Evaluation of Quantitative EEG by Classification and Regression Trees to Characterize Responders to Antidepressant and Placebo Treatment

The study objective was to evaluate the usefulness of Classification and Regression Trees (CART), to classify clinical responders to antidepressant and placebo treatment, utilizing symptom severity and quantitative EEG (QEEG) data. Patients included 51 adults with unipolar depression who completed treatment trials using either fluoxetine, venlafaxine or placebo. Hamilton Depression Rating Scale (HAM-D) and single electrodes data were recorded at baseline, 2, 7, 14, 28 and 56 days. Patients were classified as medication and placebo responders or non-responders. CART analysis of HAM-D scores showed that patients with HAM-D scores lower than 13 by day 7 were more likely to be treatment responders to fluoxetine or venlafaxine compared to non-responders (p=0.001). Youden’s index γ revealed that CART models using QEEG measures were more accurate than HAM-D-based models. For patients given fluoxetine, patients with a decrease at day 2 in θ cordance at AF2 were classified by CART as treatment responders (p=0.02). For those receiving venlafaxine, CART identified a decrease in δ absolute power at day 7 at the PO2 region as characterizing treatment responders (p=0.01). Using all patients receiving medication, CART identified a decrease in δ absolute power at day 2 in the FP1 region as characteristic of nonresponse to medication (p=0.003). Optimal trees from the QEEG CART analysis primarily utilized cordance values, but also incorporated some δ absolute power values. The results of our study suggest that CART may be a useful method for identifying potential outcome predictors in the treatment of major depression

The net effects of medical malpractice tort reform on health insurance losses: the Texas experience

In this paper, we examine the influence of medical malpractice tort reform on the level of private health insurance company losses incurred. We employ a natural experiment framework centered on a series of tort reform measures enacted in Texas in 2003 that drastically altered the medical malpractice environment in the state. The results of a difference-in-differences analysis using a variety of comparison states, as well as a difference-in-difference-in-differences analysis, indicate that ameliorating medical malpractice risk has little effect on health insurance losses incurred by private health insurers

Exploring perceptions of advertising ethics: an informant-derived approach

Whilst considerable research exists on determining consumer responses to pre-determined statements within numerous ad ethics contexts, our understanding of consumer thoughts regarding ad ethics in general remains lacking. The purpose of our study therefore is to provide a first illustration of an emic and informant-based derivation of perceived ad ethics. The authors use multi-dimensional scaling as an approach enabling the emic, or locally derived deconstruction of perceived ad ethics. Given recent calls to develop our understanding of ad ethics in different cultural contexts, and in particular within the Middle East and North Africa (MENA) region, we use Lebanon—the most ethically charged advertising environment within MENA—as an illustrative context for our study. Results confirm the multi-faceted and pluralistic nature of ad ethics as comprising a number of dimensional themes already salient in the existing literature but in addition, we also find evidence for a bipolar relationship between individual themes. The specific pattern of inductively derived relationships is culturally bound. Implications of the findings are discussed, followed by limitations of the study and recommendations for further research

Long-term retention on treatment with lumiracoxib 100 mg once or twice daily compared with celecoxib 200 mg once daily: A randomised controlled trial in patients with osteoarthritis

BACKGROUND: The efficacy, safety and tolerability of lumiracoxib, a novel selective cyclooxygenase-2 (COX-2) inhibitor, has been demonstrated in previous studies of patients with osteoarthritis (OA). As it is important to establish the long-term safety and efficacy of treatments for a chronic disease such as OA, the present study compared the effects of lumiracoxib at doses of 100 mg once daily (o.d.) and 100 mg twice daily (b.i.d.) with those of celecoxib 200 mg o.d. on retention on treatment over 1 year. METHODS: In this 52-week, multicentre, randomised, double-blind, parallel-group study, male and female patients (aged at least 40 years) with symptomatic primary OA of the hip, knee, hand or spine were randomised (1:2:1) to lumiracoxib 100 mg o.d. (n = 755), lumiracoxib 100 mg b.i.d. (n = 1,519) or celecoxib 200 mg o.d. (n = 758). The primary objective of the study was to demonstrate non-inferiority of lumiracoxib at either dose compared with celecoxib 200 mg o.d. with respect to the 1-year retention on treatment rate. Secondary outcome variables included OA pain in the target joint, patient's and physician's global assessments of disease activity, Short Arthritis assessment Scale (SAS) total score, rescue medication use, and safety and tolerability. RESULTS: Retention rates at 1 year were similar for the lumiracoxib 100 mg o.d., lumiracoxib 100 mg b.i.d. and celecoxib 200 mg o.d. groups (46.9% vs 47.5% vs 45.3%, respectively). It was demonstrated that retention on treatment with lumiracoxib at either dose was non-inferior to celecoxib 200 mg o.d. Similarly, Kaplan-Meier curves for the probability of premature discontinuation from the study for any reason were similar across the treatment groups. All three treatments generally yielded comparable results for the secondary efficacy variables and all treatments were well tolerated. CONCLUSION: Long-term treatment with lumiracoxib 100 mg o.d., the recommended dose for OA, was as effective and well tolerated as celecoxib 200 mg o.d. in patients with OA. TRIAL REGISTRATION: clinicaltrials.gov NCT00145301

Mind your step: the effects of mobile phone use on gaze behavior in stair climbing

Stair walking is a hazardous activity and a common cause of fatal and non-fatal falls. Previous studies have assessed the role of eye movements in stair walking by asking people to repeatedly go up and down stairs in quiet and controlled conditions, while the role of peripheral vision was examined by giving participants specific fixation instructions or working memory tasks. We here extend this research to stair walking in a natural environment with other people present on the stairs and a now common secondary task: Using one's mobile phone. Results show that using the mobile phone strongly draws one's attention away from the stairs, but that the distribution of gaze locations away from the phone is little influenced by using one's phone. Phone use also increased the time needed to walk the stairs, but handrail use remained low. These results indicate that limited foveal vision suffices for adequate stair walking in normal environments, but that mobile phone use has a strong influence on attention, which may pose problems when unexpected obstacles are encountered

The role of a probiotics mixture in the treatment of childhood constipation: a pilot study

<p>Abstract</p> <p>Background</p> <p>Inconsistent data exist about the efficacy of probiotics in the treatment of constipation. Several studies in adults with constipation showed positive effects of probiotics on constipation. Inconsistent data exist regarding the effect of a single probiotic strain in constipated children. The aim of this pilot study was to determine the effect of a mixture of probiotics containing bifidobacteria and lactobacilli in the treatment of childhood constipation.</p> <p>Methods</p> <p>Children aged 4–16 years with constipation as defined by the Rome III criteria were eligible for the study. During a 4 week period, children received a daily mix of 4 × 10⁹colony forming units of a probiotic mixture (<it>Ecologic</it>^®<it>Relief</it>) containing Bifidobacteria (B.) bifidum, B. infantis, B. longum, Lactobacilli (L.) casei, L. plantarum and L. rhamnosus. Primary outcome measures were frequency of bowel movements (BMs) per week and stool consistency. Secondary outcome measures were number of faecal incontinence episodes per week, abdominal pain and side effects.</p> <p>Results</p> <p>Twenty children, 50% male, median age 8 (range 4–16) were included.</p> <p>The frequency of BMs per week increased from 2.0 (1.0–5.0) to 4.2 (0.0–16.0) in week 2 (p = 0.10) and 3.8 (2.1–7.0) in week 4 (p = 0.13). In 12 children presenting with <3 BMs/week, BMs per week increased significantly from 1.0 (0.0–2.0) to 3.0 (0.0–7.0) in week 2 (p = 0.01) and 3.0 (0.0–10.0) in week 4 (p = 0.01). The stool consistency was reported as hard in 7 children at baseline, in 4 children at week 2 (p = 0.23) and in 6 children after 4 weeks of treatment (p = 1.00). A significant decrease in number of faecal incontinence episodes per week was found in the entire group: 4.0 (0.0–35.0) to 1.5 (0.0–14.0) in week 2 (p = 0.01) and 0.3 (0.0–7.0) in week 4 (p = 0.001). The presence of abdominal pain decreased significantly from 45% to 25% in week 2 (p = 0.04) and 20% at week 4 (p = 0.006). No side effects were reported.</p> <p>Conclusion</p> <p>This pilot study shows that a mixture of probiotics, has positive effects on symptoms of constipation. To confirm these findings, a large randomised placebo controlled trial is required.</p

Identifying subtypes of patients with neovascular age-related macular degeneration by genotypic and cardiovascular risk characteristics

<p>Abstract</p> <p>Background</p> <p>One of the challenges in the interpretation of studies showing associations between environmental and genotypic data with disease outcomes such as neovascular age-related macular degeneration (AMD) is understanding the phenotypic heterogeneity within a patient population with regard to any risk factor associated with the condition. This is critical when considering the potential therapeutic response of patients to any drug developed to treat the condition. In the present study, we identify patient subtypes or clusters which could represent several different targets for treatment development, based on genetic pathways in AMD and cardiovascular pathology.</p> <p>Methods</p> <p>We identified a sample of patients with neovascular AMD, that in previous studies had been shown to be at elevated risk for the disease through environmental factors such as cigarette smoking and genetic variants including the complement factor H gene (<it>CFH</it>) on chromosome 1q25 and variants in the <it>ARMS2</it>/HtrA serine peptidase 1 (<it>HTRA1</it>) gene(s) on chromosome 10q26. We conducted a multivariate segmentation analysis of 253 of these patients utilizing available epidemiologic and genetic data.</p> <p>Results</p> <p>In a multivariate model, cigarette smoking failed to differentiate subtypes of patients. However, four meaningfully distinct clusters of patients were identified that were most strongly differentiated by their cardiovascular health status (histories of hypercholesterolemia and hypertension), and the alleles of <it>ARMS2</it>/<it>HTRA1 </it>rs1049331.</p> <p>Conclusions</p> <p>These results have significant personalized medicine implications for drug developers attempting to determine the effective size of the treatable neovascular AMD population. Patient subtypes or clusters may represent different targets for therapeutic development based on genetic pathways in AMD and cardiovascular pathology, and treatments developed that may elevate CV risk, may be ill advised for certain of the clusters identified.</p

Physician Perception of Blood Pressure Control and Treatment Behavior in High-Risk Hypertensive Patients: A Cross-Sectional Study

Objective: We examined physician perception of blood pressure control and treatment behavior in patients with previous cardiovascular disease and uncontrolled hypertension as defined by European Guidelines. Methods: A cross-sectional study was conducted in which 321 primary care physicians throughout Spain consecutively studied 1,614 patients aged ≥18 years who had been diagnosed and treated for hypertension (blood pressure ≥140/90 mmHg), and had suffered a documented cardiovascular event. The mean value of three blood pressure measurements taken using standardized procedures was used for statistical analysis. Results: Mean blood pressure was 143.4/84.9 mmHg, and only 11.6% of these cardiovascular patients were controlled according to 2007 European Guidelines for Hypertension Management target of <130/80 mmHg. In 702 (49.2%) of the 1426 uncontrolled patients, antihypertensive medication was not changed, and in 480 (68.4%) of these cases this was due to the physicianś judgment that blood pressure was adequately controlled. In 320 (66.7%) of the latter patients, blood pressure was 130-139/80-89 mmHg. Blood pressure level was the main factor associated (inversely) with no change in treatment due to physician perception of adequate control, irrespective of sociodemographic and clinical factors. Conclusions: Physicians do not change antihypertensive treatment in many uncontrolled cardiovascular patients because they considered it unnecessary, especially when the BP values are only slightly above the guideline target. It is possible that the guidelines may be correct, but there is also the possibility that the care by the physicians is appropriate since BP <130/80 mmHg is hard to achieve, and recent reviews suggest there is insufficient evidence to support such a low BP targetFunding for this study was obtained from RECORDATI ESPAÑA, S.L through an unrestricted grant. Krista Lundelin has a ‘‘Rio Hortega’’ research training contract (Expediente CM10/00327) from the Ministry of Science and Innovation (Instituto de Salud Carlos III), Spain Governmen

Disrupting astrocyte-neuron lactate transfer persistently reduces conditioned responses to cocaine.

A central problem in the treatment of drug addiction is the high risk of relapse often precipitated by drug-associated cues. The transfer of glycogen-derived lactate from astrocytes to neurons is required for long-term memory. Whereas blockade of drug memory reconsolidation represents a potential therapeutic strategy, the role of astrocyte-neuron lactate transport in long-term conditioning has received little attention. By infusing an inhibitor of glycogen phosphorylase into the basolateral amygdala of rats, we report that disruption of astrocyte-derived lactate not only transiently impaired the acquisition of a cocaine-induced conditioned place preference but also persistently disrupted an established conditioning. The drug memory was rescued by L-Lactate co-administration through a mechanism requiring the synaptic plasticity-related transcription factor Zif268 and extracellular signal-regulated kinase (ERK) signalling pathway but not the brain-derived neurotrophic factor (Bdnf). The long-term amnesia induced by glycogenolysis inhibition and the concomitant decreased expression of phospho-ERK were both restored with L-Lactate co-administration. These findings reveal a critical role for astrocyte-derived lactate in positive memory formation and highlight a novel amygdala-dependent reconsolidation process, whose disruption may offer a novel therapeutic target to reduce the long-lasting conditioned responses to cocaine