Methods to reduce prescribing errors in elderly patients with multimorbidity

The global population of multimorbid older people is growing steadily. Multimorbidity is the principal cause of complex polypharmacy, which in turn is the prime risk factor for inappropriate prescribing and adverse drug reactions and events. Those who prescribe for older frailer multimorbid people are particularly prone to committing prescribing errors of various kinds. The causes of prescribing errors in this patient population are multifaceted and complex, including prescribers’ lack of knowledge of aging physiology, geriatric medicine, and geriatric pharmacotherapy, overprescribing that frequently leads to major polypharmacy, inappropriate prescribing, and inappropriate drug omission. This review examines the various ways of minimizing prescribing errors in multimorbid older people. The role of education in physician prescribers and clinical pharmacists, the use of implicit and explicit prescribing criteria designed to improve medication appropriateness in older people, and the application of information and communication-technology systems to minimize errors are discussed in detail. Although evidence to support any single intervention to prevent prescribing errors in multimorbid elderly people is inconclusive or lacking, published data support focused prescriber education in geriatric pharmacotherapy, routine application of STOPP/START (screening tool of older people’s prescriptions/screening tool to alert to right treatment) criteria for potentially inappropriate prescribing, electronic prescribing, and close liaison between clinical pharmacists and physicians in relation to structured medication review and reconciliation. Carrying out a structured medication review aimed at optimizing pharmacotherapy in this vulnerable patient population presents a major challenge. Another challenge is to design, build, validate, and test by clinical trials suitably versatile and efficient software engines that can reliably and swiftly perform complex medication reviews in older multimorbid people. The European Union-funded SENATOR and OPERAM clinical trials commencing in 2016 will examine the impact of customized software engines in reducing medication-related morbidity, avoidable excess cost, and rehospitalization in older multimorbid people

Development of a microelectromechanical system (MEMS)-based multisensor platform for environmental monitoring

Recent progress in data processing, communications and electronics miniaturization is now enabling the development of low-cost wireless sensor networks (WSN), which consist of spatially distributed autonomous sensor modules that collaborate to monitor real-time environmental conditions unobtrusively and with appropriate levels of spatial and temporal granularity. Recent and future applications of this technology range from preventative maintenance and quality control to environmental modelling and failure analysis. In order to fabricate these low-cost, low-power reliable monitoring platforms, it is necessary to improve the level of sensor integration available today. This paper outlines the microfabrication and characterization results of a multifunctional multisensor unit. An existing fabrication process for Complementary Metal Oxide Semiconductor CMOS-compatible microelectromechanical systems (MEMS) structures has been modified and extended to manufacture temperature, relative humidity, corrosion, gas thermal conductivity, and gas flow velocity sensors on a single silicon substrate. A dedicated signal conditioning circuit layer has been built around this MEMS multisensor die for integration on an existing low-power WSN module. The final unit enables accurate readings and cross-sensitivity compensation thanks to a combination of simultaneous readings from multiple sensors. Real-time communication to the outside world is ensured via radio-frequency protocols, and data collection in a serial memory is also made possible for diagnostics applications

Interventions for raising breast cancer awareness in women

Background: Breast cancer continues to be the most commonly diagnosed cancer in women globally. Early detection, diagnosis and treatment of breast cancer are key to better outcomes. Since many women will discover a breast cancer symptom themselves, it is important that they are breast cancer aware i.e. have the knowledge, skills and confidence to detect breast changes and present promptly to a healthcare professional.Objectives: To assess the effectiveness of interventions for raising breast cancer awareness in women.Search methods: We searched the Cochrane Breast Cancer Group's Specialised Register (searched 25 January 2016), Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 12) in the Cochrane Library (searched 27 January 2016), MEDLINE OvidSP (2008 to 27 January 2016), Embase (Embase.com, 2008 to 27 January 2016), the World Health Organization’s International Clinical Trials Registry Platform (ICTRP) search portal and ClinicalTrials.gov (searched 27 Feburary 2016). We also searched the reference lists of identified articles and reviews and the grey literature for conference proceedings and published abstracts. No language restriction was applied.Selection criteriaRandomised controlled trials (RCTs) focusing on interventions for raising women’s breast cancer awareness i.e. knowledge of potential breast cancer symptoms/changes and the confidence to look at and feel their breasts, using any means of delivery, i.e. one-to-one/group/mass media campaign(s).Data collection and analysis: Two authors selected studies, independently extracted data and assessed risk of bias. We reported the odds ratio (OR) and 95% confidence intervals (CIs) for dichotomous outcomes and mean difference (MD) and standard deviation (SD) for continuous outcomes. Since it was not possible to combine data from included studies due to their heterogeneity, we present a narrative synthesis. We assessed the quality of evidence using GRADE methods.Main results: We included two RCTs involving 997 women: one RCT (867 women) randomised women to receive either a written booklet and usual care (intervention group 1), a written booklet and usual care plus a verbal interaction with a radiographer or research psychologist (intervention group 2) or usual care (control group); and the second RCT (130 women) randomised women to either an educational programme (three sessions of 60 to 90 minutes) or no intervention (control group).Knowledge of breast cancer symptoms: In the first study, knowledge of non-lump symptoms increased in intervention group 1 compared to the control group at two years postintervention, but not significantly (OR 1.1, 95% CI 0.7 to 1.6; P = 0.66; 449 women; moderate-quality evidence). Similarly, at two years postintervention, knowledge of symptoms increased in the intervention group 2 compared to the control group but not significantly (OR 1.4, 95% CI 0.9 to 2.1; P = 0.11; 434 women; moderate-quality evidence). In the second study, women’s awareness of breast cancer symptoms had increased one month post intervention in the educational group (MD 3.45, SD 5.11; 65 women; low-quality evidence) compared to the control group (MD −0.68, SD 5.93; 65 women; P < 0.001), where there was a decrease in awareness.Knowledge of age-related risk: In the first study, women’s knowledge of age-related risk of breast cancer increased, but not significantly, in intervention group 1 compared to control at two years postintervention (OR 1.8; 95% CI 0.9 to 3.5; P < 0.08; 447 women; moderate-quality evidence). Women's knowledge of risk increased significantly in intervention group 2 compared to control at two years postintervention (OR 4.8, 95% CI 2.6 to 9.0; P < 0.001; 431 women; moderate-quality evidence). In the second study, women’s perceived susceptibility (how at risk they considered themselves) to breast cancer had increased significantly one month post intervention in the educational group (MD 1.31, SD 3.57; 65 women; low-quality evidence) compared to the control group (MD −0.55, SD 3.31; 65 women; P = 0.005), where a decrease in perceived susceptibility was noted.Frequency of Breast Checking: In the first study, no significant change was noted for intervention group 1 compared to control at two years postintervention (OR 1.1, 95% CI 0.8 to 1.6; P = 0.54; 457 women; moderate-quality evidence). Monthly breast checking increased, but not significantly, in intervention group 2 compared to control at two years postintervention (OR 1.3, 95% CI 0.9 to 1.9; P = 0.14; 445 women; moderate-quality evidence). In the second study, women’s breast cancer preventive behaviours increased significantly one month post intervention in the educational group (MD 1.21, SD 2.54; 65 women; low-quality evidence) compared to the control group (MD 0.15, SD 2.94; 65 women; P < 0.045).Breast Cancer Awareness: Women’s overall breast cancer awareness did not change in intervention group 1 compared to control at two years postintervention (OR 1.8, 95% CI 0.6 to 5.30; P = 0.32; 435 women; moderate-quality evidence) while overall awareness increased in the intervention group 2 compared to control at two years postintervention (OR 8.1, 95% CI 2.7 to 25.0; P < 0.001; 420 women; moderate-quality evidence). In the second study, there was a significant increase in scores on the Health Belief Model (that included the constructs of awareness and perceived susceptibility) at one month postintervention in the educational group (mean 1.21, SD 2.54; 65 women) compared to the control group (mean 0.15, SD 2.94; 65 women; P = 0.045).Neither study reported outcomes relating to motivation to check their breasts, confidence to seek help, time from breast symptom discovery to presentation to a healthcare professional, intentions to seek help, quality of life, adverse effects of the interventions, stages of breast cancer, survival estimates or breast cancer mortality rates.Authors' conclusions: Based on the results of two RCTs, a brief intervention has the potential to increase women’s breast cancer awareness. However, findings of this review should be interpreted with caution, as GRADE assessment identified moderate-quality evidence in only one of the two studies reviewed. In addition, the included trials were heterogeneous in terms of the interventions, population studied and outcomes measured. Therefore, current evidence cannot be generalised to the wider context. Further studies including larger samples, validated outcome measures and longitudinal approaches are warranted

Miniaturised multi-MEMS sensor development

This paper describes the design, fabrication and initial characterisation of a MEMS-based environmental monitoring system. Intended for use with miniaturised Wireless Sensor Network (WSN) motes, the die measures 3 × 3 mm and incorporates humidity, temperature, corrosion, gas and gas flow velocity sensors on a single substrate. Fabricated using a combination of surface and bulk micromachining technologies, the sensor system is designed to replace discrete components on WSN module boards, thereby minimising space consumption and enabling smaller, cheaper wireless motes. Sensors have been characterised over a wide range of environmental conditions. An analysis of the effects of changes in environmental parameters other than the measurand of interest on the performance of the temperature and humidity sensors has been carried out, and corrections applied where necessary. A variety of corrosion monitors have been demonstrated. A gas flow velocity sensor, based on forced convective heat transfer and which has been thermally isolated from the silicon substrate in order to reduce power consumption and improve sensitivity at low flow-rates, has also been presented. The paper also outlines the design of the next generation sensing platform using the novel 10 mm wireless cube developed at Tyndall

Bifidobacterium animalis AHC7 protects against pathogen-induced NF-κB activation in vivo

BACKGROUND: Bifidobacteria and lactobacilli are among the early and important colonizers of the gastrointestinal tract and are generally considered to be part of a normal, healthy microbiota. It is believed that specific strains within the microbiota can influence host immune-reactivity and may play a role in protection from infection and aberrant inflammatory activity. One such strain, Bifidobacterium animalis AHC7, has been previously shown to protect against Salmonella typhimurium infection in mice and helps resolve acute idiopathic diarrhea in dogs. The aim of this study was to investigate the potential molecular and cellular mechanisms underpinning the Bifidobacterium animalis AHC7 protective effect. RESULTS: Following 4 hours of infection with Salmonella typhimurium, NF-κB activation was significantly elevated in vivo in placebo and Enterococcus faecium-fed animals while Bifidobacterium animalis AHC7 consumption significantly attenuated the NF-κB response. In vitro anti-CD3/CD28 stimulated Peyer's patch cells secreted significantly less TNF-α and IFN-γ following Bifidobacterium animalis AHC7 consumption. Stimulated cells released more IL-12p70 but this difference did not reach statistical significance. No alteration in mucosal IL-6, IL-10 or MCP-1 levels were observed. No statistically significant change in the cytokine profile of mesenteric lymph node cells was noted. In vitro, Bifidobacterium animalis AHC7 was bound by dendritic cells and induced secretion of both IL-10 and IL-12p70. In addition, co-culture of CD4+ T cells with Bifidobacterium animalis AHC7-stimulated dendritic cells resulted in a significant increase in CD25+Foxp3+ T cell numbers. CONCLUSION: Bifidobacterium animalis AHC7 exerts an anti-inflammatory effect via the attenuation of pro-inflammatory transcription factor activation in response to an infectious insult associated with modulation of pro-inflammatory cytokine production within the mucosa. The cellular mechanism underpinning Bifidobacterium animalis AHC7 mediated attenuation of NF-κB activation may include recognition of the bacterium by dendritic cells and induction of CD25+Foxp3+ T cells

The influence of protein concentration on key quality attributes of chickpea-based alternatives to cheese

In response to consumer demands, plant protein ingredients are increasingly being used in the formulation of plant-based alternatives to cheese. The aim of this study was to determine the influence of protein concentration on key quality attributes of chickpea-based alternatives to cheese. Moreover, the age-induced changes in such attributes were assessed, with samples analysed after 1 month of storage. After characterisation of the ingredients, the chickpea-based formulations were prepared by blending chickpea flour and protein concentrate in different proportions to obtain four samples of increasing protein content (i.e., 8.68–21.5%). Formulations were developed at pH ∼4.5, and a moisture content of 50%, with shea butter used to obtain 15% fat content. The differential scanning calorimetry thermograms of the samples showed a main peak around 30 °C, corresponding to transition of the shea butter, and a smaller peak around 70 °C related to starch gelatinisation. Analysis of microstructure showed formation of a protein matrix with more extensive protein structure at high protein concentration. Furthermore, none of the chickpea-based samples melted under the testing conditions and all samples showed increasing values for adhesiveness, springiness and cohesiveness with increasing protein content. However, hardness was the highest for the sample with the lowest protein content, likely due to starch retrogradation. After storage, hardness increased further for all samples. This work improves our understanding of the role of chickpea protein in developing plant-based alternatives to cheese and the challenges therein

Commensal-Induced Regulatory T Cells Mediate Protection against Pathogen-Stimulated NF-κB Activation

Host defence against infection requires a range of innate and adaptive immune responses that may lead to tissue damage. Such immune-mediated pathologies can be controlled with appropriate T regulatory (Treg) activity. The aim of the present study was to determine the influence of gut microbiota composition on Treg cellular activity and NF-κB activation associated with infection. Mice consumed the commensal microbe Bifidobacterium infantis 35624 followed by infection with Salmonella typhimurium or injection with LPS. In vivo NF-κB activation was quantified using biophotonic imaging. CD4+CD25+Foxp3+ T cell phenotypes and cytokine levels were assessed using flow cytometry while CD4+ T cells were isolated using magnetic beads for adoptive transfer to naïve animals. In vivo imaging revealed profound inhibition of infection and LPS induced NF-κB activity that preceded a reduction in S. typhimurium numbers and murine sickness behaviour scores in B. infantis–fed mice. In addition, pro-inflammatory cytokine secretion, T cell proliferation, and dendritic cell co-stimulatory molecule expression were significantly reduced. In contrast, CD4+CD25+Foxp3+ T cell numbers were significantly increased in the mucosa and spleen of mice fed B. infantis. Adoptive transfer of CD4+CD25+ T cells transferred the NF-κB inhibitory activity. Consumption of a single commensal micro-organism drives the generation and function of Treg cells which control excessive NF-κB activation in vivo. These cellular interactions provide the basis for a more complete understanding of the commensal-host-pathogen trilogue that contribute to host homeostatic mechanisms underpinning protection against aberrant activation of the innate immune system in response to a translocating pathogen or systemic LPS

Continuous stochastic Schrodinger equations and localization

The set of continuous norm-preserving stochastic Schrodinger equations associated with the Lindblad master equation is introduced. This set is used to describe the localization properties of the state vector toward eigenstates of the environment operator. Particular focus is placed on determining the stochastic equation which exhibits the highest rate of localization for wide open systems. An equation having such a property is proposed in the case of a single non-hermitian environment operator. This result is relevant to numerical simulations of quantum trajectories where localization properties are used to reduce the number of basis states needed to represent the system state, and thereby increase the speed of calculation.Comment: 18 pages in LaTeX + 6 figures (postscript), uses ioplppt.sty. To appear in J. Phys.

Prognostic Threshold for Circulating Tumor Cells in Patients With Pancreatic and Midgut Neuroendocrine Tumors

BACKGROUND: Circulating tumour cells (CTCs) are detectable in patients with NET and are accurate prognostic markers although the optimum threshold has not been defined. OBJECTIVE: To define optimal prognostic CTC threshold in pancreatic and midgut NET. PATIENTS AND METHODS: CellSearch was used to enumerate CTCs in 199 patients with metastatic pancreatic (PanNET) (90) or midgut NET (109). Patients were followed for progression free survival (PFS) and overall survival (OS) for a minimum of 3 years or until death. RESULTS: AUROC for progression at 12 months in PanNET and midgut NET identified the optimal CTC threshold as ≥1 and ≥2 respectively. In multivariate logistic regression analysis, these thresholds were predictive for 12 month progression with OR of 6.69 (p< 0.01) for PanNET and 5.88 (p<0.003) for midgut. The same thresholds were found to be optimal for predicting death at 36 months with an OR of 2.87 (p< 0.03) and 5.09 (p<0.005) for PanNET and midgut NET respectively. In multivariate Cox hazard regression analysis for PFS in PanNET, ≥ 1 CTC had HR 2.6 (p <0.01) whilst ≥ 2 CTCs had HR 2.25 (p < 0.01) in midgut NET. In multivariate analysis OS in PanNET, ≥ 1 CTC had HR 3.16 (p < 0.01) and in midgut NET, ≥ 2 CTCs had HR of 1.73 (p < 0.06). CONCLUSIONS: The optimal CTC threshold to predict PFS and OS in metastatic PanNET and midgut NET is 1 and 2, respectively. These thresholds can be used to stratify patients in clinical practice and clinical trials