Quality of life after involuntary psychiatric admission.

Studies seeking predictors of outcomes after involuntary admission, including quality of life (QoL), are limited and results inconsistent. We aimed to describe QoL 3 months after involuntary psychiatric admission and to investigate associated factors. One hundred and fifty-three involuntarily admitted inpatients were assessed for a range of sociodemographic and clinical variables. Structured scales included the Brief Psychiatric Rating Scale (BPRS), the MacArthur Admission Experience Survey, the Heinrichs Quality of Life Scale and the World Health Organisation Quality of Life Brief Assessment (WHOQOL-BREF, n = 124). The mean total score on the Heinrichs QoL scale at 3 months was 69.3 (SD = 24.1). Predictors of higher 3 month QoL after involuntary admission in a multiple regression model (adjusted R2 = 0.37, F = 7.1 (14, 138), p ≤0.001) were less severe negative symptoms on the BPRS at baseline (B = -4.56, p < 0.001), improvement in negative symptom scores between baseline and follow up (B = 4.58, p < 0.001) and higher current social class (B = -14.31, p = 0.001). Events during involuntary admission, such as being subject to coercive experiences, were not significantly associated with QoL after admission. The results suggest that a core determinant of service users' QoL after involuntary admission is negative symptom severity and change over time.

The effect of supplementing pony diets with yeast on 2. The faecal microbiome.

There is a need to develop feeding strategies to prevent the adverse effect of concentrate feeding in high-performance horses fed energy-dense diets aiming to maintain their health and welfare. The objective of this study is to determine the effect of a VistaEQ product containing 4% live yeast Saccharomyces cerevisiae (S. cerevisiae), with activity 5 × 108 colony-forming unit/g and fed 2 g/pony per day, on faecal microbial populations when supplemented with high-starch and high-fibre diets using Illumina next generation sequencing of the V3-V4 region of the 16S ribosomal RNA gene. The four treatments were allocated to eight mature Welsh section A pony geldings enrolled in a 4-period × 8 animal crossover design. Each 19-day experimental period consisted of an 18-day adaptation phase and a single collection day, followed by a 7-day wash out period. After DNA extraction from faeces and library preparation, α-diversity and linear discriminant analysis effect size were performed using 16S metagenomics pipeline in Quantitative Insights Into Microbial Ecology (QIIME™) and Galaxy/Hutlab. Differences between the groups were considered significant when linear discriminant analysis score was >2 corresponding to P < 0.05. The present study showed that S. cerevisiae used was able to induce positive changes in the equine microbiota when supplemented to a high-fibre diet: it increased relative abundance (RA) of Lachnospiraceae and Dehalobacteriaceae family members associated with a healthy core microbiome. Yeast supplementation also increased the RA of fibrolytic bacteria (Ruminococcus) when fed with a high-fibre diet and reduced the RA of lactate producing bacteria (Streptococcus) when a high-starch diet was fed. In addition, yeast increased the RA of acetic, succinic acid producing bacterial family (Succinivibrionaceae) and butyrate producing bacterial genus (Roseburia) when fed with high-starch and high-fibre diets, respectively. VistaEQ supplementation to equine diets can be potentially used to prevent acidosis and increase fibre digestibility. It may help to meet the energy requirements of performance horses while maintaining gut health.

Pregabalin-induced sexual disinhibition.

INTRODUCTION: Sexual side effects have rarely been reported secondary to treatment with Pregabalin, a structural analogue of the inhibitory neurotransmitter gamma amino butyric acid (GABA). METHOD: We present the case of AB, a 27-year-old single man with a diagnosis of recurrent depressive disorder who was prescribed pregabalin to alleviate the significant anxiety symptoms he was experiencing. RESULTS: A significant amelioration in anxiety symptoms was attained; however, he developed the adverse effects of acute sexual disinhibition and increased libido. These adverse effects were temporally related to treatment with pregabalin and reduced with dose reduction of this agent. CONCLUSIONS: To date, limited published data are available relating such a reaction to pregabalin. A greater clinical recognition of this association between pregabalin and sexual disinhibition, would allow clinicians to intervene at an earlier stage of this adverse effect and potentially as in this case, management may only require dose reduction rather than treatment discontinuation.

Health-related quality of life in patients with a germline BRCA mutation and metastatic pancreatic cancer receiving maintenance olaparib.

BACKGROUND: Patients with metastatic pancreatic cancer often have a detriment in health-related quality of life (HRQoL). In the randomized, double-blind, phase III POLO trial progression-free survival was significantly longer with maintenance olaparib, a poly(ADP-ribose) polymerase inhibitor, than placebo in patients with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and metastatic pancreatic cancer whose disease had not progressed during first-line platinum-based chemotherapy. The prespecified HRQoL evaluation is reported here. PATIENTS AND METHODS: Patients were randomized to receive maintenance olaparib (300 mg b.i.d.; tablets) or placebo. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item module at baseline, every 4 weeks until disease progression, at discontinuation, and 30 days after last dose. Scores ranged from 0 to 100; a ≥10-point change or difference between arms was considered clinically meaningful. Adjusted mean change from baseline was analysed using a mixed model for repeated measures. Time to sustained clinically meaningful deterioration (TSCMD) was analysed using a log-rank test. RESULTS: Of 154 randomized patients, 89 of 92 olaparib-arm and 58 of 62 placebo-arm patients were included in HRQoL analyses. The adjusted mean change in Global Health Status (GHS) score from baseline was <10 points in both arms and there was no significant between-group difference [-2.47; 95% confidence interval (CI) -7.27, 2.33; P = 0.31]. Analysis of physical functioning scores showed a significant between-group difference (-4.45 points; 95% CI -8.75, -0.16; P = 0.04). There was no difference in TSCMD for olaparib versus placebo for GHS [P = 0.25; hazard ratio (HR) 0.72; 95% CI 0.41, 1.27] or physical functioning (P = 0.32; HR 1.38; 95% CI 0.73, 2.63). CONCLUSIONS: HRQoL was preserved with maintenance olaparib treatment with no clinically meaningful difference compared with placebo. These results support the observed efficacy benefit of maintenance olaparib in patients with a gBRCAm and metastatic pancreatic cancer. CLINCALTRIALS.GOV NUMBER: NCT02184195.

Opinions of key stakeholders concerning involuntary admission of patients under the Mental Health Act 2001.

OBJECTIVES: To evaluate and compare the opinions of key stakeholders involved in the involuntary admission and treatment of patients under the Mental Health Act (MHA) 2001 regarding their views towards the operation of the legislation. METHODS: We employed a descriptive survey design. A questionnaire was distributed to stakeholders involved in the operation of the MHA 2001 (except service users, whose views were explored in a separate qualitative study) via paper or online versions evaluating their opinions regarding the operation of the MHA 2001 in relation to assessment, care, rights, transfer and information available. RESULTS: Stakeholders agreed that in their opinion that patients generally benefit from the care they receive (79%) and that the MHA 2001 ensures an independent and fair review of the person's detention (65%). However, only 23% of stakeholders were satisfied with the process of transferring patients to hospital and with the clinical assessment procedures therein (37%), with the greatest levels of dissatisfaction amongst Gardai (Police), general practitioners (GPs) and family members. CONCLUSIONS: While the introduction of the MHA 2001 has assisted delivery of care to patients with improved adherence to international human rights frameworks applicable at the time of its enactment, substantial dissatisfaction with the implementation of the MHA 2001 in practice is experienced by stakeholders particularly at the distressing phase of clinical assessment and transfer to hospital.

Service users' experiences of mental health tribunals in Ireland: a qualitative analysis.

OBJECTIVES: To explore the mental health tribunal experiences of people admitted involuntarily under the Mental Health Act 2001. METHODS: Employing a qualitative descriptive study design, data were collected from 23 service users who had experienced mental health tribunals during a recent involuntary admission. Face-to-face semi-structured interviews were conducted ~3 months post-revocation of their involuntary admission order. Data were analysed using an inductive thematic process. RESULTS: The majority of participants reported mixed experiences comprising positive and negative aspects in relation to information provision, emotional support and an inclusive atmosphere. Some participants reported receiving accessible information about the tribunal process, felt emotionally supported throughout, and encountered respectful and dignifying practices during the tribunal proceedings. However, many participants described experiencing non-inclusive practices, reported feeling ill-informed regarding the tribunal process, emotionally unsupported during and after the tribunal, and distressed by what they perceived as adversarial tribunal proceedings. CONCLUSIONS: Systemic changes could ensure that the positive experiences encountered by the minority of participants in this study are more consistently experienced. Ongoing education and training of stakeholders in the provision of inclusive tribunal practices, and the provision of accessible information and emotional support to service users through the stages of the involuntary admission process appear likely to be beneficial. Service users should automatically be offered the option of having a support person of their choosing present during tribunals.

Foundation doctors working at night: what training opportunities exist?

INTRODUCTION: Foundation Training is designed for doctors in their first two years of post-graduation. The number of foundation doctors (FD) in the UK working nights has reduced because of a perception that clinical supervision at night is unsatisfactory and that minimal training opportunities exist. We aimed to assess the value of night shifts to FDs and hypothesised that removing FDs from nights may be detrimental to training. METHODS: Using a survey, we assessed the number of FDs working nights in London, FDs views on working nights and their supervision at night. We evaluated whether working at night, compared to daytime working provided opportunities to achieve foundation competencies. RESULTS: 83% (N = 2157/2593) of FDs completed the survey. Over 90% of FDs who worked nights felt that the experience they gained improved their ability to prioritise, make decisions and plan. FDs who worked nights reported higher scores for achieving competencies in history taking (2.67 vs. 2.51; p = 0.00), examination (2.72 vs. 2.59; p = 0.01) and resuscitation (2.27 vs. 1.96; p = 0.00). The majority (65%) felt adequately supervised. CONCLUSIONS: Our survey has demonstrated that FDs find working nights a valuable experience, providing important training opportunities, which are additional to those encountered during daytime working.

Experiences of involuntary admission in an approved mental health centre.

The aim of this qualitative study was to gain an understanding of what it means to have an involuntary hospital admission. A sample of six people who were detained at an approved Irish mental health centre consented to recount their experiences were interviewed. The interview transcripts were analysed using Interpretative Phenomenological Analysis. Three superordinate themes were identified: 'The early days', 'Experiences of treatment' and 'Moving on?'. 'The early days' represented participants' initial feelings and opinions of the experience of coming into the approved centre. 'Experiences of treatment' refers to participants' experiences of medication and relationships with staff. Finally, the theme 'Moving on?' represented participants' views on how they adjusted to involuntary admission. 'Learning the way' was central to the participants' notion of moving on. The findings suggest that the meaning of detention is a varied one that evokes an array of emotional responses for participants and highlights the need for a renewed way of thinking and doing concerning those subject to involuntary.

Methylphenidate-induced erections in a prepubertal child.

Methylphenidate is a medication used routinely in the management of attention deficit hyperactivity disorder. We report a case of a prepubertal child who developed unwanted erections after commencing a response-adjusted dosing regimen of sustained release methylphenidate. Despite priapism being a rare adverse reaction associated with methylphenidate, physicians and parents need to be aware as it can have significant long-term complications.

Sirtuins, bioageing, and cancer.

The Sirtuins are a family of orthologues of yeast Sir2 found in a wide range of organisms from bacteria to man. They display a high degree of conservation between species, in both sequence and function, indicative of their key biochemical roles. Sirtuins are heavily implicated in cell cycle, cell division, transcription regulation, and metabolism, which places the various family members at critical junctures in cellular metabolism. Typically, Sirtuins have been implicated in the preservation of genomic stability and in the prolongation of lifespan though many of their target interactions remain unknown. Sirtuins play key roles in tumourigenesis, as some have tumour-suppressor functions and others influence tumours through their control of the metabolic state of the cell. Their links to ageing have also highlighted involvement in various age-related and degenerative diseases. Here, we discuss the current understanding of the role of Sirtuins in age-related diseases while taking a closer look at their roles and functions in maintaining genomic stability and their influence on telomerase and telomere function.

Upregulation of MAPK pathway is associated with survival in castrate-resistant prostate cancer.

BACKGROUND: Recent evidence has implicated the MAP kinase (MAPK) pathway with the development of castrate-resistant prostate cancer (CRPC). We have previously reported gene amplification of critical members of this pathway with the development of castrate-resistant disease. In addition, we have shown that rising Raf-1 expression, with the development of CRPC, influences time to biochemical relapse. We therefore sought to further analyse the role of both Raf-1 and its downstream target MAPK in the molecular pathogenesis of CRPC. METHODS: Protein expression of Raf-1 and MAPK, including their activation status, was analysed using immunohistochemistry in a database of 65 paired tumour specimens obtained before and after the development of CRPC and correlated with other members of the pathway. RESULTS: Patients whose nuclear expression of MAPK rose with the development of CRPC had a significantly shorter median time to death following biochemical relapse (1.40 vs 3.00 years, P=0.0255) as well as reduced disease-specific survival when compared with those whose expression fell or remained unchanged (1.16 vs 2.62 years, P=0.0005). Significant correlations were observed between protein expression of Raf-1 and MAPK with the type 1 receptor tyrosine kinases, Her2 and epidermal growth factor receptor, as well as the transcription factor AP-1 in CRPC tumours. CONCLUSION: We conclude that the Her2/Raf-1/MAPK/AP-1 axis may promote the development of CRPC, leading to early relapse, and reduced disease-specific survival. In addition, members of the pathway may act as novel therapeutic and/or diagnostic targets for prostate cancer.

Self-adhesive microculture system for extended live cell imaging.

Gas permeable and biocompatible soft polymers are convenient for biological applications. Using the soft polymer poly(dimethylsiloxane) (PDMS), we established a straightforward technique for in-house production of self-adhesive and optical grade microculture devices. A gas permeable PDMS layer effectively protects against medium evaporation, changes in osmolarity, contamination and drug diffusion. These chip-based devices can be used effectively for long term mammalian cell culture and support a range of bioassays used in pharmacological profiling of anti-cancer drugs. Results obtained on a panel of hematopoietic and solid tumor cell lines during screening of investigative anti-cancer agents corresponded well to those obtained in a conventional cell culture on polystyrene plates. The cumulative correlation analysis of multiple cell lines and anti-cancer drugs showed no adverse effects on cell viability or cell growth retardation during microscale static cell culture. PDMS devices also can be custom modified for many bio-analytical purposes and are interfaced easily with both inverted and upright cell imaging platforms. Moreover, PDMS microculture devices are suitable for extended real time cell imaging. Data from the multicolor, real time analysis of apoptosis on human breast cancer MCF-7 cells provided further evidence that elimination of redundant centrifugation/washing achieved during microscale real time analysis facilitates preservation of fragile apoptotic cells and provides dynamic cellular information at high resolution. Because only small reaction volumes are required, such devices offer reduced use of consumables as well as simplified manipulations during all stages of live cell imaging.

Positive experiences and the relationship between stress and asthma in children.

UNLABELLED: Ninety children aged 6 to 13 y and suffering from chronic asthma were included in a prospective follow-up study lasting 18 mo in order to assess whether life events involving substantial positive effects on the child can protect against the increased risk associated with stressful life events. The main outcome measures included positive life events, positive long-term experiences, severely negative life events, chronic psychosocial stress and new asthma exacerbation. The results showed that, provided they occurred in close proximity to severely negative life events, positive life events, generally related to the child's own achievements, afforded protection against the increased risk of a new asthma exacerbation precipitated by severe events in children whose lives were marked by low to medium levels of chronic stress. No such effect was found in children exposed to high chronic stress nor did long-term positive experiences, such as when the child has a rewarding hobby, affect the asthma risk. CONCLUSION: Life events with a definite positive effect can counteract the increased risk of an asthma exacerbation precipitated by a severely negative life event, provided the chronic stress is only of low to medium level. Because this protective influence does not apply where there is high chronic stress, reducing this condition must be seen as a priority in children suffering from asthma, as these children are also more vulnerable to negative life events precipitating asthma exacerbation.

Oxidative addition of the imidazolium cation to zerovalent Ni, Pd, and Pt: a combined density functional and experimental study.

Oxidative addition of different imidazolium cations to zerovalent group 10 metals, to afford heterocyclic carbene complexes, has been investigated by both density functional theory (DFT) and experimental studies. The theoretical analysis shows that addition of imidazoliums to Pt(0) and Ni(0) is more exothermic than to Pd(0), and Ni(0) is predicted to react with a much lower barrier than either Pt(0) or Pd(0). Strongly basic supporting ligands on the metal, as well as cis-chelating ligands, increase the exothermicity of the reaction and also lower the activation barrier. The addition of 2-H imidazoliums is easier and more exothermic than addition of 2-alkylimidazoliums, and a halo-imidazolium is expected to further lower the barrier to oxidative addition and increase the exothermicity. The DFT results show that all three of the metals should be able to oxidatively add imidazolium cations under appropriate conditions. Experimental studies confirmed that oxidative addition is possible, and a number of Pt- and Pd-carbene complexes were prepared via oxidative addition of imidazolium salts to M(0) precursors. Most significantly, oxidative addition of 2-H azolium salts was found to readily occur, and the reaction of 1,3-dimethylimidazolium tetrafluoroborate with Pt(PPh(3))(2) and Pt(PCy(3))(2) affords [PtH(dmiy)(PPh(3))(2)]BF(4) (10) and [PtH(dmiy)(PCy(3))(2)]BF(4) (11), while reaction between 3,4-dimethylthiazolium tetrafluoroborate and Pt(PCy(3))(2) yields [PtH(dmty)(PCy(3))(2)]BF(4) (12) (dmiy = 1,3-dimethylimidazolin-2-ylidene, dmty = 3,4-dimethylthiazolin-2-ylidene). Addition of 2-iodo-1,3,4,5-tetramethylimidazolium tetrafluoroborate to Pt(PPh(3))(4) or Pd(dcype)(dba) yields [PtI(tmiy)(PPh(3))(2)]BF(4) (9) and [PdI(tmiy)(dcype)]BF(4) (14), respectively (tmiy = 1,3,4,5-tetramethylimidazolin-2-ylidene, dcype = 1,3-bis(dicyclohexylphosphino)ethane)). X-ray crystal structures are reported for complexes 9 and 11 (cis and trans). These studies clearly show for the first time that oxidative addition of imidazolium and thiazolium cations is possible, and the results are discussed in terms of the ramifications for catalysis in imidazolium-based ionic liquids with both carbene-based and non-carbene-based complexes.

Kinetic and density functional studies on alkyl-carbene elimination from Pd(II) heterocylic carbene complexes: a new type of reductive elimination with clear implications for catalysis.

A number of new methyl-Pd(II) complexes of heterocyclic carbenes of the form [PdMe(tmiy)L(2)]BF(4) have been prepared, and their reaction behavior has been studied (tmiy = 1,3,4,5-tetramethylimidazolin-2-ylidene, L = cyclooctadiene (8), methyldiphenylphosphine (9), triphenyl phosphite (10), triphenylphosphine (11)). In common with other hydrocarbyl-M carbene complexes (M = Pd, Ni) the complexes are predisposed to a facile decomposition process. A detailed mechanism for the process and of the decomposition pathway followed is presented herein. All complexes decompose with first-order kinetics to yield 1,2,3,4,5-pentamethylimidazolium tetrafluoroborate and Pd(0) species. The kinetic investigations combined with density functional studies show that the complexes decompose via a mechanism of concerted reductive elimination of the methyl group and carbene. The reaction represents a new type of reductive elimination from transition metals and also represents a low-energy pathway to catalyst deactivation for catalysts based on heterocyclic carbenes. The theoretical studies indicate extensive involvement of the p(pi) orbital on the carbene carbon in the transition structure. Methods of stabilizing catalysts based on heterocyclic carbene complexes are suggested, and the possibility of involvement of carbene species during catalysis in ionic liquids is discussed.

Do high-threat life events really provoke the onset of psychiatric disorder in children?

Studies on adults have suggested important effects of stressful life events in provoking onset of psychiatric disorder. Only a few comparable studies on children exist, and their results are inconsistent in relation to definite timing effects. Meeting some important methodological challenges overlooked in the past research, this study set out to examine whether the onset of psychiatric disorder in children was more likely to occur shortly after a severe event, as compared with other times. The sample consisted of 99 consecutive, newly referred patients, aged 8-16 years, from a child psychiatry service in London. PACE (Psychosocial Assessment of Childhood Experiences), an investigator-based, standardized interview was used to assess the timing and impact of life events over the preceding 18 months. CAPA (Child and Adolescent Psychiatric Assessment), a standardized diagnostic assessment, was used to establish the presence, timing, and consequential impairment of child and adolescent psychiatric symptoms. In a within-subject, over-time design, conditional logistic regression techniques were employed to examine whether risk of onset was greater in the 9 weeks following a high-threat life event than at other times. There was a small but statistically significant association between child-reported events and child-reported onset; the associations with parent-reported onset were inconsistent. Parent-reported events failed to relate to onset by either source. The study offers only quite limited support to the notion of negative life events provoking onset of psychiatric disorder in children and young people. The possible reasons for this are discussed, together with important conceptual and methodological issues to problems of defining onset, and the choice of appropriate designs for data analysis.

Frequent and persistent, asymptomatic Plasmodium falciparum infections in African infants, characterized by multilocus genotyping.

To determine the duration and complexity of naturally acquired Plasmodium falciparum infections in small children, a longitudinal cohort study of 143 newborns was conducted in coastal Ghana. On average, children experienced 2 episodes of infection in their first 2 years of life, the median duration of an asymptomatic infection was <4 weeks, and estimates of the mean number of parasite genotypes per infection were 1.15-2.28. Nevertheless, 40% of the children experienced infections lasting 5 months old. The ability of very young children to clear or control malaria infections indicates the presence of effective innate or immune antiparasite mechanisms.

The role of acute and chronic stress in asthma attacks in children.

BACKGROUND: High levels of stress have been shown to predict the onset of asthma in children genetically at risk, and to correlate with higher asthma morbidity. Our study set out to examine whether stressful experiences actually provoke new exacerbations in children who already have asthma. METHODS: A group of child patients with verified chronic asthma were prospectively followed up for 18 months. We used continuous monitoring of asthma by the use of diaries and daily peak-flow values, accompanied by repeated interview assessments of life events and long-term psychosocial experiences. The key measures included asthma exacerbations, severely negative life events, and chronic stressors. FINDINGS: Severe events, both on their own and in conjunction with high chronic stress, significantly increased the risk of new asthma attacks. The effect of severe events without accompanying chronic stress involved a small delay; they had no effect within the first 2 weeks, but significantly increased the risk in the subsequent 4 weeks (odds ratio 1.71 [95% CI 1.04-2.82], p < or = 0.05 for weeks 2-4 and 2.17 [1.32-3.57], p < or = 0.01 for weeks 4-6). When severe events occurred against the backdrop of high chronic stress, the risk increased sharply and almost immediately within the first fortnight (2.98 [1.20-7.38], p < or = 0.05). The overall attack frequency was affected by several factors, some related to asthma and some to child characteristics. Female sex, higher baseline illness severity, three or more attacks within 6 months, autumn to winter season, and parental smoking were all related to increased risk of new exacerbations; social class and chronic stress were not. INTERPRETATION: Severely negative life events increase the risk of children's asthma attacks over the coming few weeks. This risk is magnified and brought forward in time if the child's life situation is also characterised by multiple chronic stressors.

Lack of association between maternal antibody and protection of African infants from malaria infection.

Maternally derived antibodies are believed to protect infants against infection, but there is little direct evidence for a protective role of passively acquired antibodies against malaria. A longitudinal study of malaria infection in 143 infants was conducted in a region of southern Ghana where Plasmodium falciparum is endemic. Infants born in the high-transmission season were less likely to become infected in the first 20 weeks of life than children born in the low-transmission season. Plasma, obtained at birth, was tested for immunoglobulin G (IgG) and IgG subclasses to P. falciparum schizonts and recombinant circumsporozoite antigen, MSP-1(19), MSP-2, AMA-1, and Pf155 (also called ring-infected erythrocyte surface antigen). Antibody levels at birth were not associated with resistance to malaria infection. On the contrary, antibodies at birth were positively associated with infection, indicating that high levels of maternally derived antibodies represent a marker for intensity of exposure to malaria infection in infants. However, all five children who experienced high-density infections (>100 parasites/microl of blood) were seronegative for MSP-1(19) at the time of infection.