Factors associated with use of psychiatric intensive care and seclusion in adult inpatient mental health services.

AIMS: Within acute psychiatric inpatient services, patients exhibiting severely disturbed behaviour can be transferred to a psychiatric intensive care unit (PICU) and/or secluded in order to manage the risks posed to the patient and others. However, whether specific patient groups are more likely to be subjected to these coercive measures is unclear. Using robust methodological and statistical techniques, we aimed to determine the demographic, clinical and behavioural predictors of both PICU and seclusion. METHODS: Data were extracted from an anonymised database comprising the electronic medical records of patients within a large South London mental health trust. Two cohorts were derived, (1) a PICU cohort comprising all patients transferred from general adult acute wards to a non-forensic PICU ward between April 2008 and April 2013 (N = 986) and a randomly selected group of patients admitted to general adult wards within this period who were not transferred to PICU (N = 994), and (2) a seclusion cohort comprising all seclusion episodes occurring in non-forensic PICU wards within the study period (N = 990) and a randomly selected group of patients treated in these wards who were not secluded (N = 1032). Demographic and clinical factors (age, sex, ethnicity, diagnosis, admission status and time since admission) and behavioural precursors (potentially relevant behaviours occurring in the 3 days preceding PICU transfer/seclusion or random sample date) were extracted from electronic medical records. Mixed effects, multivariable logistic regression analyses were performed with all variables included as predictors. RESULTS: PICU cases were significantly more likely to be younger in age, have a diagnosis of bipolar disorder and to be held on a formal section compared with patients who were not transferred to PICU; female sex and longer time since admission were associated with lower odds of transfer. With regard to behavioural precursors, the strongest predictors of PICU transfer were incidents of physical aggression towards others or objects and absconding or attempts to abscond. Secluded patients were also more likely to be younger and legally detained relative to non-secluded patients; however, female sex increased the odds of seclusion. Likelihood of seclusion also decreased with time since admission. Seclusion was significantly associated with a range of behavioural precursors with the strongest associations observed for incidents involving restraint or shouting. CONCLUSIONS: Whilst recent behaviour is an important determinant, patient age, sex, admission status and time since admission also contribute to risk of PICU transfer and seclusion. Alternative, less coercive strategies must meet the needs of patients with these characteristics.

Management of an acute catecholamine-induced cardiomyopathy and circulatory collapse: a multidisciplinary approach.

A phaeochromocytoma (PC) is a rare, catecholamine-secreting neuroendocrine tumour arising from the adrenal medulla. Presenting symptoms of this rare tumour are highly variable but life-threatening multiorgan dysfunction can occur secondary to catecholamine-induced hypertension or hypotension and subsequent cardiovascular collapse. High levels of circulating catecholamines can induce an acute stress cardiomyopathy, also known as Takotsubo cardiomyopathy. Recent studies have focused on early diagnosis and estimation of the prevalence of acute stress cardiomyopathy in patients with PC, but very little is reported about management of these complex cases. Here, we report the case of a 38-year-old lady who presented with an acute Takotsubo or stress cardiomyopathy and catecholamine crisis, caused by an occult left-sided 5 cm PC. The initial presenting crisis manifested with symptoms of severe headache and abdominal pain, triggered by a respiratory tract infection. On admission to hospital, the patient rapidly deteriorated, developing respiratory failure, cardiogenic shock and subsequent cardiovascular collapse due to further exacerbation of the catecholamine crisis caused by a combination of opiates and intravenous corticosteroid. An echocardiogram revealed left ventricular apical hypokinesia and ballooning, with an estimated left ventricular ejection fraction of 10-15%. Herein, we outline the early stabilisation period, preoperative optimisation and intraoperative management, providing anecdotal guidance for the management of this rare life-threatening complication of PC. LEARNING POINTS: A diagnosis of phaeochromocytoma should be considered in patients presenting with acute cardiomyopathy or cardiogenic shock without a clear ischaemic or valvular aetiology.Catecholamine crisis is a life-threatening medical emergency that requires cross-disciplinary expertise and management to ensure the best clinical outcome.After initial resuscitation, treatment of acute catecholamine-induced stress cardiomyopathy requires careful introduction of alpha-blockade followed by beta-blockade if necessary to manage ß-receptor-mediated tachycardia.Prolonged α-adrenergic receptor stimulation by high levels of circulating catecholamines precipitates arterial vasoconstriction and intravascular volume contraction, which can further exacerbate hypotension. Invasive pressure monitoring can aid management of intravascular volume in these complex patients.

Presacral abscess as a rare complication of sacral nerve stimulator implantation.

A 50-year-old man with intractable anal pain attributed to proctalgia fugax underwent insertion of a sacral nerve stimulator via the right S3 vertebral foramen for pain control with good symptomatic relief. Thirteen months later, he presented with signs of sepsis. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a large presacral abscess. MRI demonstrated increased enhancement along the pathway of the stimulator electrode, indicating that the abscess was caused by infection introduced at the time of sacral nerve stimulator placement. The patient was treated with broad spectrum antibiotics, and the sacral nerve stimulator and electrode were removed. Attempts were made to drain the abscess transrectally using minimally invasive techniques but these were unsuccessful and CT guided transperineal drainage was then performed. Despite this, the presacral abscess progressed, developing enlarging gas locules and extending to the pelvic brim to involve the aortic bifurcation, causing hydronephrosis and radiological signs of impending sacral osteomyelitis. MRI showed communication between the rectum and abscess resulting from transrectal drainage. In view of the progressive presacral sepsis, a laparotomy was performed with drainage of the abscess, closure of the upper rectum and formation of a defunctioning end sigmoid colostomy. Following this, the presacral infection resolved. Presacral abscess formation secondary to an infected sacral nerve stimulator electrode has not been reported previously. Our experience suggests that in a similar situation, the optimal management is to perform laparotomy with drainage of the presacral abscess together with simultaneous removal of the sacral nerve stimulator and electrode.

Covert stroke after non-cardiac surgery: a prospective cohort study.

BACKGROUND: Overt stroke after non-cardiac surgery has a substantial impact on the duration and quality of life. Covert stroke in the non-surgical setting is much more common than overt stroke and is associated with an increased risk of cognitive decline and dementia. Little is known about covert stroke after non-cardiac, non-carotid artery surgery. METHODS: We undertook a prospective, international cohort study to determine the incidence of covert stroke after non-cardiac, non-carotid artery surgery. Eligible patients were ≥65 yr of age and were admitted to hospital for at least three nights after non-cardiac, non-carotid artery surgery. Patients underwent a brain magnetic resonance study between postoperative days 3 and 10. The main outcome was the incidence of perioperative covert stroke. RESULTS: We enrolled a total of 100 patients from six centres in four countries. The incidence of perioperative covert stroke was 10.0% (10/100 patients, 95% confidence interval 5.5-17.4%). Five of the six centres that enrolled patients reported an incident covert stroke, and covert stroke was found in patients undergoing major general (3/27), major orthopaedic (3/41), major urological or gynaecological (3/22), and low-risk surgery (1/12). CONCLUSIONS: This international multicentre study suggests that 1 in 10 patients ≥65 yr of age experiences a perioperative covert stroke. A larger study is required to determine the impact of perioperative covert stroke on patient-important outcomes. CLINICAL TRIAL REGISTRATION: NCT01369537.

InVO4/TiO2 composite for visible-light photocatalytic degradation of 2-chlorophenol in wastewater.

InVO4/TiO2 composite was synthesized via amalgamation of InVO4 with TiO2 (Degussa P-25) powders. Application of the produced composite was evaluated as a catalyst for visible-light photocatalytic degradation of 2-chlorophenol (2-CP) in synthetic wastewater solutions. The catalyst was characterized by X-ray diffraction (XRD), scanning electron microscopy energy dispersive X-ray microanalyses and nitrogen physisorption. The degradation of 2-CP was affected by solution pH, light intensity, photocatalyst dosage and 2-CP initial concentration. InVO4/TiO2 showed higher photocatalytic degradation of 2-CP as compared with Degussa P-25 TiO2. Complete degradation of 2-CP was achieved with the InVO4/TiO2 catalyst under optimized conditions (1 g/L catalyst with a pollutant concentration of 50 mg/L at solution pH 5 and irradiation time of 180 min). Comparatively, 2-CP degradation efficiency of 50.5% was achieved with the TiO2 (Degussa P-25) at the same experimental conditions. The study confirmed that InVO4/TiO2 has high potential for degradation of 2-CP from wastewater under visible-light irradiation.

Two case reports of perineal hernia after laparoscopic abdominoperineal resection with a proposed modification to the operative technique.

Perineal hernia is a rare complication following laparoscopic abdominoperineal resection (APR) for rectal cancer. We present two case reports of perineal hernia following laparoscopic APR and discuss their management. We suggest that they developed because the pelvic peritoneum was left open during laparoscopic APR and propose that closure of the pelvic peritoneum should be routine in this operation.

Post-traumatic appendicular-cutaneous fistula: a case report.

Appendicular-cutaneous fistula is an uncommon condition that usually occurs as a complication of appendicitis. We report the case of a 28-year-old woman with a chronic appendicular-cutaneous fistula following a road traffic accident in which she sustained a penetrating injury to the abdomen.

A call for more integrated cardiovascular safety assessment.

Cardiovascular safety concerns are a significant cause of attrition in the development of new drugs (Lasser et al., 2002). This attrition has significant public health implications and also contributes to the rising cost of developing new drugs. However, a better understanding of the inter-relationship between nonclinical and clinical predictors/measures of cardiovascular risk as well as a more integrated and predictive development strategy could dramatically augment the development of safe and effective medicines for patients in need. In response to this need, a consortium of industrial, academic, and government scientists designed and executed a three day 'think tank' under the auspices of the non-profit ILSI Health and Environmental Sciences Institute (ILSI HESI) in June 2009 in Washington, D.C. This highly interactive scientific forum provided a unique opportunity for experts with diverse cardiovascular-related expertise to collectively discuss issues, challenges, and opportunities to improve the overall pharmaceutical cardiovascular safety assessment paradigm. This article identifies the major points of consensus and recommendations stemming from this workshop.

The pharmacology and therapeutic relevance of endocannabinoid derived cyclo-oxygenase (COX)-2 products.

The discovery of anandamide and 2-arachidonyl glycerol (2-AG) as naturally occurring mammalian endocannabinoids has had important and wide-reaching therapeutic implications. This, to a large extent, ensues from the complexity of endocannabinoid biology. One facet of endocannabinoid biology now receiving increased attention is the cyclo-oxygenase-2 (COX-2) derived oxidation products. Anandamide and 2-AG are oxidized to a range of PG-ethanolamides and PG-glyceryl esters that closely approaches that of the prostaglandins (PGs) formed from arachidonic acid. The pharmacology of these electrochemically neutral PG-ethanolamides (prostamides) and PG-glyceryl esters appears to be unique. No meaningful interaction with natural or recombinant prostanoid receptors is apparent. Nevertheless, in certain cells and tissues, prostamides and PG-glyceryl esters exert potent effects. The recent discovery of selective antagonists for the putative prostamide receptor has been a major advance in further establishing prostamide pharmacology as an entity distinct from prostanoid receptors. Since discovery of the prototype prostamide antagonist (AGN 204396), rapid progress has been made. The latest prostamide antagonists (AGN 211334-6) are 100 times more potent than the prototype and are, therefore, sufficiently active to be used in living animal studies. These compounds will allow a full evaluation of the role of prostamides in health and disease. To date, the only therapeutic application for prostamides is in glaucoma. The prostamide analog, bimatoprost, being the most effective ocular hypotensive drug currently available. Interestingly, PGE(2)-glyceryl ester and its chemically stable analog PGE(2)-serinolamide also lower intraocular pressure in dogs. Nevertheless, the therapeutic future of PGE(2)-glyceryl ester is more likely to reside in inflammation.

Identification and pharmacological characterization of the prostaglandin FP receptor and FP receptor variant complexes.

BACKGROUND AND PURPOSE: A prostamide analogue, bimatoprost, has been shown to be effective in reducing intraocular pressure, but its precise mechanism of action remains unclear. Hence, to elucidate the molecular mechanisms of this effect of bimatoprost, we focused on pharmacologically characterizing prostaglandin FP receptor (FP) and FP receptor variant (altFP) complexes. EXPERIMENTAL APPROACH: FP receptor mRNA variants were identified by reverse transcription-polymerase chain reaction. The FP-altFP4 heterodimers were established in HEK293/EBNA cells co-expressing FP and altFP4 receptor variants. A fluorometric imaging plate reader was used to study Ca2+ mobilization. Upregulation of cysteine-rich angiogenic protein 61 (Cyr61) mRNA was measured by Northern blot analysis, and phosphorylation of myosin light chain (MLC) by western analysis. KEY RESULTS: Six splicing variants of FP receptor mRNA were identified in human ocular tissues. Immunoprecipitation confirmed that the FP receptor is dimerized with altFP4 receptors in HEK293/EBNA cells co-expressing FP and altFP4 receptors. In the studies of the kinetic profile for Ca2+ mobilization, prostaglandin F2alpha (PGF2alpha) elicited a rapid increase in intracellular Ca2+ followed by a steady state phase. In contrast, bimatoprost elicited an immediate increase in intracellular Ca2+ followed by a second phase. The prostamide antagonist, AGN211335, selectively and dose-dependently inhibited the bimatoprost-initiated second phase of Ca2+ mobilization, Cyr61 mRNA upregulation and MLC phosphorylation, but did not block the action of PGF2alpha. CONCLUSION AND IMPLICATIONS: Bimatoprost lacks effects on the FP receptor but may interact with the FP-altFP receptor heterodimer to induce alterations in second messenger signalling. Hence, FP-altFP complexes may represent the underlying basis of bimatoprost pharmacology.

Survey of infection in patients receiving antibody replacement treatment for immune deficiency.

BACKGROUND: Primary antibody deficiency disorders are a heterogeneous group of disorders, which are treated by regular infusions of immunoglobulin. Despite replacement treatment, patients remain susceptible to infection. Effective management of infections is necessary to prevent the complications of chronic infection. AIMS: This retrospective survey of clinical practice examined the management of infections in patients who receive immunoglobulin replacement for immune deficiency. METHODS: Patients who received immunoglobulin replacement treatment in Newcastle during the year 2000 were identified. Medical records were reviewed. Basic clinical information and details of immunoglobulin replacement treatment were recorded. Episodes of infection were defined by documented symptoms, signs, or investigation results, and by the prescription of an antibiotic course. Details of episodes of infection and antimicrobial treatment were recorded. RESULTS: Thirty seven patients received immunoglobulin replacement during 2000. There were 101 episodes of infection. There was no correlation between the frequency of infection and the IgG trough value. Respiratory tract infections were most common (71 of 101). Where documented, 80% of infections were associated with clinical signs, 21% with pyrexia, and 64% with a raised C reactive protein value. Microbiological culture was performed in 30% of infections. Antimicrobial treatment was instituted along "best guess" lines in 99 of 101 episodes of infection. CONCLUSIONS: Management of respiratory tract infections represents the largest problem in antibody deficient patients. Greater use of microbiological culture might allow more effective prescription of antimicrobial treatment. The generation of treatment guidelines and improved communication with general practitioners could improve the management of all episodes of infection.

Outbreak of tuberculosis at a Newcastle public house: the role and effectiveness of contact screening.

We report an outbreak of tuberculosis (TB) that originated in a public house, involving 12 cases. The presumed index case was a regular patron. Initial screening of close contacts identified no further cases. Six cases of TB then presented symptomatically among other regular patrons. Contact screening was extended to include all regular patrons and bar staff. In total, 110 individuals were screened. One case was detected and three children were placed on chemoprophylaxis. Transmission of M. tuberculosis between patrons of a public house may cause community outbreaks of TB. Where cases present outside a close-contact screening program, extended contact screening must be considered.

Panel discussion on the application of alternative models to cancer risk assessment.

The International Life Sciences Institute Alternative Carcinogenicity Testing (ILSI ACT) Workshop concluded with a panel discussion that addressed the framework issue of the appropriate application of alternative models to human cancer risk assessment. This discussion encompassed both technical issues relating to the level of understanding of these models and their output as well as issues relating to the regulatory acceptance of these data. Although there were many different perspectives represented by the panelists, there was also significant consensus on many broad issues. This article focuses on several key areas of emphasis that were addressed by panelists and are considered critical issues for future discussions and evaluations.

Proteolytic processing of the p2/nucleocapsid cleavage site is critical for human immunodeficiency virus type 1 RNA dimer maturation.

Differences in virion RNA dimer stability between mature and protease-defective (immature) forms of human immunodeficiency virus type 1 (HIV-1) suggest that maturation of the viral RNA dimer is regulated by the proteolytic processing of the HIV-1 Gag and Gag-Pol precursor proteins. However, the proteolytic processing of these proteins occurs in several steps denoted primary, secondary, and tertiary cleavage events and, to date, the processing step associated with formation of stable HIV-1 RNA dimers has not been identified. We show here that a mutation in the primary cleavage site (p2/nucleocapsid [NC]) hinders formation of stable virion RNA dimers, while dimer stability is unaffected by mutations in the secondary (matrix/capsid [CA], p1/p6) or a tertiary cleavage site (CA/p2). By introducing mutations in a shared cleavage site of either Gag or Gag-Pol, we also show that the cleavage of the p2/NC site in Gag is more important for dimer formation and stability than p2/NC cleavage in Gag-Pol. Electron microscopy analysis of viral particles shows that mutations in the primary cleavage site in Gag but not in Gag-Pol inhibit viral particle maturation. We conclude that virion RNA dimer maturation is dependent on proteolytic processing of the primary cleavage site and is associated with virion core formation.

Back to sleep: good advice for parents but not for hospitals?

BACKGROUND: In October 1998, when we surveyed nurses working in Iowa obstetric units about infant sleeping position in the hospital and recommendations for infant sleeping position at home, we learned that the side position was used frequently in the hospital and also was considered to be an acceptable alternative for sleeping position at home. OBJECTIVE: The purpose of our present study was to determine why nurses continued to use and endorse the side sleeping position rather than the supine position. DESIGN: We surveyed all Iowa hospitals that had an obstetric service as of July 1999 to learn why the side position was used. RESULTS: All 94 hospitals with obstetric services responded to the survey and revealed that 2 major factors were considered when an infant was put to sleep on his/her side. The most frequent response was fear of aspiration (57 responses or 51.4%) and the second was adherence to a federal brochure that lists side sleeping as a reasonable alternative (38 responses or 34.2%). CONCLUSION: We conclude that the reasons reported for use of the side position in Iowa maternity hospitals do not justify its continuing use. We believe that information about the importance of placing an infant on his/her back to sleep and its superiority over placing an infant on his/her side to sleep is sufficient to warrant its availability in every maternity hospital. We speculate that if the infant sleeping position used in the hospital is not different from that taught to parents, there will be less parental confusion and greater adherence to infant positioning shown to reduce sudden infant death syndrome.

Regulation of T-cell apoptosis: a mixed lymphocyte reaction model.

Despite the capacity for antigen-specific activation and rapid clonal expansion, homeostatic mechanisms ensure that the mature immune system contains a relatively stable number of T cells. In recent years, it has become apparent that this stability is a consequence of apoptotic death of most of the specific T cells generated during an immune response. Clearly this process must be tightly regulated in order to retain sufficient T-cell progeny to mediate an effective response, whilst allowing the rapid deletion of these cells at the end of the response to prevent lymphadenopathy and cross-reactive autoimmunity. In this study, the factors that regulate the sensitivity of T cells to apoptosis were investigated in vitro after the induction of primary T-cell activation within a mixed lymphocyte reaction (MLR). It was found that activated T cells rapidly acquire the expression of both Fas and Fas ligand (FasL) on their surface and contain high levels of the precursor form of the pro-apoptotic enzyme, caspase 8 (FLICE). However, these T cells were resistant for up to 5 days to apoptosis following the stimulation of Fas; a maximal apoptotic response was observed after 7 days. This time point coincided with a marked reduction in expression of the FLICE inhibitory protein (FLIP) and maximal activity of caspase 8. At time points beyond day 7, the number of viable cells in the MLR decreased further despite a reduction in the expression of FasL. However, the expression of interleukin-2 (IL-2) at these late time points was low, resulting in a decrease in expression of the anti-apoptotic protein Bcl-2. This can produce apoptosis by allowing leakage of cytochrome-c from mitochondria resulting in direct activation of the caspase cascade. In this study, it is shown that T cells are resistant to apoptosis for the first 5 days after activation as a consequence of insensitivity of the Fas pathway and the presence of intracellular Bcl-2. After between 5 and 7 days, the cells become sensitive to Fas-mediated apoptosis while retaining Bcl-2 expression. At later time points, Fas ligation is reduced but the cells respond to a decreased availability of IL-2 by reducing Bcl-2 expression; this encourages further apoptosis by allowing the direct activation of caspase enzymes.

Immune selection in neoplasia: towards a microevolutionary model of cancer development.

The dual properties of genetic instability and clonal expansion allow the development of a tumour to occur in a microevolutionary fashion. A broad range of pressures are exerted upon a tumour during neoplastic development. Such pressures are responsible for the selection of adaptations which provide a growth or survival advantage to the tumour. The nature of such selective pressures is implied in the phenotype of tumours that have undergone selection. We have reviewed a range of immunologically relevant adaptations that are frequently exhibited by common tumours. Many of these have the potential to function as mechanisms of immune response evasion by the tumour. Thus, such adaptations provide evidence for both the existence of immune surveillance, and the concept of immune selection in neoplastic development. This line of reasoning is supported by experimental evidence from murine models of immune involvement in neoplastic development. The process of immune selection has serious implications for the development of clinical immunotherapeutic strategies and our understanding of current in vivo models of tumour immunotherapy.

Gender differences in cardiovascular and catecholamine responses to cold-air exposure at rest.

Metabolic and cardiovascular responses were examined in 8 men and 9 women during 2 hrs of sitting at rest in 5 degrees C. The men and women had similar body fatness and both groups responded with similar changes relative to control in cardiac output, blood pressure, total peripheral resistance, VO2, respiratory exchange ratio, and rectal temperature. However, greater increases in stroke volume and decreases in heart rate and skin temperature were observed in men compared to women (p < 0.05). The contribution of CHO and fat to the total energy expended differed (p < 0.05) between genders; the CHO:fat ratio was 47:53 in men and 36:64 in women. No gender differences could be observed in plasma catecholamines. It is concluded that there are striking cardiovascular and metabolic gender differences in response to cold stress which cannot be accounted for by body fatness or catecholamine responses.

Bladder cancer immunogenicity: expression of CD80 and CD86 is insufficient to allow primary CD4+ T cell activation in vitro.

Transitional cell carcinomas (TCC) of the urinary bladder are known to express proteins which can yield potentially immunogenic peptide epitopes for expression in the context of cell surface class I or class II MHC antigens. However, additional costimulatory ligands must also be expressed before such a cell might directly induce full activation and proliferation of resting, antigen-specific T lymphocytes. Intravesical therapy might be used to manipulate T cell costimulation in order to promote specific rejection of TCC cells. This in vitro study examined the potential of such a strategy by transfection of the prototypical TCC line J82 with the important costimulatory molecules CD80 (B7-1) and CD86 (B7-2). Untransfected J82 cells expressed class I and II MHC antigens, a range of cell adhesion molecules, though did not induce T cell proliferation in a robust, allogeneic co-culture system. Transfected J82 cells expressed CD80 or CD86 at levels comparable to an antigen-presenting B cell line. Furthermore, functional surface expression of CD80 and CD86 was demonstrated in a mitogen-dependent assay of costimulation. However, neither CD80+ nor CD86+ transfectant J82 cells could induce significant proliferation of antigen-specific CD4+ T cells. Further analysis showed that bystander J82 cells could inhibit independent T cell activation in an effect dependent on direct cell contact. This inhibitory effect was associated with increased cell death in the responding lymphocyte population and is concordant with surface expression of CD95L by the J82 cell line.

Selection of metastatic tumour phenotypes by host immune systems.

Metastasis and the processes underlying this phenomenon make epithelial cancers so malignant. Local control of cancers by surgery is sometimes possible but locoregional and distant recurrence commonly lead to the failure of treatment with ensuing morbidity and mortality. Tumour cells express a range of new antigens during growth and there are opportunities for the host immune system to interact with these antigens. This immune interaction eliminates the tumour or allows selection of phenotypic variants. Cell phenotypes selected by an incomplete immune response resemble the cell type commonly associated with metastases. Thus we propose that the host immune system may be responsible for selection of this phenotype and progression of the disease.