Use of different combination diphtheria-tetanus-acellular pertussis vaccines does not increase risk of 30-day infant mortality. A population-based linkage cohort study using administrative data from the Australian Childhood Immunisation Register and the National Death Index.

Objective

To determine whether differences in combination DTaP vaccine types at 2, 4 and 6?months of age were associated with mortality (all-cause or non-specific), within 30?days of vaccination.

Deep Brain Stimulation Compared With Contingency Management for the Treatment of Cocaine Use Disorders: A Threshold and Cost-Effectiveness Analysis

ObjectivesCocaine is the second most frequently used illicit drug worldwide (after cannabis), and cocaine use disorder (CUD)-related deaths increased globally by 80% from 1990 to 2013. There is yet to be a regulatory-approved treatment. Emerging preclinical evidence indicates that deep brain stimulation (DBS) of the nucleus accumbens may be a therapeutic option. Prior to expanding the costly investigation of DBS for treatment of CUD, it is important to ensure societal cost-effectiveness.AimsWe conducted a threshold and cost-effectiveness analysis to determine the success rate at which DBS would be equivalent to contingency management (CM), recently identified as the most efficacious therapy for treatments of CUDs.Materials and MethodsQuality of life, efficacy, and safety parameters for CM were obtained from previous literature. Costs were calculated from a societal perspective. Our model predicted the utility benefit based on quality-adjusted life-years (QALYs) and incremental-cost-effectiveness ratio resulting from two treatments on a one-, two-, and five-year timeline.ResultsOn a one-year timeline, DBS would need to impart a success rate (ie, cocaine free) of 70% for it to yield the same utility benefit (0.492 QALYs per year) as CM. At no success rate would DBS be more cost-effective (incremental-cost-effectiveness ratio <$50,000) than CM during the first year. Nevertheless, as DBS costs are front loaded, DBS would need to achieve success rates of 74% and 51% for its cost-effectiveness to exceed that of CM over a two- and five-year period, respectively.ConclusionsWe find DBS would not be cost-effective in the short term (one year) but may be cost-effective in longer timelines. Since DBS holds promise to potentially be a cost-effective treatment for CUDs, future randomized controlled trials should be performed to assess its efficacy.     

Enantiomeric interaction of flurbiprofen in the rat

Flurbiprofen [FL, (+/-)-2-(2-fluoro-4-biphenylyl)propionic acid] is a 2-arylpropionic acid nonsteroidal anti-inflammatory drug which is commercially available as a racemate. The anti-inflammatory activity of FL, however, appears to be mainly due to the S enantiomer. Recently, it has been postulated that, in both humans and rats, the two enantiomers of FL may interact when racemic doses are given. This study examines the above postulate in the rat by administration of single iv doses of racemic FL (10 mg/kg), and R- and S-FL (5 mg/kg of each). Plasma concentrations (0-12 h) of the enantiomers were measured using a stereospecific HPLC assay. A significant interaction was noticed between the enantiomers: mean AUC +/- SD of R-FL was reduced from 115.3 +/- 21.3 to 49.0 +/- 10.4 mg/L.h as a result of S-FL coadministration. A trend towards reduced S-FL plasma concentration was also evident when the enantiomer was given as the racemate [mean AUC +/- SD; 176.8 +/- 37.7 racemate versus 241.4 +/- 86.2 mg/L.h alone]. The reduction in S-FL, however, was not significant due perhaps to the observed interanimal variation. While the enantiomeric interaction caused a significant enlargement of the volume of distribution of R-FL, it failed to alter the terminal half-life of the enantiomer. It is suggested that the interaction is a result of displacement from plasma protein binding sites of one enantiomer by the other.     

Changes in the biophysical properties and ultrastructure of lungs, and intrapulmonary fibrin deposition in experimental acute pancreatitis

Using an experimental model of acute pancreatitis in the rat, we have studied changes in the biophysical properties of lungs and intrapulmonary fibrin deposition in this condition. Acute pancreatitis is associated with a significant decrease in pulmonary compliance (p less than 0.01) and a significant increase in lung weight (p less than 0.01) compared with a control sham operation group. These changes are associated with a 24% increase in intrapulmonary 125I fibrinogen deposition (p less than 0.01), and an 18% increase in 125I fibrinogen deposition per gram of lung tissue (p less than 0.05) in acute pancreatitis, compared with a control sham operation group. The increased fibrinogen deposition is abolished by treatment with low dose heparin. Using the same animal model changes in pulmonary ultrastructure are shown using scanning electron microscopy. The results indicate that pulmonary abnormalities are associated with intrapulmonary fibrin deposition in experimental acute pancreatitis and these findings may be relevant to the well described respiratory complications of the condition in man.