Research participants' opinions of delayed consent for a randomised controlled trial of glucose control in intensive care.

PURPOSE: Critically ill patients are often unable to give informed consent to participate in clinical research. A process of delayed consent, enrolling patients into clinical trials and obtaining consent as soon as practical from either the participant or their substitute decision maker, has sometimes been used. The objective of this study was to determine the opinion of participants, previously enrolled in the NICE-SUGAR study, of the delayed consent process. METHODS: This observational study was conducted from 2009 to 2010 in the ICU of a tertiary referral hospital in Australia. Participants who were enrolled in the NICE-SUGAR study with delayed consent who survived, were cognitively intact, and proficient in English were posted a questionnaire regarding their opinion of the delayed consent process. The questionnaire was returned by post, fax, email, or completed during a telephone interview. RESULTS: Of 298 eligible participants, 210 responded, with an overall response rate of 79 %. Delayed consent to participate in the NICE-SUGAR study was obtained from participants (57/210; 27.1 %) or the substitute decision maker (152/210; 72.4 %). Most respondents (195/204; 95.6 %) would have consented to participate in the NICE-SUGAR study if asked before enrolment; most (163/198; 82.3 %) ranked first "the person who consented on their behalf for the NICE Study" as most preferred to make decisions, should they be unable; and most (177/202; 87.6 %) agreed with the decision made by their relative. CONCLUSION: Delayed consent to participate in a clinical trial that includes critically ill patients is acceptable from research participant's perspectives.

Prospective study of early bereavement on psychological and behavioural cardiac risk factors.

BACKGROUND: Increasing evidence supports the role of emotional stress in the onset of cardiovascular disease. Although bereavement is a major emotional stress with both acute and more long-term features, the mechanism of its association with cardiovascular risk is not well understood, in particular because of limited studies of acute bereavement. The aim of the study was to identify psychological and behavioural changes in acute bereavement and potential modifiers of these changes. METHODS: Bereaved (n= 62) and non-bereaved individuals (n= 50) were evaluated within 2 weeks and at 6 months following loss using the Centre for Epidemiologic Studies -- Depression, Spielberger State Anxiety and Anger, Social Support Questionnaire and changes in appetite, cigarette and alcohol consumption, cortisol and lipids. RESULTS: Compared with non-bereaved, acutely bereaved had increased symptoms of depression (26.7 +/- 1.7 vs 5.9 +/- 0.7, P < 0.001), anxiety (47.4 +/- 2.0 vs 28.2 +/- 1.4, P < 0.001) and anger (median 16.0 vs 15.0, P < 0.001). Greater depressive symptoms were associated with being unprepared for the death, decreased sleep duration and younger age. Acutely, bereaved slept less than non-bereaved (5.8 +/- 0.2 vs 7.2 +/- 0.2 h, P < 0.001). Reduced sleep time was associated with increased anger and depression and decreased satisfaction with social support. Compared with the non-bereaved, the acutely bereaved had higher cortisol (median 306 vs 266, P= 0.003), reduced appetite (P < 0.001) and lower total cholesterol (median 4.9 vs 5.4, P= 0.006) and low-density lipoprotein (median 2.4 vs 2.9, P < 0.001). CONCLUSION: These results offer insight into the psychological, behavioural and physical changes that may contribute to cardiovascular risk in bereavement.

Flesh quality of market-size farmed and wild British Columbia salmon.

This study compared the flesh quality of farmed and wild sources of British Columbia (BC) salmon with respect to concentrations of polychlorinated biphenyl compounds, polychlorinated dibenzodioxins/dibenzofurans and their associated toxic equivalents, total mercury (THg), methylmercury (MeHg), and selected fatty acids of known importance for human health viz., omega-3 (n-3) highly unsaturated fatty acids (n-3 HUFAs) and (n-6) fatty acids. Skinned fillets from known sources of farmed Atlantic, coho, and chinook salmon (n = 110) and wild coho, chinook, chum, sockeye, and pink salmon (n = 91) were examined. Atlantic salmon contained higher PCB concentrations (means, 28-38 ng/g) than farmed coho or chinook salmon, and levels in these latter species were similar to those in wild counterparts (means, 2.8-13.7 ng/g). PCB levels in Atlantic salmon flesh were, nevertheless, 53-71-fold less than the level of concern for human consumption of fish, i.e., 2000 ng/g as established by Health Canada and the U.S. Food and Drug Administration (US-FDA). Similarly, THg and MeHg levels in all samples were well below the Health Canada guideline (0.5 microg/g) and the US-FDA action level (1.0 microg/g). On average, THg in farmed salmon (0.021 microg/g) was similar to or lower than wild salmon (0.013-0.077 microg/g). Atlantic salmon were a richer source (mean, 2.34 g/100 g fillet) of n-3 HUFAs than the other farmed and wild sources of salmon examined (means, 0.39-1.17 g/100 g). The present findings support the recommended weekly consumption guidelines for oily fish species (includes all BC salmon sources) for cardio-protective benefits as made by the American Heart Association and the UK Food Standards Agency.

The effect of education and counselling on knowledge, attitudes and beliefs about responses to acute myocardial infarction symptoms.

The time that elapses from the onset of symptoms of acute myocardial infarction (AMI) to treatment has a significant effect on mortality and morbidity. This study reports the effectiveness of an education and counselling intervention on knowledge, attitudes and beliefs about AMI symptoms and the appropriate response to symptoms. The intervention was tested in a randomised controlled trial of 200 people with a history of coronary heart disease (CHD). The groups were equivalent at baseline on study outcomes, clinical history and sociodemographic characteristics with the exception of more women in the intervention group (38% vs. 24%). The results of repeated measures ANOVA showed that the intervention resulted in improved knowledge of CHD, AMI symptoms and the appropriate response to symptoms that was sustained to 12 months (p=0.02). There were no differences between groups' attitudes and beliefs over time. It is concluded that a short individual teaching and counselling intervention resulted in improved knowledge of CHD, AMI symptoms and the appropriate response to symptoms in people at risk of AMI sustained to 12 months.

Impact of operator expertise on collection of the APACHE II score and on the derived risk of death and standardized mortality ratio.

We assessed the impact of operator expertise on collection of the APACHE II score, the derived risk of death and standardized mortality ratio in 465 consecutive patients admitted to a multi-disciplinary tertiary hospital ICU. Research coordinators and junior clinical staff independently collected the APACHE II variables; experts (senior clinical staff) rescored 20% of the records. Agreement was moderate between junior clinical staff and research coordinators or senior clinical staff for most variables of the acute physiology score (weighted kappa<0.6); agreement between research coordinators and senior clinical staff data collectors was good (weighted kappa >0.75). The APACHE II score and its derived risk of death (ROD) were significantly lower using the junior clinical staff dataset compared to research coordinators and senior clinical staff (APACHE II score: 13.4+/-9.2 vs 16.8+/-8.5 vs 17.1+/-7 7, P<0.001; ROD: 14.7%+/-22.4% vs 21.6%+/-22.6% vs 20.8%+/-22.4%, P<0.01 respectively). The discriminative capacity was not altered by the lack of agreement (area under Receiver Operator Characteristic curve >0.8) but calibration of ROD from the junior clinical staff dataset was poor (Goodness-of-fit: P= 0.001). The standardized mortality ratio (SMR) was higher with the junior clinical staff dataset (SMR: 1.22, 95% CI: 0.96-1.52 vs 0.87, 95% CI: 0.70-1.06 vs 0.76, 95% CI: 0.40-1.3 calculated from junior clinical staff research coordinators and senior clinical staff datasets respectively). We conclude that the expertise of data collectors significantly influences the APACHE II score, the derived risk of death and the standardized mortality ratio. Given the importance of such scores, ICUs should be provided with sufficient resources to train and employ dedicated data collectors.

Nurses' beliefs about the conditions that hinder or support evidence-based nursing.

The aim of this study was to identify the conditions that Australian nurses believe support or hinder the development of evidence-based nursing. A survey instrument was developed from the results of content analysis of the UK and the USA research and of interviews with 12 Australian nurses. Eight hundred and sixteen nurses working in three large hospitals responded representing a response rate of 65%. Principal axis factor analysis of the survey results revealed six conditions that the participants believed were necessary for evidence-based nursing to take place. The results of this study may be used to develop models for the improvement of evidence-based nursing in Australia.

Commentary. Balancing sedation and analgesia in the critically ill.

The authors have presented a template for a systematic approach to comforting critically ill patients that can be modified to suit institutional preferences. In this algorithm, the cause of patient discomfort is sought with the priority given to pain and then to anxiety. Special attention is directed to the identification of correctable causes of pain and anxiety with application of nonpharmacologic techniques or medications to control patient discomfort. This step is followed by subsequent reassessment of the need for sedation or anxiolysis and titration or discontinuation of therapy as able. The benefits of protocol-driven care are becoming increasingly evident, and the authors believe the algorithm outlined here provides a rational and practical approach to patient management. It also prompts the caregiver to reevaluate patients' needs and to keep to patients at target sedation levels. Doing so can promote cost effectiveness, reduce side effects caused by drugs, and decrease morbidity and ICU stay. Any treatment protocol or algorithm is simply a guide to therapy and cannot address every clinical situation. The importance of individualized care and physician or care team judgment must be emphasized.

Treatment-seeking behavior for acute myocardial infarction symptoms in North America and Australia.

OBJECTIVE: The goal of this study was to compare North American and Australian patients' sociodemographic, clinical, cognitive, emotional, and social factors associated with behavior in seeking treatment for symptoms of acute myocardial infarction. PATIENTS: Subjects included 277 North Americans (mean age, 58 +/- 12 years; 72% men) and 147 Australians (mean age, 62 +/- 13 years; 66% men) with acute myocardial infarction. METHODS: Data were obtained with the Response to Symptoms Questionnaire and from the patients' hospital records. RESULTS: In both groups, patients who delayed longer (P

Differences between men and women in anxiety early after acute myocardial infarction.

BACKGROUND: Anxiety after acute myocardial infarction influences both short- and long-term recovery. Therefore, determining specific subgroups of patients who have relatively higher anxiety levels is important. Published findings about gender differences in anxiety after acute myocardial infarction are conflicting. OBJECTIVES: To determine whether gender differences in anxiety after acute myocardial infarction exist and whether any of the sociodemographic and clinical variables that often differ between men and women with acute myocardial infarction interact with gender to influence anxiety. METHODS: A total of 424 patients with confirmed acute myocardial infarction were enrolled in this multicenter prospective study. Patients' anxiety level was measured within 72 hours of their arrival at the hospital by using the State Anxiety Inventory and the Brief Symptom Inventory. RESULTS: Women had significantly higher anxiety than did men according to both the State Anxiety Inventory (42 +/- 12.9 vs 37.7 +/- 12.5; P = .001) and the Brief Symptom Inventory (0.83 +/- 0.97 vs 0.63 +/- 0.71; P = .02). Of the sociodemographic and clinical variables examined, only marital status and income significantly interacted with gender to influence anxiety. Married women had higher anxiety than did single and widowed women, and married men had lower anxiety than did single men. Women with lower income had higher anxiety than did women with higher income; income was not related to anxiety in men. CONCLUSION: Women report significantly greater anxiety early after acute myocardial infarction than men do. Women's greater anxiety may be partially explained by marital status and lower income at the time of the infarction.

Prolactin levels in juvenile and adult rats following acute restraint and the open field.

Acute restraint and exposure to a novel environment alter behavior and increase prolactin levels in rats quickly and reliably. However, little research is available that examines behavior and levels of prolactin as a result of acute exposure to one stressor immediately followed by a second stressor. Similarly, a relationship between prolactin and behavior has not been established. In the present study, juvenile (35-day-old) and adult (5-month-old) rats were either placed in a novel open field for 10 min or restrained for 10 min prior to exposure to the open field. Restrained juveniles groomed more than control juveniles and restrained adults. Conversely, restraint + open field reduced ambulation and rearing among juvenile males and females, and adult females ambulated less than control females and restrained males across both behaviors. In addition, results from the present study demonstrated the first reported relationship between prolactin and open-field behaviors. Prolactin was positively correlated with rearing and number of fecal boli, and levels were negatively correlated with freezing. Among adult females, prolactin levels were lower following restraint + open field than after exposure only to the open field. This may be explained by the psychological response to the open field when it directly followed the physical stressor of acute restraint.

Patients' experiences of being in an intensive care unit: a select literature review.

A total of 26 research studies on patients' experiences of being in an intensive care unit were reviewed. The studies were selected because they focused on experiences typical in intensive care units. Many patients recalled their time in the intensive care unit, sometimes in vivid detail. Patients recalled not only experiences that were negative but also ones that were neutral and even positive. Positive experiences included a sense of safety and security promoted especially by nurses. Negative experiences included impaired cognitive functioning and discomforts such as problems with sleeping, pain, and anxiety. The review indicates steps critical care staff can take to develop better ways to understand patients' experiences. Meeting such challenges can improve the quality of patients' experiences and reduce anxiety and may offset potential adverse effects of being a patient in an intensive care unit.

Does membrane fluidity contribute to thermal compensation of beta-adrenergic signal transduction in isolated trout hepatocytes?

The potential role of compensatory adjustments to membrane components in determining the function of the (&bgr;)-adrenergic receptor/adenylyl cyclase ((&bgr;)-AR/AC) signal-transduction system was studied in isolated hepatocytes of 5 degrees C- and 20 degrees C-acclimated rainbow trout Oncorhynchus mykiss. Rates of epinephrine-stimulated cyclic AMP (cAMP) production, although slowed (by a factor of 1.6- to 2.4-fold) by an acute drop in assay temperature from 20 to 5 degrees C, were significantly temperature-compensated, being approximately twofold higher in hepatocytes of 5 degrees C- than of 20 degrees C-acclimated trout. Membrane order in the bilayer interior of hepatocyte plasma membranes (as assessed by fluorescence polarization of 1, 6-diphenyl-1,3,5-hexatriene) was consistently lower in cold- than in warm-acclimated trout, reflecting an efficacy of homeoviscous adaptation of approximately 50 %. Temperature-induced changes in plasma membrane fatty acid composition (i.e. an increase in the proportions of polyunsaturated fatty acids with acclimation to 5 degrees C) were consistent with both the observed changes in the order of the bilayer interior and the extent of homeoviscous adaptation. However, isothermal fluidization of the bilayer interior by the addition of benzyl alcohol (30 mmol l(-)(1)) decreased rather than increased the rate of cAMP production. Significantly more (1. 81-fold) beta-adrenergic receptors were present in plasma membranes of hepatocytes from 5 degrees C-acclimated (6. 23x10(4)+/-4206 receptors per cell; mean +/- s.e.m., N=3) than 20 degrees C-acclimated fish (3.44x10(4)+/-4360 receptors per cell; N=3) when assayed at the acclimation temperature, whereas the equilibrium dissociation constants (K(d)) (13.73+/-4.33 nmol l(-)(1) at 5 degrees C; 9.75+/-3.29 nmol l(-)(1) at 20 degrees C; N=3) were similar. On the basis of a strong correlation between beta-adrenoceptor number and the rate of cAMP production (r(2)=0. 956), regardless of assay or acclimation temperature, we conclude that modulation of receptor number is the primary acclimatory response of this signal-transduction pathway to temperature change in trout liver.

Outcomes, problems and quality of life with the implantable cardioverter defibrillator.

The survey aimed to assess the outcomes, problems and quality of life (QOL) in recipients of the implantable cardioverter defibrillator (ICD). Average QOL was 6.4 (1-10 scale), but lower in those who had received shocks (p < 0.05); 54% of patients had been shocked at least once. Usual daily activities were resumed by 72%, and driving by 76% of patients; 96% would recommend the ICD to others. Primary information sources were the implanting cardiologist and manufacturer's booklet. This study concluded that most ICD recipients have good QOL, but it is reduced in those who have been shocked by the defibrillator. Most eventually know enough about living with the ICD, but desire more education and support at the time of ICD insertion. Nurses could meet this need.

Implantable defibrillator recipients' responses to device implantation and design.

The implantable cardioverter defibrillator (ICD) is a surgically inserted device that follows a well-established pattern of technology innovation and rapid adoption without extensive clinical trials. Few devices are as obviously life-saving in potentially fatal situations and deliver such sudden and sometimes painful therapy. Although patients' quality of life and adjustment to the device both physically and psychologically are relatively well-documented, few studies have explored recipients' responses to the device itself or elicited their thoughts on the technological design. The findings presented here are from a prospective Australian study that surveyed 110 ICD recipients pre-insertion and at 3, 12, and 18 months post-insertion. Recipients' responses to the device and their thoughts on design were sought. Respondents were overwhelmingly willing to: 1) accept the ICD, 2) recommend it to others, and 3) welcome such innovations as warning tones, device-controlled drug delivery, and telephone interrogation of the device.

Incidence and predictors of central venous catheter related infection in intensive care patients.

This study investigated the incidence of and risk factors for central venous catheter (CVC) infection in intensive care. CVCs were prospectively studied in patients who had lines inserted in general or neurosurgical intensive care and were expected to have the line in situ for at least 72 hours. Catheters (n = 119) were cultured for CVC-related infection (CRI; > 15 colony forming units) and blood cultures done when indicated. CRI was identified in 32 (26.9%) catheters, CVC related bacteraemia in five cases (4.2%) and CVC related sepsis in none. After adjustment for duration of catheterization, independent predictors of CVC related infection were catheter insertion site, with jugular sites having the highest risk, and primary diagnosis, with neurosurgical patients at least risk.

Mild hemophilia A caused by increased rate of factor VIII A2 subunit dissociation: evidence for nonproteolytic inactivation of factor VIIIa in vivo.

Approximately 5% of hemophilia A patients have normal amounts of a dysfunctional factor VIII (FVIII) protein and are termed cross-reacting material (CRM)-positive. FVIII is a heterodimer (domain structure A1-A2-B/A3-C1-C2) that requires thrombin cleavage to elicit procoagulant activity. Thrombin-activated FVIII is a heterotrimer with the A2 subunit (amino acid residues 373 to 740) in a weak ionic interaction with the A1 and A3-C1-C2 subunits. Dissociation of the A2 subunit correlates with inactivation of FVIII. Recently, a phenotype of CRM-positive hemophilia A patients has been characterized whose plasma displays a discrepancy between their FVIII activities, where the one-stage clotting assay displays greater activity than the two-stage clotting assay. One example is a missense mutation where ARG531 has been substituted by HIS531. An FVIII cDNA construct was prepared containing the ARG531(HIS) mutation and the protein was expressed in COS-1 monkey cells by transient DNA transfection. Metabolic labeling with [35S]-methionine demonstrated that ARG531(HIS) was synthesized at an equal rate compared with FVIII wild-type (WT) but had slightly reduced antigen in the conditioned medium, suggesting a modest secretion defect. A time course of structural cleavage of ARG531(HIS) demonstrated identical thrombin cleavage sites and rates of proteolysis as FVIII WT. Similar to the patient phenotypes, ARG531(HIS) had discrepant activity as measured by a one-stage activated partial thromboplastin time (aPTT) clotting assay (36% +/- 9.6% of FVIII WT) and a variation of the two-stage assay using a chromogenic substrate (COAMATIC; 19% +/- 6.9% of FVIII WT). Partially purified FVIII WT and ARG531(HIS) proteins were subjected to functional activation by incubation with thrombin. ARG531(HIS) demonstrated significantly reduced peak activity and was completely inactivated after 30 seconds, whereas FVIII WT retained activity until 2.5 minutes after activation. Because the ARG531(HIS) missense mutation predicts a charge change to the A2 subunit, we hypothesized that the ARG531(HIS) A2 subunit could be subject to more rapid dissociation from the heterotrimer. The rate of A2 dissociation, using an optical biosensor, was determined to be fourfold faster for ARG531(HIS) compared with FVIII WT. Because the two-stage assay involves a preincubation phase before assay measurement, an increased rate of A2 dissociation would result in an increased rate of inactivation and reduced specific activity.

Thermal acclimation of phase behavior in plasma membrane lipids of rainbow trout hepatocytes.

The fluorescent probes laurdan (6-dodecanoyl-2-dimethylaminonapthalene) and N-[7-nitrobenz-2-oxa-1, 3-diazol-4-yl] dipalmitoyl-L-alpha-phosphatidylethanolamine (NBD-PE) in addition to Fourier transform infrared spectroscopy (FTIR) were employed to measure the phase behavior and physical properties of hepatocyte plasma membranes isolated from the livers of thermally acclimated (5 and 20 degreesC) rainbow trout (Oncorhynchus mykiss). The primary objective was to determine the extent to which the phase behavior of membrane lipids is conserved at different growth temperatures. Arrhenius plots of laurdan-generalized polarization revealed a single discontinuity believed to reflect either the onset of the gel-fluid phase transition or the formation of gel phase microdomains, and this discontinuity occurred at significantly higher temperatures in membranes of 20 degrees C (13.2 +/- 0.7 degrees C)- than 5 degrees C (7.2 +/- 0.1 degrees C)-acclimated trout. Similarly, acclimation from 5 to 20 degrees C increased both the onset temperature (from 2.0 +/- 0.3 to 7.2 +/- 0.6 degrees C) and the thermal range (from 10.9 +/- 0.5 to 16.0 +/- 1.0) of the gel-fluid transition as assessed by FTIR. The gel-fluid transition midpoint (approximately -2 degrees C) and completion temperatures (-9 degrees C) were unchanged by thermal acclimation. The anisotropy of NBD-PE fluorescence displayed a distinct minimum in membranes of both warm- and cold-acclimated trout (reflecting alterations in lipid packing that in pure lipid membranes ultimately lead to the formation of nonlamellar phases) in the range of 56-58 degrees C; only membranes of 5 degrees C-acclimated trout displayed an additional minimum at significantly lower temperatures (24.5 +/- 1.7 degrees C). Collectively, these data suggest that the regulation of both the temperature at which gel phase lipids begin to form in response to cooling as well as the propensity of membrane lipids to form nonlamellar phases at higher temperatures may be key features of membrane organization subject to adaptive regulation.