Survey Outcome on Immunogenicity Risk Assessment Tools for Biotherapeutics: an Insight into Consensus on Methods, Application, and Utility in Drug Development.

A survey conducted by the Therapeutic Product Immunogenicity (TPI) community within the American Association of Pharmaceutical Scientists (AAPS) posed questions to the participants on their immunogenicity risk assessment strategies prior to clinical development. The survey was conducted in 2 phases spanning 5 years, and queried information about in silico algorithms and in vitro assay formats for immunogenicity risk assessments and how the data were used to inform early developability effort in discovery, chemistry, manufacturing and control (CMC), and non-clinical stages of development. The key findings representing the trends from a majority of the participants included the use of high throughput in silico algorithms, human immune cell-based assays, and proteomics based outputs, as well as specialized assays when therapeutic mechanism of action could impact risk assessment. Additional insights into the CMC-related risks could also be gathered with the same tools to inform future process development and de-risk critical quality attributes with uncertain and unknown risks. The use of the outputs beyond supporting early development activities was also noted with participants utilizing the risk assessments to drive their clinical strategy and streamline bioanalysis.

Clinical outcome and predictors of adverse events of an enhanced older adult psychiatric liaison service: Rapid Assessment Interface and Discharge (Newport).

BACKGROUND: Hospitals are currently admitting an increasing number of older people, and more than one-third could have an underlying mental health problem. The existing Older Adult Mental Health (OAMH) liaison service was increasingly unable to meet the escalating needs of older and frail patients. Therefore, the service was modernized and enhanced on an "invest-to-save" principle to provide a prompt holistic assessment for older adults with mental health problems. The objective of this study was a service evaluation to appraise clinical outcome, minimize the length of stay, and measure the predictors of adverse outcomes to streamline this enhanced service. MATERIALS AND METHODS: Patient demographics, social care needs, comorbidity burden (Charlson comorbidity index, CCI), and functional status (Barthel index, BI) were recorded from November 2014 to February 2015. Frailty status (frailty index, FI) was measured by an index (Rockwood index) of accumulated deficits. The outcomes were compared with the previous OAMH liaison service data over the same period a year earlier. RESULTS: The new Rapid Assessment Interface and Discharge service assessed 339 patients compared to 179 by the previous liaison team over the 4-month period. Mean age was 82.18±8.04 years, with 60% women; preadmission BI was 14.96±4.35, and admission BI was 11.38±5.73 (P<0.001, paired t-test); mean CCI was 1.66±1.53, and mean FI was 0.34±0.99, and 80% were on polypharmacy. The direct discharges from front door were increased by 7%. The mean hospital stay reduced from 35 to 20 days in acute site and from 108 to 47 days in long-stay wards. The cost benefits were based on the mean reduction in hospital stay (41.8 days) and admission reduction (2.2 days), leading to a total annualized bed savings of 44 days. FI was the most highly significant factor between patient groups with a good and poor outcome (P=0.00003, independent groups t-test, t=-4.38, df 98). CONCLUSION: Prompt mental health assessments for acutely unwell frail older people are not only cost effective but also improve clinical outcomes.

Reducing inpatient falls in a 100% single room elderly care environment: evaluation of the impact of a systematic nurse training programme on falls risk assessment (FRA).

Inpatient falls (IF) are the most commonly reported safety incidents. The high rate of inpatient falls was reported in a newly built hospital, within Aneurin Bevan University Health Board, Wales (UK). The aim of the project is to reduce the incidence of IF and associated adverse clinical outcomes in a hospital with 100% single rooms. The key mechanism for improvement was education and training of nursing staff around falls risk factors. A Plan-Do-Study-Act methodology was used and a geriatrician-led, systematic nurse training programme on the understanding and correct use of existing multifactorial falls risk assessment (FRA) tool was implemented in April 2013. Pre-training baseline data revealed inadequate falls assessment and low completion rates of the FRA tool. Subsequent, post-training data showed improvement in compliance with all aspects of FRA. Concurrent with nurse training, the actual falls incidence/1000 patient-bed-days fell significantly from the baseline of 18.19±3.46 (Nov 2011-March 2013) to 13.36±2.89 (p<0.001) over next 12 months (April 2013-March 2014) and remained low (mean falls 12.81±2.85) until November 2015. Improved clinical outcomes have been observed in terms of a reduction of length of stay and new care home placements, making total annualised savings of £642,055.

The Rapid Assessment Interface and Discharge service and its implications for patients with dementia.

The rising prevalence of dementia will have an effect on acute care hospitals around the world. At present, around 40% of patients older than 70 years with acute medical admissions have dementia, but only half of these patients have been diagnosed. Patients with dementia have poorer health outcomes, longer hospital stays, and higher rates of readmissions and institutionalization. Worldwide, health care budgets are severely constrained. National Institute for Health and Care Excellence (NICE) has listed ten quality standards for supporting people in living well with dementia. NICE resource implications and commissioning support to implement these guidelines and improve dementia services have been recently published. Although most of the frail elderly patients with dementia are cared for by geriatricians, obstacles to making a diagnosis and to the management of dementia have been recognized. To provide a timely diagnosis of dementia, better care in acute hospital settings, and continuity of care in the community, services integrating all these elements are warranted. Extra resources also will be required for intermediate, palliative care, and mental health liaison services for people with dementia. The Birmingham Rapid Assessment Interface and Discharge service model uses a multiskilled team that provides comprehensive assessment of a person's physical and psychological well-being in a general hospital setting. It has been shown to be an effective model in terms of reducing both length of stay and avoiding readmission. The aim of this review is to discuss the implications of the Rapid Assessment Interface and Discharge model in people with dementia and to critically compare this model with similar published service provisions.

Predictors of adverse outcomes on an acute geriatric rehabilitation ward.

BACKGROUND: multidisciplinary rehabilitation is of proven benefit in the management of older inpatients. However, the identification of patients who will do well with rehabilitation currently lacks a strong evidence base. OBJECTIVES: the aims of this study were to compare the importance of chronological age, gender, co-morbidities and frailty in the prediction of adverse outcomes for patients admitted to an acute geriatric rehabilitation ward. DESIGN: prospective observational cohort study. SUBJECTS AND SETTING: two hundred and sixty-five patients admitted consecutively to an acute geriatric rehabilitation ward at a tertiary care teaching hospital. METHODS: frailty status was measured by an index of accumulated deficits, giving a potential score from 0 (no deficits) to 1.0 (all 40 deficits present). Patients were stratified into three outcomes: good (discharged to original residence within 28 days), intermediate (discharged to original residence but longer hospital stay) and poor (newly institutionalised or died). RESULTS: patients were old (82.6 ± 8.6 years) and frail (mean frailty index (FI) 0.34 ± 0.09). Frailty status correlated significantly with length of stay and was a predictor of poor functional gain. The odds ratio of intermediate and poor outcome relative to a good outcome was 4.95 (95% CI = 3.21, 7.59; P < 0.001) per unit increase in FI. Chronological age, gender and co-morbidity showed no significant association with outcomes. CONCLUSION: frailty is associated with adverse rehabilitation outcomes. The FI may have clinical utility, augmenting clinical judgement in the management of older inpatients.

An immunologic model for rapid vaccine assessment -- a clinical trial in a test tube.

While the duration and size of human clinical trials may be difficult to reduce, there are several parameters in pre-clinical vaccine development that may be possible to further optimise. By increasing the accuracy of the models used for pre-clinical vaccine testing, it should be possible to increase the probability that any particular vaccine candidate will be successful in human trials. In addition, an improved model will allow the collection of increasingly more-informative data in pre-clinical tests, thus aiding the rational design and formulation of candidates entered into clinical evaluation. An acceleration and increase in sophistication of pre-clinical vaccine development will thus require the advent of more physiologically-accurate models of the human immune system, coupled with substantial advances in the mechanistic understanding of vaccine efficacy, achieved by using this model. We believe the best viable option available is to use human cells and/or tissues in a functional in vitro model of human physiology. Not only will this more accurately model human diseases, it will also eliminate any ethical, moral and scientific issues involved with use of live humans and animals. An in vitro model, termed "MIMIC" (Modular IMmune In vitro Construct), was designed and developed to reflect the human immune system in a well-based format. The MIMIC System is a laboratory-based methodology that replicates the human immune system response. It is highly automated, and can be used to simulate a clinical trial for a diverse population, without putting human subjects at risk. The MIMIC System uses the circulating immune cells of individual donors to recapitulate each individual human immune response by maintaining the autonomy of the donor. Thus, an in vitro test system has been created that is functionally equivalent to the donor's own immune system and is designed to respond in a similar manner to the in vivo response.