The purpose of this study was to evaluate heart rate and blood pressure responses to a commercially available source of ma-haung, a natural source of the sympathomimetic substance, ephedrine, and to evaluate the pharmacokinetic properties of the product in normotensive, healthy adults. On day 1, twelve study participants were monitored with an ambulatory blood pressure device between hours 7 and 20. On day 2, they ingested four capsules of powdered ma-huang at hours 8 and 17 while again wearing the monitor between hours 7 and 20. Serial plasma samples were obtained and concentrations of ephedrine were analyzed by high-performance liquid chromatography. Pharmacokinetic parameters of ephedrine were determined from plasma concentration-time profiles. The ephedrine alkaloid content of each capsule was also determined by high-performance liquid chromatography. Six participants experienced a statistically significant increase in heart rate, but the effects on blood pressure were variable. The half-life, volume of distribution, clearance, and maximum concentration in plasma of ephedrine in the ma-huang product were similar to values previously reported for a 20 mg, immediate-release ephedrine tablet. Values for the absorption rate were considerably lower and time to reach maximum concentration was longer for the capsules, compared with the standard tablet. Variability in alkaloid content of ephedrine was low and yielded a mean dose of ephedrine at 19.4 mg; pseudoephedrine at 4.9 mg; and methylephedrine at 1.2 mg for a four-capsule dose. In summary, ma-haung had variable effects on blood pressure and increased heart rate in healthy, normotensive adults. Pharmacokinetic parameters for ephedrine were in agreement with those previously reported; however, the absorption rate was much slower after ingestion of ma-huang.

The development of new antimalarial compounds remains a pivotal part of the strategy for malaria elimination. Recent large-scale phenotypic screens have provided a wealth of potential starting points for hit-to-lead campaigns. One such public set is explored, employing an open source research mechanism in which all data and ideas were shared in real time, anyone was able to participate, and patents were not sought. One chemical subseries was found to exhibit oral activity but contained a labile ester that could not be replaced without loss of activity, and the original hit exhibited remarkable sensitivity to minor structural change. A second subseries displayed high potency, including activity within gametocyte and liver stage assays, but at the cost of low solubility. As an open source research project, unexplored avenues are clearly identified and may be explored further by the community; new findings may be cumulatively added to the present work.

Pseudomonas aeruginosa infection is associated with poorer outcomes in non-cystic fibrosis bronchiectasis. It is unknown whether early eradication improves outcomes. This retrospective study assessed clinical and microbiological outcomes of eradication therapy following initial Pseudomonas infection. All patients undergoing Pseudomonas eradication therapy from 2004 to 2010 were identified retrospectively and assessed for microbiological eradication, exacerbation frequency, hospital admissions, clinical symptoms and lung function. 30 patients were identified with median follow-up time 26.4 months. Eradication therapy involved intravenous antibiotics (n = 12), intravenous antibiotics followed by oral ciprofloxacin (n = 13) or ciprofloxacin alone (n = 5), combined with 3 months of nebulised colistin. Pseudomonas was initially eradicated from sputum in 24 patients (80.0%). 13/24 patients remained Pseudomonas-free and 11/24 were subsequently reinfected (median time 6.2 months). Exacerbation frequency was significantly reduced from 3.93 per year pre-eradication and 2.09 post-eradication (p = 0.002). Admission rates were similar, at 0.39 per year pre-eradication and 0.29 post-eradication (p = NS). 20/30 patients reported initial clinical improvement, whilst at one-year follow up, 19/21 had further improved or remained stable. Lung function was unchanged. This study demonstrates that Pseudomonas can be eradicated from a high proportion of patients, which may lead to prolonged clearance and reduced exacerbation rates. This important outcome requires confirmation in a prospective study.

No abstract

Nutritional supplements containing Ephedra sinica (ma huang), a botanical source of ephedrine alkaloids, have been linked to several episodes of ephedrine toxicity and at least 17 deaths, yet these products remain unregulated. Ten subjects were enrolled in a randomized, crossover study aimed at characterizing the pharmacokinetics of ephedrine after the ingestion of three commercially available ma huang products compared with a 25-mg ephedrine capsule. Pharmacokinetic parameters for botanical ephedrine were similar to those for synthetic ephedrine hydrochloride. Gender-based comparisons of Vss/F and CL/F revealed higher values for women than for men (Vss/F, 3.49 +/- 1.04 vs 2.98 +/- 0.73 l/kg; CL/F, 0.48 +/- 0.11 vs 0.37 +/- 0.11 l/hour x kg). The current study suggests that the increased incidence of ma huang toxicity does not stem from differences in the absorption of botanical ephedrine compared with synthetic ephedrine; rather, it results from accidental overdose often prompted by exaggerated off-label claims and a belief that "natural" medicinal agents are inherently safe.

Objectives To compare health care use and spending of Medicaid enrollees seen at federally qualified health centers versus non–health center settings in a context of significant growth. Methods Using fee-for-service Medicaid claims from 13 states in 2009, we compared patients receiving the majority of their primary care in federally qualified health centers with propensity score–matched comparison groups receiving primary care in other settings. Results We found that health center patients had lower use and spending than did non–health center patients across all services, with 22% fewer visits and 33% lower spending on specialty care and 25% fewer admissions and 27% lower spending on inpatient care. Total spending was 24% lower for health center patients. Conclusions Our analysis of 2009 Medicaid claims, which includes the largest sample of states and more recent data than do previous multistate claims studies, demonstrates that the health center program has provided a cost-efficient setting for primary care for Medicaid enrollees.

We have successfully implemented data sharing in our institution without the support of an academic institution. This has been associated with reductions in violent crime, but it is not clear whether this association is causal.

Patients with severe left ventricular dysfunction and chronic renal insufficiency who are being considered for procedures that necessitate bowel cleansing with PEG-ELS may be at risk for sodium and water retention and exacerbation of CHF.