Metabotropic glutamate II receptor agonists in panic disorder: a double blind clinical trial with LY354740

Preclinical studies with metabotropic glutamate (mGlu) type 2 receptor agonists have shown promising results in the treatment of anxiety. The mGlu receptor agonist LY354740 has shown anxiolytic properties in animal models of anxiety. We present the results obtained with LY354740, in a placebo-controlled double-blind randomized study with paroxetine as an active comperator in outpatients with panic disorder. This study was part of a multicentre phase II efficacy study. Patients were randomly assigned to receive LY354740 (100 or 200 mg), paroxetine (60 mg) or placebo for 9 weeks. The primary outcome parameter was the percentage of patients having no panic attacks during the final 3 weeks of treatment. Secondary outcome measures were the Panic Disorder Severity Scale (PDSS) and the clinical global impression (CGI). Patients treated on paroxetine improved on the PDSS and CGI but, due to small sample size, these effects just failed to reach statistical significance. LY354740 was well tolerated (with gastrointestinal complaints as the most common side-effects) but failed to show treatment effects that were different from placebo. Because preclinical data collectively indicate anxiolytic properties of mGlu type 2 receptor agonists, clinical studies with other agents are warranted.     

Frequency of use of QT-interval prolonging drugs in psychiatry in Belgium

Introduction Drug-induced QT-prolongation is an established risk factor for Torsade de pointes and sudden cardiac death. The list of QT-prolonging drugs is extensive and includes many drugs commonly used in psychiatry. Aim In this study we performed a cross-sectional analysis of medication profiles to assess the prevalence of drug interactions potentially leading to QT-prolongation. Setting 6 psychiatric hospitals in Flanders, Belgium. Methods For each patient, the full medication list was screened for the presence of interactions, with special attention to those with an increased risk for QT-prolongation. Current practice on QT monitoring and prevention of drug-induced arrhythmia was assessed. Main outcome measure Number of drug interactions with risk of QT-prolongation. Results 592 patients (46 % female; mean age 55.7 ± 17.1 years) were included in the analysis. 113 QT-prolonging interactions were identified in 43 patients (7.3 %). QT-prolonging interactions occurred most frequently with antidepressants (n = 102) and antipsychotics (n = 100). The precautions and follow-up provided by the different institutions when combining QT-prolonging drugs were very diverse. Conclusion Drug combinations that are associated with QT-prolongation are frequently used in the chronic psychiatric setting. Persistent efforts should be undertaken to provide caregivers with clear guidelines on how to use these drugs in a responsible and safe way.     

Barriers to Implementation of Treatment Guidelines for ADHD in Adults With Substance Use Disorder

Objective: Attention deficit hyperactivity disorder (ADHD) is common among adult patients with a substance use disorder, yet often goes undetected. This is a qualitative study to explore implementation barriers to a guideline developed in Belgium for the recognition and treatment of ADHD in adult patients with substance use disorder and to gain a better understanding of the strategies to overcome these barriers.

Methods: Focus groups were conducted with caregivers and patients to explore experiences with comorbid substance use disorder and ADHD. The barriers reported in these focus groups became the subject of further study in focus groups with addiction professionals (physicians, psychiatrists, and psychologists) who had tried the guideline and with psychiatrists specializing in addiction but without experience with ADHD.

Results: Our analysis revealed a number of barriers to the implementation of this guideline, including lack of information from the family, pressure from patients and caregivers to make an ADHD diagnosis, and the potential for abuse of ADHD medication. Furthermore, diagnostic instruments for ADHD have not been validated in people with substance use disorder. Although patients with ADHD are usually treated in an outpatient setting, patients with ADHD comorbid with substance use disorder are difficult to identify in an outpatient setting for various reasons. Finally, there is a lack of specific ADHD expertise in substance use treatment organizations.

Conclusions: Despite the availability of an approved guideline for recognizing and treating adult ADHD in patients with a substance use disorder, underdiagnosis and inadequate treatment still persist. As in general substance use treatment, medication only plays a supportive role in the treatment of substance use disorder with comorbid ADHD. An integrated approach and further improvements in the competence of practitioners may help to reduce the resistance to diagnosing ADHD in substance use treatment centers. Practitioners who specialize in addiction medicine and therapists without medical education view the problem from different perspectives and therefore each group needs specific information and training. Targeted interventions need to be developed to keep these patients in treatment.     

Invasive Salmonella enterica Serotype Typhimurium Infections,Democratic Republic of the Congo, 2007–2011

Infection with Salmonella enterica serotype Typhimurium sequence type (ST) 313 is associated with high rates of drug resistance, bloodstream infections, and death. To determine whether ST313 is dominant in the Democratic Republic of the Congo, we studied 180 isolates collected during 2007–2011; 96% belonged to CRISPOL type CT28, which is associated with ST313.     

Environmental factors influencing older adults' walking for transportation: a study using walk-along interviews

ABSTRACT: BACKGROUND: Current knowledge on the relationship between the physical environment and walking for transportation among older adults ([greater than or equal to] 65 years) is limited. Qualitative research can provide valuable information and inform further research. However, qualitative studies are scarce and fail to include neighborhood outings necessary to study participants' experiences and perceptions while interacting with and interpreting the local social and physical environment. The current study sought to uncover the perceived environmental influences on Flemish older adults' walking for transportation. To get detailed and context-sensitive environmental information, it used walk-along interviews. METHODS: Purposeful convenience sampling was used to recruit 57 older adults residing in urban or semi-urban areas. Walk-along interviews to and from a destination (e.g. a shop) located within a 15 minutes' walk from the participants' home were conducted. Content analysis was performed using NVivo 9 software (QSR International). An inductive approach was used to derive categories and subcategories from the data. RESULTS: Data were categorized in the following categories and subcategories: access to facilities (shops & services, public transit, connectivity), walking facilities (sidewalk quality, crossings, legibility, benches), traffic safety (busy traffic, behavior of other road users), familiarity, safety from crime (physical factors, other persons), social contacts, aesthetics (buildings, natural elements, noise & smell, openness, decay) and weather. CONCLUSIONS: The findings indicate that to promote walking for transportation a neighborhood should provide good access to shops and services, well-maintained walking facilities, aesthetically appealing places, streets with little traffic and places for social interaction. In addition, the neighborhood environment should evoke feelings of familiarity and safety from crime. Future quantitative studies should investigate if (changes in) these environmental factors relate to (changes in) older adults' walking for transportation.     

Drawing on international experience to reform the Belgian market for ostomy appliances

This article aims to review the regulatory framework governing the Belgian ostomy appliance market in the light of the experience of Denmark, France, the Netherlands and Ontario (Canada) with regulation of ostomy appliances. Information about the regulatory framework was derived from the international literature, analysis of legal texts and a survey completed by national experts. The comparative analysis revealed that these countries have adopted varying approaches towards regulating their domestic ostomy appliance market. Strategies to keep down prices include public procurement in Denmark, maximum prices in France and exclusion of expensive appliances from reimbursement in the Netherlands. To contain public expenditure on ostomy appliances, consumption patterns are monitored in the Netherlands, the quantity of reimbursed appliances is limited in Belgium and public reimbursement is restricted in Ontario. Ostomy appliances are generally distributed by community pharmacies and medical equipment shops. In countries that emphasise home care delivery such as Denmark, domiciliary distributors dominate the market to the detriment of community pharmacies which do not seem to be able to offer this service at a competitive price. An avenue for reforming the Belgian ostomy appliance market is proposed which valorizes the role of ostomy care nurses in guiding the choice of ostomy appliances. Furthermore, it is recommended that a competitive tendering process determines the price of ostomy appliances, that reimbursement for service provision by distributors is separated from reimbursement of appliances, and that patients receive a fixed grant from the third-party payer to buy ostomy appliances.     

Peptide and nonpeptide antagonist interaction with constitutively active human AT1 receptors

Wild type human AT(1) receptors (WT-AT(1)) and mutant receptors, in which Asn(111) was replaced by glycine (N111G), alanine (N111A) and serine (N111S), or in which Asp(281) was replaced by alanine (D281A) or in which N111G and D281A replacements were combined, were transiently expressed in CHO-K1 cells. While the biphenyltetrazole compound candesartan dissociated slowly and behaved as an insurmountable antagonist for WT-AT(1), it dissociated swiftly and only produced a rightward shift of the angiotensin Ang II- and -IV dose-response curves for inositol phosphate (IP) accumulation in cells expressing N111G. [3H]candesartan competition binding yielded the same potency order of the related biphenyltetrazoles for WT-AT(1) and mutated receptors, i.e. candesartan>EXP3174>irbesartan>losartan. Affinities were equal for WT-AT(1) and D281A and 40- to 400-fold lower for all Asn(111) mutants. Mutations did not affect the affinity of the peptide antagonist [Sar(1)Ile(8)]Ang II (SARILE). Basal IP accumulation in cells with WT-AT(1) was not affected by any biphenyltetrazole antagonists and was increased by SARILE to 19% of the maximal Ang II stimulation. Basal IP accumulation was higher for cells expressing the Asn(111)-mutated receptors. For N111G, this accumulation was partially inhibited by all the biphenyltetrazoles upon long-term (18hr) exposure. In these cells SARILE produced the same maximal stimulation as Ang II. Asn(111)-mutated AT(1) receptors are thought to mimic the pre-activated state of the wild type receptor and comparing the efficacy and affinity of ligands for such mutated receptors facilitate the distinction of partial (SARILE) and inverse (biphenyltetrazoles) agonists from true antagonists.     

Evaluation of the micro-CATT,CATT/Trypanosoma brucei gambiense,and LATEX/T b gambiense methods for serodiagnosis and surveillance of human African trypanosomiasis in West and Central Africa

OBJECTIVE: To evaluate the performance of serological tests using dried blood on filter-papers (micro-card agglutination test for trypanosomiasis (micro-CATT)) performed under field and laboratory conditions and using whole blood ((CATT/T.b. gambiense) (wb-CATT) and latex agglutination (LATEX/T.b. gambiense) (wb-LATEX)) for the serodiagnosis and surveillance of human African trypanosomiasis in West and Central Africa. METHODS: We evaluated the micro-CATT, wb-CATT and wb-LATEX methods in Côte d''Ivoire and the Central African Republic by screening 940 people. Sensitivity and specificity were calculated for each serological test; only patients with the confirmed presence of trypanosomes in the blood or lymph aspirate were considered true positives. Positive and negative predictive values were also calculated. FINDINGS: Each of the tests showed a lower sensitivity in the Central African Republic than in Côte d''Ivoire. CONCLUSION: The results confirmed the efficiency of the classic wb-CATT to detect sleeping sickness patients. The micro-CATT method can be used for human African trypanosomiasis surveillance if the test is performed on the same day as the blood collection, or if samples are stored at 4 degrees C. Otherwise, micro-CATT can be used when absolute sensitivity is not required. wb-LATEX should only be used for high-specificity screening.     

Pre- and postprandial changes in plasma hormone and metabolite levels and hepatic deiodinase activities in meal-fed broiler chickens

The present study aimed to study the effects of food deprivation and subsequent postprandial changes in plasma somatotrophic and thyrotrophic hormone levels and focused on the inter-relationships between these hormonal axes and representative metabolites of the intermediary metabolism of meal-fed broiler chickens. Male broiler chickens (2 weeks old) were fed a meal of 40-45 g/bird per d for two consecutive weeks (food-restricted (FR) treatment). The daily allowance was consumed in about 30 min. At 4 weeks of age, FR chickens were killed at several time intervals (ten per sampling time) in relation to the daily food allowance: before feeding (about 23.5 h of food deprivation), and at 10, 20, 30 (end of feeding), 40, 50, 60, 90, 120 and 200 min after initiation of feeding. Birds fed ad libitum served as controls (ad-libitum (AL) treatment). Liver tissue was collected for deiodinase type I and type III activity measurements and blood samples for analysis of growth hormone (GH), insulin-like growth factor (IGF)-I, thyroxine (T4), 3,3',5-triiodothyronine (T3), glucose, non-esterified fatty acids (NEFA), uric acid, triacylglycerol (TG) and lactate levels. Food deprivation caused a shift from lipogenesis to lipolysis and increased fatty acid turnover, a reduction in protein anabolism and reduced metabolic rate. Food intake was followed immediately by a pronounced increase in metabolic rate, initially mainly based on anaerobic mechanisms. Refeeding gradually reversed the fasting-induced alterations in plasma hormone and metabolite levels, but the time course of changes differed between metabolites, which clearly preceded those of the hormones investigated. The order of responsiveness after food provision were glucose>uric acid>or=NEFA>lactate>TG for the plasma metabolites and for hormones. Based on these different postprandial time courses, several functional relationships are proposed. Glucose is believed to be the primary trigger for the normalisation of the effects of fasting on these plasma variables by restoring hepatic GH receptor capacity, as well as decreasing deiodinase type III activity.     

Effects of environmental pollution on microsatellite DNA diversity in wood mouse (Apodemus sylvaticus) populations

Ten microsatellite DNA loci were surveyed to investigate the effects of heavy metal pollution on the genetic diversity and population genetic structure of seven wood mouse (Apodemus sylvaticus) populations along a heavy metal pollution gradient away from a nonferrous smelter in the south of Antwerp (Flanders, Belgium). Analysis of soil heavy metal concentrations showed that soil Ag, As, Cd, Cu, and Pb decreased with increasing distance from the smelter. Genetic analyses revealed high levels of genetic variation in all populations, but populations from the most polluted sites in the gradient did not differ from those of less-polluted sites in terms of mean observed and expected heterozygosity level and mean allelic richness. No correlation was found between measures of genetic diversity and the degree of heavy metal pollution. However, an analysis of molecular variance and a neighbor-joining tree suggested a contamination-related pattern of genetic structuring between the most polluted and less polluted sites. Pairwise F(ST) values indicated that populations were significantly genetically differentiated, and assignment tests and direct estimates of recent migration rates suggested restricted gene flow among populations. Additionally, genetic differentiation increased significantly with geographical distance, which is consistent with an isolation-by-distance model. We conclude that, at least for our microsatellite DNA markers, genetic diversity in the studied wood mouse populations is not affected greatly by the heavy metal pollution.