Goal-directed fluid therapy using uncalibrated pulse contour analysis and balanced crystalloid solutions during hip revision arthroplasty: a quality implementation project.

BACKGROUND: To implement a goal-directed fluid therapy (GDFT) protocol using crystalloids in hip revision arthroplasty surgery within a quality management project at a tertiary hospital using a monocentric, prospective observational study. METHODS: Adult patients scheduled for elective hip revision arthroplasty surgery were screened for inclusion in this prospective study. Intraoperatively stroke volume (SV) was optimized within a previously published protocol using uncalibrated pulse contour analysis and balanced crystalloids. Quality of perioperative GDFT was assessed by protocol adherence, SV increase as well as the rate of perioperative complications. Findings were then compared to two different historical groups of a former trial: one receiving GDFT with colloids (prospective colloid group) and one standard fluid therapy (retrospective control group) throughout surgery. Statistical analysis constitutes exploratory data analyses and results are expressed as median with 25th and 75th percentiles, absolute and relative frequencies, and complication rates are further given with 95% confidence intervals for proportions using the normal approximation without continuity correction. RESULTS: Sixty-six patients underwent GDFT using balanced crystalloids and were compared to 130 patients with GDFT using balanced colloids and 130 controls without GDFT fluid resuscitation. There was a comparable increase in SV (crystalloids: 65 (54-74 ml; colloids: 67.5 (60-75.25 ml) and total volume infused (crystalloids: 2575 (2000-4210) ml; colloids: 2435 (1760-3480) ml; and controls: 2210 (1658-3000) ml). Overall perioperative complications rates were similar (42.4% (95%CI 30.3-55.2%) for crystalloids and 49.2% (95%CI 40.4-58.1%) for colloids and lower compared to controls: 66.9% (95%CI 58.1-74.9)). Interestingly, a reduced number of hemorrhagic complications was observed within crystalloids: 30% (95%CI 19.6-42.9); colloids: 43% (95%CI 34.4-52.0); and controls: 62% (95%CI 52.6-69.9). There were no differences in the rate of admission to the post-anesthesia care unit or intensive care unit as well as the length of stay. CONCLUSIONS: Perioperative fluid management using a GDFT protocol with crystalloids in hip revision arthroplasty surgery was successfully implemented in daily clinical routine. Perioperative complications rates were reduced compared to a previous management without GDFT and comparable when using colloids. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01753050.

Gut microbiota dysbiosis associated with glucose metabolism disorders and the metabolic syndrome in older adults.

Obesity and associated metabolic disorders have become highly prevalent diseases worldwide, and the human gut microbiota, due to its influence on host energy metabolism, has been attributed an important role therein. This pilot study explores host-microbiota relationships in men and women affected by various types of glucose metabolism disorder. Among 20 individuals aged 58 to 71 years with either normal glucose tolerance, prediabetes, or type 2 diabetes mellitus the gut bacterial communities were compared based on barcoded 454 sequencing of 16S rRNA genes amplified from stool samples. We found that specific microbiota groups were relatively enriched or reduced in different metabolic states. Further, positive or negative associations with clinical manifestations of metabolic disease suggest that these organisms indicate and possibly contribute to metabolic impairment or health. For instance, a higher prevalence of Erysipelotrichaceae and Lachnospiraceae was found associated with metabolic disorders, and the Holdemania and Blautia genera correlated with clinical indicators of an impaired lipid and glucose metabolism. The Bacteroidetes and groups therein, by contrast, displayed inverse relationships with metabolic disease parameters and were found relatively enriched in participants not diagnosed with metabolic syndrome or obesity. Further, the prevalence of specific Clostridia and Rikenellaceae members also pointed towards a healthier metabolic state. Links with diet as an intermediate factor included positive and negative associations of Lachnospiraceae with relative consumption rates of fat and carbohydrates, respectively, and positive associations of Turicibacteraceae with the consumption of protein. Identifying critical roles of major gut microbiota components in metabolic disorders has important translational implications regarding the prevention and treatment of metabolic diseases by means of preventing or reversing dysbiosis and by controlling exacerbating diet and life style factors particularly in sensitive population groups.

Brain abnormalities in high-risk violent offenders and their association with psychopathic traits and criminal recidivism.

Measures of psychopathy have been proved to be valuable for risk assessment in violent criminals. However, the neuronal basis of psychopathy and its contribution to the prediction of criminal recidivism is still poorly understood. We compared structural imaging data from 40 male high-risk violent offenders and 37 non-delinquent healthy controls via voxel-based morphometry. Psychopathic traits and risk of violence recidivism were correlated with gray matter volume (GMV) of regions of interest previously shown relevant for criminal behavior. Relative to controls, criminals showed less GMV in the prefrontal cortex (PFC) and more GMV in cerebellar regions and basal ganglia structures. Within criminals, we found a negative correlation between prefrontal GMV and psychopathy. Additionally, there was a positive correlation between cerebellar GMV and psychopathy as well as risk of recidivism for violence. Moreover, GMVs of the basal ganglia and supplementary motor area (SMA) were positively correlated with anti-sociality. GMV of the amygdala was negatively correlated with dynamic risk for violence recidivism. In contrast, GMV of (para)limbic areas (orbitofrontal cortex, insula) was positively correlated with anti-sociality and risk of violence recidivism. The current investigation revealed that in violent offenders deviations in GMV of the PFC as well as areas involved in the motor component of impulse control (cerebellum, basal ganglia, SMA) are differentially related to psychopathic traits and the risk of violence recidivism. The results might be valuable for improving existing risk assessment tools.

Isolation of Nocardia mexicana from focal proliferative tenosynovitis and arthritis in a steer.

CASE REPORT: An 18-month-old Charolais steer was presented with lameness and fluctuant swelling of the right stifle joint, which yielded neutrophils on fine-needle aspiration. A diagnosis of bacterial proliferative tenosynovitis and arthritis was made on postmortem and histological examination. Culture and 16S rRNA sequencing identified a Nocardia sp. with 99% homology with the corresponding DNA fragment of N. mexicana DSM 44952. Antimicrobial susceptibility testing revealed the isolate was susceptible to co-trimoxazole and third-generation cephalosporins. CONCLUSION: We report the first case, both in Australia and internationally, of proliferative tenosynovitis and arthritis caused by Nocardia spp. infection in a bovine and the first report of pathology attributed to N. mexicana in a veterinary patient. Given the limited susceptibility of the bacteria, the poor antimicrobial penetration that would be expected and the morphological changes that had taken place in the joint; the steer would have required protracted antimicrobial treatment in addition to invasive debridement of the lesion. This case emphasises the importance of routinely performing cytology and extended incubation of cultures in cases of arthritis in order to make ethical and economically viable treatment decisions.

A systematic review of risk assessment strategies for populations at high risk of engaging in violent behaviour: update 2002-8.

BACKGROUND: This review systematically examines the research literature published in the period 2002-8 on structured violence risk assessment instruments designed for use in mental health services or the criminal justice system. It adopted much broader inclusion criteria than previous reviews in the same area in order to capture and summarise data on the widest possible range of available instruments. OBJECTIVES: To address two questions: (1) what study characteristics are associated with a risk assessment instrument score being significantly associated with a violent outcome? and (2) which risk assessment instruments have the highest level of predictive validity for a violent outcome? DATA SOURCES: Nineteen bibliographic databases were searched from January 2002 to April 2008, including PsycINFO, MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, British Nursing Index, International Bibliography of the Social Sciences, Education Resources Information Centre, The Cochrane Library and Web of Knowledge. REVIEW METHODS: Inclusion criteria for studies were (1) evaluation of a structured risk tool; (2) outcome measure of interpersonal violence; (3) participants aged 17 years or over; and (4) participants with a mental disorder and/or at least one offence and/or at least one indictable offence. A series of bivariate analyses using either a chi-squared test or Spearman's rank-order correlation were conducted to explore associations between study characteristics and outcomes. Data from a subset of studies reporting area under the curve (AUC) analysis were combined to provide estimates of mean validity. RESULTS: For the overall set of included studies (n = 959), over three-quarters (77%) were conducted in the USA, Canada or the UK. Two-thirds of all studies were conducted with offenders who had either no formal mental health diagnosis (43%) or forensic samples with a formal diagnosis (25%). The Psychopathy Checklist-Revised was tested in the largest number of studies (n = 192). Most studies (78%) reported a statistically significant (p < 0.05) relationship between the instrument score and a violent outcome. Prospective data collection (chi-squared = 4.4, p = 0.035), number of people recruited (U = 27.8, p = 0.012) and number of participants at end point (U = 26.9, p = 0.04) were significantly associated with predictive validity. For those instruments tested in five or more studies reporting AUC values, the General Statistical Information on Recidivism instrument had the highest mean AUC (0.73). LIMITATIONS: Agreement between pairs of reviewers in the initial pilot exercises was good but less than perfect, so discrepancies may be present given the complexity and subjectivity of some aspects of violence research. Only five of the seven calendar years (2003-7) are completely covered, with partial coverage of 2002 and 2008. There is no weighting for sample or effect sizes when results from studies are aggregated. CONCLUSIONS: A very large number of studies examining the relationship between a structured instrument and a violent outcome were published in this relatively short 7-year period. The general quality of the literature is weak in places (e.g. over-reliance on cross-sectional designs) and a vast range of distinct instruments have been tested to varying degrees. However, there is evidence of some convergence around a small number of high-performing instruments and identification of the components of a high-quality evaluation approach, including AUC analysis. The upper limits (AUC ≥ 0.85) of instrument-based prediction have probably been achieved and are unlikely to be exceeded using instruments alone. FUNDING: The National Institute for Health Research Health Technology Assessment and Research for Patient Benefit programmes.

[Gender-specific differences in age-associated endocrinology]. / Geschlechtsspezifische Unterschiede der Endokrinologie im Alter.

The endocrine system is intimately involved in modulating lifespan and quality of life. Facing an ever increasing proportion of aged people in the western society, there is great interest in understanding the complex interrelations between increasing age and hormonal regulation. Age-associated endocrinological changes comprise the decline of basal hormonal levels, pulsatile hormone distribution, and activity of hormonal axis, which result in changes in body composition. Men and women experience different age-associated alterations of the hormonal system. Aging per se is a risk factor for diseases like diabetes mellitus type 2, thyroid disorders, osteoporosis, frailty, and sarcopenia. Gender-specific differences with respect to symptoms, interactions, diagnosis, and therapy must be taken into consideration. Current data do not allow a general recommendation for hormonal substitution, neither for women nor for men. New research approaches following a multifactorial pathway are required to elucidate the complexity of age-associated endocrinological changes and to develop gender-specific therapies for endocrinological diseases.

Factor VIII Bypassing Activity (FEIBA) assays: standardization and development of the 1st NIBSC Working Standard for FEIBA--results from a collaborative study.

Factor-Eight-Inhibitor-Bypassing-Activity (FEIBA) is a bypassing-agent used to control spontaneous bleeding or cover surgical interventions in Haemophiliacs who develop neutralizing antibodies against FVIII/FIX. The market lot-release of FEIBA is dependent on specific clot-based assays, carried out by both the manufacturer and regulatory authorities, relative to manufacturer's in-house standards, which are produced on a small-scale and are replaced frequently. We sought to standardize the FEIBA assay by developing a FEIBA primary standard which would be internationally available in sufficiently large quantities, with a predicted lifetime of many years. A collaborative study involving the manufacturer and three regulatory authorities, was carried out in which a candidate material, sample B (06/172), was calibrated by assays relative to the manufacturer's in-house FEIBA standards (C and D). All laboratories used their routine validated methods (16 APTT-assays, 8 ACTIN-FS-assays and 27 DAPTTIN-assays). Intra-laboratory geometric coefficients of variation (GCVs) for candidate B ranged from 3% to 29% (GCVs <9% from majority of labs). Assessment of inter-laboratory variability gave overall GCV values of 6.9% and 4.4% relative to standards C and D, respectively, for all methods. There was good agreement in potency estimation between laboratories using each of the three methods, with the overall potencies by the three methods differing by less than 10% of the overall mean, giving an overall combined potency of 28.0 units per ampoule. All participants agreed that candidate B (06/172) be established as the 1st NIBSC Working Standard for FEIBA with an assigned potency of 28.0 units per ampoule, based on combined results for both methods, relative to either standard C or D.

A systematic review of prevention and intervention strategies for populations at high risk of engaging in violent behaviour: update 2002-8.

BACKGROUND: It has been estimated that violence accounts for more than 1.6 million deaths worldwide each year and these fatal assaults represent only a fraction of all assaults that actually occur. The problem has widespread consequences for the individual and for the wider society in physical, psychological, social and economic terms. A wide range of pharmacological, psychosocial and organisational interventions have been developed with the aim of addressing the problem. This review was designed to examine the effectiveness of these interventions when they are developed in mental health and criminal justice populations. OBJECTIVE: To update a previous review that examined the evidence base up to 2002 for a wide range of pharmacological, psychosocial and organisational interventions aimed at reducing violence, and to identify the key variables associated with a significant reduction in violence. DATA SOURCES: Nineteen bibliographic databases were searched from January 2002 to April 2008, including PsycINFO (CSA) MEDLINE (Ovid), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED), British Nursing Index/Royal College of Nursing, International Bibliography of the Social Sciences (IBSS), Education Resources Information Center (ERIC)/International ERIC, The Cochrane Library (Cochrane reviews, other reviews, clinical trials, methods studies, technology assessments, economic evaluations), Web of Science [Science Citation Index Expanded (SCIE), Social Sciences Citation Index (SSCI), Arts & Humanities Citation Index (A&HCI)]. REVIEW METHODS: The assessment was carried out according to accepted procedures for conducting and reporting systematic reviews, including identification of studies, application of inclusion criteria, data extraction and appropriate analysis. Studies were included in meta-analyses (MAs) if they followed a randomised control trial (RCT) design and reported data that could be converted into odds ratios (ORs). For each MA, both a fixed-effects model and a random-effects model were fitted, and both Q statistic and I2 estimates of heterogeneity were performed. RESULTS: A total of 198 studies were identified as meeting the inclusion criteria; of these, 51 (26%) were RCTs. Bivariate analyses exploring possible sources of variance in whether a study reported a statistically significant result or not, identified six variables with a significant association. An outcome was less likely to be positive if the primary intervention was something other than a psychological or pharmacological intervention, the study was conducted in an penal institution, the comparator was another active treatment or treatment as usual and if a between-groups design had been used. An outcome was more likely to be positive if it was conducted with people with a mental disorder. The variation attributable to these variables when added to a binary logistic regression was not large (Cox and Snell R(2) = 0.12), but not insignificant given the small number of variables included. The pooled results of all included RCTs suggested a statistically significant advantage for interventions over the various comparators [OR 0.59, 95% confidence interval (CI) 0.53 to 0.65, fixed effects; OR 0.35, 95% CI 0.26 to 0.49 random effects, 40 studies]. However, there was high heterogeneity {I(2) = 86, Q = 279 [degrees of freedom (df) = 39], p < 0.0001}, indicating the need for caution in interpreting the observed effect. Analysis by subgroups showed that most results followed a similar pattern, with statistically significant advantages of treatments over comparators being suggested in fixed- and/or random-effects models but in the context of large heterogeneity. Three exceptions were atypical antipsychotic drugs [OR 0.21, 95% CI 0.16 to 0.27, fixed effects; OR 0.24, 95% CI 0.14 to 0.43, random effects; 10 studies, I(2) = 72.2, Q = 32.4 (df = 9), p < 0.0001], psychological interventions [OR 0.63, 95% CI 0.48 to 0.83, fixed effects; OR 0.53, 95% CI 0.31 to 0.93, random effects; nine studies, I(2) = 62.1, Q = 21.1 (df = 8), p = 0.007] and cognitive behavioural therapy (CBT) as a primary intervention [OR 0.61, 95% CI 0.42 to 0.88, fixed effects; OR 0.61, 95% CI 0.37 to 0.99, random effects; seven studies, I(2) = 21.6, Q = 7.65 (df = 6), p = 0.26]. LIMITATIONS: The heterogenity of the included studies inhibits both robust MA and the clear application of findings to establishing improvements in clinical practice. CONCLUSIONS: Results from this review show small-to-moderate effects for CBT, for all psychological interventions combined, and larger effects for atypical antipsychotic drugs, with relatively low heterogeneity. There is also evidence that interventions targeted at mental health populations, and particularly male groups in community settings, are well supported, as they are more likely to achieve stronger effects than interventions with the other groups. Future work should focus on improving the quality of evidence available and should address the issue of heterogenity in the literature. FUNDING: The National Institute for Health Research Health Technology Assessment programme and the Research for Patient Benefit programme.

Non-destructive analysis of tablet coatings with optical coherence tomography.

Optical coherence tomography (OCT) is a non-invasive analysis technique allowing fast and high-quality cross-sectional imaging of scattering media. OCT is based on the physical phenomenon of low coherence interferometry and is thus well suited to image layered structures. In this paper, high-speed spectral domain OCT was used for the characterization of pharmaceutical tablet coatings, sampled at different stages of an industrial drum spray coating process, comprising tablets with a coating thickness ranging from uncoated to a target coating thickness of about 70 µm. In addition to the OCT investigation of layer thickness and homogeneity, tablet weight gain and tablet diameters were determined on a single-tablet level. Scanning electron microscopy (SEM) was applied for referencing the coating thickness obtained with OCT. We demonstrated that OCT allows rapid evaluation of coating properties, such as thickness and homogeneity independently from variations of the tablet core. In contrast to indirect methods, deviations observed with OCT can be related directly to the coating properties. Furthermore, for an extended morphological coating characterization, three dimensional images were reconstructed. Pending further developments, the high axial resolution and fast data acquisition rate of OCT has the potential for highly accurate, fast and low-cost coating control during and after manufacturing.

Near Field Communication-based telemonitoring with integrated ECG recordings.

OBJECTIVES: Telemonitoring of vital signs is an established option in treatment of patients with chronic heart failure (CHF). In order to allow for early detection of atrial fibrillation (AF) which is highly prevalent in the CHF population telemonitoring programs should include electrocardiogram (ECG) signals. It was therefore the aim to extend our current home monitoring system based on mobile phones and Near Field Communication technology (NFC) to enable patients acquiring their ECG signals autonomously in an easy-to-use way. METHODS: We prototypically developed a sensing device for the concurrent acquisition of blood pressure and ECG signals. The design of the device equipped with NFC technology and Bluetooth allowed for intuitive interaction with a mobile phone based patient terminal. This ECG monitoring system was evaluated in the course of a clinical pilot trial to assess the system's technical feasibility, usability and patient's adherence to twice daily usage. RESULTS: 21 patients (4f, 54 ± 14 years) suffering from CHF were included in the study and were asked to transmit two ECG recordings per day via the telemonitoring system autonomously over a monitoring period of seven days. One patient dropped out from the study. 211 data sets were transmitted over a cumulative monitoring period of 140 days (overall adherence rate 82.2%). 55% and 8% of the transmitted ECG signals were sufficient for ventricular and atrial rhythm assessment, respectively. CONCLUSIONS: Although ECG signal quality has to be improved for better AF detection the developed communication design of joining Bluetooth and NFC technology in our telemonitoring system allows for ambulatory ECG acquisition with high adherence rates and system usability in heart failure patients.

The third generation superconducting 28 GHz electron cyclotron resonance ion source VENUS (invited).

VENUS is a third generation electron cyclotron resonance (ECR) ion source, which incorporates a high field superconducting NbTi magnet structure, a 28 GHz gryotron microwave source and a state of the art closed cycle cryosystem. During the decade from initial concept to regular operation, it has demonstrated both the feasibility and the performance levels of this new generation of ECR ion sources and required innovation on magnet construction, plasma chamber design, and beam transport. In this paper, the development, performance, and major innovations are described as well as a look to the potential to construct a fourth generation ECR ion source.

A tandem-based compact dual-energy gamma generator.

A dual-energy tandem-type gamma generator has been developed at E. O. Lawrence Berkeley National Laboratory and Sandia National Laboratories. The tandem accelerator geometry allows higher energy nuclear reactions to be reached, thereby allowing more flexible generation of MeV-energy gammas for active interrogation applications. Both positively charged ions and atoms of hydrogen are created from negative ions via a gas stripper. In this paper, we show first results of the working tandem-based gamma generator and that a gas stripper can be utilized in a compact source design. Preliminary results of monoenergetic gamma production are shown.

Tissue reaction to implants of different metals: a study using guide wires in cannulated screws.

Cannulated screws, along with guide wires, are typically used for surgical fracture treatment in cancellous bone. Breakage or bending deformation of the guide wire is a clinical concern. Mechanically superior guide wires made of Co-Cr alloys such as MP35N and L605 may reduce the occurrence of mechanical failures when used in combination with conventional (316L stainless steel) cannulated screws. However the possibility of galvanic or crevice corrosion and adverse tissue reaction, exists when using dissimilar materials, particularly in the event that a guide wire breaks, and remains in situ. Therefore, we designed an experiment to determine the tissue reaction to such an in vivo environment. Implant devices were designed to replicate a clinical situation where dissimilar metals can form a galvanic couple. Histological and SEM analyses were used to evaluate tissue response and corrosion of the implants. In this experiment, no adverse in vivo effects were detected from the use of dissimilar materials in a model of a broken guide wire in a cannulated screw.

Monitoring anticoagulation of primary haemostasis--estimation of platelet function in whole blood assays.

This article provides an overview on current commercially available methods to determine primary haemostasis as a target of drug-mediated anticoagulation. It focuses on whole blood methods only, and references the currently major achievements that have been reported with each method in respect to its clinical use. Advantages and disadvantages of the various methods are presented, based on considerations of platelet physiology, and on feasibility of the procedures.

Longitudinal as well as age-matched assessments of bone changes in the mature ovariectomized rat model.

In the past, bone loss in the ovariectomized (OVX) osteoporotic rat model has been monitored using in vitro micro-computed tomography (micro-CT) to assess bone structure (bone volume/total volume, BV/TV). The purpose of this study was to assess the importance of baseline control and sham groups in 12-16-week-old, reproductively mature rats. Measurements were carried out in a longitudinal and age-matched fashion using newer in vivo peripheral quantitative computed tomography (pQCT), which measures apparent bone mineral density (BMD). BMD was measured at the distal femoral metaphysis of 12-week-old female Wistar rats with pQCT. Subsequently, animals were either OVX or sham operated, and pQCT measurements were repeated four weeks later. Then, all rats were euthanized and in vitro BMD and BV/TV were obtained by micro-CT imaging. Results from three consistently differentiated regions of interest showed that there was significant bone loss and growth during the four weeks in the OVX and sham group, respectively. Taking this into account, i.e. a posteriori superimposing growth to loss, no differences resulted between BMD values measured in a longitudinal fashion with pQCT and that measured in comparison with an age-matched sham group with micro-CT and pQCT. In addition, there was a strong linear correlation between BMD measured with pQCT and BV/TV obtained from micro-CT. In conclusion, this outcome provides new insights into individual bone changes due to OVX and growth in Wistar rats during the age period of 12-16 weeks, which is often applied in osteoporosis research as the 'mature' rat model. Data can be used as baseline information upon which future in vivo study designs with this rat model can refer to reduce and minimize animal use.

Drift compression of an intense neutralized ion beam.

Longitudinal compression of a velocity-tailored, intense neutralized beam at 300 keV, 25 mA has been demonstrated. The compression takes place in a 1-2 m drift section filled with plasma to provide space-charge neutralization. An induction cell produces a head-to-tail velocity ramp that longitudinally compresses the neutralized beam, enhancing the beam peak current by a factor of 50 and producing a pulse duration of about 3 ns. This measurement has been confirmed independently with two different diagnostic systems.

Sertindole for schizophrenia.

BACKGROUND: Sertindole is an atypical antipsychotic, which is thought to give a lower incidence of extrapyramidal side effects at clinically effective doses than typical antipsychotic drugs. In December 1998, Lundbeck Ltd., the manufacturers of sertindole, voluntarily suspended the availability of the drug due to concerns about cardiac arrhythmia and sudden cardiac death associated with its use. However, based on the advice of an appointed expert group, the Committee for Proprietary Medicinal Products (CPMP) lifted the suspension of sertindole in October 2001, a decision that was ratified by the European Commission on the 26th of June 2002. Lundbeck have committed to the CPMP to carry out two post-marketing surveillance (PMS) studies (which were initiated in July 2002) to provide additional epidemiological data under conditions of normal drug usage. Initial marketing of the product will be restricted and Lundbeck is currently in discussions with the US health authorities (FDA) to investigate whether, and if so when, it would be possible to launch Serdolect in the US market. OBJECTIVES: To determine the effects of sertindole compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses. SEARCH STRATEGY: Our Initial searches included electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 1, 1999), The Cochrane Schizophrenia Group's Register (August 2000), EMBASE (1980-1999), LILACS (1982-1996), MEDLINE (1966-1999), PSYNDEX (1977-1995) and PsycLIT (1974-1999). In addition, we searched pharmaceutical databases on the Dialog Corporation Datastar and Dialog services. We searched references of all identified studies for further trials. We contacted the manufacturer of sertindole and authors of trials. We updated the literature search by searching the Cochrane Schizophrenia Group's Trials Register in April 2003. SELECTION CRITERIA: All randomised controlled trials that compared sertindole to placebo or other antipsychotic (atypical or typical) drug treatments for patients with schizophrenia or related psychosis . DATA COLLECTION AND ANALYSIS: We independently inspected citations and, where possible abstracts; ordered papers for re-inspection and quality assessment and independently extracted data. For homogeneous dichotomous data, we calculated the risk ratio (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) or number needed to harm (NNH) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). We inspected all data for heterogeneity. MAIN RESULTS: Currently the review includes three studies with a total of 1,104 participants. One was a medium term (eight weeks) placebo controlled study that examined three different doses of sertindole (8, 12 and 20mg/day). The remaining two studies compared the use of sertindole with haloperidol (10mg/day). One was a short term study (six weeks) that looked at four different doses of sertindole (8, 16, 20, 24mg/day) and the other was a long term study (one year) that evaluated the use of sertindole 24mg/day in participants attending outpatients. We excluded two large important studies because they did not report any usable data. (Both had greater than 50% loss to follow-up and data on 'leaving the study early' was inadequately reported). SERTINDOLE VERSUS PLACEBO: Sertindole at 20mg/day was found to be more effective than placebo in terms of BPRS total scores (1 study, n=78, MD 6.2, CI -11.8 to -0.6) and CGI total end point scores (1 study, n=78, MD -0.9, CI -1.6 to -0.2). A marginally statistically significantly greater number of participants that were treated with 20 mg of sertindole were reported to have been 'very much improved' as compared to those taking placebo (1 study, n=102, RR 7.6, CI 1.0 to 57.9, NNT 7.9, CI 4.3 to 41.1). There was no statistically significant difference between sertindole at 8 or 12 mg/day and placebo for these three outcome measures. There were no statistically significant differences between sertindole (8, 12 or 20 mg) and placebo for the incidence of extrapyramidal symptoms, extrapyramidal related events or use of medication to avoid extrapyramidal symptoms. There were no statistically significant differences found between sertindole and placebo for the movement disorders akathisia, cogwheel rigidity, hypertonia and tremor or somnolence. At eight weeks a statistically significant difference between placebo and all sertindole groups (8, 12 and 20 mg) for mean change from baseline in the QT and QTc intervals were observed (p values and SD were not reported). There was a statistically significant greater mean weight gain among participants taking sertindole (20 mg, mean weight gain of 3.3 kg) as compared to placebo (mean weight gain of 0.8 kg; p<0.05). SERTINDOLE VERSUS HALOPERIDOL: At one year, a greater number of participants who were treated with haloperidol as compared to sertindole (24mg/day) were leaving the study early due to any reason (1 study, n=282, RR 0.6, CI 0.4 to 1.0, NNH 8.8, CI 4.7 to 74.0) or non-compliance (1 study, n=282, RR 0.2, CI 0.0 to 0.7, NNH 12.8, CI 7.7 to 37.8). However, at six weeks, there was no statistically significant difference between sertindole (at 8, 16, 20, or 24mg) and haloperidol for this latter outcome. The incidence of EPS was higher among those treated with haloperidol than sertindole at 8, 16, 20 or 24mg/day (8mg: 1 study, n=245, RR 0.1, CI 0.0 to 0.7, NNH 11.4, CI 7.1 to 29.8; 16mg: 1 study, n=252, RR 0.3, CI 0.1 to 1.0, NNH 15.5, CI 8.0 to 217.9; and 20mg: 1 study, n=253, RR 0.2, CI 0.1 to 0.8, NNH 13.7, CI 7.7 to 68.3; 24mg: 2 studies, n=524, RR 0.6, CI 0.4 to 0.8, NNH 8.7, CI 5.4 to 23.0). More participants treated with haloperidol experienced akathisia, tremor and hypertonia than those treated with sertindole (Akathisia - 8mg: 1 study, n=245, RR 0.2, CI 0.1 to 0.5, NNH 6.0, CI 4.1 to 11.2; 16mg: 1 study, n=252, RR 0.1, CI 0.0 to 0.3, NNH 5.4, CI 3.9 9.0; 20mg: 1 study, n=253, RR 0.3, CI 0.2 to 0.7, NNH 7.3, CI 4.6 to 17.9; 24mg: 2 studies, n=524, RR 0.5, CI 0.3 to 0.7, NNH 8.6, CI 5.6 to 18.3. Tremor - 8mg: 1 study, n=245, RR 0.3, CI 0.1 to 0.7, NNH 8.5, CI 5.2 to 24.0; 16mg: 1 study, n=252, RR 0.2, CI 0.1 to 0.5, NNH 7.3, 4.8 to 15.6; 20mg: 1 study, n=253, RR 0.2, CI 0.1 to 0.6, NNH 7.8, CI 4.9 to 18.1; 24mg: 2 studies, n=524, RR 0.4, CI 0.2 to 0.6, NNH 8.2, CI 5.6 to 15.3. For Hypertonic - 24mg: 2 studies, n=524, RR 0.5, CI 0.3 to 0.8, NNH 12.4, CI 7.5 to 35.0; for sertindole 8, 16 and 20mg there was no statistically significant differences between the treatment groups). One study reported that at six weeks, there was a statistically significant greater increase from baseline to final value in mean QTc interval in the sertindole 16, 20 and 24mg groups (20, 26, and 24msec, respectively) than in the haloperidol group (0msec; p value was not reported), but no SD or any other measure of variance for the effect sizes were reported. For one long term study only one participant from the sertindole group (24mg) had a QT interval that exceeded 500msec (1 study, n=282, RR 3.0 CI 0.1 to 73.0), but 11participants treated with Sertindole had QTc intervals of at least 500msec, compared to none in the haloperidol treated group (1 study, n=282, RR 23.0, CI 1.4 to 386.6, NNH 12.8, CI 8.2 to 29.6). At six weeks, fewer participants treated with sertindole at 8mg or 24mg were affected by somnolence than those treated with haloperidol (sertindole 8mg: 1 study, n=245, RR 0.1, CI 0.0 to 0.7, NNH 11.4, CI 7.1 to 29.8; 24mg: 2 studies, n=524, RR 0.6, CI 0.4 to 1.0, NNH 14.8, CI 7.7 to 205.2). The incidence of rhinitis was found to be statistically significantly higher among those taking sertindole at 16 or 24mg as compared to haloperidol (16mg: 1 study, n=252, RR 10.8, CI 1.4 to 82.6, NNH 12.7, CI 7.7 to 36.7; 24mg: 2 studies, n= 524, RR 2.1, CI 1.4 to 3.1, NNH 8.7, CI 5.6 to 18.6). At one year, 33 participants treated with sertindole (24mg) had experienced the sexual adverse event of decreased ejaculatory volume, compared with six participants treated with haloperidol. However the number of included male participants was not reported and therefore the RR could not be calculated. At one year, more participants taking sertindole (24mg/day) had put on weight compared to those taking haloperidol (1 study, n=282, RR 6.3, CI 1.9 to 20.9, NNH 8.8, CI 5.7 to 19.1). At six weeks, all of the sertindole groups showed an increase in body weight from baseline to final evaluation ranging from 1.3kg to 1.9kg, all of which represented a statistically significantly different weight change than that recorded for the haloperidol treatment group (-0.1Kg). However, the actual weight gain for each sertindole dosage group was not reported and no SD or any other measure of variance was given. AUTHORS' CONCLUSIONS: Sertindole at a dose of 20mg/day was found to be more antipsychotic than placebo. When used at 8, 12 or 20mg/day it appears to be as acceptable as placebo (in terms of various adverse events including movement disorders and somnolence), but seems to be associated with more cardiac problems (8, 12 or 20mg/day) and an increase in weight gain (20mg/day) than placebo. Sertindole at a dose of 24mg/day was better tolerated than haloperidol (in terms of participants leaving the study early). It was also found to be was associated with fewer movement disorders (at 8, 16, 20 or 24mg/day) and sedation (8 or 24mg/day) than haloperidol. However, it was shown to cause more cardiac anomalies (16, 20 or 24mg/day), weight gain (all doses combined), rhinitis (16 or 24mg/day), and problems with sexual functioning (24mg/day) than haloperidol. One short term study reported that sertindole 16mg/day was the most optimal dose.

Psychosocial assessment of patients who attend an accident and emergency department with self-harm.

It has been recommended that all patients attending hospital accident and emergency departments in the United Kingdom (UK) with self-harm should be offered adequate psychosocial assessment to identify those at risk of completed suicide or repeated self-harm. This paper focuses on the extent to which this recommendation has been implemented in a large district general hospital in Wales, and compares the characteristics and hospital management of patients who received no specialist assessment with those who were assessed by a psychiatric liaison nurse or a psychiatrist. Data were routinely collected as part of the hospital annual audit procedure and confirm previous findings that guidelines for the general hospital management of self-harm patients have not been well implemented. Whilst we found some evidence that certain high risk patient groups were more likely to receive specialist assessment, this was far from universal. We conclude that if there is to be a reduction in the rate of suicide in Wales and the UK as a whole, it is crucial that services for people who self-harm are more appropriately targeted on patients who are at greatest risk.

Short shrift for the sane? The hospital management of self-harm patients with and without mental illness.

In recent years the British government has sought to target service provision both on people with severe enduring mental illness and on those considered to be at risk of suicide. The study reported here suggests these policies may have had unforeseen repercussions on services for people who self-harm but have no identifiable mental illness. This paper compares the hospital management of self-harm patients with and without mental illness. Over the years 1996-2000, a total of 4,329 self-harm patient attendances were recorded at the accident and emergency department of a British hospital. Whilst patients in 63.7% of attendances could reasonably have been considered to have some form of mental illness, we found that in the remaining 36.3% of attendances (where patients had no indicator of mental illness) a particularly poor standard of service was given. We suggest that if government targets for a reduction in the suicide rate are to be met, it is crucial that there should be marked improvements in services for all self-harm patients presenting at accident and emergency departments. However, in improving services we must be vigilant to the danger that targeting those with a mental illness may mean we fail to provide even basic levels of care for others.

Morphological changes of the endometrial epithelium in the bitch during metoestrus and anoestrus.

Although cyclic changes of the endometrium in dogs involving both stromal and glandular compartments have been described, the fate of the surface epithelium after progressive growth and secretion is still unclear. In the present study, uteri of 43 healthy bitches in metoestrus and anoestrus were examined macroscopically and histologically. Tissue biopsies were taken from three different locations (cranial and middle parts of uterine horns and bifurcation). The stage of the oestrous cycle was determined by evaluation of progesterone and oestradiol levels in plasma hormone and was also confirmed clinically. Crypts formed in the luteal phase were covered with a columnar epithelium which gradually underwent fatty degeneration. In addition, the stromal part of the crypts disappeared and finally, in early anoestrus, epithelial sheaths desquamated and shed off into the uterine lumen. The surface epithelium was replaced by new cuboidal cells proliferating and migrating from the glandular openings. These findings were confirmed by oil red O staining and immunohistochemical detection of proliferation with Ki-67 marker.