Outreach and Early Warning Systems (EWS) for the prevention of intensive care admission and death of critically ill adult patients on general hospital wards

BACKGROUND: Despite the fact that outreach and early warning systems (EWS) are an integral part of a hospital wide systems approach to improve the early identification and management of deteriorating patients on general hospital wards, the widespread implementation of these interventions in practice is not based on robust research evidence. OBJECTIVES: The primary objective was to determine the impact of critical care outreach services on hospital mortality rates. Secondary objectives included determining the effect of outreach services on intensive care unit (ICU) admission patterns, length of hospital stay and adverse events. SEARCH STRATEGY: The review authors searched the following electronic databases: EPOC Specialised Register, The Cochrane Central Register of Controlled Trials (CENTRAL) and other Cochrane databases (all on The Cochrane Library 2006, Issue 3), MEDLINE (1996-June week 3 2006), EMBASE (1974-week 26 2006), CINAHL (1982-July week 5 2006), First Search (1992-2005) and CAB Health (1990-July 2006); also reference lists of relevant articles, conference abstracts, and made contact with experts and critical care organisations for further information. SELECTION CRITERIA: Randomised controlled trials (RCTs), controlled clinical trials (CCTs), controlled before and after studies (CBAs) and interrupted time series designs (ITS) which measured hospital mortality, unanticipated ICU admissions, ICU readmissions, length of hospital stay and adverse events following implementation of outreach and EWS in a general hospital ward to identify deteriorating adult patients versus general hospital ward setting without outreach and EWS were included in the review. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data and two review authors assessed the methodological quality of the included studies. Meta-analysis was not possible due to heterogeneity. Summary statistics and descriptive summaries of primary and secondary outcomes are presented for each study. MAIN RESULTS: Two cluster-randomised control trials were included: one randomised at hospital level (23 hospitals in Australia) and one at ward level (16 wards in the UK). The primary outcome in the Australian trial (a composite score comprising incidence of unexpected cardiac arrests, unexpected deaths and unplanned ICU admissions) showed no statistical significant difference between control and medical emergency team (MET) hospitals (adjusted P value 0.640; adjusted odds ratio (OR) 0.98; 95% confidence interval (CI) 0.83 to 1.16). The UK-based trial found that outreach reduced in-hospital mortality (adjusted OR 0.52; 95% CI 0.32 to 0.85) compared with the control group. AUTHORS' CONCLUSIONS: The evidence from this review highlights the diversity and poor methodological quality of most studies investigating outreach. The results of the two included studies showed either no evidence of the effectiveness of outreach or a reduction in overall mortality in patients receiving outreach. The lack of evidence on outreach requires further multi-site RCT's to determine potential effectiveness.

The cost-effectiveness of the SPHERE intervention for the secondary prevention of coronary heart disease

Objectives: The Secondary Prevention of Heart disEase in geneRal practicE (SPHERE) trial has recently reported. This study examines the cost-effectiveness of the SPHERE intervention in both healthcare systems on the island of Ireland. Methods: Incremental cost-effectiveness analysis. A probabilistic model was developed to combine within-trial and beyond-trial impacts of treatment to estimate the lifetime costs and benefits of two secondary prevention strategies: Intervention - tailored practice and patient care plans; and Control - standardized usual care. Results: The intervention strategy resulted in mean cost savings per patient of 512.77 (95 percent confidence interval [CI], 1086.46-91.98) and an increase in mean quality-adjusted life-years (QALYs) per patient of 0.0051 (95 percent CI, 0.0101-0.0200), when compared with the control strategy. The probability of the intervention being cost-effective was 94 percent if decision makers are willing to pay €45,000 per additional QALY. Conclusions: Decision makers in both settings must determine whether the level of evidence presented is sufficient to justify the adoption of the SPHERE intervention in clinical practice. Copyright © Cambridge University Press 2010.

The use of lytic bacteriophages in the prevention and eradication of biofilms of Proteus mirabilis and Escherichia coli.

Antibiotics have been the cornerstone of the clinical management of bacterial infections since their discovery in the early part of the last century. Eight decades later, their widespread, often indiscriminate use, has resulted in an overall reduction in their effectiveness, with reports of multidrug-resistant bacteria now commonplace. Increasing reliance on indwelling medical devices, which are inherently susceptible to biofilm-mediated infections, has contributed to unacceptably high rates of nosocomial infections, placing a strain on healthcare budgets. This study investigates the use of lytic bacteriophages in the treatment and prevention of biofilms of bacterial species commonly associated with infections of indwelling urological devices and catheter-associated urinary tract infections. The use of lytic bacteriophages against established biofilms of Proteus mirabilis and Escherichia coli is described, whereby biofilm populations have been reduced successfully by three to four log cycles (99.9-99.99% removal). The prevention of biofilm formation on Foley catheter biomaterials following impregnation of hydrogel-coated catheter sections with a lytic bacteriophage has also been investigated. This has revealed an approximate 90% reduction in both P. mirabilis and E. coli biofilm formation on bacteriophage-treated catheters when compared with untreated controls.

Mandated prevention in child welfare: Considerations from a framework shaping ethical inquiry

Summary: This article outlines a framework for approaching ethical dilemmas arising from the development, evaluation and implementation of child welfare policies. As such, it is relevant to policy-makers, social researchers and social workers. The central tenets of the framework are developed by drawing on ideas from moral philosophy and critical social theory. These ideas are presented as axioms, theorems and corollaries, a format which has been employed in the social sciences to offer a rational justification for a set of claims. • Findings: This process of reasoning leads to four principle axioms that are seen to shape the ethical scrutiny of social policy: 1) problematizing knowledge; 2) utilizing structured forms of inquiry to enhance understanding; 3) engendering enabling communication with those affected by the ethical concern; and 4) enhancing self-awareness. • Applications: The four axioms are then applied, by way of example, to the current and contentious, 'third way' policy of mandated prevention in child welfare, where the aim is to obviate deleterious outcomes in later life. It is argued that the framework can be applied beyond this specific concern to other pressing, ethical challenges in child welfare.

Systematic review of the effect of diet and exercise lifestyle interventions in the secondary prevention of coronary heart disease.

The effectiveness of lifestyle interventions within secondary prevention of coronary heart disease(CHD)remains unclear.This systematic review aimed to determine their effectiveness and included randomized controlled trials of lifestyle interventions, in primary care or community settings, with a minimum follow-up of three months, published since 1990. 21 trials with 10,799 patients were included; the interventions were multifactorial (10), educational (4), psychological (3), dietary (1), organisational (2), and exercise(1). The overall results for modifiable risk factors suggested improvements in dietary and exercise outcomes but no overall effect on smoking outcomes. In trials that examined mortality and morbidity,significant benefits were reported for total mortality (in 4 of 6 trials;overall risk ratio(RR) 0.75 (95%confidence intervals (CI) 0.65, 0.87)), cardiovascular mortality (3 of 8 trials; overall RR 0.63(95%CI 0.47, 0.84)), and nonfatal cardiac events(5 of 9 trials; overall RR 0.68(95%CI 0.55, 0.84)). The heterogeneity between trials and generally poor quality of trials make any concrete conclusions difficult. However, the beneficial effects observed in this review are encouraging and should stimulate further research.

The Delta Np63 Proteins Are Key Allies of BRCA1 in the Prevention of Basal-Like Breast Cancer

Little is known about the origin of basal-like breast cancers, an aggressive disease that is highly similar to BRCA1-mutant breast cancers. p63 family proteins that are structurally related to the p53 suppressor protein are known to function in stem cell regulation and stratified epithelia development in multiple tissues, and p63 expression may be a marker of basal-like breast cancers. Here we report that Delta Np63 isoforms of p63 are transcriptional targets for positive regulation by BRCA1. Our analyses of breast cancer tissue microarrays and BRCA1-modulated breast cancer cell lines do not support earlier reports that p63 is a marker of basal-like or BRCA1 mutant cancers. Nevertheless, we found that BRCA1 interacts with the specific p63 isoform Delta Np63 gamma along with transcription factor isoforms AP-2 alpha and AP-2 gamma. BRCA1 required Delta Np63 gamma and AP-2 gamma to localize to an intronic enhancer region within the p63 gene to upregulate transcription of the Delta Np63 isoforms. In mammary stem/progenitor cells, siRNA- mediated knockdown of Delta Np63 expression resulted in genomic instability, increased cell proliferation, loss of DNA damage checkpoint control, and impaired growth control. Together, our findings establish that transcriptional upregulation of Delta Np63 proteins is critical for BRCA1 suppressor function and that defects in BRCA1-Delta Np63 signaling are key events in the pathogenesis of basal-like breast cancer. Cancer Res; 71( 5); 1933-44. (c) 2011 AACR.

Blood pressure lowering in patients without prior cerebrovascular disease for prevention of cognitive impairment and dementia

Background: This is an update of a previous review (McGuinness 2006). Hypertension and cognitive impairment are prevalent in older people. Hypertension is a direct risk factor for vascular dementia (VaD) and recent studies have suggested hypertension impacts upon prevalence of Alzheimer's disease (AD). Therefore does treatment of hypertension prevent cognitive decline?
Objectives: To assess the effects of blood pressure lowering treatments for the prevention of dementia and cognitive decline in patients with hypertension but no history of cerebrovascular disease.
Search strategy: The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group, The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS as well as many trials databases and grey literature sources were searched on 13 February 2008 using the terms: hypertens$ OR anti-hypertens$. Selection criteria: Randomized, double-blind, placebo controlled trials in which pharmacological or non-pharmacological interventions to lower blood pressure were given for at least six months.
Data collection and analysis: Two independent reviewers assessed trial quality and extracted data. The following outcomes were assessed: incidence of dementia, cognitive change from baseline, blood pressure level, incidence and severity of side effects and quality of life.
Main results: Four trials including 15,936 hypertensive subjects were identified. Average age was 75.4 years. Mean blood pressure at entry across the studies was 171/86 mmHg. The combined result of the four trials reporting incidence of dementia indicated no significant difference between treatment and placebo (236/7767 versus 259/7660, Odds Ratio (OR) = 0.89, 95% CI 0.74, 1.07) and there was considerable heterogeneity between the trials. The combined results from the three trials reporting change in Mini Mental State Examination (MMSE) did not indicate a benefit from treatment (Weighted Mean Difference (WMD) = 0.42, 95%CI 0.30, 0.53). Both systolic and diastolic blood pressure levels were reduced significantly in the three trials assessing this outcome (WMD = -10.22, 95% CI -10.78, -9.66 for systolic blood pressure, WMD = -4.28, 95% CI -4.58, -3.98 for diastolic blood pressure). Three trials reported adverse effects requiring discontinuation of treatment and the combined results indicated no significant difference (OR = 1.01, 95% CI 0.92, 1.11). When analysed separately, however, more patients on placebo in Syst Eur 1997 were likely to discontinue treatment due to side effects; the converse was true in SHEP 1991. Quality of life data could not be analysed in the four studies. Analysis of the included studies in this review was problematic as many of the control subjects received antihypertensive treatment because their blood pressures exceeded pre-set values. In most cases the study became a comparison between the study drug against a usual antihypertensive regimen.
Authors' conclusions: There is no convincing evidence fromthe trials identified that blood pressure lowering in late-life prevents the development of dementia or cognitive impairment in hypertensive patients with no apparent prior cerebrovascular disease. There were significant problems identified with analysing the data, however, due to the number of patients lost to follow-up and the number of placebo patients who received active treatment. This introduced bias. More robust results may be obtained by conducting a meta-analysis using individual patient data.