Variation in timing of decisions to withdraw life-sustaining treatment in adult ICU patients from three centres in different geographies: Do clinical factors explain the difference?

Background: Decisions to withdraw life-sustaining treatment (WLST) are common in intensive care units (ICUs). Clinical and non-clinical factors are important, although the extent to which each plays a part is uncertain. Objectives: To determine whether the timing of decisions to WLST varies between ICUs in a single centre in three countries and whether differences in timing are explained by differences in clinical decision-making. Methods: The study involved a convenience sample of three adult ICUs - one in each of the UK, USA and South Africa (SA). Data were prospectively collected on patients whose life-sustaining treatment was withdrawn over three months. The timing of decisions was collected, as were patients' premorbid functional status and illness severity 24 hours prior to decision to WLST. Multivariate analysis was used to identify factors associated with decisions to WLST. Clinicians participated in interviews involving hypothetical case studies devoid of non-clinical factors. Results: Deaths following WLST accounted for 23% of all deaths during the study period at the USA site v. 37% (UK site) and 70% (SA site) (p<0.0010 across the three sites). Length of stay (LOS) prior to WLST decision varied between sites. Controlling for performance status, age, and illness severity, study site predicted LOS prior to decision (p<0.0010). In the hypothetical cases, LOS prior to WLST was higher for USA clinicians (p<0.017). Conclusion: There is variation in the proportion of ICU patients in whom WLST occurs and the timing of these decisions between sites; differences in clinical decision-making may explain the variation observed, although clinical and non-clinical factors are inextricably linked. Contributions of the study: This study has identified variation in the timing of decisions to withdraw life-sustaining treatment in adult ICUs in three centres in three different healthcare systems. Although differences in clinical decision-making likely explain some of the variation, non-clinical factors (relating to the society in which the clinicians live and work) may also play a part.

Are people at risk of psychosis also at risk of suicide and self-harm? A systematic review and meta-analysis.

BACKGROUND: Suicide and self-harm are prevalent in individuals diagnosed with psychotic disorders. However, less is known about the level of self-injurious thinking and behaviour in those individuals deemed to be at ultra-high risk (UHR) of developing psychosis, despite growing clinical interest in this population. This review provides a synthesis of the extant literature concerning the prevalence of self-harm and suicidality in the UHR population, and the predictors and correlates associated with these events. METHOD: A search of electronic databases was undertaken by two independent reviewers. A meta-analysis of prevalence was undertaken for self-harm, suicidal ideation and behaviour. A narrative review was also undertaken of analyses examining predictors and correlates of self-harm and suicidality. RESULTS: Twenty-one eligible studies were identified. The meta-analyses suggested a high prevalence of recent suicidal ideation (66%), lifetime self-harm (49%) and lifetime suicide attempts (18%). Co-morbid psychiatric problems, mood variability and a family history of psychiatric problems were among the factors associated with self-harm and suicide risk. CONCLUSIONS: Results suggest that self-harm and suicidality are highly prevalent in the UHR population, with rates similar to those observed in samples with diagnosed psychotic disorders. Appropriate monitoring and managing of suicide risk will be important for services working with the UHR population. Further research in this area is urgently needed considering the high rates identified.

Cognitive behavioural therapy for psychosis prevention: a systematic review and meta-analysis.

BACKGROUND: Clinical equipoise regarding preventative treatments for psychosis has encouraged the development and evaluation of psychosocial treatments, such as cognitive behavioural therapy (CBT). METHOD: A systematic review and meta-analysis was conducted, examining the evidence for the effectiveness of CBT-informed treatment for preventing psychosis in people who are not taking antipsychotic medication, when compared to usual or non-specific control treatment. Included studies had to meet basic quality criteria, such as concealed and random allocation to treatment groups. RESULTS: Our search produced 1940 titles, out of which we found seven completed trials (six published). The relative risk (RR) of developing psychosis was reduced by more than 50% for those receiving CBT at every time point [RR at 6 months 0.47, 95% confidence interval (CI) 0.27-0.82, p = 0.008 (fixed-effects only: six randomized controlled trials (RCTs), n = 800); RR at 12 months 0.45, 95% CI 0.28-0.73, p = 0.001 (six RCTs, n = 800); RR at 18-24 months 0.41, 95% CI 0.23-0.72, p = 0.002 (four RCTs, n = 452)]. Heterogeneity was low in every analysis and the results were largely robust to the risk of an unpublished 12-month study having unfavourable results. CBT was also associated with reduced subthreshold symptoms at 12 months, but not at 6 or 18-24 months. No effects on functioning, symptom-related distress or quality of life were observed. CBT was not associated with increased rates of clinical depression or social anxiety (two studies). CONCLUSIONS: CBT-informed treatment is associated with a reduced risk of transition to psychosis at 6, 12 and 18-24 months, and reduced symptoms at 12 months. Methodological limitations and recommendations for trial reporting are discussed.

Patients with faecal peritonitis admitted to European intensive care units: an epidemiological survey of the GenOSept cohort.

INTRODUCTION: Faecal peritonitis (FP) is a common cause of sepsis and admission to the intensive care unit (ICU). The Genetics of Sepsis and Septic Shock in Europe (GenOSept) project is investigating the influence of genetic variation on the host response and outcomes in a large cohort of patients with sepsis admitted to ICUs across Europe. Here we report an epidemiological survey of the subset of patients with FP. OBJECTIVES: To define the clinical characteristics, outcomes and risk factors for mortality in patients with FP admitted to ICUs across Europe. METHODS: Data was extracted from electronic case report forms. Phenotypic data was recorded using a detailed, quality-assured clinical database. The primary outcome measure was 6-month mortality. Patients were followed for 6 months. Kaplan-Meier analysis was used to determine mortality rates. Cox proportional hazards regression analysis was employed to identify independent risk factors for mortality. RESULTS: Data for 977 FP patients admitted to 102 centres across 16 countries between 29 September 2005 and 5 January 2011 was extracted. The median age was 69.2 years (IQR 58.3-77.1), with a male preponderance (54.3%). The most common causes of FP were perforated diverticular disease (32.1%) and surgical anastomotic breakdown (31.1%). The ICU mortality rate at 28 days was 19.1%, increasing to 31.6% at 6 months. The cause of FP, pre-existing co-morbidities and time from estimated onset of symptoms to surgery did not impact on survival. The strongest independent risk factors associated with an increased rate of death at 6 months included age, higher APACHE II score, acute renal and cardiovascular dysfunction within 1 week of admission to ICU, hypothermia, lower haematocrit and bradycardia on day 1 of ICU stay. CONCLUSIONS: In this large cohort of patients admitted to European ICUs with FP the 6 month mortality was 31.6%. The most consistent predictors of mortality across all time points were increased age, development of acute renal dysfunction during the first week of admission, lower haematocrit and hypothermia on day 1 of ICU admission.

Spontaneous multiarterial dissection immediately after childbirth.

Spontaneous coronary artery dissection and vertebral artery dissection are rare, life-threatening conditions. The pathophysiology of spontaneous coronary artery dissection during the peripartum period is poorly understood. We present a case of spontaneous multivessel dissection in a 32-year-old postpartum woman who presented with neck and chest pain. The patient's coronary and vertebral artery dissections were diagnosed with use of multiple imaging methods, and dissection of the internal mammary artery was discovered during surgery. The patient underwent successful coronary artery bypass grafting and remained asymptomatic 2 years later. To our knowledge, this is the first report of simultaneous coronary, vertebral, and internal mammary artery dissection in a postpartum woman. Early recognition and treatment is crucial, given the high mortality rate associated with spontaneous dissection.

Three-dimensional echocardiographic features of unicuspid aortic valve stenosis correlate with surgical findings.

A unicuspid aortic valve (UAV) is a rare congenital defect that may manifest clinically as severe aortic stenosis or regurgitation in the third to fifth decade of life. This report describes two cases of UAV stenosis in adult patients diagnosed by transesophageal echocardiography (TEE). The utility of three-dimensional TEE in confirming valve morphology and its relevance to transcatheter valve replacement are discussed.

Effects of drop-out on efficacy estimates in five Cochrane reviews of popular antipsychotics for schizophrenia.

OBJECTIVE: Our aim was to find out how Cochrane reviews of five popular or frequently prescribed second-generation antipsychotics in the UK (olanzapine, risperidone, quetiapine, amisulpride and aripiprazole) approached the problem of high drop-out in placebo-controlled trials. METHOD: We examined the following: (i) whether reviews included data from studies with a level of drop-out exceeding their stated exclusion criterion; (ii) the level of missing data each efficacy outcome in each review relied upon; and (iii) impact of excluding studies with high drop-out. RESULTS: All reviews included data they stated they would exclude because of unacceptable levels of attrition, four (risperidone, olanzapine, amisulpride, aripiprazole) without clear acknowledgement or justification. Several reviews also excluded data from a number of relatively low-attrition studies because of missing standard deviations. CONCLUSION: Cochrane reviews of five popular antipsychotics for schizophrenia misrepresented the available evidence on their efficacy. The impact of including high-attrition studies was difficult to quantify because of the exclusion of relevant low-attrition studies. Further analysis of the efficacy of these drugs in studies with acceptable rates of attrition is required. To reduce the problem of high attrition, trialists should gather follow-up data from people who leave the double-blind process early.

Cognitive therapy for people with a schizophrenia spectrum diagnosis not taking antipsychotic medication: an exploratory trial.

BACKGROUND: Although antipsychotic medication is the first line of treatment for schizophrenia, many service users choose to refuse or discontinue their pharmacological treatment. Cognitive therapy (CT) has been shown to be effective when delivered in combination with antipsychotic medication, but has yet to be formally evaluated in its absence. This study evaluates CT for people with psychotic disorders who have not been taking antipsychotic medication for at least 6 months. METHOD: Twenty participants with schizophrenia spectrum disorders received CT in an open trial. Our primary outcome was psychiatric symptoms measured using the Positive and Negative Syndromes Scale (PANSS), which was administered at baseline, 9 months (end of treatment) and 15 months (follow-up). Secondary outcomes were dimensions of hallucinations and delusions, self-rated recovery and social functioning. RESULTS: T tests and Wilcoxon's signed ranks tests revealed significant beneficial effects on all primary and secondary outcomes at end of treatment and follow-up, with the exception of self-rated recovery at end of treatment. Cohen's d effect sizes were moderate to large [for PANSS total, d=0.85, 95% confidence interval (CI) 0.32-1.35 at end of treatment; d=1.26, 95% CI 0.66-1.84 at follow-up]. A response rate analysis found that 35% and 50% of participants achieved at least a 50% reduction in PANSS total scores by end of therapy and follow-up respectively. No patients deteriorated significantly. CONCLUSIONS: This study provides preliminary evidence that CT is an acceptable and effective treatment for people with psychosis who choose not to take antipsychotic medication. An adequately powered randomized controlled trial is warranted.

Hyperperfusion syndrome following carotid artery stenting: the largest single-operator series to date.

BACKGROUND: Cerebral hyperperfusion syndrome (HPS) results from autoregulatory failure of cerebral blood flow following carotid endarterectomy (CEA) or carotid artery stenting (CAS) and encompasses a range of neurological findings including headache, seizure, intracranial hemorrhage (ICH), altered mental status and focal neurological changes. This report is the largest single-operator series evaluating the incidence and predictors of HPS following CAS. METHODS: A retrospective review was conducted on 482 consecutive patients who underwent CAS between August 1999 and December 2007 at Baptist Medical Center--Princeton, Birmingham, Alabama. All interventions were performed by a single operator (FM). The mean patient age was 70.4 +/- 10.3 years and 36% were symptomatic. All patients were high-risk for CEA. After cerebral protection catheters were routinely available, they were used in all but 6 cases (98.1%) where the anatomy precluded delivery. Brain computed tomography (CT) was performed immediately for any neurological change or significant headache following CAS. After neurological consultation and imaging, HPS was diagnosed if: 1) a neurological change occurred (not simply a headache); 2) CT revealed ipsilateral sulcal effacement/cerebral edema; and 3) stroke or transient ischemic attack (TIA) was excluded. RESULTS: Seven patients (1.45%) developed HPS following CAS. All patients achieved complete neurological recovery 6-24 hours following the procedure. Patients who developed HPS were significantly more likely to have had recent transient ischemic attack (TIA) symptoms than patients without HPS (p = 0.04). Unlike previous reports, there were no significant differences in procedural details, lesion characteristics and post-procedure blood pressure between the HPS and non-HPS patients, although the number of cases was small. Overall, the HPS cohort had a higher prevalence of comorbidities, though these differences did not reach statistical significance. Hypertension was present in all 7 HPS patients. Other complications in the series were death (0.83%), stroke (1.87%) and TIA (1.45%). CONCLUSIONS: The incidence of HPS is low (1.45%) following CAS, but it is an important complication to distinguish from stroke and TIA. Patients with a recent TIA may be predisposed to HPS. This report may underestimate the incidence of HPS, since patients with an isolated headache did not meet our diagnostic criteria and routine post-procedure brain CT imaging was not performed. The clinical predictors of HPS and its optimum management remain to be determined.

Eremophila glabra is an Australian plant that reduces lactic acid accumulation in an in vitro glucose challenge designed to simulate lactic acidosis in ruminants.

Lactic acidosis is a major welfare issue affecting animal health and production systems such as dairy and feedlot beef. We used two bioassays to identify bioactive plants of Australia with the potential to prevent acidosis in ruminants. In the first bioassay, a potentially acidotic environment was induced by adding glucose to rumen fluid and pH and gas production were used to estimate the effect on acid production and microbial fermentation after 5-h incubation. Australian plants (n = 104) were screened for their ability to prevent a decline in the pH without inhibiting normal gas production, and five plants namely Eremophila glabra, Kennedia eximia, Acacia saligna, Acacia decurrens and Kennedia prorepens with such properties were identified. We investigated further the two top ranking plants, E. glabra and K. prorepens, in the second bioassay to determine the extent of their effect in vitro, by extending the incubation to 24 h and measuring d-lactate, and volatile fatty acids (VFA) in addition to pH and gas production. These were measured at 0, 5, 10, 16 and 24 h after inoculation. Eremophila glabra maintained pH values that were higher and d-lactate concentrations that were lower than the control (P < 0.001), and comparable to the antibiotic-protected environment (AB; 12 µg of virginiamycin/ml). Eremophila glabra and AB treatments did not restrict fermentation, as judged by gas production and VFA. Kennedia prorepens slowed the decline in pH and reduced the accumulation of lactate but inhibited gas production. We concluded that, in vitro, E. glabra was effective at controlling events that can lead to acidosis and the effect was comparable to that of virginiamycin, while K. prorepens was less effective than E. glabra and also inhibited fermentation.

A comparison of eltanolone and propofol anaesthesia for minor gynaecological surgery.

We have used eltanolone and propofol to induce anaesthesia and by intermittent injection to supplement nitrous oxide during maintenance in 67 patients undergoing minor gynaecological surgery. This study was a controlled randomized phase III with two parallel groups and a blinded assessment of post-operative recovery. Complications during induction and maintenance were few. Urticaria occurred in two patients given eltanolone and in none of those given propofol. Time to orientation and time to eye opening were significantly shorter in the propofol group (P < 0.001). Systolic and diastolic blood pressure decreased in both groups but the decrease was significantly greater in the propofol group (P < 0.005 systolic blood pressure; P < 0.001 diastolic blood pressure). Heart rate decreased significantly in the propofol group (P < 0.002). We conclude that eltanolone anaesthesia is associated with a greater haemodynamic stability than propofol anaesthesia but that early recovery occurs more slowly.

Prevention of remote organ injury in cardiopulmonary bypass: the impact of flow generation technique.

The purpose of this study was to investigate the effects of 3 different types of flow generation for cardiopulmonary bypass on gastrointestinal permeability and on neutrophil expression of CD11b, a surface marker of neutrophil activation. Fourteen patients undergoing elective coronary revascularization were selected randomly to receive 1 of the 3 flow generation techniques (roller, pulsatile, or centrifugal). Intestinal permeability was assessed by the fraction of an oral dose of 51chromium-ethylenediaminetetraacetate (51Cr-EDTA) recovered in the urine over 24 h. Neutrophil activation was determined by expression of CD11b markers at 6 time points. Overall, the 14 patients showed significant increases in intestinal permeability. It was not possible to demonstrate statistically significant differences among the flow generation groups; however, when compared to both roller pump groups, the centrifugal pump group showed a 3.2% reduction in intestinal permeability. There was no change in the expression of CD11b receptors throughout the time points, nor was there a relationship of CD11b markers to the flow generation technique.

Manual compared with target-controlled infusion of propofol.

We studied 160 ASA I-II patients, anaesthetized with propofol by infusion, using either a manually controlled or target-controlled infusion system. Patients were anaesthetized by eight consultant anaesthetists who had little or no previous experience of the use of propofol by infusion. In addition to propofol, patients received temazepam premedication, a single dose of fentanyl and 67% nitrous oxide in oxygen. Each consultant anaesthetized 10 patients in sequential fashion with each system. Use of the target-controlled infusion resulted in more rapid induction of anaesthesia and allowed earlier insertion of a laryngeal mask airway. There was a tendency towards less movement in response to the initial surgical stimulus and significantly less movement during the remainder of surgery. Significantly more propofol was administered during both induction and maintenance of anaesthesia with the target-controlled system. This was associated with significantly increased end-tidal carbon dioxide measurements during the middle period of maintenance only, but recovery from anaesthesia was not significantly prolonged in the target-controlled group. With the exception of a clinically insignificant difference in heart rate, haemodynamic variables were similar in the two groups. Six of the eight anaesthetists found the target-controlled system easier to use, and seven would use the target-controlled system in preference to a manually controlled infusion. Anaesthetists without prior experience of propofol infusion anaesthesia quickly became familiar with both manual and target-controlled techniques, and expressed a clear preference for the target-controlled system.