Predictors of psychosocial outcome of bipolar disorder: data from the Stanley Foundation Bipolar Network.

BACKGROUND: Impairments in psychosocial functioning have been demonstrated in 30-60% of adults with bipolar disorder (BD). However, the majority of studies investigating the effect of comorbid mental health disorders and age at onset outcomes in BD have focused on traditional outcome measures such as mood symptoms, mortality and treatment response. Therefore, this project aimed to investigate the impact of comorbid mental health disorders and age at onset on longitudinal psychosocial outcome in participants with BD. METHOD: Mixed effects modelling was conducted using data from the Stanley Foundation Bipolar Network. Baseline factors were entered into a model, with Global Assessment of Functioning (GAF) score as the longitudinal outcome measure. Relative model fits were calculated using Akaike's Information Criterion. RESULTS: No individual comorbidities predicted lower GAF scores, however an interaction effect was demonstrated between attention deficit hyperactivity disorder (ADHD) and any anxiety disorder (t = 2.180, p = 0.030). Participants with BD I vs BD II (t = 2.023, p = 0.044) and those in the lowest vs. highest income class (t = 2.266, p = 0.024) predicted lower GAF scores. Age at onset (t = 1.672, p = 0.095) did not significantly predict GAF scores. CONCLUSIONS: This is the first study to demonstrate the negative psychosocial effects of comorbid anxiety disorders and ADHD in BD. This study adds to the growing database suggesting that comorbid mental health disorders are a significant factor hindering psychosocial recovery.

Evaluation of a complex healthcare intervention to increase smoking cessation in pregnant women: interrupted time series analysis with economic evaluation.

OBJECTIVES: To evaluate the effectiveness of a complex intervention to improve referral and treatment of pregnant smokers in routine practice, and to assess the incremental costs to the National Health Service (NHS) per additional woman quitting smoking. DESIGN: Interrupted time series analysis of routine data before and after introducing the intervention, within-study economic evaluation. SETTING: Eight acute NHS hospital trusts and 12 local authority areas in North East England. PARTICIPANTS: 37 726 records of singleton delivery including 10 594 to mothers classified as smoking during pregnancy. INTERVENTIONS: A package of measures implemented in trusts and smoking cessation services, aimed at increasing the proportion of pregnant smokers quitting during pregnancy, comprising skills training for healthcare and smoking cessation staff; universal carbon monoxide monitoring with routine opt-out referral for smoking cessation support; provision of carbon monoxide monitors and supporting materials; and an explicit referral pathway and follow-up protocol. MAIN OUTCOME MEASURES: Referrals to smoking cessation services; probability of quitting smoking during pregnancy; additional costs to health services; incremental cost per additional woman quitting. RESULTS: After introduction of the intervention, the referral rate increased more than twofold (incidence rate ratio=2.47, 95% CI 2.16 to 2.81) and the probability of quitting by delivery increased (adjusted OR=1.81, 95% CI 1.54 to 2.12). The additional cost per delivery was £31 and the incremental cost per additional quit was £952; 31 pregnant women needed to be treated for each additional quitter. CONCLUSIONS: The implementation of a system-wide complex healthcare intervention was associated with significant increase in rates of quitting by delivery.

Facial emotion labeling in unaffected offspring of adults with bipolar I disorder.

BACKGROUND: Young people 'at risk' for developing Bipolar Disorder have been shown to have deficits in facial emotion labeling across emotions with some studies reporting deficits for one or more particular emotions. However, these have included a heterogeneous group of young people (siblings of adolescents and offspring of adults with bipolar disorder), who have themselves diagnosed psychopathology (mood disorders and neurodevelopmental disorders including ADHD). METHODS: 24 offspring of adults with bipolar I disorder and 34 offspring of healthy controls were administered the Diagnostic Analysis of Non Verbal Accuracy 2 (DANVA 2) to investigate the ability of participants to correctly label 4 emotions: happy, sad, fear and anger using both child and adult faces as stimuli at low and high intensity. RESULTS: Mixed effects modelling revealed that the offspring of adults with bipolar I disorder made more errors in both the overall recognition of facial emotions and the specific recognition of fear compared with the offspring of healthy controls. Further more errors were made by offspring that were male, younger in age and also in recognition of emotions using 'child' stimuli. LIMITATIONS: The sample size, lack of blinding of the study team and the absence of any stimuli that assess subjects' response to a neutral emotional stimulus are limitations of the study. CONCLUSIONS: Offspring (with no history of current or past psychopathology or psychotropic medication) of adults with bipolar I disorder displayed facial emotion labeling deficits (particularly fear) suggesting facial emotion labeling may be an endophenotype for bipolar disorder.

Neuropsychological study of IQ scores in offspring of parents with bipolar I disorder.

INTRODUCTION: Studies comparing IQ in Offspring of Bipolar Parents (OBP) with Offspring of Healthy Controls (OHC) have reported conflicting findings. They have included OBP with mental health/neurodevelopmental disorders and/or pharmacological treatment which could affect results. This UK study aimed to assess IQ in OBP with no mental health/neurodevelopmental disorder and assess the relationship of sociodemographic variables with IQ. METHODS: IQ data using the Wechsler Abbreviated Scale of Intelligence (WASI) from 24 OBP and 34 OHC from the North East of England was analysed using mixed-effects modelling. RESULTS: All participants had IQ in the average range. OBP differed statistically significantly from OHC on Full Scale IQ (p = .001), Performance IQ (PIQ) (p = .003) and Verbal IQ (VIQ) (p = .001) but not on the PIQ-VIQ split. OBP and OHC groups did not differ on socio-economic status (SES) and gender. SES made a statistically significant contribution to the variance of IQ scores (p = .001). CONCLUSIONS: Using a robust statistical model of analysis, the OBP with no current/past history of mental health/neurodevelopmental disorders had lower IQ scores compared to OHC. This finding should be borne in mind when assessing and recommending interventions for OBP.

Cytokine responses in birds challenged with the human food-borne pathogen Campylobacter jejuni implies a Th17 response.

Development of process orientated understanding of cytokine interactions within the gastrointestinal tract during an immune response to pathogens requires experimentation and statistical modelling. The immune response against pathogen challenge depends on the specific threat to the host. Here, we show that broiler chickens mount a breed-dependent immune response to Campylobacter jejuni infection in the caeca by analysing experimental data using frequentist and Bayesian structural equation models (SEM). SEM provides a framework by which cytokine interdependencies, based on prior knowledge, can be tested. In both breeds important cytokines including pro-inflammatory interleukin (IL)-1ß, , IL-4, IL-17A, interferon (IFN)-γ and anti-inflammatory IL-10 and transforming growth factor (TGF)-ß4 were expressed post-challenge. The SEM revealed a putative regulatory pathway illustrating a T helper (Th)17 response and regulation of IL-10, which is breed-dependent. The prominence of the Th17 pathway indicates the cytokine response aims to limit the invasion or colonization of an extracellular bacterial pathogen but the time-dependent nature of the response differs between breeds.

Family environment of bipolar families: a UK study.

BACKGROUND: Aspects of family environment (FE) such as family support, organisational structure and levels of conflict can increase risk of Bipolar Disorder (BD) in offspring of BD parents. METHODS: The family environment of 16 BD and 23 healthy control (HC) families was assessed using the Family Environment Scale (FES). Canonical Correspondence Analysis (CCA) was used to determine the degree of variation in scores on the FES dimensions within each family and a Generalised Linear Modelling (GLM) approach was used to investigate the extent to which scores on the different FES dimensions differed between families. RESULTS: On the FES, BD families experienced an environment with higher levels of conflict and lower levels of expressiveness, organisation, intellectual-cultural orientation and active-recreational orientation than healthy control families. Differences in FES scores were driven by presence of parental BD and total number of children in the family. However, socio-economic status (SES) was not found to have an effect in this study. LIMITATIONS: As an American instrument the FES may not have been sensitive enough to the cultural context of a UK sample. The relatively small sample size used may have limited the statistical power of the study. CONCLUSIONS: Greater numbers of children have the same effect on levels of conflict as the presence of BD, while SES does not appear to be as important a factor in FE as previously thought. Our results suggest that family based interventions focusing on psychoeducation and improved communication within these families may address issues of conflict, organisation and expressiveness.

Relative effectiveness of robot-assisted and standard laparoscopic prostatectomy as alternatives to open radical prostatectomy for treatment of localised prostate cancer: a systematic review and mixed treatment comparison meta-analysis.

OBJECTIVE: To compare the effectiveness of robot-assisted and standard laparoscopic prostatectomy. METHODS: A care pathway was described. We performed a systematic literature review based on a search of Medline, Medline in Process, Embase, Biosis, Science Citation Index, Cochrane Controlled Trials Register, Current Controlled Trials, Clinical Trials, WHO International Clinical Trials Registry and NIH Reporter, the Health Technology Assessment databases, the Database of Abstracts of Reviews of Effects, and relevant conference abstracts up to 31st October 2010). Additionally, reference lists were scanned, an expert panel consulted, and websites of manufacturers, professional organisations, and regulatory bodies were checked. We selected randomised controlled trials (RCTs) and non-randomised comparative studies, published after 1st January 1995, including men with localised prostate cancer undergoing robot-assisted or laparoscopic prostatectomy compared with the other procedure or with open prostatectomy. Studies where at least 90% of included men had clinical tumour stages T1 to T2 and which reported at least one of our specified outcomes were eligible for inclusion. A mixed-treatment comparison meta-analysis was performed to generate comparative statistics on specified outcomes. RESULTS: We included data from 19 064 men across one RCT and 57 non-randomised comparative reports. Robotic prostatectomy had a lower risk of major intra-operative harms such as organ injury [0.4% robotic vs 2.9% laparoscopic], odds ratio ([OR] {95% credible interval [CrI]} 0.16 [0.03 to 0.76]), and a lower rate of surgical margins positive for cancer [17.6% robotic vs 23.6% laparoscopic], OR [95% CrI] 0.69 [0.51 to 0.96]). There was no evidence of a difference in the proportion of men with urinary incontinence at 12 months (OR [95% CrI] 0.55 [0.09 to 2.84]). There were insufficient data on sexual dysfunction. Surgeon learning rates for the procedures did not differ, although data were limited. CONCLUSIONS: Men undergoing robotic prostatectomy appear to have reduced surgical morbidity, and a lower risk of a positive surgical margin, which may reduce rates of cancer recurrence and the need for further treatment, but considerable uncertainty surrounds these results. We found no evidence that men undergoing robotic prostatectomy are disadvantaged in terms of early outcomes. We were unable to determine longer-term relative effectiveness.

A longitudinal study simultaneously exploring the carriage of APEC virulence associated genes and the molecular epidemiology of faecal and systemic E. coli in commercial broiler chickens.

Colibacillosis is an economically important syndromic disease of poultry caused by extra-intestinal avian pathogenic Escherichia coli (APEC) but the pathotype remains poorly defined. Combinations of virulence-associated genes (VAGs) have aided APEC identification. The intestinal microbiota is a potential APEC reservoir. Broiler chickens are selectively bred for fast, uniform growth. Here we simultaneously investigate intestinal E. coli VAG carriage in apparently healthy birds and characterise systemic E. coli from diseased broiler chickens from the same flocks. Four flocks were sampled longitudinally from chick placement until slaughter. Phylogrouping, macro-restriction pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) were performed on an isolate subset from one flock to investigate the population structure of faecal and systemic E. coli. Early in production, VAG carriage among chick intestinal E. coli populations was diverse (average Simpson's D value  = 0.73); 24.05% of intestinal E. coli (n = 160) from 1 day old chicks were carrying ≥5 VAGs. Generalised Linear models demonstrated VAG prevalence in potential APEC populations declined with age; 1% of E. coli carrying ≥5 VAGs at slaughter and demonstrated high strain diversity. A variety of VAG profiles and high strain diversity were observed among systemic E. coli. Thirty three new MLST sequence types were identified among 50 isolates and a new sequence type representing 22.2% (ST-2999) of the systemic population was found, differing from the pre-defined pathogenic ST-117 at a single locus. For the first time, this study takes a longitudinal approach to unravelling the APEC paradigm. Our findings, supported by other studies, highlight the difficulty in defining the APEC pathotype. Here we report a high genetic diversity among systemic E. coli between and within diseased broilers, harbouring diverse VAG profiles rather than single and/or highly related pathogenic clones suggesting host susceptibility in broilers plays an important role in APEC pathogenesis.

The acceptability of meadow plants to the slug Deroceras reticulatum and implications for grassland restoration.

BACKGROUND AND AIMS: Despite the selective pressure slugs may exert on seedling recruitment there is a lack of information in this context within grassland restoration studies. Selective grazing is influenced by interspecific differences in acceptability. As part of a larger study of how slug-seedling interactions may influence upland hay meadow restoration, an assessment of relative acceptability is made for seedlings of meadow plants to the slug, Deroceras reticulatum. METHODS: Slug feeding damage to seedling monocultures of 23 meadow species and Brassica napus was assessed in microcosms over 14 d. The severity and rate of damage incurred by each plant species was analysed with a generalized additive mixed model. Plant species were then ranked for their relative acceptability. KEY RESULTS: Interspecific variation in relative acceptability suggested seedlings of meadow species form a hierarchy of acceptability to D. reticulatum. The four most acceptable species were Achillea millefolium and the grasses Holcus lanatus, Poa trivialis and Festuca rubra. Trifolium pratense was acceptable to D. reticulatum and was the second highest ranking forb species. The most unacceptable species were mainly forbs associated with the target grassland, and included Geranium sylvaticum, Rumex acetosa, Leontodon hispidus and the grass Anthoxanthum odoratum. A strong positive correlation was found for mean cumulative feeding damage and cumulative seedling mortality at day 14. CONCLUSIONS: Highly unacceptable species to D. reticulatum are unlikely to be selectively grazed by slugs during the seedling recruitment phase, and were predominantly target restoration species. Seedlings of highly acceptable species may be less likely to survive slug herbivory and contribute to seedling recruitment at restoration sites. Selective slug herbivory, influenced by acceptability, may influence community-level processes if seedling recruitment and establishment of key functional species, such as T. pratense is reduced.

Comparative cost-effectiveness of robot-assisted and standard laparoscopic prostatectomy as alternatives to open radical prostatectomy for treatment of men with localised prostate cancer: a health technology assessment from the perspective of the UK National Health Service.

BACKGROUND: Robot-assisted laparoscopic prostatectomy is increasingly used compared with a standard laparoscopic technique, but it remains uncertain whether potential benefits offset higher costs. OBJECTIVE: To determine the cost-effectiveness of robotic prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: We conducted a care pathway description and model-based cost-utility analysis. We studied men with localised prostate cancer able to undergo either robotic or laparoscopic prostatectomy for cure. We used data from a meta-analysis, other published literature, and costs from the UK National Health Service and commercial sources. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Care received by men for 10 yr following radical prostatectomy was modelled. Clinical events, their effect on quality of life, and associated costs were synthesised assuming 200 procedures were performed annually. RESULTS AND LIMITATIONS: Over 10 yr, robotic prostatectomy was on average (95% confidence interval [CI]) £1412 (€1595) (£1304 [€1473] to £1516 [€1713]) more costly than laparoscopic prostatectomy but more effective with mean (95% CI) gain in quality-adjusted life-years (QALYs) of 0.08 (0.01-0.15). The incremental cost-effectiveness ratio (ICER) was £18 329 (€20 708) with an 80% probability that robotic prostatectomy was cost effective at a threshold of £30 000 (€33 894)/QALY. The ICER was sensitive to the throughput of cases and the relative positive margin rate favouring robotic prostatectomy. CONCLUSIONS: Higher costs of robotic prostatectomy may be offset by modest health gain resulting from lower risk of early harms and positive margin, provided >150 cases are performed each year. Considerable uncertainty persists in the absence of directly comparative randomised data.