IT-assisted comprehensive geriatric assessment for residents in care homes: quasi-experimental longitudinal study.

BACKGROUND: Frailty interventions such as Comprehensive Geriatric Assessment (CGA) can provide significant benefits for older adults living with frailty. However, incorporating such proactive interventions into primary care remains a challenge. We developed an IT-assisted CGA (i-CGA) process, which includes advance care planning (ACP). We assessed if, in older care home residents, particularly those with severe frailty, i-CGA could improve access to advance care planning discussions and reduce unplanned hospitalisations. METHOD: As a quality improvement project we progressively incorporated our i-CGA process into routine primary care for older care home residents, and used a quasi-experimental approach to assess its interim impact. Residents were assessed for frailty by General Practitioners. Proactive i-CGAs were completed, including consideration of traditional CGA domains, deprescribing and ACP discussions. Interim analysis was conducted at 1 year: documented completion, preferences and adherence to ACPs, unplanned hospital admissions, and mortality rates were compared for i-CGA and control (usual care) groups, 1-year post-i-CGA or post-frailty diagnosis respectively. Documented ACP preferences and place of death were compared using the Chi-Square Test. Unplanned hospital admissions and bed days were analysed using the Mann-Whitney U test. Survival was estimated using Kaplan-Meier survival curves. RESULTS: At one year, the i-CGA group comprised 196 residents (severe frailty 111, 57%); the control group 100 (severe frailty 56, 56%). ACP was documented in 100% of the i-CGA group, vs. 72% of control group, p < 0.0001. 85% (94/111) of severely frail i-CGA residents preferred not to be hospitalised if they became acutely unwell. For those with severe frailty, mean unplanned admissions in the control (usual care) group increased from 0.87 (95% confidence interval ± 0.25) per person year alive to 2.05 ± 1.37, while in the i-CGA group they fell from 0.86 ± 0.24 to 0.68 ± 0.37, p = 0.22. Preferred place of death was largely adhered to in both groups, where documented. Of those with severe frailty, 55% (62/111) of the i-CGA group died, vs. 77% (43/56) of the control group, p = 0.0013. CONCLUSIONS: Proactive, community-based i-CGA can improve documentation of care home residents' ACP preferences, and may reduce unplanned hospital admissions. In severely frail residents, a mortality reduction was seen in those who received an i-CGA.

The Pathfields Tool: a frailty case-finding tool using primary care IT-implications for population health management.

BACKGROUND: older people living with frailty benefit from targeted interventions which improve health and independence. However, it has been challenging within primary care to systematically identify patients living with frailty. METHODS: primary care IT was re-programmed to create a 'Pathfields High Risk Cohort' (PHRC, patients felt likely to have undiagnosed frailty) and invite clinicians to opportunistically assess and diagnose frailty. Results were compared with NHS England's current approach to frailty identification using Electronic Frailty Index (eFI) to see which approach had the highest diagnostic yield. RESULTS: the Pathfields Tool identified 1,348 patients in PHRC group, of whom 951 (70.5%) were clinically assessed and diagnosed:eFI (moderate and severe) identified 683 patients of whom 598 (87.6%) were clinically assessed and diagnosed:Extrapolated data would estimate frailty prevalence at 22.5% (1,024/4,552) (5.5% severe, 8.8% moderate, and 8.1% mild) in the practice population aged 65+. CONCLUSIONS: the Pathfields Tool identified more patients with clinically confirmed previously undiagnosed frailty than eFI 'moderate and severe frailty' alone.Sub-segmenting frailty by residential status could significantly improve the population health management of older people.

In Vitro Evaluation of Third Generation PAMAM Dendrimer Conjugates.

The present study compares the use of high generation G3 and low generation G0 Polyamidoamine (PAMAM) dendrimers as drug carriers of naproxen (NAP), a poorly water soluble drug. Naproxen was conjugated to G3 in different ratios and to G0 in a 1:1 ratio via a diethylene glycol linker. A lauroyl chain (L), a lipophilic permeability enhancer, was attached to G3 and G0 prodrugs. The G3 and G0 conjugates were more hydrophilic than naproxen as evaluated by the measurement of partitioning between 1-octanol and a phosphate buffer at pH 7.4 and pH 1.2. The unmodified surface PAMAM-NAP conjugates showed significant solubility enhancements of NAP at pH 1.2; however, with the number of NAP conjugated to G3, this was limited to 10 molecules. The lactate dehydrogenase (LDH) assay indicated that the G3 dendrimer conjugates had a concentration dependent toxicity towards Caco-2 cells. Attaching naproxen to the surface of the dendrimer increased the IC50 of the resulting prodrugs towards Caco-2 cells. The lauroyl G3 conjugates showed the highest toxicity amongst the PAMAM dendrimer conjugates investigated and were significantly more toxic than the lauroyl-G0-naproxen conjugates. The permeability of naproxen across monolayers of Caco-2 cells was significantly increased by its conjugation to either G3 or G0 PAMAM dendrimers. Lauroyl-G0 conjugates displayed considerably lower cytotoxicity than G3 conjugates and may be preferable for use as a drug carrier for low soluble drugs such as naproxen.

Cost prediction following traumatic brain injury: model development and validation.

OBJECTIVE: The ability to predict costs following a traumatic brain injury (TBI) would assist in planning treatment and support services by healthcare providers, insurers and other agencies. The objective of the current study was to develop predictive models of hospital, medical, paramedical, and long-term care (LTC) costs for the first 10 years following a TBI. METHODS: The sample comprised 798 participants with TBI, the majority of whom were male and aged between 15 and 34 at time of injury. Costing information was obtained for hospital, medical, paramedical, and LTC costs up to 10 years postinjury. Demographic and injury-severity variables were collected at the time of admission to the rehabilitation hospital. RESULTS: Duration of PTA was the most important single predictor for each cost type. The final models predicted 44% of hospital costs, 26% of medical costs, 23% of paramedical costs, and 34% of LTC costs. Greater costs were incurred, depending on cost type, for individuals with longer PTA duration, obtaining a limb or chest injury, a lower GCS score, older age at injury, not being married or defacto prior to injury, living in metropolitan areas, and those reporting premorbid excessive or problem alcohol use. CONCLUSIONS: This study has provided a comprehensive analysis of factors predicting various types of costs following TBI, with the combination of injury-related and demographic variables predicting 23-44% of costs. PTA duration was the strongest predictor across all cost categories. These factors may be used for the planning and case management of individuals following TBI.

RESTORE: REcovery after Serious Trauma--Outcomes, Resource use and patient Experiences study protocol.

BACKGROUND: Traumatic injury is a leading contributor to the overall global burden of disease. However, there is a worldwide shortage of population data to inform understanding of non-fatal injury burden. An improved understanding of the pattern of recovery following trauma is needed to better estimate the burden of injury, guide provision of rehabilitation services and care to injured people, and inform guidelines for the monitoring and evaluation of disability outcomes. OBJECTIVE: To provide a comprehensive overview of patient outcomes and experiences in the first 5 years after serious injury. DESIGN: This is a population-based, nested prospective cohort study using quantitative data methods, supplemented by a qualitative study of a seriously injured participant sample. PARTICIPANTS: All 2547 paediatric and adult major trauma patients captured by the Victorian State Trauma Registry with a date of injury from 1 July 2011 to 30 June 2012 who survived to hospital discharge and did not opt-off from the registry. ANALYSIS: To analyse the quantitative data and identify factors that predict poor or good outcome, whether there is change over time, differences in rates of recovery and change between key participant subgroups, multilevel mixed effects regression models will be fitted. To analyse the qualitative data, thematic analysis will be used to identify important themes and the relationships between themes. CONTRIBUTION TO THE FIELD: The results of this project have the potential to inform clinical decisions and public health policy, which can reduce the burden of non-fatal injury and improve the lives of people living with the consequences of severe injury.

Does proactive care in care homes improve survival? A quality improvement project.

BACKGROUND: NHS England's 'Enhanced Health in Care Homes' specification aims to make the healthcare of care home residents more proactive. Primary care networks (PCNs) are contracted to provide this, but approaches vary widely: challenges include frailty identification, multidisciplinary team (MDT) capability/capacity and how the process is structured and delivered. AIM: To determine whether a proactive healthcare model could improve healthcare outcomes for care home residents. DESIGN AND SETTING: Quality improvement project involving 429 residents in 40 care homes in a non-randomised crossover cohort design. The headline outcome was 2-year survival. METHOD: All care home residents had healthcare coordinated by the PCN's Older Peoples' Hub. A daily MDT managed the urgent healthcare needs of residents. Proactive healthcare, comprising information technology-assisted comprehensive geriatric assessment (i-CGA) and advanced care planning (ACP), were completed by residents, with prioritisation based on clinical needs.Time-dependent Cox regression analysis was used with patients divided into two groups:Control group: received routine and urgent (reactive) care only.Intervention group: additional proactive i-CGA and ACP. RESULTS: By 2 years, control group survival was 8.6% (n=108), compared with 48.1% in the intervention group (n=321), p<0.001. This represented a 39.6% absolute risk reduction in mortality, 70.2% relative risk reduction and the number needed to treat of 2.5, with little changes when adjusting for confounding variables. CONCLUSION: A PCN with an MDT-hub offering additional proactive care (with an i-CGA and ACP) in addition to routine and urgent/reactive care may improve the 2-year survival in older people compared with urgent/reactive care alone.

The influence of the degree of esterification on the release characteristics of in situ gelling pectin formulations for oral sustained delivery of paracetamol.

The aim of this study was to examine the effect of a change of the degree of esterification of pectin on the in situ gelation and release characteristics of 1.5% (w/v) pectin solutions over a wide pH range. Formulations of pectin with degrees of esterification of 9% (DE9) and 31% (DE31) containing complexed calcium ions formed gels in vitro at pH 1.2 as a consequence of cross-linking of the pectin chains by free calcium ions released from the complex. In vitro release of paracetamol from these gels was diffusion controlled. A sustained release of paracetamol was observed following oral administration of pectin DE9 and DE31 formulations to gastric acidity-controlled rats at pH 2.5 but only with DE9 formulations at pH 5.5. Examination of the stomach contents confirmed effective in situ gelation of pectin DE9 formulations at a gastric pH of 6 but there was no evidence of the gelation of pectin DE31 formulations at this pH.

Oral liquid in situ gelling methylcellulose/alginate formulations for sustained drug delivery to dysphagic patients.

BACKGROUND: Elderly patients with swallowing dysfunction may benefit from the oral administration of liquid dosage forms with in situ gelling properties. AIM: We have designed in situ gelling liquid dosage formulations composed of mixtures of methylcellulose, which has thermally reversible gelation properties and sodium alginate, the gelation of which is ion-responsive, with suitable rheological characteristics for ease of administration to dysphagic patients and suitable integrity in the stomach to achieve a sustained release of drug. METHOD: The rheological and gelation characteristics of solutions containing methylcellulose (2.0%) and sodium alginate (0.25-1.0%) were assessed for their suitability for administration to dysphagic patients. The gel strength and in vitro and in vivo release characteristics of gels formed by selected formulations were compared using paracetamol as a model drug. RESULTS: Mixtures of 2.0% methylcellulose and 0.5% alginate containing 20% d-sorbitol were of suitable viscosity for ease of swallowing by dysphagic patients and formed gels at temperatures between ambient and body temperature allowing administration in liquid form and in situ gelation in the stomach. In vitro release of paracetamol from 2.0% methylcellulose/0.5% alginate gels was diffusion-controlled at pH 1.2 and 6.8. Measurement of plasma levels of paracetamol after oral administration to rats of a 2.0% methylcellulose/0.5% alginate formulation showed improved sustained release compared to that from 2.0% methylcellulose and 0.5% alginate solutions and from an aqueous solution of paracetamol. CONCLUSIONS: Solutions of mixtures of methylcellulose and alginate in appropriate proportions are of suitable consistency for administration to dysphagic patients and form gels in situ with sustained release characteristics.

Modeling Peptide Nucleic Acid Binding Enthalpies Using MM-GBSA.

The binding enthalpies of peptide nucleic acid (PNA) homoduplexes were predicted using a molecular mechanics generalized Born surface area approach. Using the nucleic acid nearest-neighbor model, these were decomposed into sequence parameters which could replicate the enthalpies from thermal melting experiments with a mean error of 8.7%. These results present the first systematic computational investigation into the relationship between sequence and binding energy for PNA homoduplexes and identified a stabilizing helix initiation enthalpy not observed for nucleic acids with phosphoribose backbones.

WHODAS 2.0: Associations of functional disability with sex, age, and length of care in outpatients with schizophrenia-spectrum disorders.

Schizophrenia is a disabling mental disorder that is associated with impairments in both social and occupational functioning. Few studies, however, have explored functional domains of disability and its associations with age, sex, and length of care. As part of a hospital quality improvement initiative, data were collected on outpatients' age, sex, length of care, and levels of disability (using the WHODAS 2.0; N=180; M=45.72; 68% male). Mean disability summary and domain scores were compared with population norms from international samples and two published studies in schizophrenia. A series of three-way ANOVAs and post-hoc tests evaluated differences in levels of disability based on age, sex, and length of care categories. Sample mean summary scores were comparable to published studies in schizophrenia (M=24.81; SD=17.37; 85th percentile). Statistically significant main effects of sex and age on summary and domain-specific scores were found, whereas length of care was not significant. A statistically significant three-way interaction of sex x length of care x age was found for summary and mobility scores. Findings provide support for the reliability and validity of the WHODAS 2.0 in outpatients with schizophrenia. Although causal inferences cannot be made, findings show that age and sex are important factors to consider in addressing disability.

Soft X-ray microscopy at a spatial resolution better than 15 nm.

Analytical tools that have spatial resolution at the nanometre scale are indispensable for the life and physical sciences. It is desirable that these tools also permit elemental and chemical identification on a scale of 10 nm or less, with large penetration depths. A variety of techniques in X-ray imaging are currently being developed that may provide these combined capabilities. Here we report the achievement of sub-15-nm spatial resolution with a soft X-ray microscope--and a clear path to below 10 nm--using an overlay technique for zone plate fabrication. The microscope covers a spectral range from a photon energy of 250 eV (approximately 5 nm wavelength) to 1.8 keV (approximately 0.7 nm), so that primary K and L atomic resonances of elements such as C, N, O, Al, Ti, Fe, Co and Ni can be probed. This X-ray microscopy technique is therefore suitable for a wide range of studies: biological imaging in the water window; studies of wet environmental samples; studies of magnetic nanostructures with both elemental and spin-orbit sensitivity; studies that require viewing through thin windows, coatings or substrates (such as buried electronic devices in a silicon chip); and three-dimensional imaging of cryogenically fixed biological cells.

Carrageenan gels for oral sustained delivery of acetaminophen to dysphagic patients.

We have designed gel formulations for the oral administration of acetaminophen with suitable rheological characteristics for ease of administration to patients with swallowing difficulties and sufficient integrity in the stomach to achieve a sustained release of this drug. Gels formed by agar and ι-carrageenan were assessed for suitable gel strength and in vitro and in vivo release characteristics. Comparison of 1.5% ι-carrageenan gel with 0.5% agar gel demonstrated improved sustained release properties of the ι-carrageenan gel. Gel formed by ι-carrageenan has suitable rheological and sustained release characteristics for potential use as vehicles for oral delivery of drugs to dysphagic patients.

In situ gelling formulation based on methylcellulose/pectin system for oral-sustained drug delivery to dysphagic patients.

BACKGROUND: Oral-sustained release gel formulations with suitable rheological properties have been proposed as a means of improving the compliance of dysphagic and geriatric patients who have difficulties with handling and swallowing oral dosage forms. AIM: We have modified the rheological and release properties of thermally reversible methylcellulose solutions by admixture with pectin, the gelation of which is ion-responsive, with the aim of formulating an in situ gelling vehicle suitable for oral-sustained drug delivery. METHOD: Gels formed by solutions containing methylcellulose (1.0-2.0%) and pectin (0.5-2.0%) were assessed for suitable gel strength, and in vitro and in vivo release of paracetamol. RESULTS: Addition of 1.5% pectin to a 2.0% methylcellulose formulation containing 20% d-sorbitol and calcium ions in complexed form increased the gel strength and provided a formulation with a suitable viscosity for ease of swallowing by dysphagic patients. Gels formed in situ after oral administration of this formulation retained their integrity in the rat stomach for sufficient time for sustained release to be achieved. In vitro release of paracetamol from methylcellulose, pectin, and methylcellulose/pectin gels was diffusion-controlled. Plasma levels of paracetamol after oral administration to rats (gastric pH 2.6 and 5.5) of a solution including 2.0% methylcellulose/1.5% pectin showed improved sustained release compared with that from both 2.0% methylcellulose and 1.5% pectin solutions. CONCLUSIONS: The addition of suitable concentrations of pectin to methylcellulose solutions produces in situ gelling formulations with suitable viscosity for administration to dysphagic patients and improved sustained release characteristics.

Extreme ultraviolet laser-based table-top aerial image metrology of lithographic masks.

We have realized the first demonstration of a table-top aerial imaging microscope capable of characterizing pattern and defect printability in extreme ultraviolet lithography masks. The microscope combines the output of a 13.2 nm wavelength, table-top, plasma-based, EUV laser with zone plate optics to mimic the imaging conditions of an EUV lithographic stepper. We have characterized the illumination of the system and performed line-edge roughness measurements on an EUVL mask. The results open a path for the development of a compact aerial imaging microscope for high-volume manufacturing.

Effect of D-sorbitol on the thermal gelation of methylcellulose formulations for drug delivery.

The aim of this study was to examine the effect of D-sorbitol on the gelation characteristics of methylcellulose in aqueous solution. The addition of D-sorbitol at concentrations of between 25 and 30% (w/v) to 1.0-2.0% (w/v) methylcellulose solutions reduced the gelation temperature from approximately 53 degrees Celsius to values between ambient and 37 degrees Celsius and increased the strength of the gel. The in vitro release of acetaminophen (paracetamol) from 2.0% (w/v) methylcellulose gels containing 20-30% (w/v) D-sorbitol gel was diffusion-controlled.

In situ gelling xyloglucan/alginate liquid formulation for oral sustained drug delivery to dysphagic patients.

BACKGROUND: The oral administration of liquid dosage forms of suitable consistency and with sustained release characteristics may provide a means of improving the compliance of geriatric patients who experience difficulties in swallowing conventional solid dosage forms. AIM: We have designed and evaluated liquid preparations for administration to dysphagic patients, composed of aqueous mixtures of xyloglucan, which has thermally reversible gelation characteristics, and sodium alginate, which has ion-responsive gelation characteristics. METHOD: The gelation and in vitro and in vivo release characteristics of liquid formulations containing appropriate concentrations of xyloglucan and sodium alginate with mannuronate/guluronate ratios of either 0.5 or 0.8 were assessed. RESULTS: Aqueous mixtures of 1.5% xyloglucan and 0.5% alginate had suitable viscosities for ease of swallowing and appropriate gelation temperatures (approximately 33 degrees C) to ensure in situ gelation following oral administration. The in vitro release of paracetamol at pH 5.0 from gels formed by these formulations and also by a 1.5% xyloglucan solution was diffusion-controlled. Plasma levels of paracetamol after oral administration to gastric-acidity controlled rats (pH 5) of a solution containing 1.5% xyloglucan/0.5% alginate showed that a more sustained release was achieved from the gels formed by the in situ gelation of this formulation compared with that of a 1.5% xyloglucan solution. Visual observation of the contents of the rat stomach after oral administration showed that the inclusion of alginate in the xyloglucan solutions was effective in reducing gel erosion, so sustaining drug release. CONCLUSIONS: Liquid formulations of xyloglucan and sodium alginate in appropriate proportions are of suitable consistency for ease of administration to dysphagic patients and form gels in situ in the rat stomach capable of sustaining the release of paracetamol over a 6-hour period.

A non-contact impedimetric biosensing system for classification of toxins associated with cytotoxicity testing.

We report on a novel impedance spectroscopy measurement and data analysis technique for cytotoxicity testing. The technique combines non-contact measurement with real-time impedance data analysis based on the toxin dose dependency of the outputs, making it suitable for high throughput screening. A multi-electrode array was designed and fabricated such that a standard well plate could be positioned above the electrodes, negating the requirement for bespoke culture wells with integrated electrodes. For cytotoxicity testing, endothelial cells, type ECV304, within the wells were exposed to various concentrations of 3 toxins, dimethyl sulphoxide, cadmium chloride and saponin, which exhibit different modes of action on cells. Impedance spectra were recorded every 30 min over a 24 h period. From the spectra 'toxin maps' were produced which presented the correlation between impedance output and dose of toxin versus frequency and time. The results demonstrated characteristic toxin maps for each toxin and significantly differences between the three toxins studied. Using complementary measurement methods, we showed that these differences in toxin maps related to morphological and physiological changes in the cells due to the differing mode of action of each toxin.

Incidental finding of age and time disorientation in a clinical sample of patients with schizophrenia: Findings from a short term follow up survey regarding cannabis use.

Age disorientation has been described in a subtype of patients with schizophrenia. The current article reports on an incidental finding from our survey study on patterns of cannabis use pre-post legalization in patients with schizophrenia. For the purpose of the survey study, patients were asked to fill out a total of 41 survey questions. The same participants were contacted over the phone 8 weeks post-legalization. Responses to the survey questions were consistent pre- and post-legalization except for four items which required estimation of time/age. This incidental finding highlights the need for further exploration of this phenomenon by future studies.