Bupropion for smoking cessation

Smoking tobacco is the leading cause of preventable death. Bupropion is the only antidepressant recommended as first-line pharmacotherapy for smoking cessation. Bupropion is as effective as nicotine replacement therapy and can be used in diverse populations.     

Secondary outcomes of a pilot randomized trial of azithromycin treatment for asthma

Objectives:     

… But Does It Stick? Evaluating the Durability of Improved Knowledge Following an Undergraduate Experiential Geriatrics Learning Session

Canada's aging population, fewer medical students training in geriatric medicine, and inadequate geriatric curricula require that medical schools immediately address how future physicians will be able to care for older people effectively. The medical literature suggests that experiential learning strategies improve undergraduate medical students' knowledge of and interest in less-popular subjects, but the durability of improvements resulting from these resource-intensive learning approaches remains unclear. In October 2001, a convenience sample of all University of Western Ontario medical students attending the geriatric component of their first year was randomized to attend one 3-hour didactic lecture or 3-hour experiential learning session. Approximately 1 year later, students completed a follow-up knowledge and attitudes survey that was matched to their first-year surveys using date-of-birth data. Of 100 completed follow-up surveys, 42 were used in formal analysis. Although initially the experiential group demonstrated a better knowledge score, at 1-year follow-up, there was no significant difference in knowledge, attitudes toward older people, or interest in geriatric medicine between the didactic (n=17) and experiential (n=25) groups. Nevertheless, these students (n=42) demonstrated better attitude scores than those (n=22) who had not attended either educational intervention. This study challenges the belief that an experiential approach is a superior training method to a didactic approach. One year after an educational intervention, there was no difference in geriatric knowledge, attitude scores, or interest in geriatric medicine between students who underwent a didactic lecture or a participatory, experiential learning session.     

Effect of weight loss due to lifestyle intervention on subclinical cardiovascular dysfunction in obesity (body mass index >30 kg/m2)

Subclinical myocardial and vascular dysfunctions occur in subjects with obesity. We investigated whether these changes were reversible with weight loss due to lifestyle intervention. Quantitative assessment of myocardial and vascular functions was performed at baseline and after a minimum of 8 weeks of a lifestyle intervention program in 106 subjects with significant risk factors but no history of cardiovascular disease and normal ejection fractions. Myocardial function was assessed using strain rate, strain, regional myocardial systolic velocity, and diastolic velocity (e(m)). Myocardial reflectivity was assessed by calibrated integrated backscatter. Vascular function was assessed using brachial arterial reactivity and arterial compliance. Exercise capacity was measured by peak oxygen consumption per unit time (VO(2)). Weight loss (-4.5 +/- 2.0%) was achieved by 48 subjects, and 58 maintained or increased weight (+1 +/- 1.5%, p <0.001). Compared with the stable weight group, the weight loss group showed significant improvement in brachial arterial reactivity (8.6 +/- 4.9% vs 6.7 +/- 4.9%, p <0.05), e(m) (6.4 +/- 1.9 vs 5.5 +/- 1.9 cm/s, p <0.01), and reflectivity (calibrated integrated backscatter, 18.3 +/- 4.9 vs 16.2 +/- 5.2 dB, p <0.01). The magnitude of weight change correlated with changes in e(m) (r = 0.36) and calibrated integrated backscatter (r = 0.33). The change in e(m) correlated with peak VO(2) (r = 0.38, p <0.001) and was an independent predictor for peak VO(2) even after adjustment for age and body mass index in a multivariate model (R(2) = 0.45, p <0.001). Weight loss was not associated with a significant change in systolic parameters (regional myocardial systolic velocity, global strain, and strain rate) or arterial compliance.     

Predictors of endoscopic findings after Roux-en-Y gastric bypass

OBJECTIVES: To evaluate predictors of endoscopic findings in symptomatic patients after Roux-en-Y gastric bypass (RYGBP) for obesity. METHODS: A retrospective chart review of 1,001 RYGBP procedures was performed. Two hundred twenty-six (23%) patients were identified as having endoscopy to evaluate upper gastrointestinal symptoms following surgery. Polychotomous logistic regression analysis was used to assess predictors of normal endoscopy, marginal ulcers, stomal stenosis, and staple-line dehiscence. RESULTS: The most common endoscopic findings were 99 (44%) normal postsurgical anatomy, 81 (36%) marginal ulcer, 29 (13%) stomal stenosis, and 8 (4%) staple-line dehiscence. Factors that significantly increase the risk of marginal ulcers following surgery include smoking (AOR = 30.6, 95% CI 6.4-146) and NSAID use (AOR = 11.5, 95% CI 4.8-28). PPI therapy following surgery was protective against marginal ulcers (AOR = 0.33, 95% CI 0.11-0.97). Median time for diagnosis of marginal ulcers following surgery was 2 months, and 77 of 81 (95%) presented within 12 months. CONCLUSIONS: Following RYGBP surgery for obesity, smoking and NSAID use significantly increase the risk of marginal ulceration, and PPI therapy is protective. Because a significant majority of marginal ulcers present within 12 months of surgery, it may be reasonable to consider prophylactic PPI therapy during this time period, especially for high risk patients.     

Antigenic differences and conservation among placental Plasmodium falciparum-infected erythrocytes and acquisition of variant-specific and cross-reactive antibodies

Background. Pregnant women are infected by Plasmodium falciparum with novel antigenic phenotypes that adhere to chondroitin sulfate A (CSA) and other receptors in the placenta. The diverse and variant parasite protein P. falciparum erythrocyte membrane protein 1 (PfEMP1), which is encoded by var genes, is a ligand for CSA and a major target of antibodies associated with protective immunity.Methods. Serum samples from pregnant women exposed to malaria were tested for immunoglobulin G, adhesion-inhibitory antibodies, and agglutinating antibodies to different CSA-binding isolates expressing conserved var2csa-type genes and to parasite isolates from infected placentas. Parasite isolates also were examined to assess PfEMP1 expression, the effect of trypsin treatment of infected erythrocytes on parasite adhesion and cleavage of PfEMP1, and inhibition of adhesion by rabbit antiserum raised against a CSA-binding isolate.Results. Findings demonstrated that (1) there are significant antigenic differences between CSA-binding isolates that correspond with polymorphisms in var2csa; (2) there are differences in the properties of PfEMP1 and antibody reactivity between CSA-binding and placental isolates, which express multiple PfEMP1 forms; (3) acquired antibodies target diverse and cross-reactive epitopes expressed by CSA-binding infected erythrocytes, and cross-reactive antibodies are not necessarily cross-inhibitory; and (4) the breadth of antibody reactivity is greater among multigravidae than among primigravidae.Conclusions. Immunity may be mediated by a repertoire of antibodies to diverse and common epitopes. Strategies based on vaccination with a single domain or isolate might be hindered by antigenic diversity.     

Percentage of body fat and plasma glucose predict plasma sialic acid concentration in type 2 diabetes mellitus

Circulating sialic acid is an independent risk factor for cardiovascular disease and is higher in people with type 2 diabetes mellitus. Sialic acid is associated with body mass index, but it is uncertain whether body fat contributes to the higher levels of sialic acid in type 2 diabetes mellitus. Therefore, we have investigated whether the higher levels of sialic acid observed in type 2 diabetes mellitus persist when controlling for fatness. Fasting plasma samples were collected from 24 individuals with type 2 diabetes mellitus and 24 controls. Percentage of body fat was measured by bioelectrical impedance. Plasma sialic acid was quantified by an enzymatic method. Plasma sialic acid was higher in the group with type 2 diabetes mellitus than controls (602 +/- 14 vs 545 +/- 14 mg/L, P = .007). Percentage of body fat was associated with plasma sialic acid concentration in both the control group (r = 0.481, P = .020) and the group with type 2 diabetes mellitus (r = 0.527, P = .007). Fasting glucose was also associated with plasma sialic acid in the group with type 2 diabetes mellitus (r = 0.700, P < .001). Adjustment for percentage of body fat accounted for the higher levels of sialic acid in type 2 diabetes mellitus. Using linear regression, 54.3% of the variation of plasma sialic acid was explained by percentage of body fat and glucose concentrations in the whole group. Seventy-four percent of sialic acid variation was explained by the same model in type 2 diabetes mellitus. In conclusion, this is the first study to show that percentage of body fat predicts plasma sialic acid concentration and contributes toward higher levels of sialic acid in type 2 diabetes mellitus.     

Phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 alphal-antitrypsin (AAT) vector in AAT-deficient adults

A phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 (rAAV2) alpha1-antitrypsin (AAT) vector was performed in 12 AAT-deficient adults, 10 of whom were male. All subjects were either homozygous for the most common AAT mutation (a missense mutation designated PI*Z) or compound heterozygous for PI*Z and another mutation known to cause disease. There were four dose cohorts, ranging from 2.1 x 10(12) vector genomes (VG) to 6.9 x 10(13) VG, with three subjects per cohort. Subjects were injected sequentially in a dose-escalating fashion with a minimum of 14 days between patients. Subjects who had been receiving AAT protein replacement discontinued that therapy 28 days before vector administration. There were no vector-related serious adverse events in any of the 12 participants. Vector DNA sequences were detected in the blood between 1 and 3 days after injection in nearly all patients receiving doses of 6.9 x 10(12) VG or higher. Anti-AAV2 capsid antibodies were present and rose after vector injection, but no other immune responses were detected. One subject who had not been receiving protein replacement exhibited low-level expression of wild-type M-AAT in the serum (82 nM), which was detectable 30 days after receiving an injection of 2.1 x 10(13) VG. Unfortunately, residual but declining M-AAT levels from the washout of the protein replacement elevated background levels sufficiently to obscure any possible vector expression in that range in most of the other individuals in the higher dose cohorts.