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We determined the variability in enteral feeding practices in mechanically ventilated patients in four adult intensive care units of a tertiary-care, referral hospital. Patients who had been mechanically ventilated for at least 48 h and received enteral nutrition were prospectively followed. Fifty-five of 101 consecutive mechanically ventilated patients received enteral nutrition; in 93% of patients, feedings were infused into the stomach. Patients who were cared for in the medical intensive care unit, where a nutritional protocol was operational, received enteral nutrition earlier in their ventilatory course ( P = 0.004) and feedings were advanced to target rates faster ( P = 0.043) than those who received care in other units. The number ( P = 0.243) and duration ( P = 0.668) of interruptions in feeding did not differ by patient location. On average, patients received only 50% to 70% of their targeted caloric goals during the first 6 days of enteral nutrition. Most feeding discontinuations (41%) were secondary to procedures. Gastrointestinal intolerances, including vomiting, aspiration, abdominal distention, and increased gastric residuals, were uncommon despite allowing gastric residuals up to 300 mL. The practice of providing enteral feeds to mechanically ventilated patients varies widely, even within one hospital. A protocol enhanced early initiation of enteral feeds and advancement to target feeding rates but did not alter the number or duration of interruptions in enteral feedings. Procedures represented the most common reason for stopping enteral feeds, and gastrointestinal intolerances (vomiting, aspiration, and increased gastric residuals) caused few feeding interruptions. The gastric route was safe and well tolerated for early enteral feeding in most mechanically ventilated patients.

Abstract Rationale Nitrogen oxide (NO) species are markers for oxidative stress that may be pathogenic in acute lung injury (ALI). Objectives We tested two hypotheses in patients with ALI: (1) higher levels of urine NO would be associated with worse clinical outcomes, and (2) ventilation with lower Vt would reduce urine NO as a result of less stretch injury. Methods Urine NO levels were measured by chemiluminescence in 566 patients enrolled in the National Heart Lung and Blood Institute Acute Respiratory Distress Syndrome Network trial of 6 ml/kg versus 12 ml/kg Vt ventilation. The data were expressed corrected and uncorrected for urine creatinine (Cr). Results Higher baseline levels of urine NO to Cr were associated with lower mortality (odds ratio, 0.43 per log(10) increase in the ratio), more ventilator-free days (mean increase, 1.9 d), and more organ-failure–free days (mean increase, 2.3 d) on multivariate analysis (p < 0.05 for all analyses). Similar results were obtained using urine NO alone. NO to Cr levels were higher on Day 3 in the 6 ml/kg than in the 12 ml/kg Vt group (p = 0.04). Conclusions Contrary to our hypothesis, higher urine NO was associated with improved outcomes in ALI at baseline and after treatment with the 6 ml/kg Vt strategy. Higher endogenous NO may reflect less severe lung injury and better preservation of the pulmonary and systemic endothelium or may serve a protective function in patients with ALI.

The gypsum caves of western Oklahoma are situated in three separate areas of evaporite karst: (1) the Cimarron Gypsum Hills, in the northwest, along the Cimarron River; (2) the Weatherford Gypsum Hills, in west-central Oklahoma, to the north of the Wichita Mountains; and (3) the Mangum Gypsum Hills, in the southwest, west of the Wichita Mountains. Caves of the Cimarron Gypsum Hills and the Mangum Gypsum Hills are developed in the alternating dolomite, gypsum/anhydrite, and shale beds of the Permian Blaine Formation. Ranging from natural bridges to extensive cave systems, the largest is the 10km of passages in Jester Cave in the Mangum Gypsum Hills. Cave passages formed in the normally paired gypsum and dolomite beds exhibit narrow (1.5–5 m wide), sinuous, canyon-like profiles. The development of broader passages, with widths from 5 m to more than 35 m, involve the shale beds. Some are bedding-plane passages with extremely low ceilings, whereas others are comfortable, walking-height passages with ceilings from 3–15 m high. The Blaine Formation, in the area of humanly mappable cave development, is from 12 m to approximately 50 m thick. The caves drain the bluffs/escarpments and normally end in karst spring resurgences. Roof collapse often modifies these resurgences into breakdown mazes. The Weatherford Gypsum Hills caves are formed in the Permian Cloud Chief Formation. The Cloud Chief gypsum is chalkier than the Blain gypsums and the resultant cave development is more segmented, ranging from natural bridges (1.5–15 m in length) to cave segments (locally referred to as “tunnels”) that are tens of meters to more than one kilometer in length. These caves exhibit very little vertical development, and none of the bedding-plane development found in the Blaine Formation.

Background. Rifapentine administered 5 days per week has potent activity in mouse models of antituberculosis chemotherapy, but efficacy and safety data are limited in humans. We compared the antimicrobial activity and safety of rifapentine vs rifampin during the first 8 weeks of pulmonary tuberculosis treatment. Methods. In total, 531 adults with sputum smear-positive pulmonary tuberculosis were randomized to rifapentine 10 mg/kg/dose or rifampin 10 mg/kg/dose, administered 5 days per week for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. Coprimary outcomes were negative sputum culture on liquid and on solid media at completion of intensive phase. Results. Negative cultures on solid media occurred in 145 of 174 participants (83.3%) in the rifampin group and 171 of 198 participants (86.4%) in the rifapentine group (difference, 3.0%; 95% confidence interval [CI]: −4.3, 10.5); negative cultures in liquid media occurred in 110 of 169 (65.1%) in the rifampin group and 133 of 196 (67.9%) in the rifapentine group (difference, 2.8%; 95% CI: −6.9, 12.4). Among 529 participants who received study therapy, 40 of 254 participants (15.7%) in the rifampin group and 40 of 275 participants (14.5%) in the rifapentine group prematurely discontinued treatment (P= .79). Conclusions. The rifapentine regimen was safe but not significantly more active than a standard rifampin regimen, by the surrogate endpoint of culture status at completion of intensive phase. Assessment of higher exposures to rifapentine for tuberculosis treatment is warranted.

Background. Although vaccination with trivalent inactivated influenza vaccine (TIV) is recommended for all pregnant women, no vaccine effectiveness (VE) studies of TIV in pregnant women have assessed laboratory-confirmed influenza outcomes. Methods. We conducted a case-control study over 2 influenza seasons (2010–2011 and 2011–2012) among Kaiser Permanente health plan members in 2 metropolitan areas in California and Oregon. We compared the proportion vaccinated among 100 influenza cases (confirmed by reverse transcription polymerase chain reaction) with the proportions vaccinated among 192 controls with acute respiratory illness (ARI) who tested negative for influenza and 200 controls without ARI (matched by season, site, and trimester). Results. Among influenza cases, 42% were vaccinated during the study season compared to 58% and 63% vaccinated among influenza-negative controls and matched ARI-negative controls, respectively. The adjusted VE of the current season vaccine against influenza A and B was 44% (95% confidence interval [CI], 5%–67%) using the influenza-negative controls and 53% (95% CI, 24%–72%) using the ARI-negative controls. Receipt of the prior season's vaccine, however, had an effect similar to receipt of the current season's vaccine. As such, vaccination in either or both seasons had statistically similar adjusted VE using influenza-negative controls (VE point estimates range = 51%–76%) and ARI-negative controls (48%–76%). Conclusions. Influenza vaccination reduced the risk of ARI associated with laboratory-confirmed influenza among pregnant women by about one-half, similar to VE observed among all adults during these seasons.

Abstract Rationale Rifapentine has potent activity in mouse models of tuberculosis chemotherapy but its optimal dose and exposure in humans are unknown. Objectives We conducted a randomized, partially blinded dose-ranging study to determine tolerability, safety, and antimicrobial activity of daily rifapentine for pulmonary tuberculosis treatment. Methods Adults with sputum smear-positive pulmonary tuberculosis were assigned rifapentine 10, 15, or 20 mg/kg or rifampin 10 mg/kg daily for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. The primary tolerability end point was treatment discontinuation. The primary efficacy end point was negative sputum cultures at completion of intensive phase. Measurements and Main Results A total of 334 participants were enrolled. At completion of intensive phase, cultures on solid media were negative in 81.3% of participants in the rifampin group versus 92.5% (P = 0.097), 89.4% (P = 0.29), and 94.7% (P = 0.049) in the rifapentine 10, 15, and 20 mg/kg groups. Liquid cultures were negative in 56.3% (rifampin group) versus 74.6% (P = 0.042), 69.7% (P = 0.16), and 82.5% (P = 0.004), respectively. Compared with the rifampin group, the proportion negative at the end of intensive phase was higher among rifapentine recipients who had high rifapentine areas under the concentration–time curve. Percentages of participants discontinuing assigned treatment for reasons other than microbiologic ineligibility were similar across groups (rifampin, 8.2%; rifapentine 10, 15, or 20 mg/kg, 3.4, 2.5, and 7.4%, respectively). Conclusions Daily rifapentine was well-tolerated and safe. High rifapentine exposures were associated with high levels of sputum sterilization at completion of intensive phase. Further studies are warranted to determine if regimens that deliver high rifapentine exposures can shorten treatment duration to less than 6 months. Clinical trial registered with www.clinicaltrials.gov (NCT 00694629).

Abstract Rationale Moxifloxacin has potent activity against Mycobacterium tuberculosis in vitro and in a mouse model of antituberculosis (TB) chemotherapy, but data regarding its activity in humans are limited. Objectives Our objective was to compare the antimicrobial activity and safety of moxifloxacin versus isoniazid during the first 8 weeks of combination therapy for pulmonary TB. Methods Adults with sputum smear–positive pulmonary TB were randomly assigned to receive either moxifloxacin 400 mg plus isoniazid placebo, or isoniazid 300 mg plus moxifloxacin placebo, administered 5 days/week for 8 weeks, in addition to rifampin, pyrazinamide, and ethambutol. All doses were directly observed. Sputum was collected for culture every 2 weeks. The primary outcome was negative sputum culture at completion of 8 weeks of treatment. Measurements and Main Results Of 433 participants enrolled, 328 were eligible for the primary efficacy analysis. Of these, 35 (11%) were HIV positive, 248 (76%) had cavitation on baseline chest radiograph, and 213 (65%) were enrolled at African sites. Negative cultures at Week 8 were observed in 90/164 (54.9%) participants in the isoniazid arm, and 99/164 (60.4%) in the moxifloxacin arm (P = 0.37). In multivariate analysis, cavitation and enrollment at an African site were associated with lower likelihood of Week-8 culture negativity. The proportion of participants who discontinued assigned treatment was 31/214 (14.5%) for the moxifloxacin group versus 22/205 (10.7%) for the isoniazid group (RR, 1.35; 95% CI, 0.81, 2.25). Conclusions Substitution of moxifloxacin for isoniazid resulted in a small but statistically nonsignificant increase in Week-8 culture negativity. Clinical trial registered with www.clinicaltrials.gov (NCT00144417).

Objectives. We describe the prevalence of risk behaviors at baseline among men who have sex with men (MSM) who were enrolled in a randomized behavioral intervention trial conducted in 6 US cities. Methods. Data analyses involved MSM who were negative for HIV antibodies and who reported having engaged in anal sex with 1 or more partners in the previous year. Results. Among 4295 men, 48.0% and 54.9%, respectively, reported unprotected receptive and insertive anal sex in the previous 6 months. Unprotected sex was significantly more likely with 1 primary partner or multiple partners than with 1 nonprimary partner. Drug and alcohol use were significantly associated with unprotected anal sex. Conclusions. Our findings support the continued need for effective intervention strategies for MSM that address relationship status, serostatus of partners, and drug and alcohol use.

Tuberculosis Trials Consortium Study 28, was a double blind, randomized, placebo-controlled, phase 2 clinical trial examining smear positive pulmonary Mycobacterium tuberculosis. Over the course of intensive phase therapy, patients from African sites had substantially delayed and lower rates of culture conversion to negative in liquid media compared to non-African patients. We explored potential explanations of this finding. In TBTC Study 28, protocol-correct patients (n = 328) provided spot sputum specimens for M. tuberculosis culture in liquid media, at baseline and weeks 2, 4, 6 and 8 of study therapy. We compared sputum culture conversion for African and non-African patients stratified by four baseline measures of disease severity: AFB smear quantification, extent of disease on chest radiograph, cavity size and the number of days to detection of M. tuberculosis in liquid media using the Kaplan-Meier product-limit method. We evaluated specimen processing and culture procedures used at 29 study laboratories serving 27 sites. African TB patients had more extensive disease at enrollment than non-African patients. However, African patients with the least disease by the 4 measures of disease severity had conversion rates on liquid media that were substantially lower than conversion rates in non-African patients with the greatest extent of disease. HIV infection, smoking and diabetes did not explain delayed conversion in Africa. Some inter-site variation in laboratory processing and culture procedures within accepted practice for clinical diagnostic laboratories was found. Compared with patients from non-African sites, African patients being treated for TB had delayed sputum culture conversion and lower sputum conversion rates in liquid media that were not explained by baseline severity of disease, HIV status, age, smoking, diabetes or race. Further investigation is warranted into whether modest variation in laboratory processes substantially influences the efficacy outcomes of phase 2 TB treatment trials or if other factors (e.g., nutrition, host response) are involved. ClinicalTrials.gov NCT00144417.