Staff regard towards working with patients with co-morbid depression and substance misuse : an exploratory study

Funding: Funding was received from the European Commission (contract number 2005322).Background. Patients having co-morbid mental health and substance misuse experience poorer treatment outcomes than those treated for either condition alone. Studies suggest health professionals regard towards these patients is a factor. Aims. To compare regard towards patients with co-morbid depression and substance misuse across different health professions and services, relative to independent conditions (depression, diabetes, alcohol and/or drug misuse). Methods. A cross-sectional comparative exploratory study of regard towards five patient groups conducted on multi-disciplinary staff (general practitioners, psychiatrists, psychologists, nurses and social workers. Total n=113) in three Scottish NHS board regions-NHS Fife, Tayside and Forth Valley. Services from three main treatment entry points were recruited in each region - 10 primary care services (43.5%), 7 mental health (70%) and 4 specialist addiction (100%). Descriptive statistics were calculated for regard towards each patient group. Multifactorial between subjects ANOVA examined influences on Medical Condition Regard Scale (MCRS) scores. Results. Regard towards patients with co-morbid depression and substance misuse was frequently lower than towards patients with independent conditions. Male professionals held lower regard towards these patients than female (p=0.03). Addiction services held the highest regard and general practice lowest (p >0.001). Over-45‘s held the lowest regard towards these patients (p=0.02). Health professional’s satisfaction with working with these patients was also low (mean 1.98, sd 1.22) compared to other conditions. Conclusions. Regard towards patients with co-morbid depression and substance misuse is lower than either condition independently, particularly among older, male professionals and those in general practice.Publisher PDFPeer reviewe

Post-Newtonian gravitational effects in quantum interferometry

We investigate general properties of optical interferometry in stationary spacetimes and apply the obtained results focusing on quantum-optical experiments in near-Earth environments. We provide a rigorous expression for the {gravitationally induced} phase difference and adapt the parametrized post-Newtonian formalism for calculations of polarization rotation. We investigate two optical versions of the Colella-Overhauser-Werner experiment and show that the phase difference is independent of the post-Newtonian parameter $\gamma$, making it a possible candidate for an optical test of the Einstein equivalence principle. Polarization rotation provides an example of the quantum clock variable, and while related to the optical Lense-Thirring effects, shows a qualitatively different behaviour.Comment: 11 pages, 1 figure. Comments welcom

Tidal breathing parameters measured using structured light plethysmography in healthy children and those with asthma before and after bronchodilator

Structured light plethysmography (SLP) is a light‐based, noncontact technique that measures tidal breathing by monitoring displacements of the thoracoabdominal (TA) wall. We used SLP to measure tidal breathing parameters and their within‐subject variability (v) in 30 children aged 7–16 years with asthma and abnormal spirometry (forced expiratory volume in 1 sec [FEV1] <80% predicted) during a routine clinic appointment. As part of standard care, the reversibility of airway obstruction was assessed by repeating spirometry after administration of an inhaled bronchodilator. In this study, SLP was performed before and after bronchodilator administration, and also once in 41 age‐matched controls. In the asthma group, there was a significant increase in spirometry‐assessed mean FEV1 after administration of bronchodilator. Of all measured tidal breathing parameters, the most informative was the inspiratory to expiratory TA displacement ratio (IE50SLP, calculated as TIF50SLP/TEF50SLP, where TIF50SLP is tidal inspiratory TA displacement rate at 50% of inspiratory displacement and TEF50SLP is tidal expiratory TA displacement rate at 50% of expiratory displacement). Median (m) IE50SLP and its variability (vIE50SLP) were both higher in children with asthma (prebronchodilator) compared with healthy children (mIE50SLP: 1.53 vs. 1.22, P < 0.001; vIE50SLP: 0.63 vs. 0.47, P < 0.001). After administration of bronchodilators to the asthma group, mIE50SLP decreased from 1.53 to 1.45 (P = 0.01) and vIE50SLP decreased from 0.63 to 0.60 (P = 0.04). SLP‐measured tidal breathing parameters could differentiate between children with and without asthma and indicate a response to bronchodilator

Tidal breathing parameters measured by structured light plethysmography in children aged 2-12 years recovering from acute asthma/wheeze compared with healthy children

© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.Peer reviewedPublisher PD

Clinical progression of progressive supranuclear palsy: impact of trials bias and phenotype variants.

Funder: Cambridge Brain BankProgressive supranuclear palsy causes diverse clinical presentations, including classical Richardson's syndrome and several variant phenotypes. Clinical trials of disease-modifying therapies have recently been completed, with more planned for the next 2 years. However, many people with progressive supranuclear palsy do not meet eligibility criteria for these clinical trials. Understanding clinical progression with different phenotypes would improve trial design and enhance the accuracy of risk-benefit and cost-benefit assessments of new treatments for progressive supranuclear palsy. We set out to determine rates of motor and cognitive progression of possible, probable and definite progressive supranuclear palsy, with different phenotypes, from a representative cohort in a regional UK healthcare service. Longitudinal clinical data from people with Richardson's syndrome and variant phenotypes were analysed using linear mixed-modelling, using both the full and modified versions of the Progressive Supranuclear Palsy Rating Scale, Mini-Mental State Examination and the revised Addenbrooke's Cognitive Examination. Subgroup analyses considered patients meeting recent Phase II trial entry criteria and patients with neuropathological confirmation. Two hundred and twenty-seven patients [male = 59%, mean age (±standard deviation), 71.8 (±7.0) years] were followed for a mean 21.6 (±15.6) months. One hundred and seventy-four (77%) had Richardson's syndrome at the outset, 25 had cortical variant presentations (13%, frontal, corticobasal, speech and language variants) and 28 had subcortical variant presentations (14%, parkinsonism, postural instability and gait freezing variants). Across all participants, annual progression in Richardson's syndrome was faster than variant phenotypes on the Mini-Mental State Examination (-1.8 versus -0.9/year, P = 0.005) and revised Addenbrooke's Cognitive Examination (-5.3 versus -3.0/year, P = 0.01) but not the Progressive Supranuclear Palsy Rating Scale (9.0 versus 7.1/year, P = 0.2) nor the modified Progressive Supranuclear Palsy Rating Scale (2.7 versus 2.3/year, P = 0.4). However, for those with more than 1 years' follow-up, a significant difference was observed between Richardson's syndrome and variant phenotypes in Progressive Supranuclear Palsy Rating Scale (8.7 versus 6.3/year, P = 0.04). Survival was longer in variant phenotypes than Richardson's syndrome [7.3 (±3.9) versus 5.6 (±2.0) years, P = 0.02]. Pathologically confirmed cases (n = 49) supported these findings. Patients meeting basic trial-eligibility criteria (n = 129) progressed faster on the Progressive Supranuclear Palsy Rating Scale than trial-not-eligible patients (10.1 versus 6.1/year, P = 0.001). In conclusion, phenotypes other than Richardson's syndrome show slower progression and longer survival. Trial criteria do not select representative progressive supranuclear palsy cases. This has implications for trial design, and application of trial results to clinically more diverse patient populations

Antagonist activity of Trichoderma Asperellum (Fungi: ascomycota) at different temperatures

ABSTRACT: The genus Trichoderma (Fungi: Ascomycota: Sordariomycetes: Hypocreaceae) contains species with high antagonistic capacity. It has been determined that the temperature can be a limiting factor for growth of these species. Evaluation in vitro may suggest their eld performance, allowing evidence of viable isolates for use in biological control. In this paper, 27 isolates of Trichoderma spp. were assayed using a dual culture against Rhizoctonia sp. (Fungi: Agaricomycetes) and Colletotrichum sp. (Fungi: Sordariomycetes). From those, 16 and 9 showed an inhibition ≥ 70% against Rhizoctonia sp. and Colletotrichum sp., respectively. The isolates T46, T84, T92, and T109 achieved an inhibition ≥ 75% for both phytopathogens. These isolates were submitted to different temperatures: 4, 10, 15, 20, 25, and 30 °C in order to evaluate their antagonism against Rhizoctonia sp. With the exception of 4 °C, for every temperature assayed the inhibition in growth of the phytopathogen was ≥ 75%. For 30 °C both antagonists inhibited the growth of Rhizoctonia sp.; T46 at 94% and T109 at 95%. Biological activity was shown for all the temperatures, con rming the antagonistic potential of this microorganism.RESUMEN: El género Trichoderma (Fungi: Ascomycota: Sordariomycetes: Hypocreaceae) contiene especies con gran capacidad antagónica. Se ha determinado a la temperatura puede ser un factor limitante para el crecimiento de dichas especies. La evaluación in vitro puede sugerir su desempeño en campo, lo que permite evidenciar aislamientos viables para el uso en control biológico. En este trabajo se evaluó el efecto de la temperatura sobre el crecimiento y la actividad antagónica de 27 aislamientos de Trichoderma spp. sobre Rhizoctonia sp. (Fungi: Agaricomycetes) y Colletotrichum sp. (Fungi: Sordariomycetes). De ellos, 16 y 9 presentaron inhibición ≥ 70% contra Rhizoctonia sp. y Colletotrichum sp., respectivamente. Los aislamientos T46, T84, T92 y T109 alcanzaron inhibición ≥75% para ambos topatógenos. Los aislamientos T46 y T109 fueron evaluados por su antagonismo frente a Rhizoctonia sp. a las temperaturas: 4, 10, 15, 20, 25, 30 °C. A excepción de 4 °C, en todas las temperaturas evaluadas, la inhibición del crecimiento del topatógeno fue ≥ 75%. A 30 °C, ambos antagonistas inhibieron el crecimiento de Rhizoctonia sp. T46 en un 94% y T109 en un 95%. Se demostró actividad biológica en todas las temperaturas, con rmando el potencial antagónico de este microorganismo

BAT117213: Ileal bile acid transporter (IBAT) inhibition as a treatment for pruritus in primary biliary cirrhosis: study protocol for a randomised controlled trial

Background: Pruritus (itch) is a symptom commonly experienced by patients with cholestatic liver diseases such as primary biliary cholangitis (PBC, previously referred to as primary biliary cirrhosis). Bile acids (BAs) have been proposed as potential pruritogens in PBC. The ileal bile acid transporter (IBAT) protein expressed in the distal ileum plays a key role in the enterohepatic circulation of BAs. Pharmacological inhibition of IBAT with GSK2330672 may reduce BA levels in the systemic circulation and improve pruritus. Methods: This clinical study (BAT117213 study) is sponsored by GlaxoSmithKline (GSK) with associated exploratory studies supported by the National Institute for Health Research (NIHR). It is a phase 2a, multi-centre, randomised, double bind, placebo controlled, cross-over trial for PBC patients with pruritus. The primary objective is to investigate the safety and tolerability of repeat doses of GSK2330672, and explore whether GSK2330672 administration for 14 days improves pruritus compared with placebo. The key outcomes include improvement in pruritus scores evaluated on a numerical rating scale and other PBC symptoms in an electronic diary completed twice daily by the patients. The secondary outcomes include the evaluation of the effect of GSK2330672 on total serum bile acid (BA) concentrations, serum markers of BA synthesis and steady-state pharmacokinetics of ursodeoxycholic acid (UDCA). Discussion: BAT117213 study is the first randomised controlled crossover trial of ileal bile acid transporter inhibitor, a novel class of drug to treat pruritus in PBC. The main strengths of the trial are utility of a novel, study specific, electronic symptom diary as patient reported outcome to measure the treatment response objectively and the crossover design that allows estimating the treatment effect in a smaller number of patients. The outcome of this trial will inform the trial design of future development phase of the IBAT inhibitor drug. The trial will also provide opportunity to conduct metabonomic and gut microbiome studies as explorative and mechanistic research in patients with cholestatic pruritus

Network connectivity and structural correlates of survival in progressive supranuclear palsy and corticobasal syndrome

There is a pressing need to understand the factors that predict prognosis in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), with high heterogeneity over the poor average survival. We test the hypothesis that the magnitude and distribution of connectivity changes in PSP and CBS predict the rate of progression and survival time, using datasets from the Cambridge Centre for Parkinson-plus and the UK National PSP Research Network (PROSPECT-MR). Resting-state functional MRI images were available from 146 participants with PSP, 82 participants with CBS, and 90 healthy controls. Large-scale networks were identified through independent component analyses, with correlations taken between component time series. Independent component analysis was also used to select between-network connectivity components to compare with baseline clinical severity, longitudinal rate of change in severity, and survival. Transdiagnostic survival predictors were identified using partial least squares regression for Cox models, with connectivity compared to patients' demographics, structural imaging, and clinical scores using five-fold cross-validation. In PSP and CBS, between-network connectivity components were identified that differed from controls, were associated with disease severity, and were related to survival and rate of change in clinical severity. A transdiagnostic component predicted survival beyond demographic and motion metrics but with lower accuracy than an optimal model that included the clinical and structural imaging measures. Cortical atrophy enhanced the connectivity changes that were most predictive of survival. Between-network connectivity is associated with variability in prognosis in PSP and CBS but does not improve predictive accuracy beyond clinical and structural imaging metrics

Bacterial distribution in the lungs of children with protracted bacterial bronchitis

OBJECTIVES: Flexible bronchoscopy with bronchoalveolar lavage (FB-BAL) is increasingly used for the microbiological confirmation of protracted bacterial bronchitis (PBB) in children with a chronic wet cough. At our centre, when performing FB-BAL for microbiological diagnosis we sample 6 lobes (including lingula) as this is known to increase the rate of culture positive procedures in children with cystic fibrosis. We investigated if this is also the case in children with PBB. METHODS: We undertook a retrospective case note review of 50 children investigated for suspected PBB between May 2011 and November 2013. RESULTS: The median (IQR) age at bronchoscopy was 2.9 (1.7-4.4) years and the median (IQR) duration of cough was 11 (8.0-14) months. Positive cultures were obtained from 41/50 (82%) and 16 (39%) of these patients isolated ≥2 organisms. The commonest organisms isolated were Haemophilus influenzae (25 patients), Moraxella catarrhalis (14 patients), Staphylococcus aureus (11 patients) and Streptococcus pneumoniae (8 patients). If only one lobe had been sampled (as per the European Respiratory Society guidance) 17 different organisms would have been missed in 15 patients, 8 of whom would have had no organism cultured at all. The FB-BAL culture results led to an antibiotic other than co-amoxiclav being prescribed in 17/41 (41%) patients. CONCLUSIONS: Bacterial distribution in the lungs of children with PBB is heterogeneous and organisms may therefore be missed if only one lobe is sampled at FB-BAL. Positive FB-BAL results are useful in children with PBB and can influence treatment