First-line therapy with latanoprost 0.005% results in improved ocular circulation in newly diagnosed primary open-angle glaucoma patients: a prospective, 6-month, open-label study

Purpose To evaluate the effect of latanoprost 0.005% on the optic nerve head (ONH) and retinal circulation of newly diagnosed and previously untreated primary open-angle glaucoma (POAG) patients. Methods Twenty-two newly diagnosed and previously untreated POAG patients (mean age±SD: 68.38±11.92 years) were included in this longitudinal open-label study. Patients were treated with latanoprost 0.005% once a day. Intraocular pressure (IOP), systemic blood pressure (BP), mean ocular perfusion pressure (MOPP), and ocular perfusion parameters ‘volume’, ‘velocity’, and ‘flow’ measured at the optic nerve head (ONH) and retina by means of Heidelberg Retina Flowmeter system were evaluated during a 6-month follow-up period. Results Treatment with latanoprost 0.005% resulted in a significant decrease in IOP (P<0.0001) and increase in MOPP (P<0.0001). After correcting for changes in MOPP, the blood velocity measured at the ONH level was significantly higher after 6 months of treatment than at baseline (P=0.0310). In addition, blood volume and flow measured at the peripapillary retina level improved after 3 and 6 months of treatment (P=0.0170; P=0.0260, and P=0.0170; P=0.0240 respectively). Conclusion Previously untreated POAG patients exhibit reduced IOP, increased MOPP and improved ocular perfusion at the ONH and retina levels when treated with Latanoprost 0.005%. These effects could be beneficial for glaucoma patients suffering from ocular vascular dysregulation.

Discovering biomarkers for antidepressant response:protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Background: Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers ("biomarkers") of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods: CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10-20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2-10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion: From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research. Trial registration: ClinicalTrials.gov identifier NCT01655706. Registered July 27, 2012.

A review of non-pharmacological and pharmacological management of seasonal and perennial allergic conjunctivitis

Allergic eye disease encompasses a group of hypersensitivity disorders which primarily affect the conjunctiva and its prevalence is increasing. It is estimated to affect 8% of patients attending optometric practice but is poorly managed and rarely involves ophthalmic assessment. Seasonal allergic conjunctivitis (SAC) is the most common form of allergic eye disease (90%), followed by perennial allergic conjunctivitis (PAC; 5%). Both are type 1 IgE mediated hypersensitivity reactions where mast cells play an important role in pathophysiology. The signs and symptoms are similar but SAC occurs periodically whereas PAC occurs year round. Despite being a relatively mild condition, the effects on the quality of life can be profound and therefore they demand attention. Primary management of SAC and PAC involves avoidance strategies depending on the responsible allergen(s) to prevent the hypersensitivity reaction. Cooled tear supplements and cold compresses may help bring relief. Pharmacological agents may become necessary as it is not possible to completely avoid the allergen(s). There are a wide range of anti-allergic medications available, such as mast cell stabilisers, antihistamines and dual-action agents. Severe cases refractory to conventional treatment require anti-inflammatories, immunomodulators or immunotherapy. Additional qualifications are required to gain access to these medications, but entry-level optometrists must offer advice and supportive therapy. Based on current evidence, the efficacy of anti-allergic medications appears equivocal so prescribing should relate to patient preference, dosing and cost. More studies with standardised methodologies are necessary elicit the most effective anti-allergic medications but those with dual-actions are likely to be first line agents.

Metformin and the gastrointestinal tract

Metformin is an effective agent with a good safety profile that is widely used as a first-line treatment for type 2 diabetes, yet its mechanisms of action and variability in terms of efficacy and side effects remain poorly understood. Although the liver is recognised as a major site of metformin pharmacodynamics, recent evidence also implicates the gut as an important site of action. Metformin has a number of actions within the gut. It increases intestinal glucose uptake and lactate production, increases GLP-1 concentrations and the bile acid pool within the intestine, and alters the microbiome. A novel delayed-release preparation of metformin has recently been shown to improve glycaemic control to a similar extent to immediate-release metformin, but with less systemic exposure. We believe that metformin response and tolerance is intrinsically linked with the gut. This review examines the passage of metformin through the gut, and how this can affect the efficacy of metformin treatment in the individual, and contribute to the side effects associated with metformin intolerance.

Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development

Mood stabilising drugs such as lithium (LiCl) and valproic acid (VPA) are the first line agents for treating conditions such as Bipolar disorder and Epilepsy. However, these drugs have potential developmental effects that are not fully understood. This study explores the use of a simple human neurosphere-based in vitro model to characterise the pharmacological and toxicological effects of LiCl and VPA using gene expression changes linked to phenotypic alterations in cells. Treatment with VPA and LiCl resulted in the differential expression of 331 and 164 genes respectively. In the subset of VPA targeted genes, 114 were downregulated whilst 217 genes were upregulated. In the subset of LiCl targeted genes, 73 were downregulated and 91 were upregulated. Gene ontology (GO) term enrichment analysis was used to highlight the most relevant GO terms associated with a given gene list following toxin exposure. In addition, in order to phenotypically anchor the gene expression data, changes in the heterogeneity of cell subtype populations and cell cycle phase were monitored using flow cytometry. Whilst LiCl exposure did not significantly alter the proportion of cells expressing markers for stem cells/undifferentiated cells (Oct4, SSEA4), neurons (Neurofilament M), astrocytes (GFAP) or cell cycle phase, the drug caused a 1.4-fold increase in total cell number. In contrast, exposure to VPA resulted in significant upregulation of Oct4, SSEA, Neurofilament M and GFAP with significant decreases in both G2/M phase cells and cell number. This neurosphere model might provide the basis of a human-based cellular approach for the regulatory exploration of developmental impact of potential toxic chemicals.

A review of non-pharmacological and pharmacological management of seasonal and perennial allergic conjunctivitis

Allergic eye disease encompasses a group of hypersensitivity disorders which primarily affect the conjunctiva and its prevalence is increasing. It is estimated to affect 8% of patients attending optometric practice but is poorly managed and rarely involves ophthalmic assessment. Seasonal allergic conjunctivitis (SAC) is the most common form of allergic eye disease (90%), followed by perennial allergic conjunctivitis (PAC; 5%). Both are type 1 IgE mediated hypersensitivity reactions where mast cells play an important role in pathophysiology. The signs and symptoms are similar but SAC occurs periodically whereas PAC occurs year round. Despite being a relatively mild condition, the effects on the quality of life can be profound and therefore they demand attention. Primary management of SAC and PAC involves avoidance strategies depending on the responsible allergen(s) to prevent the hypersensitivity reaction. Cooled tear supplements and cold compresses may help bring relief. Pharmacological agents may become necessary as it is not possible to completely avoid the allergen(s). There are a wide range of anti-allergic medications available, such as mast cell stabilisers, antihistamines and dual-action agents. Severe cases refractory to conventional treatment require anti-inflammatories, immunomodulators or immunotherapy. Additional qualifications are required to gain access to these medications, but entry-level optometrists must offer advice and supportive therapy. Based on current evidence, the efficacy of anti-allergic medications appears equivocal so prescribing should relate to patient preference, dosing and cost. More studies with standardised methodologies are necessary elicit the most effective anti-allergic medications but those with dual-actions are likely to be first line agents. © 2011 British Contact Lens Association.

Take up of property-level flood protection:an exploratory study in Worcester

Significant numbers of homes within the UK are at risk of flooding. Although community level flood protection schemes are the first line of defence for mitigating flood risk, not all properties are protectable. Property-Level Flood Protection (PLFP) provides those unprotected homeowners with an approach for protecting their homes from flooding. This study sought to establish why property-level flood protection is needed and secondly assess the extent of take up using Worcester as the study area. An exploratory questionnaire survey was conducted to achieve these objectives. After consultation of available literature it was established that the introduction of PLFP protection provided numerous benefits including limiting the health & psychological effects flooding poses, the direct financial benefits and also the possible influence on gaining flood insurance. Despite the benefits and the recognition given to PLFP by the government it was found that the overall take up of the measures was low, findings which were further backed up by data collected in the study area of Worcester with only 23% of the sample having introduced PLFP measures. Reasoning for the low take up numbers typically included; unawareness of the measures, low risk of flood event, installation costs and inability to introduce due to tenancy. Age was noted as a significant impacting factor in the study area with none of the respondents under 25 suggesting they had “a good amount of knowledge of PLFP measures” even when they claimed their properties to be at risk of flooding. Guidance and support is especially recommended to those who are unable to manage their own flood risk for e.g. social housing/rental tenants.

Phenobarbital for neonatal seizures:response rate and predictors of refractoriness

Background : Phenobarbital is the first-line choice for neonatal seizures treatment, despite a response rate of approximately 45%. Failure to respond to acute anticonvulsants is associated with poor neurodevelopmental outcome, but knowledge on predictors of refractoriness is limited. Objective : To quantify response rate to phenobarbital and to establish variables predictive of its lack of efficacy. Methods : We retrospectively evaluated newborns with electrographically confirmed neonatal seizures admitted between January 1999 and December 2012 to the neonatal intensive care unit of Parma University Hospital (Italy), excluding neonates with status epilepticus. Response was categorized as complete (cessation of clinical and electrographic seizures after phenobarbital administration), partial (reduction but not cessation of electrographic seizures with the first bolus, response to the second bolus), or absent (no response after the second bolus). Multivariate analysis was used to identify independent predictors of refractoriness. Results : Out of 91 newborns receiving phenobarbital, 57 (62.6%) responded completely, 15 (16.5%) partially, and 19 (20.9%) did not respond. Seizure type (p = 0.02), background electroencephalogram (EEG; p ≤ 0.005), and neurologic examination (p ≤ 0.005) correlated with response to phenobarbital. However, EEG (p ≤ 0.02) and seizure type (p ≤ 0.001) were the only independent predictors. Conclusion : Our results suggest a prominent role of neurophysiological variables (background EEG and electrographic-only seizure type) in predicting the absence of response to phenobarbital in high-risk newborns.

Leadership and organisational outcomes in healthcare

This research examined to what extent and how leadership is related to organisational outcomes in healthcare. Based on the Job Demands-Resource model, a set of hypotheses was developed, which predicted that the effect of leadership on healthcare outcomes would be mediated by job design, employee engagement, work pressure, opportunity for involvement, and work-life balance. The research focused on the National Health Service (NHS) in England, and examined the relationships between senior leadership, first line supervisory leadership and outcomes. Three years of data (2008 – 2010) were gathered from four data sources: the NHS National Staff Survey, the NHS Inpatient Survey, the NHS Electronic Record, and the NHS Information Centre. The data were drawn from 390 healthcare organisations and over 285,000 staff annually for each of the three years. Parallel mediation regressions modelled both cross sectional and longitudinal designs. The findings revealed strong relationships between senior leadership and supervisor support respectively and job design, engagement, opportunity for involvement, and work-life balance, while senior leadership was also associated with work pressure. Except for job design, there were significant relationships between the mediating variables and the outcomes of patient satisfaction, employee job satisfaction, absenteeism, and turnover. Relative importance analysis showed that senior leadership accounted for significantly more variance in relationships with outcomes than supervisor support in the majority of models tested. Results are discussed in relation to theoretical and practical contributions. They suggest that leadership plays a significant role in organisational outcomes in healthcare and that previous research may have underestimated how influential senior leaders may be in relation to these outcomes. Moreover, the research suggests that leaders in healthcare may influence outcomes by the way they manage the work pressure, engagement, opportunity for involvement and work-life balance of those they lead.

Strategic orientations in practice:Exploring the strategic belief structures of line-managers embedded in practice

Recently researchers have started to investigate the cognitive strategic orientations of individual top managers and have pointed out these may be key in determining the direction and success of their organizations in terms of performance, but they have been unable to effectively operationalize this notion in empirical research and this is holding up knowledge development. To make a contribution that helps overcome this limitation a theoretical framework is developed which specifies the different possible cognitive strategic orientations of top managers as well as those of managers at lower organizational levels involved in the strategy process. This theoretical framework is investigated in the empirical phase of the study into strategic orientations in practice. Additional contributions to knowledge of strategic orientation are made in three main domains. Firstly, current knowledge of strategic orientation is largely limited to analysis at the level of the firm whereas there is a lack of understanding of any relationships with practice at lower organizational levels. The exploratory research undertaken for this thesis contributes to new knowledge of different rational, developmental and interactive strategic orientations of front-line managers and this contributes to a cognitive explanation for emergent strategy linked to strategy processes embedded in practice. In theorising the presence of different strategic orientations in practice the discussion highlights the importance of network and spatial embeddedness within enacted environments. Secondly, a contribution to further knowledge of the links between strategy processes and the content of strategies within a retail context is made. The research highlights different strategy processes used in practice by retail front-line managers in a branch network of stores and these are linked to consequences such as different objectives, performance expectations and the fulfilment of personal goals. Thirdly, a contribution to research methodology is made by addressing problems associated with the comparison of cognitive maps.

The role of line managers in employee career management:an attachment theory perspective

Line managers increasingly play a key role in organizational career development systems, yet few studies have examined the nature of this role or its implications for employee career attitudes and behaviors. In two studies, we used attachment theory to explore this issue. In Study 1, in-depth interviews (N = 20) showed that employees viewed career management as a relational process in which line managers are expected to act as ‘caregiver’ to support individualized career development. Study 2 was a large-scale international survey (N = 891). Participants scoring higher on attachment avoidance in their line manager relationships reported more negative perceptions of career growth opportunities, lower participation in organizational career development activities and higher turnover intentions. Trust in the organization partially mediated the relationship. Theoretical and practical implications for HRM are discussed.