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.

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.

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.

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.

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.

Home visits: A new screening tool for frailty? A retrospective exploratory study.

BACKGROUND: In the United Kingdom, the new NHS contract for primary care mandates that practices use the Electronic Frailty Index (EFI) to screen for frailty and apply clinical judgment, based on knowledge of the patient, to decide whether they have a diagnosis of frailty. EFI has not yet been validated for this purpose. Many primary care clinicians would agree that although not formally investigated, there seems to be a strong association between being housebound or in institutional care and having a diagnosis of frailty. Although being housebound or in institutional care is not commonly coded in primary care computer record systems (IT), this cohort of patients do require home visits if they become unwell. Home visits are coded and it is simple to run a search on primary care IT to generate a list of older people who have received a home over given period. AIM: This study assessed whether being housebound and requiring home visits could form a new screening tool for frailty. DESIGN AND SETTING: Retrospective cohort study from 1/3/15 to 29/2/16. Primary care, South Devon. METHOD: Medical records of 154 patients over 65 years of age were evaluated. Patients were divided into two groups: a group (n = 82) that had received a home visit and a second group consisting of a randomized sample of patients (n = 72) with similar baseline characteristics who had not. Patient records were analyzed by two clinicians to determine whether a frailty syndrome was present. Researchers were blinded to each other's results. An arbitrator determined the frailty status on disagreement. RESULTS: Home visits have a sensitivity of 87.23% [95% confidence interval (CI): 74.35%-95.17%] and specificity of 61.68% (95% CI: 51.78%-70.92%). For frailty, Cohen's Kappa showed fair interobserver reliability. CONCLUSION: This study suggests that home visits are a good screen for frailty; the data are easy to retrieve from primary care IT and could be used as a valid screening tool to assist with identifying frailty in primary care.

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.

Lenghty reverse poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) polymeric micelles and gels for sustained release of antifungal drugs.

In this work, we present a detailed study of the potential application of polymeric micelles and gels of four different reverse triblock poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) copolymers (BOnEOmBOn, where n denotes the respective block lengths), specifically BO8EO90BO8, BO14EO378BO14, BO20EO411BO20 and BO21EO385BO21, as effective drug transport nanocarriers. In particular, we tested the use of this kind of polymeric nanostructures as reservoirs for the sustained delivery of the antifungals griseofulvin and fluconazole for oral and topical administration. Polymeric micelles and gels formed by these copolymers were shown to solubilize important amounts of these two drugs and to have a good stability in physiologically relevant conditions for oral or topical administration. These polymeric micellar nanocarriers were able to release drugs in a sustained manner, being the release rate slower as the copolymer chain hydrophobicity increased. Different sustained drug release profiles were observed depending on the medium conditions. Gel nanocarriers were shown to display longer sustained release rates than micellar formulations, with the existence of a pulsatile-like release mode under certain solution conditions as a result of their inner network structure. Certain bioadhesive properties were observed for the polymeric physical gels, being moderately tuned by the length and hydrophobicity of the polymeric chains. Furthermore, polymeric gels and micelles showed activity against the yeast Candida albicans and the mould demartophytes (Trichophyton rubrum and Microsporum canis) and, thus, may be useful for the treatment of different cutaneous fungal infections.

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.

Solubility enhancement of paclitaxel using a linear-dendritic block copolymer.

The solubilising capacities of micelles of a linear-dendritic copolymer (BE-PAMAM), formed by conjugating the poly(butylene oxide) (B)-poly(ethylene oxide) (E) block copolymer B16E42 (BE) with a G2 PAMAM dendrimer, have been compared with those of the diblock copolymer B16E42 for the anti-cancer drug paclitaxel. The BE-PAMAM copolymer showed a greater solubility enhancement than BE under equivalent conditions. Drug-loading efficiency was improved using a solvent-loading method compared with the conventional solution-loading method. The solubility of paclitaxel was increased 3700-fold by micellar encapsulation in a 2% (w/v) BE-PAMAM copolymer solution at 37°C using this solubilisation technique. Dynamic light scattering and transmission electron microscopy studies indicated a transition of spherical to worm-like micelles of the BE copolymer induced by the encapsulation of drug molecules. A sustained release of encapsulated drug was observed, with approximately 80% and 60% paclitaxel being released from 2% (w/v) solutions of BE and BE-PAMAM respectively after 24h of dialysis at 37°C.

Costs of care after traumatic brain injury.

Traumatic brain injuries (TBI) impose a significant burden on the health care system. The aim of the current study was to explore variation in costs in a group of rehabilitation patients in Victoria, Australia, following complicated mild-to-severe TBI treated under the accident compensation system administered by the Transport Accident Commission. Study participants included 1237 individuals with mild-to-severe TBI recruited consecutively from a TBI rehabilitation program. Long-term care, hospital, medical, and paramedical costs were obtained 10 years post-injury and their association with demographic and injury-related variables were examined. Significant variability in costs was evident. Long-term care costs were highest, followed by hospital, paramedical, and medical costs. Duration of post-traumatic amnesia (PTA) was a strong predictor of all costs, and stronger than Glasgow Coma Score (GCS). Longer acute hospital stay was related to higher costs. In addition to PTA duration and GCS, other factors associated with higher long-term costs were having an abnormal CT scan and epilepsy early after injury. Higher hospital and medical costs were associated with these factors, but also with other physical injuries, lower education, pre-injury unemployment, living outside the city, speaking English at home, and, in the case of medical costs, older age and having had pre-injury psychiatric treatment. Higher paramedical costs were associated with most of these variables, but also with being employed prior to injury and being female. In line with the multifaceted nature of TBI, the current findings suggest that both injury-related and demographic factors determine costs following injury.

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.

Solubilisation capacity of Brij surfactants.

The aim of this study was to investigate the potential of selected Brij non-ionic surfactants for enhancing the solubility of poorly water-soluble drugs. Griseofulvin was selected as a model drug candidate enabling comparisons to be made with the solubilisation capacities of other poly(ethylene oxide)-based copolymers. UV/Vis and (1)H NMR spectroscopies were used to quantify the enhancement of solubility of griseofulvin in 1 wt% aqueous micellar solutions of Brij 78 (C(18)H(37)E(20)), Brij 98 (C(18)H(35)E(20)) and Brij 700 (C(18)H(37)E(100)) (where E represents the OCH(2)CH(2) unit of the poly(ethylene oxide) chain) at 25, 37 and 40 °C. Solubilisation capacities (S(cp) expressed as mg griseofulvin per g Brij) were similar for Brij 78 and 98 (range 6-11 mg g(-1)) but lower for Brij 700 (3-4 mg g(-1)) as would be expected for the surfactant with the higher ethylene oxide content. The drug loading capacity of micelles of Brij 78 was higher than many di- and triblock copolymers with hydrophilic E-blocks specifically designed for enhancement of drug solubility.

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.

The effect of water-soluble polymers, PEG and PVP, on the solubilisation of griseofulvin in aqueous micellar solutions of Pluronic F127.

The purpose of this study was to investigate the possibility of enhancing the solubilisation capacity of micellar solutions of Pluronic F127 for the poorly water-soluble drug griseofulvin by co-formulating with a water-soluble polymer. The effect of the addition of the polyethylene glycols PEG6000 and 35000, and the poly(vinylpyrrolidone)s PVP K30 and K90, on the solubilisation capacity of 1wt% solutions of Pluronic F127 was related to the effect of these additives on particle size as determined by dynamic light scattering measurements. The addition of PEG35000 to 1wt% F127 solutions significantly increased the solubility capacity expressed in terms of unit weight of F127; PVP K90 had a smaller effect but no enhancement was noted following the addition of PEG6000 or PVP K30. Solubilisation enhancement was thought to be a consequence of the association of the polymers with the E-blocks of the micelle corona so providing an expanded region of reduced polarity for drug solubilisation.

Micellisation of triblock copolymers of ethylene oxide and 1,2-butylene oxide: effect of B-block length.

We have used pyrene fluorescence spectroscopy and isothermal titration calorimetry (ITC) to investigate the effect of hydrophobic-block length on values of the critical micelle concentration (cmc) for aqueous solutions of triblock poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) block copolymers (B(n)E(m)B(n), where m and n denote the respective block lengths) with hydrophobic block lengths in the range n=12-21. Combined with results from previous work on B(n)E(m)B(n) copolymers with shorter B blocks, plots of log(10)(cmc) (cmc in molar units and reduced to a common E-block length) against total number of B units (n(t)=n for diblock or n(t)=2n for triblock copolymers) display transitions in the slopes of the two plots, which indicate changes in the micellisation equilibrium. These occur at values of n(t)which can be assigned to the onset and completion of collapse of the hydrophobic B blocks, an effect not previously observed for reverse triblock copolymers. The results are compared with related data for diblock E(m)B(n) copolymers.