Synthesis and chemiluminescent high throughput screening for inhibition of acetylcholinesterase activity by imidazo[2,1-b]thiazole derivatives

The synthesis of a new series of imidazo[2,1-b]thiazole derivatives is described. They were tested as acetylcholinesterase inhibitors by means of a chemiluminescent method suitable for high throughput screening. The compounds without quaternization had no appreciable inhibitory potency probably because they are poorly soluble in water. The corresponding quaternized compounds were good inhibitors with activity related to the spacer employed.     

The impact of communicating cardiovascular risk in type 2 diabetics on patient risk perception,diabetes self-care,glycosylated hemoglobin,and cardiovascular risk

Aim

This study aims to investigate the effect of a cardiovascular risk (CVR) communication intervention on the accuracy of CVR perception, diabetes self-care (DSC), glycosylated hemoglobin percent (HbA1c%), and CVR in patients with type 2 diabetes mellitus (T2DM).

Subject and methods

A randomized controlled trial was performed in T2DM patients attending the family medicine outpatient clinic in Suez Canal University Hospital, Ismailia. The intervention group (n?=?107) received a comprehensive CVR communication. Control subjects (n?=?107) received the standard usual care. The outcome measures were: accuracy of risk perception, DSC, HbA1c%, and CVR scores. Patients were investigated at baseline and 3 months after the intervention. Differences between arms were assessed using chi-square and Student's t-test, and within-group differences were assessed using the paired t-test and McNemar’s test.

Results

After the intervention, the accuracy rate of risk perception was significantly improved (from 44.9 % to 89.7 %) in the intervention group with excellent improvement in agreement between perceived and objective risk (kappa?±?SE 83.7?±?4.4 %, p?<?0.000). Diabetes self-care sum scale scores and HbA1c% showed statistically significant improvements for within-intervention group comparisons and between groups after the intervention (p?<?0.000). Cardiovascular risk scores showed minimal, not statistically significant improvement in both groups.

Conclusion

Our intervention significantly improved CVR perception, DSC, and HbA1c% in patients with T2DM. Further research is needed to investigate the effectiveness of applying more complex and longer lifestyle interventions and to confirm the credibility and sustainability of improvement.

     

Nabilone for the Management of Pain

Nabilone, a synthetic cannabinoid, is approved in many countries including, but not limited to, Canada, the United States, Mexico, and the United Kingdom for the treatment of severe nausea and vomiting associated with chemotherapy. Clinical evidence is emerging for its use in managing pain conditions with different etiologies. We review the efficacy and safety of nabilone for various types of pain as well as its abuse potential, precautions and contraindications, and drug interactions; summarize pertinent clinical practice guidelines; and provide recommendations for dosing, monitoring, and patient education. Citations involving nabilone were identified through systematic reviews evaluating cannabinoids for pain. A systematic search (updated July 23, 2015) of the Ovid MEDLINE, EMBASE, PubMed, and Cochrane Library databases was performed. Eight randomized controlled trials, two prospective cohort trials, and one retrospective chart review were retrieved. Cancer pain, chronic noncancer pain, neuropathic pain, fibromyalgia, and pain associated with spasticity were the pain conditions evaluated. Nabilone was most commonly used as adjunctive therapy and led to small but significant reductions in pain. The most common adverse drug reactions included euphoria, drowsiness, and dizziness. Nabilone was rarely associated with severe adverse drug reactions requiring drug discontinuation, and the likelihood of abuse was thought to be low. Although the optimal role of nabilone in the management of pain is yet to be determined, certain clinical practice guidelines consider nabilone as a third‐line agent.     

Estimating the marginal value of 'better' research output: 'designed' versus 'routine' data in randomised controlled trials

We recently completed a study which demonstrated that the costs of health technology assessment (HTA) by randomised controlled trial (RCT) can be reduced by substituting routine datasets for data designed and collected specifically for a trial. This cost reduction, however, had the effect of reducing the quality of the research output. In the present study we attempted to tease out the values attached to the 'better' information provided by designed data RCTs using a mock grants committee. Two valuation techniques, implied values and willingness to pay, were used. Ex ante valuations were determined by comparing alternative research proposals - a more costly version using designed data and a cheaper version using routine data. Ex post valuations were determined by comparing results of both versions. The exercise was performed on four exemplar studies. Overall, the committee expressed a general lack of trust towards routine data both ex ante and ex post and placed high values on the better information from the designed data studies - particularly information on preferences. This suggests that currently available routine datasets are not perceived to be able to provide efficient alternatives to designed data for RCTs.     

Performance improvement based on integrated quality management models: what evidence do we have? A systematic literature review.

PURPOSE: Health care organizations have to improve their performance for multiple stakeholders and organize integrated care. To facilitate this, various integrated quality management models can be used. This article reviews the literature on the Malcolm Baldrige Quality Award (MBQA) criteria, the European Foundation Quality Management (EFQM) Excellence model (Excellence award models) and the Chronic Care Model. The focus is on the empirical evidence for improved performance by the implementation of interventions based on these models. DATA SOURCES: A systematic literature review from 1995 to May 2006 in the Pubmed, Cochrane, and ABI- databases was conducted. STUDY SELECTION: After selection, 37 studies were included, 16 in the Excellence award model search and 21 in the Chronic Care Model search. DATA EXTRACTION AND RESULTS OF ANALYSIS: Data were retrieved about the main intervention elements, study design, evidence level, setting and context factors, data collection and analysis, principal results and performance dimensions. No Excellence Award model studies with controlled designs were found. For the Chronic Care Model, one systematic review, one meta analysis and six controlled studies were included. Seventeen studies (2 in Excellence award model, 15 in Chronic Care Model) reported one or more significant results. CONCLUSION: There is some evidence that implementing interventions based on the 'evidence-based developed' Chronic Care Model may improve process or outcome performances. The evidence for performance improvement by interventions based on the 'expert-based developed' MBQA criteria and the EFQM Excellence model is more limited. Only a few studies include balanced measures on multiple performance dimensions. Considering the need for integrated care and chronic care improvement, the further development of these models for guiding improvements in integrated care settings and their specific context factors is suggested.     

Genetics of anxiety disorders: the complex road from DSM to DNA

Anxiety disorders are among the most common psychiatric disorders, affecting one in four individuals over a lifetime. Although our understanding of the etiology of these disorders is incomplete, familial and genetic factors are established risk factors. However, identifying the specific casual genes has been difficult. Within the past several years, advances in molecular and statistical genetic methods have made the genetic dissection of complex disorders a feasible project. Here we provide an overview of these developments, with a focus on their implications for genetic studies of anxiety disorders. Although the genetic and phenotypic complexity of the anxiety disorders present formidable challenges, advances in neuroimaging and experimental animal models of anxiety and fear offer important opportunities for discovery. Real progress in identifying the genetic basis of anxiety disorders will require integrative approaches that make use of these biologic tools as well as larger‐scale genomic studies. If successful, such efforts may yield novel and more effective approaches for the prevention and treatment of these common and costly disorders. Depression and Anxiety, 2009. © 2009 Wiley‐Liss, Inc.     

Double-contrast enema in antibiotic-related pseudomembranous colitis

Pseudomembranous colitis (PMC) is a potentially fatal disease often associated with antibiotic therapy. The condition is now known to be due to an enterotoxin produced byClostridium difficile. Diagnosis is based on the endoscopic finding of the typical pseudomembranes, stool culture, and assay of the stools for the specific toxin. Radiography with double-contrast medium (DCE), which can be performed in patients not critically ill, often yields pathognomonic findings and permits early diagnosis.     

RSK2 enzymatic assay as a second level diagnostic tool in Coffin-Lowry syndrome

BACKGROUND: Coffin-Lowry syndrome is a semi-dominant condition characterized by severe psychomotor retardation with facial, hand and skeletal malformations resulting from mutations in RSK2 gene, encoding for a serine/threonine kinase. More than 100 different mutations have been identified to date; however, about 50% of clinically diagnosed patients apparently do not have mutations. In order to exclude that these patients have RSK2 mutations missed by standard mutation detection techniques, a rapid and sensitive assay allowing evaluation of RSK2 activity was needed. METHODS: RSK2 capacity to phosphorylate a synthetic CREB-peptide in basal and PMA-stimulated conditions was evaluated in lymphoblasts from 3 patients with RSK2 mutations and normal controls. RESULTS: Patients RSK2 activity is normal in nonstimulated conditions but fails to grow following stimulation. The evaluation of the stimulated/non-stimulated activity ratio demonstrated a statistically significant impairment in patients. CONCLUSIONS: We have set up an assay which allows the identification of even partial alterations of RSK2 activity and seems to give good results also in females with a balanced X-chromosome inactivation and thus with a presumably normal enzymatic activity in about 50% of cells. Moreover, our data seem to confirm previous reports of a potential direct correlation between the level of RSK2 activity and the severity of cognitive impairment.