Predicting patient-reported stroke outcomes: a validation of the six simple variable prognostic model.

BACKGROUND: Case-mix represents the range of disease severity and baseline characteristics that may be the cause of variation in outcomes between individuals and populations. Adjustment for case-mix is therefore important to allow meaningful comparison of healthcare outcomes. The best available case-mix adjustment model for stroke (the Six Simple Variable [SSV] model) was developed to adjust the hard endpoints of independent survival, survival and alive and living at home. There is increasing interest in the measurement of patient-reported outcomes through self-completed questionnaires, though there are currently no robust adjustment models for any such outcome. We aimed to determine whether the SSV prognostic model derived to predict 6-month post-stroke independent survival has wider utility in case-mix adjustment of a patient-reported functional outcome measure, the Subjective Index of Physical and Social Outcome (SIPSO), collected by post 6 months after stroke onset. METHODS: We examined data from 176 patients admitted following an acute stroke and recruited into a prospective cohort study in three participating acute hospitals in Yorkshire, UK. Patients in receipt of palliative care or with transient ischaemic attack were excluded. Using the beta coefficients from the published SSV model to predict independent survival, individual probabilities of 'good' outcome as measured with the dichotomised SIPSO collected by post 6 months after stroke onset were calculated. The ability of the SSV case-mix adjustment model to discriminate patients with 'good' over 'poor' outcome was assessed through calculation of C statistics. Correct predictions were visualised with calibration plots. RESULTS: The C statistics for the SSV model to predict the physical and social subscales of the SIPSO outcome measure were 0.73 (95% CI 0.65-0.79) and 0.66 (0.58-0.82), respectively. Inclusion of patients who died prior to follow-up and ascribing them a score of 0 improved the discrimination (0.76 [0.70-0.82] and 0.70 [0.64-0.76], respectively). Calibration plots demonstrated a tendency to over-optimistic predictions, although confidence limits were wide. CONCLUSIONS: The SSV model predicts adequately the physical component of the SIPSO patient-reported outcome measure and may be useful to adjust this outcome for case-mix following stroke in survivors to follow-up. This could be of benefit in observational studies, stratified randomisation for trials, and in comparison of between-institution clinical trials. Further exploration of the generalizability of the model to adjust other patient-reported stroke outcomes may be warranted

Study protocol: Investigation of the Delirium Observation Screening Scale (DOSS) for the routine detection of delirium in the care home setting: a prospective cohort study

Introduction: Delirium is a common and distressing condition associated with frailty, dementia and co-morbidity. These are common in long-term care settings. Residents in care homes are therefore at particular risk of delirium. Despite this, methods to detect delirium in care homes are lacking, with existing diagnostic tools taking too long, or requiring specific training to deliver. This limits their feasibility for use for the routine detection of delirium by care home staff. Routine screening for delirium in care homes would allow timely attention to exacerbating factors to attenuate the episode, and facilitate future research into delirium in the care home environment. Methods: Residents from four large care homes will be asked to consent (or their consultees asked to provide a declaration of agreement) to participate in the study. Care home staff will administer the 25-item Delirium Observation Screening Scale (DOSS) – a delirium screening tool based on observed behaviours and this will be tested against the research standard Confusion Assessment Method (CAM) administered by trained research assistants performed twice per week for all participating residents. Analysis: Sensitivity, specificity, positive and negative predictive values, likelihood ratios and a diagnostic odds ratio will be calculated for the detection of delirium with the 25-item DOSS. The feasibility of routine delirium screening and the scaling properties of the 25-item DOSS will also be explored. Ethics and Dissemination: For residents lacking capacity to participate, a consultee will be approached for a declaration of agreement for inclusion in the study. Results will be published in peer-reviewed journals and disseminated in written format to Clinical Commissioning Groups, General Practitioners, and relevant third parties. Registration details: This study is registered on the ISRCTN registry (ISRCTN14608554

Real-time time-dependent self-consistent field methods with dynamic magnetic fields

The first finite basis set implementation of the real-time time-dependent self-consistent field method in a dynamic (time-dependent) magnetic field using London atomic orbitals (LAOs) is presented. The accuracy of the finite basis approach using LAOs is benchmarked against numerical results from the literature for the hydrogen atom and H2 in the presence of rapidly oscillating magnetic fields. This comparison is used to inform the choice of appropriate basis sets for studies under such conditions. Remarkably, relatively modest compact LAO basis sets are sufficient to obtain accurate results. Analysis of electron dynamics in the hydrogen atom shows that LAO calculations correctly capture the time evolution of orbital occupations. The Fourier transformation of the autocorrelation function yields a power spectrum exhibiting harmonics associated with coherent emission, which closely matches the literature and further confirms the accuracy of this approach. The dynamical response of the electron density in H2 for a magnetic field parallel to the internuclear axis shows similar behavior to benchmark studies. The flexibility of this implementation is then demonstrated by considering how the dynamical response changes as a function of the orientation of the molecule relative to the applied field. At non-parallel orientations, the symmetry of the system is lowered and numerical benchmark data, which exploit cylindrical symmetry, are no-longer readily available. The present study demonstrates the utility of LAO-based calculations for extreme dynamic magnetic fields, providing a stress-test on the choice of basis. Future applications of this approach for less extreme dynamic magnetic fields are briefly discussed

Modeling the adiabatic connection in H₂

Full configuration interaction (FCI) data are used to quantify the accuracy of approximate adiabatic connection (AC) forms in describing the ground state potential energy curve of H2, within spin-restricted density functional theory (DFT). For each internuclear separation R, accurate properties of the AC are determined from large basis set FCI calculations. The parameters in the approximate AC form are then determined so as to reproduce these FCI values exactly, yielding an exchange-correlation energy expressed entirely in terms of FCI-derived quantities. This is combined with other FCI-derived energy components to give the total electronic energy; comparison with the FCI energy quantifies the accuracy of the AC form. Initial calculations focus on a [1/1]-Padé-based form. The potential energy curve determined using the procedure is a notable improvement over those from existing DFT functionals. The accuracy near equilibrium is quantified by calculating the bond length and vibrational wave numbers; errors in the latter are below 0.5%. The molecule dissociates correctly, which can be traced to the use of virtual orbital eigenvalues in the slope in the noninteracting limit, capturing static correlation. At intermediate R, the potential energy curve exhibits an unphysical barrier, similar to that noted previously using the random phase approximation. Alternative forms of the AC are also considered, paying attention to size extensivity and the behavior in the strong-interaction limit; none provide an accurate potential energy curve for all R, although good accuracy can be achieved near equilibrium. The study demonstrates how data from correlated ab initio calculations can provide valuable information about AC forms and highlight areas where further theoretical progress is required

Topological Analysis of Functions on Arbitrary Grids: Applications to Quantum Chemistry

Algorithms are presented for performing a topological analysis of an arbitrary function, evaluated on an arbitrary grid of points. These algorithms work strictly by post-processing the data and require no additional function evaluations. This is achieved by connecting the grid points with a neighborhood graph, allowing the topological analysis to be recast as a problem in the graph theory. The flexibility of the approach is demonstrated for various applications involving analysis of the charge and magnetically induced current densities in molecules, where features of the neighborhood graph are found to correspond to chemically relevant topographical properties, such as Bader charges. These properties converge using orders of magnitude fewer grid points than uniform-grid approaches while exhibiting an appealing O[N log(N)] scaling of the computational cost. The issue of grid bias is discussed in the context of graph-based algorithms and strategies for avoiding this bias are presented. Python implementations of the algorithms are provided

A multicentre, pragmatic, cluster randomised, controlled feasibility trial of the POD system of care

Objective to provide a preliminary estimate of the effectiveness of the prevention of delirium (POD) system of care in reducing incident delirium in acute hospital wards and gather data for a future definitive randomised controlled trial. Design cluster randomised and controlled feasibility trial. Setting sixteen acute care of older people and orthopaedic trauma wards in eight hospitals in England and Wales. Participants patients 65 years and over admitted to participating wards during the trial period. Interventions participating wards were randomly assigned to either the POD programme or usual care, determined by existing local policies and practices. The POD programme is a manualised multicomponent delirium prevention intervention that targets 10 risk factors for delirium. The intervention wards underwent a 6-month implementation period before trial recruitment commenced. Main outcome measure incidence of new-onset delirium measured using the Confusion Assessment Method (CAM) measured daily for up to 10 days post consent. Results out of 4449, 3274 patients admitted to the wards were eligible. In total, 714 patients consented (713 registered) to the trial, thirty-three participants (4.6%) withdrew. Adherence to the intervention was classified as at least medium for seven wards. Rates of new-onset delirium were lower than expected and did not differ between groups (24 (7.0%) of participants in the intervention group versus 33 (8.9%) in the control group; odds ratio (95% confidence interval) 0.68 (0.37–1.26); P = 0.2225). Conclusions based on these findings, a definitive trial is achievable and would need to recruit 5220 patients in 26 two-ward hospital clusters. Trial registration: ISRCTN01187372. Registered 13 March 2014

Differentiable but exact formulation of density-functional theory

The universal density functional F of density-functional theory is a complicated and ill-behaved function of the density—in particular, F is not differentiable, making many formal manipulations more complicated. While F has been well characterized in terms of convex analysis as forming a conjugate pair (E, F) with the ground-state energy E via the Hohenberg–Kohn and Lieb variation principles, F is nondifferentiable and subdifferentiable only on a small (but dense) subset of its domain. In this article, we apply a tool from convex analysis, Moreau–Yosida regularization, to construct, for any ε > 0, pairs of conjugate functionals (ε E, ε F) that converge to (E, F) pointwise everywhere as ε → 0+, and such that ε F is (Fréchet) differentiable. For technical reasons, we limit our attention to molecular electronic systems in a finite but large box. It is noteworthy that no information is lost in the Moreau–Yosida regularization: the physical ground-state energy E(v) is exactly recoverable from the regularized ground-state energy ε E(v) in a simple way. All concepts and results pertaining to the original (E, F) pair have direct counterparts in results for (ε E, ε F). The Moreau–Yosida regularization therefore allows for an exact, differentiable formulation of density-functional theory. In particular, taking advantage of the differentiability of ε F, a rigorous formulation of Kohn–Sham theory is presented that does not suffer from the noninteracting representability problem in standard Kohn–Sham theory