RATIONALE: Data are limited regarding the safety of 12-dose once-weekly isoniazid (900 mg) plus rifapentine (900 mg) (3HP) for latent tuberculosis infection (LTBI) treatment during pregnancy. OBJECTIVE: To assess safety and pregnancy outcomes among pregnant women who were inadvertently exposed to study medications in two LTBI trials (PREVENT TB or iAdhere) evaluating 3HP and 9 months of daily isoniazid (300 mg) (9H). METHODS: Data from reproductive age (15-51 years) women who received >/=1 study dose of 3HP or 9H in either trial were analyzed. Drug exposure during pregnancy occurred if the estimated date of conception was on or before the last dose date. RESULTS: Of 126 pregnancies (125 participants) that occurred during treatment or follow-up, 87 were exposed to study drugs. Among these, fetal loss was reported for 4/31 (13%) and 8/56 (14%), 3HP and 9H, respectively (difference 13% - 14% = -1%; 95% CI -17% to +18%); and congenital anomalies in 0/20 and 2/41 (5%) live births, 3HP and 9H, respectively (difference 0 - 5% = -5%; 95% CI -18% to +16%). All fetal losses occurred in pregnancies <20 weeks. Of the total 126 pregnancies, fetal loss was reported in 8/54 (15%) and 9/72 (13%), 3HP and 9H, respectively; and congenital anomalies in 1/37 (3%) and 2/56 (4%) live births, 3HP and 9H, respectively. The overall proportion of fetal loss (17/126 [13%]) and anomalies (3/93 [3%]) were similar to those estimated for the United States, 17% and 3%, respectively. CONCLUSION: Among reported pregnancies in these two LTBI trials, there was no unexpected fetal loss or congenital anomalies. These data offer some preliminary reassurance to clinicians and patients in circumstances when these drugs and regimens are the best option in pregnancy or in women of child-bearing potential. Clinical trial registered with clinicaltrials.gov (NCT00023452 and NCT01582711).

As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950 Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each lab using a different lipidomics workflow. A total of 1527 unique lipids were measured across all laboratories, and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra- and inter-laboratory quality control and method validation. These analyses were performed using non-standardized laboratory-independent workflows. The consensus locations were also compared to a previous examination of SRM 1950 by the LIPID MAPS consortium. While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement.

SETTING: Nine months of daily isoniazid (9H) and 3 months of once-weekly rifapentine plus isoniazid (3HP) are recommended treatments for latent tuberculous infection (LTBI). The risk profile for 3HP and the contribution of hepatitis C virus (HCV) infection to hepatotoxicity are unclear. OBJECTIVES: To evaluate the hepatotoxicity risk associated with 3HP compared to 9H, and factors associated with hepatotoxicity. DESIGN: Hepatotoxicity was defined as aspartate aminotransferase (AST) >3 times the upper limit of normal (ULN) with symptoms (nausea, vomiting, jaundice, or fatigue), or AST >5 x ULN. We analyzed risk factors among adults who took at least 1 dose of their assigned treatment. A nested case-control study assessed the role of HCV. RESULTS: Of 6862 participants, 77 (1.1%) developed hepatotoxicity; 52 (0.8%) were symptomatic; 1.8% (61/3317) were on 9H and 0.4% (15/3545) were on 3HP (P < 0.0001). Risk factors for hepatotoxicity were age, female sex, white race, non-Hispanic ethnicity, decreased body mass index, elevated baseline AST, and 9H. In the case-control study, HCV infection was associated with hepatotoxicity when controlling for other factors. CONCLUSION: The risk of hepatotoxicity during LTBI treatment with 3HP was lower than the risk with 9H. HCV and elevated baseline AST were risk factors for hepatotoxicity. For persons with these risk factors, 3HP may be preferred.

A novel avian-origin influenza A H7N9 virus emerged in China in 2013 and continues to cause sporadic human infections with mortality rates approaching 35%. Currently there are no approved human vaccines for H7N9 virus. Recombinant approaches including hemagglutinin (HA) and virus-like particles (VLPs) have resulted in experimental vaccines with advantageous safety and manufacturing characteristics. While high immunogenicity of VLP vaccines has been attributed to the native conformation of HA arranged in the regular repeated patterns within virus-like structures, there is limited data regarding molecular organization of HA within recombinant HA vaccine preparations. In this study, the full-length recombinant H7 protein (rH7) of A/Anhui/1/2013 (H7N9) virus was expressed in Sf9 cells. We showed that purified full-length rH7 retained functional ability to agglutinate red blood cells and formed oligomeric pleomorphic subviral particles (SVPs) of approximately 20nm in diameter composed of approximately 10 HA0 molecules. No significant quantities of free monomeric HA0 were observed in rH7 preparation by size exclusion chromatography. Immunogenicity and protective efficacy of rH7 SVPs was confirmed in the mouse and ferret challenge models suggesting that SVPs can be used for vaccination against H7N9 virus.

The United States and other countries are grappling with the need to treat large numbers of persons with latent tuberculosis infection (LTBI) to further reduce tuberculosis (TB) incidence (1, 2). However, the success of LTBI treatment as a TB control strategy has been limited by competing priorities and by suboptimal uptake and completion. New regimens offer the promise of s horter treatment and enhanced completion (3, 4), so it is relevant to revisit screening (also referred to as targeted LTBI testing) and treatment priorities—especially given the severe fiscal constraints now confronting TB control authorities. In this context, the article by Linas and colleagues in this issue of the Journal (pp. 590) provides welcome information (5). The authors have developed a comprehensive decision analysis model, to predict costs and effectiveness of LTBI screening and treatment in various patient groups. | Two findings have very specific implications for policy and practice. The first is that in foreign-born persons, the interferon-γ release assay (IGRA) may be preferable to the tuberculin skin test (TST). This is because the IGRA has similar or slightly lower overall cost, but is more effective than the TST, primarily because it obviates the need for a return visit to obtain results. In some other groups, IGRAs are more expensive, but potentially cost-effective because of additional TB cases prevented. Much of the value of IGRAs is ascribed to reduced attrition. However, it is not entirely clear that patients who miss TST reading would initiate and complete LTBI treatment if an IGRA were used instead. Hence the apparent advantages of IGRAs may be overstated. | The second major finding, in our view, is that the relative cost-effectiveness estimates can guide programs in targeting groups for whom screening and treatment will offer the highest yield at lowest cost. Specifically, as with close contacts and HIV-infected persons, screening and treatment of foreign-born persons is likely to be relatively cost-effective—both for recent arrivals (in the United States < 5 yr), and for foreign-born persons under 45 years of age who have resided in the United States for longer. On the other hand, screening and treatment of persons with other medical or social risk factors (e.g., other immune-suppressive treatment, homelessness, injection drug use) appears less cost-effective, and is predicted to have limited impact in reducing the burden of TB in the United States.

OBJECTIVES: This report presents national estimates of hospital inpatient care in the United States during 2007 and selected trend data. Numbers and rates of discharges, diagnoses, and procedures are shown by age and sex. Average lengths of stay are presented for all discharges and for selected diagnostic categories by age and by sex. METHODS: The estimates are based on data collected through the 2007 National Hospital Discharge Survey, an annual national probability sample survey of discharges from nonfederal, general, and short-stay hospitals. Sample data are weighted to produce annual estimates of inpatient care, excluding newborns. Diagnoses and procedures are coded using the International Classification of Diseases, Ninth Revision, Clinical Modification. RESULTS: In 2007, there were an estimated 34.4 million hospital discharges, excluding newborns. The total hospitalization rate leveled off from 1995 to 2007 after declining during the period from 1980 to 1995. Throughout the period from 1970 to 2007 the rates for those aged 65 years and over were significantly higher than the rates for the younger groups. Although those aged 65 years and over accounted for only 13 percent of the total population, they comprised 37 percent of hospital discharges and 43 percent of hospital days. One-quarter of inpatients under age 15 years were hospitalized for respiratory diseases. There were 45 million inpatient procedures during 2007 and 15 percent of these were cardiovascular. Males aged 45-64 and 65 years and over had higher cardiac catheterization rates than females in these age groups each year from 1997 to 2007. From 2002 to 2007 the rate of inpatient cardiac catheterization procedures declined.

PURPOSE: An outbreak of pneumococcal conjunctivitis occurred at Dartmouth College in 2002. We describe the clinical features, outcomes, and costs associated with this outbreak. METHODS: Six hundred ninety-eight students were diagnosed with conjunctivitis; culture of conjunctival discharge was obtained for 254. A screening protocol was used to evaluate 67 patients. A retrospective survey was offered to all 698 cases and follow-up clinical examination to all patients with culture-confirmed infection (n = 110). Local ophthalmology offices were contacted to develop a cost analysis. The college health service provided conjunctivitis data for nonoutbreak years. RESULTS: Of 67 patients evaluated using the screening protocol, findings associated with culture-confirmed Streptococcus pneumoniae conjunctivitis (P < 0.01) were red eye visible from 2 feet, any type of conjunctival discharge, obscuration of tarsal conjunctival blood vessels, and chemosis. Two hundred thirty-two students responded to our retrospective survey; 89% reported bilateral eye involvement; 96% received topical antibiotics and noted symptom improvement within 3 days of treatment. No ocular sequelae were identified as a result of this infection. No recurrent outbreaks have occurred at Dartmouth since the initial event. The estimated cost of this outbreak including evaluations, cultures, and antibiotics ranged from $66,468 to $120,583. CONCLUSIONS: The ST448 strain of S. pneumoniae caused a disruptive outbreak of conjunctivitis at Dartmouth College. A screening protocol was effective at identifying culture-positive cases. Although most culture-positive patients experienced bilateral conjunctivitis, the clinical course was mild with quick resolution of symptoms after initiating antibiotics and no ocular sequelae.