Gordon S. Doig

Introduction of the medical emergency team (MET) system: a cluster-randomised controlled trial.

BACKGROUND Patients with cardiac arrests or who die in general wards have often received delayed or inadequate care. We investigated whether the medical emergency team (MET) system could reduce the incidence of cardiac arrests, unplanned admissions to intensive care units (ICU), and deaths. METHODS We randomised 23 hospitals in Australia to continue functioning as usual (n=11) or to introduce a MET system (n=12). The primary outcome was the composite of cardiac arrest, unexpected death, or unplanned ICU admission during the 6-month study period after MET activation. Analysis was by intention to treat. FINDINGS Introduction of the MET increased the overall calling incidence for an emergency team (3.1 vs 8.7 per 1000 admissions, p=0.0001). The MET was called to 30% of patients who fulfilled the calling criteria and who were subsequently admitted to the ICU. During the study, we recorded similar incidence of the composite primary outcome in the control and MET hospitals (5.86 vs 5.31 per 1000 admissions, p=0.640), as well as of the individual secondary outcomes (cardiac arrests, 1.64 vs 1.31, p=0.736; unplanned ICU admissions, 4.68 vs 4.19, p=0.599; and unexpected deaths, 1.18 vs 1.06, p=0.752). A reduction in the rate of cardiac arrests (p=0.003) and unexpected deaths (p=0.01) was seen from baseline to the study period for both groups combined. INTERPRETATION The MET system greatly increases emergency team calling, but does not substantially affect the incidence of cardiac arrest, unplanned ICU admissions, or unexpected death.

Serial Plasma Osteopontin Levels Have Prognostic Value in Metastatic Breast Cancer

Purpose: Osteopontin is a malignancy-associated protein measurable in blood and tumor tissue. To evaluate its prognostic value in advanced disease, we conducted a prospective clinical study measuring serial osteopontin plasma levels in women with metastatic breast cancer throughout the course of their disease. Experimental Design: One hundred fifty-eight women with newly diagnosed metastatic breast cancer were enrolled in the study. Plasma osteopontin was measured using our validated ELISA, at baseline and every 3 to 12 weeks during and after therapy until death. Multivariate time-dependent survival analyses were conducted using models that right censored patient outcomes 3, 6, and 12 months after the last known osteopontin measurement. Results: Osteopontin was measured in 1,378 samples (median, 9 per patient). Ninety-nine patients had elevated baseline osteopontin (median, 177 ng/mL; range, 1-2,648 ng/mL). In univariate analysis, elevated baseline osteopontin was associated with short survival (P = 0.02). In a multivariate model incorporating standard prognostic factors, baseline osteopontin was significantly associated with survival duration (relative risk, 1.001; P = 0.038). Metastasis-free interval, visceral metastases, and Eastern Cooperative Oncology Group status 2 to 4 also retained significance. In a multivariate model incorporating standard prognostic factors and changes in sequential osteopontin levels, an osteopontin increase of >250 ng/mL at any time was the variable with the most prognostic value for poor survival (relative risk, 3.26; P = 0.0003), and poor Eastern Cooperative Oncology Group status also retained significance. Conclusions: This is the first study to show that in women with metastatic breast cancer, increases in osteopontin levels over time are strongly associated with poor survival. Sequential monitoring of osteopontin may have use in making treatment decisions for these patients.

Anoxic–Ischemic Encephalopathy

Introduction: Prognostic determination of patients in coma after resuscitation from cardiac arrest is both common and difficult. We explored clinical and electrophysiological testing to determine their associations with favorable and poor outcomes.Methods: We studied 75 comatose patients resuscitated from cardiac arrest, excluding those who were brain dead or continuously sedated; none received hypothermia therapy. Clinical examinations were performed on day 1.Results: The following proportions recovered awareness: 2 of 18 patients with absent pupillary reflexes; 18 of 57 with preserved pupillary reflexes (p=0.08); 2 of 32 with absent corneal reflexes; 16 of 43 with preserved corneal reflexes (p=0.001); 0 of 15 with absent oculovestibular reflexes; and 8 of 29 with preserved oculovestibular reflexes (p<0.037). Purposeful movements were associated with a high probability of recovery, whereas other categories were unfavorable. Other categories of motor response were associated with an increased proportion of those who died without recovering awareness, but each category had some survivors. Somatosensory evoked potentials (SSEPs) were recorded from 47 patients. One of 21 patients with loss of the N20 component survived, compared with survival of 11 of 26 patients in whom it was present (p=0.003). All 5 patients with preserved N70 responses recovered awareness in a subgroup of 33 patients. Sixteen of 22 subjects with mild electroencephalogram (EEG) abnormalities recovered consciousness, compared with the survival of 3 of 50 patients with malignant EEG patterns (p= 0.0000001). Combining SSEP with EEG findings produced even greater predictive value.Conclusion: It seems unlikely that any single test will prove to have 100% predictive value for outcome; further studies combining clinical, EEG, and SSEP testing are warranted.

Metabolic and nutritional support of critically ill patients: consensus and controversies

The results of recent large-scale clinical trials have led us to review our understanding of the metabolic response to stress and the most appropriate means of managing nutrition in critically ill patients. This review presents an update in this field, identifying and discussing a number of areas for which consensus has been reached and others where controversy remains and presenting areas for future research. We discuss optimal calorie and protein intake, the incidence and management of re-feeding syndrome, the role of gastric residual volume monitoring, the place of supplemental parenteral nutrition when enteral feeding is deemed insufficient, the role of indirect calorimetry, and potential indications for several pharmaconutrients.

Early enteral nutrition reduces mortality in trauma patients requiring intensive care: A meta-analysis of randomised controlled trials

INTRODUCTION To determine whether the provision of early standard enteral nutrition (EN) confers treatment benefits to adult trauma patients who require intensive care. MATERIALS AND METHODS MEDLINE and EMBASE were searched. Hand citation review of retrieved guidelines and systematic reviews was undertaken and academic and industry experts were contacted. Methodologically sound randomised controlled trials (RCTs) conducted in adult trauma patients requiring intensive care that compared the delivery of standard EN, provided within 24 h of injury, to standard care were included.The primary analysis was conducted on clinically meaningful patient-oriented outcomes, which included mortality, functional status and quality of life. Secondary analyses considered vomiting/regurgitation, pneumonia, bacteraemia, sepsis and multiple organ dysfunction syndrome. Meta-analysis was conducted using an analytical method known to minimise bias in the presence of sparse events. The impact of heterogeneity was assessed using the I2 metric. RESULTS Three RCTs with 126 participants were found to be free from major flaws and were included in the primary analysis. The provision of early EN was associated with a significant reduction in mortality(OR = 0.20, 95% confidence interval 0.04–0.91, I2 = 0). No other outcomes could be pooled. A sensitivity analysis and a confirmatory analysis conducted using a different analytical method confirmed the presence of a mortality reduction. CONCLUSION Although the detection of a statistically significant reduction in mortality is promising,overall trial quality was low and trial size was small. The results of this meta-analysis should be confirmed by the conduct of a large multi-center trial.

A multicenter, randomized controlled trial comparing early nasojejunal with nasogastric nutrition in critical illness*

Objective: Current guidelines recommend enteral nutrition in critically ill adults; however, poor gastric motility often prevents nutritional targets being met. We hypothesized that early nasojejunal nutrition would improve the delivery of enteral nutrition. Design: Prospective, randomized, controlled trial. Setting: Seventeen multidisciplinary, closed, medical/surgical, intensive care units in Australia. Patients: One hundred and eighty-one mechanically ventilated adults who had elevated gastric residual volumes within 72 hrs of intensive care unit admission. Interventions: Patients were randomly assigned to receive early nasojejunal nutrition delivered via a spontaneously migrating frictional nasojejunal tube, or to continued nasogastric nutrition. Measurements and Main Results: The primary outcome was the proportion of the standardized estimated energy requirement that was delivered as enteral nutrition. Secondary outcomes included incidence of ventilator-associated pneumonia, gastrointestinal hemorrhage, and in-hospital mortality rate. There were 92 patients assigned to early nasojejunal nutrition and 89 to continued nasogastric nutrition. Baseline characteristics were similar. Nasojejunal tube placement into the small bowel was confirmed in 79 (87%) early nasojejunal nutrition patients after a median of 15 (interquartile range 7–32) hrs. The proportion of targeted energy delivered from enteral nutrition was 72% for the early nasojejunal nutrition and 71% for the nasogastric nutrition group (mean difference 1%, 95% confidence interval −3% to 5%, p = .66). Rates of ventilator-associated pneumonia (20% vs. 21%, p = .94), vomiting, witnessed aspiration, diarrhea, and mortality were similar. Minor, but not major, gastrointestinal hemorrhage was more common in the early nasojejunal nutrition group (12 [13%] vs. 3 [3%], p = .02). Conclusions: In mechanically ventilated patients with mildly elevated gastric residual volumes and already receiving nasogastric nutrition, early nasojejunal nutrition did not increase energy delivery and did not appear to reduce the frequency of pneumonia. The rate of minor gastrointestinal hemorrhage was increased. Routine placement of a nasojejunal tube in such patients is not recommended.

Randomized, controlled clinical trials in sepsis: has methodological quality improved over time?

Objective To systematically evaluate the methodological quality of randomized clinical trials and to determine whether randomized clinical trials of sepsis improved in methodological quality over time. Data Sources Computerized MEDLINE search of articles published in any language from 1966 to 1998 combined with a manual search of bibliographies of published articles and communication with known experts in the field. Study Selection All randomized clinical trials of sepsis, severe sepsis, and septic shock performed in adults and published as full articles. Data Extraction Abstracts of all retrieved records were reviewed and the inclusion criteria were applied. All selected articles were classified into (a) trials designed to detect differences in mortality as the primary end point, or (b) trials focusing on surrogate outcome measures (i.e., physiological or biochemical parameters). All retrieved trials were then graded for methodological quality using an objective grading scheme developed specifically for this study. The data selection and extraction process was carried out independently by two of the authors; any disagreement was resolved by discussion. Data Synthesis Seventy-four randomized clinical trials involving septic patients qualified for inclusion in this study (40 reporting mortality outcomes, 34 reporting other surrogate outcomes). Trials reporting mortality as the primary outcome had significantly higher quality scores compared with trials reporting surrogate outcome measures (29.6 ± 1.0 vs. 24.3 ± 0.8, p = .0006). From 1976 to 1998, trial methodology improved significantly over time (an average of 0.36 points per year, p = .021). Mortality outcome trials improved an average of 0.58 points per year (p = .0011) whereas surrogate outcome trials did not demonstrate an improvement in methodological quality over time (p = .249). Conclusion The methodological limitations identified in this article can help to target further improvement in trial design to enhance the validity of findings from future randomized clinical trials of sepsis.

The acute patient physiologic and laboratory evaluation (APPLE) score: a severity of illness stratification system for hospitalized dogs.

BACKGROUND Objective risk stratification models are used routinely in human critical care medicine. Applications include quantitative and objective delineation of illness severity for patients enrolled in clinical research, performance benchmarking, and protocol development for triage and therapeutic management. OBJECTIVE To develop an accurate, validated, and user-friendly model to stratify illness severity by mortality risk in hospitalized dogs. ANIMALS Eight hundred and ten consecutive intensive care unit (ICU) admissions of dogs at a veterinary teaching hospital. METHODS Prospective census cohort study. Data on 55 management, physiological, and biochemical variables were collected within 24 hours of admission. Data were randomly divided, with 598 patient records used for logistic regression model construction and 212 for model validation. RESULTS Patient mortality was 18.4%. Ten-variable and 5-variable models were developed to provide both a high-performance model and model maximizing accessibility, while maintaining good performance. The 10-variable model contained creatinine, WBC count, albumin, SpO(2) , total bilirubin, mentation score, respiratory rate, age, lactate, and presence of free fluid in a body cavity. Area under the receiver operator characteristic (AUROC) on the construction data set was 0.93, and on the validation data set was 0.91. The 5-variable model contained glucose, albumin, mentation score, platelet count, and lactate. AUROC on the construction data set was 0.87, and on the validation data set was 0.85. CONCLUSIONS AND CLINICAL IMPORTANCE Two models are presented that enable allocation of an accurate and user-friendly illness severity index for dogs admitted to an ICU. These models operate independent of primary diagnosis, and have been independently validated.

Relationship of a new histological categorization of ductal carcinoma in situ of the breast with size and the immunohistochemical expression of p53, c-erb B2, bcl-2, and ki-67

Ductal carcinoma in situ (DCIS) represents a heterogeneous group of diseases. There is no generally accepted classification for the different cytological and architectural types of DCIS. A recent study (Scott et al, 1995) indicates that over 90% of DCIS can be easily classified into the following five categories: high grade (HG), intermediate grade (IG), low grade (LG), pure micropapillary (M), and pure apocrine (A). The aim of this study was to determine if there is a relationship between lesion size and the immunohistochemical expression of p53, c-erb B2, bcl-2, and ki67 with this reproducible categorization of DCIS. Seventy cases of DCIS diagnosed between 1984 and 1995 were obtained from the Departments of Pathology at two teaching hospitals in London, Ontario. The original sections were reviewed, classified according to Scott et al (1995), and representative sections were cut for immunohistochemical (IHC) studies. IHC stains were scored using a previously described semiquantitative scoring system (Allred et al, 1993). Size was taken from the gross measurement if the lesion was palpable or recorded as the largest dimension, as measured on the histological slide, for nonpalpable cases. Of the 70 DCIS cases, 17 (24.3%) were HG, 23 (32.9%) were IG, 21 (30%) were LG, seven (10%) were pure micropapillary cases, and two (2.9%) were pure apocrine DCIS. The mean size of the DCIS for each subcategory was statistically significantly different (P = .008). In particular, the micropapillary DCIS cases were largest (mean size, 17 mm). The mean immunohistochemical scores for c-erb B2 for each category were also statistically different (P = .007), whereas the mean scores for p53 and ki67 for each category trended toward significance (P = .073, P = .062, respectively). There were no significant differences between bcl-2 mean scores and each subcategory. Size of DCIS and c-erb B2 positivity are known to be associated with more aggressive clinical behavior and more advanced histologic features, respectively. Because this combined histological cytological classification system is predictive of size and c-erb B2 positivity, our results support the clinical relevance of this classification system.

Health care costs, long-term survival, and quality of life following intensive care unit admission after cardiac arrest

IntroductionThe purpose of this study was to investigate the costs and health status outcomes of intensive care unit (ICU) admission in patients who present after sudden cardiac arrest with in-hospital or out-of-hospital cardiopulmonary resuscitation.MethodsFive-year survival, health-related quality of life (Medical Outcome Survey Short Form-36 questionnaire, SF-36), ICU costs, hospital costs and post-hospital health care costs per survivor, costs per life year gained, and costs per quality-adjusted life year gained of patients admitted to a single ICU were assessed.ResultsOne hundred ten of 354 patients (31%) were alive 5 years after hospital discharge. The mean health status index of 5-year survivors was 0.77 (95% confidence interval 0.70 to 0.85). Women rated their health-related quality of life significantly better than men did (0.87 versus 0.74; P < 0.05). Costs per hospital discharge survivor were 49,952 €. Including the costs of post-hospital discharge health care incurred during their remaining life span, the total costs per life year gained were 10,107 €. Considering 5-year survivors only, the costs per life year gained were calculated as 9,816 € or 14,487 € per quality-adjusted life year gained. Including seven patients with severe neurological sequelae, costs per life year gained in 5-year survivors increased by 18% to 11,566 €.ConclusionPatients who leave the hospital following cardiac arrest without severe neurological disabilities may expect a reasonable quality of life compared with age- and gender-matched controls. Quality-adjusted costs for this patient group appear to be within ranges considered reasonable for other groups of patients.