM

The optimisation of stochastic grammars to enable cost-effective probabilistic structural testing

Abstract The effectiveness of statistical testing, a probabilistic structural testing strategy, depends on the characteristics of the probability distribution from which test inputs are sampled. Metaheuristic search has been shown to be a practical method of optimising the characteristics of such distributions. However, the applicability of the existing search-based algorithm is limited by the requirement that the software’s inputs must be a fixed number of ordinal values. In this paper we propose a new algorithm that relaxes this limitation and so permits the derivation of probability distributions for a much wider range of software. The representation used by the new algorithm is based on a stochastic grammar supplemented with two novel features: conditional production weights and the dynamic partitioning of ordinal ranges. We demonstrate empirically that a search algorithm using this representation can optimise probability distributions over complex input domains and thereby enable cost-effective statistical testing, and that the use of both conditional production weights and dynamic partitioning can be beneficial to the search process

CNTN6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders

Contactin genes CNTN5 and CNTN6 code for neuronal cell adhesion molecules that promote neurite outgrowth in sensory-motor neuronal pathways. Mutations of CNTN5 and CNTN6 have previously been reported in individuals with autism spectrum disorders (ASDs), but very little is known on their prevalence and clinical impact. In this study, we identified CNTN5 and CNTN6 deleterious variants in individuals with ASD. Among the carriers, a girl with ASD and attention-deficit/hyperactivity disorder was carrying five copies of CNTN5. For CNTN6, both deletions (6/1534 ASD vs 1/8936 controls; P=0.00006) and private coding sequence variants (18/501 ASD vs 535/33480 controls; P=0.0005) were enriched in individuals with ASD. Among the rare CNTN6 variants, two deletions were transmitted by fathers diagnosed with ASD, one stop mutation CNTN6W923X was transmitted by a mother to her two sons with ASD and one variant CNTN6P770L was found de novo in a boy with ASD. Clinical investigations of the patients carrying CNTN5 or CNTN6 variants showed that they were hypersensitive to sounds (a condition called hyperacusis) and displayed changes in wave latency within the auditory pathway. These results reinforce the hypothesis of abnormal neuronal connectivity in the pathophysiology of ASD and shed new light on the genes that increase risk for abnormal sensory perception in ASD

Prediction of nitrogen excretion from data on dairy cows fed a wide range of diets compiled in an intercontinental database: a meta-analysis

publishedVersio

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Optimizing therapy to prevent avoidable hospital admissions in multimorbid older adults (OPERAM): cluster randomised controlled trial

OBJECTIVETo examine the effect of optimising drug treatment on drug related hospital admissions in older adults with multimorbidity and polypharmacy admitted to hospital.DESIGNCluster randomised controlled trial.SETTING110 clusters of inpatient wards within university based hospitals in four European countries (Switzerland, Netherlands, Belgium, and Republic of Ireland) defined by attending hospital doctors.PARTICIPANTS2008 older adults (>= 70 years) with multimorbidity (>= 3chronic conditions) and polypharmacy (>= 5 drugs used long term).INTERVENTIONClinical staff clusters were randomised to usual care or a structured pharmacotherapy optimisation intervention performed at the individual level jointly by a doctor and a pharmacist, with the support of a clinical decision software system deploying the screening tool of older person's prescriptions and screening tool to alert to the right treatment (STOPP/START) criteria to identify potentially inappropriate prescribing.MAIN OUTCOME MEASUREPrimary outcome was first drug related hospital admission within 12 months.RESULTS2008 older adults (median nine drugs) were randomised and enrolled in 54 intervention clusters (963 participants) and 56 control clusters (1045 participants) receiving usual care. In the intervention arm, 86.1% of participants (n=789) had inappropriate prescribing, with a mean of 2.75 (SD 2.24) STOPP/START recommendations for each participant. 62.2% (n=491) had >= 1 recommendation successfully implemented at two months, predominantly discontinuation of potentially inappropriate drugs. In the intervention group, 211 participants (21.9%) experienced a first drug related hospital admission compared with 234 (22.4%) in the control group. In the intention-to-treat analysis censored for death as competing event (n=375, 18.7%), the hazard ratio for first drug related hospital admission was 0.95 (95% confidence interval 0.77 to 1.17). In the per protocol analysis, the hazard ratio for a drug related hospital admission was 0.91 (0.69 to 1.19). The hazard ratio for first fall was 0.96 (0.79 to 1.15; 237 v263 first falls) and for death was 0.90 (0.71 to 1.13; 172 v 203 deaths).CONCLUSIONSInappropriate prescribing was common in older adults with multimorbidity and polypharmacy admitted to hospital and was reduced through an intervention to optimise pharmacotherapy, but without effect on drug related hospital admissions. Additional efforts are needed to identify pharmacotherapy optimisation interventions that reduce inappropriate prescribing and improve patient outcomes.Algorithms and the Foundations of Software technolog