Antifoams in non-aqueous diesel fuels: Thin liquid film dynamics and antifoam mechanisms.

HypothesisFoaming in diesel fuels is not well understood and leads to operational challenges. To combat deleterious effects of foaming, diesel formulations can include additives called antifoams. Existing antifoams, unfortunately, are inherently ash-generating when combusted, with unknown environmental impacts. They are prohibited in certain countries, so identifying effective alternative ash-free antifoam chemistries is needed. ExperimentsWe conduct systematic characterization of foam stabilization and antifoaming mechanisms in diesel for two different antifoams (silicone-containing & ashless chemistries). Employing a custom technique combining single-bubble/single-antifoam-droplet manipulation with white light interferometry, we also obtain mechanistic insights into foam stability and antifoam dynamics. ResultsCoalescence times from both bulk foam and single bubble experiments confirm ashless antifoams are effective at reducing foaming, demonstrating the potential of ashless antifoams. Further, we perform single-antifoam-droplet experiments and obtain direct experimental evidence revealing the elusive antifoaming mechanisms. Interestingly, the silicone-containing and ashless antifoams seemingly function via two different mechanisms: spreading and dewetting respectively. This surprising finding refutes conventional wisdom that spreading is likely the only antifoam mechanism in diesels. These results and the reported experimental framework significantly enhance the scientific understanding of non-aqueous foams and will accelerate the engineering of alternative antifoam chemistries for non-aqueous systems.

Choosing wisely in burn care.

BACKGROUND: The Choosing Wisely Campaign was launched in 2012 and has been applied to a broad spectrum of disciplines in almost thirty countries, with the objective of reducing unnecessary or potentially harmful investigations and procedures, thus limiting costs and improving outcomes. In Canada, patients with burn injuries are usually initially assessed by primary care and emergency providers, while plastic or general surgeons provide ongoing management. We sought to develop a series of Choosing Wisely statements for burn care to guide these practitioners and inform suitable, cost-effective investigations and treatment choices. METHODS: The Choosing Wisely Canada list for Burns was developed by members of the Canadian Special Interest Group of the American Burn Association. Eleven recommendations were generated from an initial list of 29 statements using a modified Delphi process and SurveyMonkey™. RESULTS: Recommendations included statements on avoidance of prophylactic antibiotics, restriction of blood products, use of adjunctive analgesic medications, monitoring and titration of opioid analgesics, and minimizing 'routine' bloodwork, microbiology or radiological investigations. CONCLUSIONS: The Choosing Wisely recommendations aim to encourage greater discussion between those involved in burn care, other health care professionals, and their patients, with a view to reduce the cost and adverse effects associated with unnecessary therapeutic and diagnostic procedures, while still maintaining high standards of evidence-based burn care.

Epidemiology of Enterotoxigenic Escherichia coli infection in Minnesota, 2016-2017.

Enterotoxigenic Escherichia coli (ETEC) is a well-established cause of traveller's diarrhoea and occasional domestic foodborne illness outbreaks in the USA. Although ETEC are not detected by conventional stool culture methods used in clinical laboratories, syndromic culture-independent diagnostic tests (CIDTs) capable of detecting ETEC have become increasingly prevalent in the last decade. This study describes the epidemiology of ETEC infections reported to the Minnesota Department of Health (MDH) during 2016-2017. ETEC-positive stool specimens were submitted to MDH to confirm the presence of ETEC DNA by polymerase chain reaction (PCR). Cases were interviewed to ascertain illness and exposures. Contemporaneous Salmonella cases were used as a comparison group in a case-case comparison analysis of risk factors. Of 222 ETEC-positive specimens received by MDH, 108 (49%) were concordant by PCR. ETEC was the sixth most frequently reported bacterial enteric pathogen among a subset of CIDT-positive specimens. Sixty-nine (64%) laboratory-confirmed cases had an additional pathogen codetected with ETEC, including enteroaggregative E. coli (n = 40) and enteropathogenic E. coli (n = 39). Although travel is a risk factor for ETEC infection, only 43% of cases travelled internationally, providing evidence for ETEC as an underestimated source of domestically acquired enteric illness in the USA.

Treatment of Ebola-related critical illness.

PURPOSE: To explore contemporary clincial case management of patients with Ebola virus disease. METHODS: A narrative review from a clinical perspective of clinical features, diagnostic tests, treatments and outcomes of patients with Ebola virus disease. RESULTS: Substantial advances have been made in the care of patients with Ebola virus disease (EVD), precipitated by the unprecedented extent of the 2014-2016 outbreak. There has been improved point-of-care diagnostics, improved characterization of the clinical course of EVD, improved patient-optimized standards of care, evaluation of effective anti-Ebola therapies, administration of effective vaccines, and development of innovative Ebola treatment units. A better understanding of the Ebola virus disease clinical syndrome has led to the appreciation of a central role for critical care clinicians-over 50% of patients have life-threatening complications, including hypotension, severe electrolyte imbalance, acute kidney injury, metabolic acidosis and respiratory failure. Accordingly, patients often require critical care interventions such as monitoring of vital signs, intravenous fluid resuscitation, intravenous vasoactive medications, frequent diagnostic laboratory testing, renal replacement therapy, oxygen and occasionally mechanical ventilation. CONCLUSION: With advanced training and adherence to infection prevention and control practices, clinical interventions, including critical care, are feasible and safe to perform in critically ill patients. With specific anti-Ebola medications, most patients can survive Ebola virus infection.

An Improved Detached-Leaf Assay for Phenotyping Net Blotch of Barley Caused by Pyrenophora teres.

Net blotch, caused by Pyrenophora teres, is a major barley (Hordeum vulgare) leaf disease worldwide. P. teres occurs as two forms-P. teres f. teres, and P. teres f. maculata-inducing net and spot-like symptoms, respectively. An intact-seedling assay, where entire seedlings are inoculated by spraying with a conidial suspension, is frequently used for phenotyping net blotch. However, this presents a biosecurity risk in the glasshouse when nonlocal isolates are being screened. Alternatively, a detached-leaf assay (DLA-droplet method) can be used in which leaf segments laid out in a covered tray are inoculated with droplets of a conidial suspension, confining the inoculum. However, using this method, net and spot form symptoms cannot be distinguished from each other. We have developed an improved DLA (DLA-spray method) in which detached whole leaves are sprayed with the inoculum to produce distinct lesions. We compare the results for the three phenotyping methods above using four isolates from both net and spot forms of the disease to inoculate a standard set of eight barley genotypes. Results indicate that the DLA-spray method is a functional, informative and rapid test that readily differentiates the two forms of the pathogen in a biosecure environment.

Zika virus-induced neurological critical illness in Latin America: Severe Guillain-Barre Syndrome and encephalitis.

Zika virus (ZIKAV) is classically described as causing minor symptoms in adult patients, however neurologic complications have been recognized. The recent outbreak in Central and South America has resulted in serious illness in some adult patients. We report adult patients in Latin America diagnosed with ZIKAV infection admitted to Intensive Care Units (ICUs). METHODS: Multicenter, prospective case series of adult patients with laboratory diagnosis of ZIKAV in 16 ICUs in 8 countries. RESULTS: Between December 1st 2015 and April 2nd 2016, 16 ICUs in 8 countries enrolled 49 critically ill patients with diagnosis of ZIKAV infection. We included 10 critically ill patients with ZIKAV infection, as diagnosed with RT-PCR, admitted to the ICU. Neurologic manifestations concordant with Guillain-Barre Syndrome (GBS) were present in all patients, although 2 evolved into an encephalitis-like picture. 2 cases died, one due to encephalitis, the other septic shock. CONCLUSIONS: Differing from what was usually reported, ZIKAV infection can result in life-threatening neurologic illness in adults, including GBS and encephalitis. Collaborative reporting to identify severe illness from an emerging pathogen can provide valuable insights into disease epidemiology and clinical presentation, and inform public health authorities about acute care priorities.

Evaluation of the BioFire FilmArray® GastrointestinalPanel in a Midwestern Academic Hospital.

The BioFire FilmArray® Gastrointestinal Panel (GIP) was implemented to replace traditional stool culture and enzyme immunoassay (EIA) testing for stool pathogens. The purpose of this study was to evaluate the detection rate, incidence of coinfection, and culture recovery rate of gastrointestinal (GI) pathogens detected by the GIP over a 1-year period. A total of 2257 stools collected from January to December 2015 were tested using the GIP. Clostridium difficile colonization was also evaluated by an antigen/toxin EIA and confirmatory polymerase chain reaction (PCR). The GIP detected one pathogen in 911 (40.4%) specimens. Coinfections were detected in 176 (7.8%) of these specimens. The most frequently detected pathogens were C. difficile (15.2%), norovirus (8.9%), enteropathogenic Escherichia coli (7.1%), enteroaggregative E. coli (3.4%), Campylobacter spp. (2.3%), and sapovirus (2.0%). Each of the remaining GIP targets had a detection rate of ≤1.6%. The recovery of bacteria for public health investigations varied, with rates as high as 77% for Salmonella to as low as 30% for Yersinia enterocolitica. Of stools positive for C. difficile on the GIP that were tested by EIA, only 42.7% (88/206) were found to be producing detectable toxin. Overall, the implementation of the GIP resulted in high detection rates of GI pathogens, including the frequent detection of coinfections. This is a promising test to streamline the testing of agents causing infectious gastroenteritis from multiple tests down to a single order with limited hands-on time. Ongoing studies will need to assess the impact that the GIP has on downstream patient care and public health practices.

Long-term outcomes and healthcare utilization following critical illness--a population-based study.

BACKGROUND: The purpose of this study was to examine hospital mortality, long-term mortality, and health service utilization among critically ill patients. We also determined whether these outcomes differed according to demographic and clinical characteristics. METHODS: We conducted a retrospective cohort study of adults (age ≥ 18 years) who survived admission to an intensive care unit (ICU) in Ontario, Canada, between 1 April 2002 and 31 March 2012, excluding isolated admissions to step-down or intermediate ICUs, coronary care ICUs, or cardiac surgery ICUs. Adults (age ≥ 18 years) who survived an acute hospitalization that did not include an ICU stay formed the comparator group. The primary outcome was mortality following hospital discharge. Secondary outcomes were healthcare utilization, including emergency room admissions and hospital readmissions during follow-up. RESULTS: Over the study interval, 500,124 patients were admitted to ICUs and 420,187 (84%) survived to hospital discharge. Median follow-up for survivors was 5.3 (interquartile range 2.5, 8.2) years. Patients admitted to an ICU were more likely to subsequently visit the emergency department, be readmitted to the hospital and ICU, receive home care support, require rehabilitation, and be admitted for long-term care. Those requiring more resources within the ICU required more resources after discharge. One-third of patients admitted to the ICU died during long-term follow-up, with overall probabilities of death of 11% and 29% at 1 year and 5 years, respectively. In the adjusted analysis, there was an increasing hazard of death with increasing age, reaching a hazard ratio of 18.08 (95 % confidence interval 16.60-19.68) for those ≥ 85 years of age compared with those aged 18-24 years. CONCLUSIONS: Healthcare utilization after hospital discharge was higher among ICU patients, and also among those requiring more healthcare resources during their ICU admission, than among all hospitalized patients as a group. One-third of ICU patients died within the 5 years following discharge, and age was the most influential determinant of outcome. These findings should help target post-ICU discharge services for high-risk groups and better inform goals-of-care discussions for elderly critically ill patients.

In vitro photoacoustic sensing of calcium dynamics with Arsenazo III.

Imaging of cellular electric potential via calcium-ion sensitive contrast agents is a useful tool, but current it lacks sufficient depth penetration. We explore contrast-enhanced photoacoustic (PA) imaging, using Arsenazo III dye, to visualize cardiac myocyte depolarization in vitro. Phantom results show strong linearity of PA signal with dye concentration (R 2 > 0.95), and agree spectrally with extinction measurements with varying calcium concentration. Cell studies indicate a significant (> 100-fold) increase in PA signal for dye-treated cells, as well as a 10-fold increase in peak-to-peak variation during a 30-second window. This suggests contrast-enhanced PA imaging may have sufficient sensitivity and specificity for depth-resolved visualization of tissue depolarization in real-time.

Therapeutic efficacy of the combination of doxorubicin-loaded liposomes with inertial cavitation generated by confocal ultrasound in AT2 Dunning rat tumour model.

The combination of liposomal doxorubicin (DXR) and confocal ultrasound (US) was investigated for the enhancement of drug delivery in a rat tumour model. The liposomes, based on the unsaturated phospholipid dierucoylphosphocholine, were designed to be stable during blood circulation in order to maximize accumulation in tumour tissue and to release drug content upon US stimulation. A confocal US setup was developed for delivering inertial cavitation to tumours in a well-controlled and reproducible manner. In vitro studies confirm drug release from liposomes as a function of inertial cavitation dose, while in vivo pharmacokinetic studies show long blood circulation times and peak tumour accumulation at 24-48 h post intravenous administration. Animals injected 6 mg kg(-1) liposomal DXR exposed to US treatment 48 h after administration show significant tumour growth delay compared to control groups. A liposomal DXR dose of 3 mg kg(-1), however, did not induce any significant therapeutic response. This study demonstrates that inertial cavitation can be generated in such a fashion as to disrupt drug carrying liposomes which have accumulated in the tumour, and thereby increase therapeutic effect with a minimum direct effect on the tissue. Such an approach is an important step towards a therapeutic application of cavitation-induced drug delivery and reduced chemotherapy toxicity.

Contribution of inertial cavitation in the enhancement of in vitro transscleral drug delivery.

In ocular drug delivery, the sclera is a promising pathway for administering drugs to both the anterior and posterior segments of the eye. Due to the low permeability of the sclera, however, efficient drug delivery is challenging. In this study, pulsed ultrasound (US) was investigated as a potential method for enhancing drug delivery to the eye through the sclera. The permeability of rabbit scleral tissue to a model drug compound, sodium fluorescein, was measured after US-irradiation at 1.1 MHz using time-averaged acoustic powers of 0.5-5.4 W (6.8-12.8 MPa peak negative pressure), with a fixed duty cycle of 2.5% for two different pulse repetition frequencies of 100 and 1000 Hz. Acoustic cavitation activity was measured during exposures using a passive cavitation detector and was used to quantify the level of bubble activity. A correlation between the amount of cavitation activity and the enhancement of scleral permeability was demonstrated with a significant enhancement in permeability of US exposed samples compared to controls. Transmission electron microscopy showed no evidence of significant alteration in viability of tissue exposed to US exposures. A pulsed US protocol designed to maximum cavitation activity may therefore be a viable method for enhancing drug delivery to the eye.

In vivo monitoring of liposomal release in tumours following ultrasound stimulation.

Dioeleoylphosphatidylethanolamine (DOPE)-based liposomes were recently reported as a new class of liposomes for ultrasound (US)-mediated drug delivery. The liposomes showed both high stability and in vitro US-mediated drug release (sonosensitivity). In the current study, in vivo proof-of-principle of US triggered release in tumoured mice was demonstrated using optical imaging. Confocal non-thermal US was used to deliver cavitation to tumours in a well-controlled manner. To detect in vivo release, the near infrared fluorochrome Al (III) Phthalocyanine Chloride Tetrasulphonic acid (AlPcS4) was encapsulated into both DOPE-based liposomes and control liposomes based on hydrogenated soy phosphatidylcholine (HSPC). Encapsulation causes concentration dependent quenching of fluorescence that is recovered upon AlPcS4 release from the liposomes. Exposure of tumours to US resulted in a significant increase in fluorescence in mice administered with DOPE-based liposomes, but no change in the mice treated with HSPC-based liposomes. Thus, DOPE-based liposomes showed superior sonosensitivity compared to HSPC-based liposomes in vivo.

Quantification of normal vaginal constituents using a new wet preparation technique.

OBJECTIVE: This study aimed to evaluate a new method for preparing vaginal wet preparations to enable quantification of cells and lactobacilli. The current nonstandardized technique allows for a variable amount of vaginal fluid collected, diluted by a variable amount of saline/KOH, and no quantification of constituents. MATERIALS: The vaginal fluids from 100 randomly selected women without vulvovaginitis symptoms presenting to the author's practice at Mayo Clinic underwent analysis by the quantification technique. Women were excluded if they were younger than 18 years, had antibiotics within the past 2 months, currently on their period, had placed anything in the vagina for the past 24 hours, used Depo-Provera, or were lactating. METHODS: All the wet preparations were made by mixing the natural vaginal fluids with 3 mL of sterile normal saline. Spinal diluting fluid was added to the saline preparation. The saline and KOH mixtures were injected into separate wells of KOVA Glasstic Grid Slide and analyzed with a phase-contrast microscope at 40× and 60×. The concentration of leukocytes, lactobacilli, and squamous cells and the degree of maturation of the majority (>50%) of squamous cells were assessed, and it was determined whether there was excessive non-lactobacilli bacteria (EB) as evident by clumps of bacteria in the background fluid and speckling on the squamous cells. RESULTS: The 3 most common patterns to occur were as follows: First, 51% (95% confidence interval [CI] = 41%-60%) of the total specimens had abundant lactobacilli, no leukocytes, more than 50% fully maturated squamous cells, and no EB. Second, 22% (95% CI = 14%-32%) of the total specimens had low lactobacilli counts, no leukocytes, more than 50% undermaturated squamous cells, and no EB. Third, 12% (95% CI = 6%-20%) of the total specimens had abundant lactobacilli, leukocytes, more than 50% fully maturated squamous cells, and no EB. CONCLUSIONS: It is imperative to be able to objectively quantify normal vaginal secretion constituents so that (1) the abnormal patterns can be demarcated and (2) treatment targets of what constitutes healthy vaginal conditions can be provided.

Measurement properties of the 6-min walk test in individuals with exercise-induced pulmonary arterial hypertension.

BACKGROUND: Exercise-induced pulmonary arterial hypertension (EIPAH) is associated with reduced peak exercise cardiac output (CO) and aerobic capacity (peak ). We investigated the validity of the encouraged 6-min walk test (6MWT) to identify exercise limitation and estimate aerobic capacity in subjects with EIPAH. METHODS: Seventeen subjects with EIPAH (56 ± 14 years, 15 women) and 20 healthy controls (57 ± 13 years, 19 women) underwent two encouraged 6MWTs and a symptom-limited cardiopulmonary exercise test (CPET). To measure central haemodynamics, subjects with EIPAH performed the CPET with a pulmonary artery catheter in situ. RESULTS: Compared with controls, subjects with EIPAH had reduced peak (1.2 ± 0.4 vs 1.7 ± 0.5, L/min, P < 0.01), 6-min walk distance (6MWD) (575 ± 86 vs 669 ± 76 m, P < 0.001) and 6-min walk work (6MWW) (39 ± 11 vs 45 ± 7 km.kg, P < 0.01). In subjects with EIPAH, there was a moderate correlation between 6MWD and peak (r= 0.72, P < 0.01) and a strong correlation between 6MWW and peak (r= 0.86, P < 0.001). There were significant correlations between 6MWD and peak CO (r= 0.59, P < 0.05), and between peak and peak CO (r= 0.55, P < 0.05). Peak heart rate was similar in the CPET and 6MWT in subjects with EIPAH (133 ± 15 vs 133 ± 19 beats/min, P= 0.8). CONCLUSIONS: The encouraged 6MWT identifies reduced exercise capacity and provides a valid estimate of aerobic capacity in EIPAH.

Epidemiology of influenza-associated hospitalization in adults, Toronto, 2007/8.

The purpose of this investigation was to identify when diagnostic testing and empirical antiviral therapy should be considered for adult patients requiring hospitalization during influenza seasons. During the 2007/8 influenza season, six acute care hospitals in the Greater Toronto Area participated in active surveillance for laboratory-confirmed influenza requiring hospitalization. Nasopharyngeal (NP) swabs were obtained from patients presenting with acute respiratory or cardiac illness, or with febrile illness without clear non-respiratory etiology. Predictors of influenza were analyzed by multivariable logistic regression analysis and likelihoods of influenza infection in various patient groups were calculated. Two hundred and eighty of 3,917 patients were found to have influenza. Thirty-five percent of patients with influenza presented with a triage temperature >or=38.0 degrees C, 80% had respiratory symptoms in the emergency department, and 76% were >or=65 years old. Multivariable analysis revealed a triage temperature >or=38.0 degrees C (odds ratio [OR] 3.1; 95% confidence interval [CI] 2.3-4.1), the presence of respiratory symptoms (OR 1.7; 95% CI 1.2-2.4), admission diagnosis of respiratory infection (OR 1.8; 95% CI 1.3-2.4), admission diagnosis of exacerbation of chronic obstructive pulmonary disease (COPD)/asthma or respiratory failure (OR 2.3; 95% CI 1.6-3.4), and admission in peak influenza weeks (OR 4.2; 95% CI 3.1-5.7) as independent predictors of influenza. The likelihood of influenza exceeded 15% in patients with respiratory infection or exacerbation of COPD/asthma if the triage temperature was >or=38.0 degrees C or if they were admitted in the peak weeks during the influenza season. During influenza season, diagnostic testing and empiric antiviral therapy should be considered in patients requiring hospitalization if respiratory infection or exacerbation of COPD/asthma are suspected and if either the triage temperature is >or=38.0 degrees C or admission is during the weeks of peak influenza activity.

Real-time clinical alerting: effect of an automated paging system on response time to critical laboratory values--a randomised controlled trial.

BACKGROUND: Timely and reliable communication of critical laboratory values is a Joint Commission National Patient Safety Goal. The objective was to evaluate the effect of an automated system for paging critical values directly to the responsible physician. METHODS: A randomised controlled trial on the general medicine clinical teaching units at an urban academic hospital was conducted from February to May 2006; the unit of randomisation was the critical laboratory value. The intervention was an automated paging system that sent the critical value directly to the responsible physician's pager. The control arm was usual care, which was a telephone call to the patient's ward by the laboratory technician. The primary outcome was response time, defined as the interval between acceptance of the critical value into the laboratory information system to the writing of an order on the patient's chart in response to the critical value. If the time of order was not documented, the time of administration of treatment was used to calculate response time. RESULTS: For primary analysis, 165 critical values were evaluated on 108 patients with full response time data. The median response time was 16 min (IQR 2-141) for the automated paging group and 39.5 min (IQR 7-104.5) for the usual care group (p=0.33). CONCLUSIONS: The automated paging system reduced the length of time physicians took to respond to critical laboratory values, but this difference was not statistically significant. Future reseach should evaluate the effects of alerts for conditions that currently do not generate a phone call and the addition of real-time decision support to the critical value alerts.

Common and rare variants of DAOA in bipolar disorder.

The D-amino acid oxidase activator (DAOA, previously known as G72) gene, mapped on 13q33, has been reported to be genetically associated with bipolar disorder (BP) in several populations. The consistency of associated variants is unclear and rare variants in exons of the DAOA gene have not been investigated in psychiatric diseases. We employed a conditional linkage method-STatistical Explanation for Positional Cloning (STEPC) to evaluate whether any associated single nucleotide polymorphisms (SNPs) account for the evidence of linkage in a pedigree series that previously has been linked to marker D13S779 at 13q33. We also performed an association study in a sample of 376 Caucasian BP parent-proband trios by genotyping 38 common SNPs in the gene region. Besides, we resequenced coding regions and flanking intronic sequences of DAOA in 555 Caucasian unrelated BP patients and 564 mentally healthy controls, to identify putative functional rare variants that may contribute to disease. One SNP rs1935058 could "explain" the linkage signal in the family sample set (P = 0.055) using STEPC analysis. No significant allelic association was detected in an association study by genotyping 38 common SNPs in 376 Caucasian BP trios. Resequencing identified 53 SNPs, of which 46 were novel SNPs. There was no significant excess of rare variants in cases relative to controls. Our results suggest that DAOA does not have a major effect on BP susceptibility. However, DAOA may contribute to bipolar susceptibility in some specific families as evidenced by the STEPC analysis.

Is a Mass Immunization Program for Pandemic (H1N1) 2009 Good Value for Money? Early Evidence from the Canadian Experience.

This work contributes informed estimates to the current debate about the pandemic (H1N1) 2009 mass immunization program's economic merits. We performed a cost-utility analysis of the (H1N1) 2009 mass immunization program in Ontario, Canada's most populous province. The analysis is based on a simulation model of a pandemic (H1N1) 2009 outbreak, surveillance data, and administrative data. We consider no immunization versus mass immunization reaching 30% of the population. Immunization program costs are expected to be $118 million in Ontario. Our analysis indicates this program will reduce influenza cases by 50%, preventing 35 deaths, and cutting treatment costs in half. A pandemic (H1N1) 2009 immunization program is likely to be highly cost-effective.

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.