BackgroundPrevious studies based on local case series estimated the annual incidence of endocarditis in the U.S. at about 4 per 100,000 population. Small-scale studies elsewhere have reported similar incidence rates. However, no nationally-representative population-based studies have verified these estimates.Methods and FindingsUsing the 1998–2009 Nationwide Inpatient Sample, which provides diagnoses from about 8 million U.S. hospitalizations annually, we examined endocarditis hospitalizations, bacteriology, co-morbidities, outcomes and costs. Hospital admissions for endocarditis rose from 25,511 in 1998 to 38, 976 in 2009 (12.7 per 100,000 population in 2009). The age-adjusted endocarditis admission rate increased 2.4% annually. The proportion of patients with intra-cardiac devices rose from 13.3% to 18.9%, while the share with drug use and/or HIV fell. Mortality remained stable at about 14.5%, as did cardiac valve replacement (9.6%). Other serious complications increased; 13.3% of patients in 2009 suffered a stroke or CNS infection, and 5.5% suffered myocardial infarction. Amongst cases with identified pathogens, Staphylococcus aureus was the most common, increasing from 37.6% in 1998 to 49.3% in 2009, 53.3% of which were MRSA. Streptococci were mentioned in 24.7% of cases, gram-negatives in 5.6% and Candida species in 1.0%. We detected no inflection in hospitalization rates after changes in prophylaxis recommendations in 2007. Mean age rose from 58.6 to 60.8 years; elderly patients suffered higher rates of myocardial infarction and death, but slightly lower rates of Staphylococcus aureus infections and neurologic complications. Our study relied on clinically diagnosed cases of endocarditis that may not meet strict criteria. Moreover, since some patients are discharged and readmitted during a single episode of endocarditis, our hospitalization figures probably slightly overstate the true incidence of this illness.ConclusionsEndocarditis is more common in the U.S. than previously believed, and is steadily increasing. Preventive efforts should focus on device-associated and health-care-associated infections.

Background-In patients with neurogenic orthostatic hypotension (NOH), the availability of the sympathetic neurotransmitter norepinephrine (NE) in the synaptic cleft is insufficient to maintain blood pressure while in the standing posture. Methods and Results-We determined the effect of oral administration of the synthetic amino acid L-threo-3,4-dihydroxyphenylserine (L-DOPS), which is decarboxylated to NE by the enzyme L-aromatic amino acid decarboxylase (L-AADC) in neural and nonneural tissue, on blood pressure and orthostatic tolerance in 19 patients with severe NOH (8 with pure autonomic failure and 11 with multiple-system atrophy). A single-blind dose-titration study determined the most appropriate dose for each patient. Patients were then enrolled in a double-blind, placebo-controlled, crossover trial. L-DOPS significantly raised mean blood pressure both supine (from 101Ϯ4 to 141Ϯ5 mm Hg) and standing (from 60Ϯ4 to 100Ϯ6 mm Hg) for several hours and improved orthostatic tolerance in all patients. After L-DOPS, blood pressure increases were closely associated with increases in plasma NE levels. Oral administration of carbidopa, which inhibits L-AADC outside the blood-brain barrier, blunted both the increase in plasma NE and the pressor response to L-DOPS in all patients Conclusions-Acute administration of L-DOPS increases blood pressure and improves orthostatic tolerance in patients with NOH. The pressor effect results from conversion of L-DOPS to NE outside the central nervous system.