Core components for effective infection prevention and control programmes: new WHO evidence-based recommendations

Abstract Health care-associated infections (HAI) are a major public health problem with a significant impact on morbidity, mortality and quality of life. They represent also an important economic burden to health systems worldwide. However, a large proportion of HAI are preventable through effective infection prevention and control (IPC) measures. Improvements in IPC at the national and facility level are critical for the successful containment of antimicrobial resistance and the prevention of HAI, including outbreaks of highly transmissible diseases through high quality care within the context of universal health coverage. Given the limited availability of IPC evidence-based guidance and standards, the World Health Organization (WHO) decided to prioritize the development of global recommendations on the core components of effective IPC programmes both at the national and acute health care facility level, based on systematic literature reviews and expert consensus. The aim of the guideline development process was to identify the evidence and evaluate its quality, consider patient values and preferences, resource implications, and the feasibility and acceptability of the recommendations. As a result, 11 recommendations and three good practice statements are presented here, including a summary of the supporting evidence, and form the substance of a new WHO IPC guideline

A systematic review of hand hygiene improvement strategies: a behavioural approach

Contains fulltext : 108114.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Many strategies have been designed and evaluated to address the problem of low hand hygiene (HH) compliance. Which of these strategies are most effective and how they work is still unclear. Here we describe frequently used improvement strategies and related determinants of behaviour change that prompt good HH behaviour to provide a better overview of the choice and content of such strategies. METHODS: Systematic searches of experimental and quasi-experimental research on HH improvement strategies were conducted in Medline, Embase, CINAHL, and Cochrane databases from January 2000 to November 2009. First, we extracted the study characteristics using the EPOC Data Collection Checklist, including study objectives, setting, study design, target population, outcome measures, description of the intervention, analysis, and results. Second, we used the Taxonomy of Behavioural Change Techniques to identify targeted determinants. RESULTS: We reviewed 41 studies. The most frequently addressed determinants were knowledge, awareness, action control, and facilitation of behaviour. Fewer studies addressed social influence, attitude, self-efficacy, and intention. Thirteen studies used a controlled design to measure the effects of HH improvement strategies on HH behaviour. The effectiveness of the strategies varied substantially, but most controlled studies showed positive results. The median effect size of these strategies increased from 17.6 (relative difference) addressing one determinant to 49.5 for the studies that addressed five determinants. CONCLUSIONS: By focussing on determinants of behaviour change, we found hidden and valuable components in HH improvement strategies. Addressing only determinants such as knowledge, awareness, action control, and facilitation is not enough to change HH behaviour. Addressing combinations of different determinants showed better results. This indicates that we should be more creative in the application of alternative improvement activities addressing determinants such as social influence, attitude, self-efficacy, or intention

Regulation of neuronal survival by the extracellular signal-regulated protein kinase 5

The extracellular signal-regulated protein kinase 5 (ERK5) is a mitogen-activated protein kinase (MAPK) that phosphorylates and regulates various transcription factors in response to growth factors and extra-cellular stresses. To address its biological function during the development of the peripheral nervous system (PNS), we have engineered a novel model of sympathetic neurons in which the erk5 gene can be deleted in vitro. Our data provide for the first time genetic evidence that ERK5 is required to mediate the survival response of neurons to nerve growth factor (NGF). Increased cell death associated with the loss of ERK5 is caused by elevated expression of the BH3-only members of the Bcl-2 family, Bad and Bim. Further investigation indicated that ERK5 suppresses the transcription of the bad and the bim genes via Ca(++)/cAMP response element binding protein (CREB) and Forkhead box 03a (Foxo3a), respectively. Consistently, we found that the phosphorylation of both p90 ribosomal S6 kinase (RSK) and protein kinase B (PKB) is impaired in neurons lacking ERK5. Together these findings reveal a novel signaling mechanism that promotes neuronal survival during the development of the PNS

Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize

Tumour resistance to radiotherapy remains a barrier to improving cancer patient outcomes. To overcome radioresistance, certain drugs have been found to sensitize cells to ionizing radiation (IR). In theory, more potent radiosensitizing drugs should increase tumour kill and improve patient outcomes. In practice, clinical utility of potent radiosensitizing drugs is curtailed by off-target side effects. Here we report potent anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize to tumours based on surface receptor expression. While two classes of potent anti-tubulins, auristatins and maytansinoids, indiscriminately radiosensitize tumour cells, conjugating these potent anti-tubulins to anti-ErbB antibodies restrict their radiosensitizing capacity. Of translational significance, we report that a clinically used maytansinoid ADC, ado-trastuzumab emtansine (T-DM1), with IR prolongs tumour control in target expressing HER2+ tumours but not target negative tumours. In contrast to ErbB signal inhibition, our findings establish an alternative therapeutic paradigm for ErbB-based radiosensitization using antibodies to restrict radiosensitizer delivery