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.

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.

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.

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.

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.

Effects of Fluosol-DA (artificial blood) on clinical chemistry tests and instruments.

Artificial blood must be added to the list of therapeutic agents that produce interference with diagnostic laboratory tests. Fluosol-DA (Alpha Therapeutic Corp., Los Angeles, CA), a stable 20% emulsion of perfluorocarbons in aqueous medium, is being evaluated in clinical trials as a blood substitute in the United States. We investigated its effects in blood and serum samples on test results and instruments in the clinical chemistry laboratory. The 20% emulsion was added to blood or serum specimens in amounts corresponding to the replacement of in-vivo plasma volumes of 10-50%, concentrations that would be expected in blood samples obtained from patients who have received Fluosol. Observed interferences mimicked those caused by high triglyceride concentrations in serum specimens: interference with chemical reactions and generation of spurious absorbance readings because of turbidity. These types of errors are often additive, and the cumulative effect may cause either erroneously high or low values for the analytes concerned. Because Fluosol may be used widely, although infrequently, for patients refusing blood transfusions on religious grounds and for patients with rare antibodies to red blood cells who require transfusion, laboratories analyzing specimens containing Fluosol should be aware of the potential errors.

Tension pneumoperitoneum.

A 26-year-old woman developed the adult respiratory distress syndrome after a post-partum haemorrhage. After mechanical ventilation was started the signs of a tense and distended acute abdomen developed. The aspiration and subsequent analysis of copious intra-peritoneal gas confirmed the diagnosis of a tension pneumoperitoneum secondary to pulmonary barotrauma.

Retrograde cerebral perfusion: clinical experience in emergency and elective aortic operations.

We recently have used retrograde cerebral perfusion via the superior vena cava in association with hypothermic circulatory arrest as an adjunct to cerebral protection during aortic arch operations. Between April 1993 and March 1994, 23 patients (14 male; 9 female; median age, 64 years; age range, 25 to 76 years; 14 emergency, 9 elective) underwent operation on the ascending aorta, aortic arch, or both for acute dissection (11) or aneurysm (12). Aortic root replacement was performed in 13 patients (7 with arch replacement), ascending aortic replacement in 7 (4 with arch replacement), isolated aortic arch replacement in 2, and repair of sinus of Valsalva aneurysm in 1. Coronary artery bypass grafting was performed in 4 patients. Hypothermic circulatory arrest (15 degrees C) and retrograde cerebral perfusion were implemented in all cases (median circulatory arrest time, 21 minutes; range, 13 to 51 minutes; median retrograde cerebral perfusion time, 20 minutes; range, 12 to 50 minutes). Three hospital deaths occurred (atheromatous embolic stroke, sepsis, rupture of infrarenal aortic aneurysm). The remaining patients had no neurologic damage (median intensive therapy unit stay, 1 day; range, 1 to 5 days). Retrograde cerebral perfusion is easy to establish and safe, and may improve brain protection during hypothermic circulatory arrest.

Clinical evaluation of sodium ion selective field effect transistors for whole blood assay.

Sodium ion selective field effect transistors (ISFETs) were evaluated for their performance in measurement of sodium ions in whole blood for 'near patient' analysis in operating theatres and intensive care units. Performance was evaluated in comparison with a standard clinical laboratory sodium/potassium ion analyser (Radiometer KNA1) and with sodium and potassium assays using flame photometry on the plasma from each whole blood specimen. The imprecisions (coefficients of variation) of three ISFETs for sodium ion assay were 1.08, 1.56 and 1.10%, respectively. Robust bivariate linear regression (reweighted least squares preceded by least median of squares) of the ISFET versus KNA1 sodium ion activity yielded a regression coefficient of 1.08 and an intercept of -18.2 mM. The influence of potassium, protein and lipid on the measurement of sodium ions by both ISFETs and the KNA1 was assessed using robust multiple regression (also based on reweighted least squares preceded by least median of squares). In the regression versus flame photometry, protein was found to be more influential for the KNA1 (glass sodium ion selective electrode) than for the ISFET. Potassium had no influence on assays using the ISFET, but had a weak negative influence on assays using the KNA1. Two ISFETs lasted for more than 200 assays each demonstrating their robustness in the assay of whole blood.

Comparison of potassium ISFETs with the Radiometer KNA1 and the Corning 902 ion selective electrode analysers for whole blood potassium ion estimation.

Evaluation of the performance of potassium ion sensitive field effect transistors (K+ ISFETs), developed by Thorn EMI in a form suitable for mass production and for incorporation in 'near the patient' analysers, showed only very small constant and proportional biases against the Radiometer KNA1 and the Corning 902 for whole blood potassium ion estimation. Between batch imprecision tests with whole blood showed the K+ ISFET was comparable in performance to the Corning 902 but inferior to the Radiometer KNA1. The evaluation demonstrated that ISFET manufacturing technology has now reached a stage of development at which ISFETs should be considered seriously for use in clinical chemical analysers.

Inhibition of glycolysis in boar sperm by alpha-chlorohydrin.

The effect of alpha-chlorohydrin (3-chloropropan-1,2-diol) on the metabolism of D-[U-14C]-fructose and L-[U-14C]-lactate by washed boar sperm has been investigated. Whereas alpha-chlorohydrin at concentrations as low as 0.1 mM inhibited the metabolism of fructose and led to an increase in the utilization of endogenous lactate, amounts up to 500 mM had no effect on the oxidation of added lactate. Low levels of alpha-chlorohydrin increased the cellular concentrations of fructose-1,6-bisphosphate and the triosephosphates, an effect consistent with the inhibition of glyceraldehyde-3-phosphate dehydrogenase. Although [U-14C]-glycerol was rapidly oxidized by boar sperm, [U-14C]-alpha-chlorohydrin was not metabolized to 14CO2, showing that it is not converted to glycerol. Extracts obtained by sonication of boar sperm after incubation with [3-36C1]-alpha-chlorohydrin, did not contain [3-36C1]-alpha-chlorohydrin-1-phosphate. This is contrary to the postulate that this phosphorylated compound is the inhibitory metabolite of alpha-chlorohydrin.

Injection-induced contractures of the quadriceps in childhood. A comparison of proximal release and distal quadricepsplasty.

Thirty-two contractures of the quadriceps induced by injection in 17 children have been reviewed. The average age at presentation was 3 years 4 months. All the children had suffered a severe illness within the first few weeks of life and all had received intramuscular injections into the thigh. Three methods of treatment were used: conservative, distal quadricepsplasty, and proximal release. At follow-up none of the patients treated by proximal release had an extension lag, which was present in 70% of those treated by distal quadricepsplasty. Apart from one case with slight improvement in the range of knee flexion, conservative treatment, at best, could only prevent further loss. The clinical presentation and management is described, and the advantages of proximal release are discussed.

The behaviour pattern of the scoliosis associated with osteoid osteoma or osteoblastoma of the spine.

The behaviour pattern of the scoliosis associated with osteoid osteoma or osteoblastoma of the spine is described. In patients presenting with symptoms at or around skeletal maturity, the scoliosis is postural. Excision of the lesion ensures complete resolution of the curve. In the growing child, however, an initial postural scoliosis may develop vertebral rotation with structural characteristics. The magnitude of the curve and the associated vertebral rotation is dependent on the time interval between the onset of symptoms and the surgical treatment. Although removal of the lesion usually results in regression of the curve, a prolonged delay in treatment may result in a progressive structural scoliosis. A possible mechanism for the behaviour of the scoliosis is discussed.

Osteoid osteoma and benign osteoblastoma of the spine. Clinical presentation and treatment.

The clinical presentation and treatment of 18 cases of osteoid osteoma or osteoblastoma of the spine are described, with an average follow-up of 4.2 years (range three months to 11.5 years). The average delay between the onset of symptoms and definitive diagnosis was 19 months. All patients presented with marked spinal stiffness and a painful scoliosis. The lesion was situated in the pedicle in the 15 patients with involvement of the thoracolumbar spine. A surgical approach allowing direct access to the pedicle without entering the spinal canal or jeopardising spinal stability is described. Surgical treatment afforded immediate relief of pain and an early return of full spinal mobility.

The timing of amputation for lower limb trauma.

We reviewed 35 patients who had an amputation following the failure of treatment for severe lower limb trauma. Seven of the amputations were for ischaemia, within one month of injury; 13 were between one month and one year for infection complicating loss of wound cover in un-united fractures; and 15 were later than one year after injury, mainly for infected non-union. The latter group of patients had had an average of 12 operations and 50 months of treatment, including eight months in hospital. We used a new limb injury score based on damage to the individual tissue elements; this indicated that, even in the absence of neurovascular injury, the presence of severe damage to skin, bone and muscle, with wound contamination, particularly in the lower tibia, had a poor prognosis. We therefore recommend, to avoid multiple operations, with prolonged hospitalisation and suffering, that these patients should have early independent review by orthopaedic and plastic surgeons with the aim of establishing an accurate prognosis for the salvage of a useful limb.

On using a self-tuning controller for blood pressure regulation during surgery in man.

The generalized minimum-variance self-tuning controller of Clarke and Gawthrop has been used to adjust the flow rate of a modified Vickers Treonic IP4 syringe pump delivering phenylephrine to 20 patients undergoing lower abdominal surgery during epidural analgesia. This proved to be a very effective method of restoring and maintaining normal arterial pressure. The method has also been used to produce controlled hypotension in 18 patients undergoing plastic or neurosurgical procedures via sodium nitroprusside infusions. Valuable insight into patient responses to surgical stimuli, blood loss, fluid loads, opioids, relaxants and other agents was provided.