Metabolically controlled reperfusion in acute myocardial infarction: should the polarizing solution be given subselectively?

BACKGROUND: In working rat hearts, metabolic support of injured tissue enhances recovery after acute myocardial infarction. Clinical experience with a systemic "polarizing solution" supports this claim. OBJECTIVES: In a dog model of ischemia/reperfusion, we tested the feasibility of subselectively supplying adapted metabolic substrates before instituting blood reperfusion. METHODS: Thirty-five dogs underwent ligation of the proximal left anterior descending artery and collaterals for 90 minutes. The animals were randomly assigned to receive direct blood reperfusion (Group I), intracoronary glucose, insulin, and potassium (Group II), or intracoronary glucose, insulin, and potassium plus propionyl-L-carnitine (PLC) (Group III). After 30 minutes of artificial reperfusion, prograde blood flow was resumed in groups II and III. A routine necropsy was performed 3 to 5 days later. Primary endpoints were severe arrhythmias, death, markers of infarct size, and specific histologic features. RESULTS: We excluded 4 dogs for technical reasons and 2 others for preexisting cardiomyopathy. In the remaining 29 animals, large apical infarctions were documented ventriculographically during arterial ligation. One dog died of irreversible ventricular fibrillation during the initial ischemic period, and 9/28 dogs (32.1%) died during early reperfusion. Ventricular fibrillation was more common with 10% (versus 5%) dextrose concentrations and was eliminated by PLC. Irreversibly injured (versus jeopardized) areas of myocardium were more common in Group III (85.9 19.3%) than in Groups I and II (16.9 10.8%). CONCLUSION: Subselective infusion of metabolically supportive solutions during acute myocardial infarction is technically feasible. To prevent osmotic endothelial damage, the perfusate must have a low (< 5%) dextrose content.     

Early identification of axial spondyloarthritis in a multi-ethnic Asian population

Clinical Rheumatology - To address the diagnostic delay in axial spondyloarthritis (axSpA), we have cross-culturally adapted the Hamilton axSpA questionnaire, a self-administered screening...     

Impact of an Evidence-Based Medicine Curriculum on Resident Use of Electronic Resources: A Randomized Controlled Study

Background  Evidence-based medicine (EBM) is widely taught in residency, but evidence for effectiveness of EBM teaching on changing residents’ behavior is limited. Objective  To investigate the impact of an EBM curriculum on residents’ use of evidence-based resources in a simulated clinical experience. Design/Participants  Fifty medicine residents randomized to an EBM teaching or control group. Measurements  A validated test of EBM knowledge (Fresno test) was administered before and after intervention. Post intervention, residents twice completed a Web-based, multiple-choice instrument (15 items) comprised of clinical vignettes, first without then with access to electronic resources. Use of electronic resources was tracked using ProxyPlus software. Within group pre–post differences and between group post-test differences were examined. Results  There was more improvement in EBM knowledge (100-point scale) for the intervention group compared to the control group (mean score increase 22 vs. 12, p = 0.012). In the simulated clinical experience, the most commonly accessed resources were Ovid (71% of residents accessed) and InfoPOEMs (62%) for the EBM group and UptoDate (67%) and MDConsult (58%) for the control group. Residents in the EBM group were more likely to use evidence-based resources than the control group. Performance on clinical vignettes was similar between the groups both at baseline (p = 0.19) and with access to information resources (p = 0.89). Conclusions  EBM teaching improved EBM knowledge and increased use of evidence-based resources by residents, but did not improve performance on Web-based clinical vignettes. Future studies will need to examine impact of EBM teaching on clinical outcomes.     

Safety and tolerability of linaclotide for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation: pooled Phase 3 analysis

Background: Linaclotide is approved for treating irritable bowel syndrome with constipation (IBS-C; 290 µg QD) and chronic idiopathic constipation (CIC; 145 µg or 72 µg QD). These analyses aimed to assess linaclotide safety in a large, pooled Phase 3 population.

Methods: In six randomized controlled trials (RCTs), patients received linaclotide (72 µg, 145 µg, 290 µg) or placebo daily for 12–26 weeks; in two long-term safety (LTS) studies, patients received open-label linaclotide for ≤78 additional weeks. Laboratory values, vital signs, and treatment-emergent adverse events (TEAEs) were assessed.

Results: Overall, 3853 patients received ≥1 dose of linaclotide. The most common TEAE was diarrhea (majority [90.5% in RCTs] mild/moderate). Linaclotide patients experienced 1.1 diarrhea TEAE per patient-year in the RCTs (0.2 in placebo), and 0.3 in the LTS studies. In RCTs, 6.9% linaclotide and 3.0% placebo patients discontinued due to any adverse event (AE); 4.0% linaclotide and 0.3% placebo patients discontinued due to diarrhea. In LTS studies, 9.4% patients discontinued due to any AE, and 3.8% due to diarrhea. Serious AEs (SAEs) were rare and similar across treatment groups; there were no SAEs of diarrhea.

Conclusion: These pooled analyses of patients treated for ≤104 weeks confirm linaclotide’s overall safety.     

Post‐traumatic stress disorder,social support and cognitive status in community‐based older veterans

Objective: The present study investigated the relationships between structural and qualitative aspects of social support, combat‐related post‐traumatic stress disorder (PTSD) and cognitive status in a New Zealand veterans sample. Methods: A random sample of 232 New Zealand veterans completed a self‐report questionnaire and participated in a face‐to‐face interview. Results: Regression analysis showed that when controlling for age, income, education, depression and general health, PTSD scores had a negative relationship with cognitive status. Those who reported having private, restricted social networks had poorer cognitive functioning. These relationships were independent of each other. Conclusions: The findings suggest that while social support might be a potential target for interventions in at‐risk older adults, health professionals need to be aware of the concomitant possible influence of past trauma when dealing with this specific population.     

Association of mannose-binding lectin genotype with cardiovascular abnormalities in Kawasaki disease

Kawasaki disease is an acute vasculitis of possible infectious cause, which in particular affects the coronary arteries. Young children rely mostly on their innate immune system for protection against invading microorganisms, of which mannose-binding lectin is an important component. We aimed to investigate the possible role of the gene for this molecule (MBL) in white Dutch patients with Kawasaki disease. In 90 patients, frequency of mutations in the MBL gene was higher than in healthy children. In children younger than 1 year, those with mutations were at higher risk of development of coronary artery lesions than were those without (odds ratio 15.7, 95% CI 1.4-176.5, p=0.026). Our findings suggest that the innate immune system contributes differently to pathophysiology of Kawasaki disease at various ages.