Objective To determine if initial lower-volume trophic enteral feeding would increase ventilator-free days and decrease gastrointestinal intolerances compared with initial full enteral feeding.

Design, Setting, and Participants The EDEN study, a randomized, open-label, multicenter trial conducted from January 2, 2008, through April 12, 2011. Participants were 1000 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network.

Interventions Participants were randomized to receive either trophic or full enteral feeding for the first 6 days. After day 6, the care of all patients who were still receiving mechanical ventilation was managed according to the full feeding protocol.

Main Outcome Measures Ventilator-free days to study day 28.

Results Baseline characteristics were similar between the trophic-feeding (n = 508) and full-feeding (n = 492) groups. The full-feeding group received more enteral calories for the first 6 days, about 1300 kcal/d compared with 400 kcal/d (P < .001). Initial trophic feeding did not increase the number of ventilator-free days (14.9 [95% CI, 13.9 to 15.8] vs 15.0 [95% CI, 14.1 to 15.9]; difference, –0.1 [95% CI, –1.4 to 1.2]; P = .89) or reduce 60-day mortality (23.2% [95% CI, 19.6% to 26.9%] vs 22.2% [95% CI, 18.5% to 25.8%]; difference, 1.0% [95% CI, –4.1% to 6.3%]; P = .77) compared with full feeding. There were no differences in infectious complications between the groups. Despite receiving more prokinetic agents, the full-feeding group experienced more vomiting (2.2% vs 1.7% of patient feeding days; P = .05), elevated gastric residual volumes (4.9% vs 2.2% of feeding days; P < .001), and constipation (3.1% vs 2.1% of feeding days; P = .003). Mean plasma glucose values and average hourly insulin administration were both higher in the full-feeding group over the first 6 days.

Conclusion In patients with acute lung injury, compared with full enteral feeding, a strategy of initial trophic enteral feeding for up to 6 days did not improve ventilator-free days, 60-day mortality, or infectious complications but was associated with less gastrointestinal intolerance.

Trial Registration clinicaltrials.gov Identifiers: NCT00609180 and NCT00883948

Objective To determine the prevalence of oral HPV infection in the United States.

Design, Setting, and Participants A cross-sectional study was conducted as part of the National Health and Nutrition Examination Survey (NHANES) 2009-2010, a statistically representative sample of the civilian noninstitutionalized US population. Men and women aged 14 to 69 years examined at mobile examination centers were eligible. Participants (N = 5579) provided a 30-second oral rinse and gargle with mouthwash. For detection of HPV types, DNA purified from oral exfoliated cells was evaluated by polymerase chain reaction and type-specific hybridization. Demographic and behavioral data were obtained by standardized interview. Statistical analyses used NHANES sample weights to provide weighted prevalence estimates for the US population.

Main Outcome Measures Prevalence of oral HPV infection.

Results The prevalence of oral HPV infection among men and women aged 14 to 69 years was 6.9% (95% CI, 5.7%-8.3%) and of HPV type 16 was 1.0% (95% CI, 0.7%-1.3%). Oral HPV infection followed a bimodal pattern with respect to age, with peak prevalence among individuals aged 30 to 34 years (7.3%; 95% CI, 4.6%-11.4%) and 60 to 64 years (11.4%; 95% CI, 8.5%-15.1%). Men had a significantly higher prevalence than women for any oral HPV infection (10.1% [95% CI, 8.3%-12.3%] vs 3.6% [95% CI, 2.6%-5.0%], P < .001; unadjusted prevalence ratio [PR], 2.80 [95% CI, 2.02-3.88]). Infection was less common among those without vs those with a history of any type of sexual contact (0.9% [95% CI, 0.4%-1.8%] vs 7.5% [95% CI, 6.1%-9.1%], P < .001; PR, 8.69 [95% CI, 3.91-19.31]) and increased with number of sexual partners (P < .001 for trend) and cigarettes smoked per day (P < .001 for trend). Associations with age, sex, number of sexual partners, and current number of cigarettes smoked per day were independently associated with oral HPV infection in multivariable models.

Conclusion Among men and women aged 14 to 69 years in the United States, the overall prevalence of oral HPV infection was 6.9%, and the prevalence was higher among men than among women.

Objective To determine the immunogenicity and reactogenicity of a multicomponent MenB vaccine (4CMenB) and routine infant vaccines when given either concomitantly or separately.

Design, Setting, and Participants Phase 2b, multicenter, open-label, parallel-group, randomized controlled study of 1885 infants enrolled at age 2 months from August 2008 to July 2010 in Europe.

Intervention Participants were randomized 2:2:1:1 to receive (1) 4CMenB at 2, 4, and 6 months with routine vaccines (7-valent pneumococcal and combined diphtheria, tetanus, acellular pertussis, inactivated polio, hepatitis B, Haemophilus influenzae type b vaccines); (2) 4CMenB at 2, 4, and 6 months and routine vaccines at 3, 5, and 7 months; (3) 4CMenB with routine vaccines at 2, 3, and 4 months; or (4) routine vaccines alone at 2, 3, and 4 months.

Main Outcome Measures Percentage of participants with human complement serum bactericidal activity (hSBA) titer of 1:5 or greater against 3 MenB strains specific for vaccine antigens (NZ98/254, 44/76-SL, and 5/99).

Results After three 4CMenB vaccinations, 99% or more of infants developed hSBA titers of 1:5 or greater against strains 44/76-SL and 5/99. For NZ98/254, this proportion was 79% (95% CI, 75.2%-82.4%) for vaccination at 2, 4, and 6 months with routine vaccines, 86.1% (95% CI, 82.9%-89.0%) for vaccination at 2, 4, and 6 months without routine vaccines, and 81.7% (95% CI, 76.6%-86.2%) for vaccination at 2, 3, and 4 months with routine vaccines. Responses to routine vaccines given with 4CMenB were noninferior to routine vaccines alone for all antigens, except for the responses to pertactin and serotype 6B pneumococcal polysaccharide. Fever was seen following 26% (158/602) to 41% (247/607) of 4CMenB doses when administered alone, compared with 23% (69/304) to 36% (109/306) after routine vaccines given alone and 51% (306/605) to 61% (380/624) after 4CMenB and routine vaccines administered together.

Conclusion A 4CMenB vaccine is immunogenic against reference strains when administered with routine vaccines at 2, 4, and 6 or at 2, 3, and 4 months of age, producing minimal interference with the response to routine infant vaccinations.

Trial Registration clinicaltrials.gov Identifier: NCT00721396

Objective To determine whether cefpodoxime is noninferior to ciprofloxacin for treatment of acute cystitis.

Design, Setting, and Patients Randomized, double-blind trial of 300 women aged 18 to 55 years with acute uncomplicated cystitis comparing ciprofloxacin (n = 150) with cefpodoxime (n = 150); patients were from a student health center in Seattle, Washington, and a referral center in Miami, Florida. The study was conducted from 2005 to 2009 and outcomes were assessed at 5 to 9 days and 28 to 30 days after completion of therapy. Intent-to-treat and per-protocol analyses were performed; 15 women in the ciprofloxacin group and 17 women in the cefpodoxime group were lost to follow-up.

Interventions Patients were given 250 mg of ciprofloxacin orally twice daily for 3 days or 100 mg of cefpodoxime proxetil orally twice daily for 3 days.

Main Outcome Measures Overall clinical cure (defined as not requiring antimicrobial treatment during follow-up) at the 30-day follow-up visit. Secondary outcomes were clinical and microbiological cure at the first follow-up visit and vaginal Escherichia coli colonization at each follow-up visit. The hypothesis that cefpodoxime would be noninferior to ciprofloxacin by a 10% margin (ie, for the difference in the primary outcome for ciprofloxacin minus cefpodoxime, the upper limit of the confidence interval would be <10%) was formulated prior to data collection.

Results The overall clinical cure rate at the 30-day visit with the intent-to-treat approach in which patients lost to follow-up were considered as having clinical cure was 93% (139/150) for ciprofloxacin compared with 82% (123/150) for cefpodoxime (difference of 11%; 95% CI, 3%-18%); and for the intent-to-treat approach in which patients lost to follow-up were considered as having not responded to treatment, the clinical cure rate was 83% (124/150) for ciprofloxacin compared with 71% (106/150) for cefpodoxime (difference of 12%; 95% CI, 3%-21%). The microbiological cure rate was 96% (123/128) for ciprofloxacin compared with 81% (104/129) for cefpodoxime (difference of 15%; 95% CI, 8%-23%). At first follow-up, 16% of women in the ciprofloxacin group compared with 40% of women in the cefpodoxime group had vaginal E coli colonization.

Conclusions Among women with uncomplicated cystitis, a 3-day regimen of cefpodoxime compared with ciprofloxacin did not meet criteria for noninferiority for achieving clinical cure. These findings, along with concerns about possible adverse ecological effects associated with other broad-spectrum β-lactams, do not support the use of cefpodoxime as a first-line fluoroquinolone-sparing antimicrobial for acute uncomplicated cystitis.

Trial Registration clinicaltrials.gov Identifier: NCT00194532

Objective To assess the association between age at diagnosis and breast cancer outcome in postmenopausal women with hormone receptor–positive breast cancer.

Design, Setting, and Patients Study analysis of 9766 patients enrolled in the TEAM (Tamoxifen Exemestane Adjuvant Multinational) randomized clinical trial between January 2001 and January 2006. Age at diagnosis was categorized as younger than 65 years (n=5349), 65 to 74 years (n=3060), and 75 years or older (n=1357).

Main Outcome Measures Primary end point was disease-specific mortality; secondary end points were other-cause mortality and breast cancer relapse.

Results During median follow-up of approximately 5.1 years, there were a total of 1043 deaths. Disease-specific mortality, as a proportion of all-cause mortality, decreased with categorical age group (78% [<65 years], 56% [65-74 years], and 36% [≥75 years]; P < .001). In multivariable analyses, compared with patients younger than 65 years, disease-specific mortality increased with age for patients aged 65 to 74 years (hazard ratio [HR], 1.25; 95% CI, 1.01-1.54); and patients aged 75 years or older (HR, 1.63; 95% CI, 1.23-2.16) (P < .001). Similarly, breast cancer relapse increased with age for patients aged 65-74 years (HR, 1.07; 95% CI, 0.91-1.25 and patients aged 75 years or older (HR, 1.29; 95% CI, 1.05-1.60) (P = .06). Other-cause mortality increased with age in patients aged 65 to 74 years (HR, 2.66; 95% CI, 1.96-3.63) and patients aged 75 years or older (HR, 7.30; 95% CI, 5.29-10.07) (P < .001).

Conclusion Among postmenopausal women with hormone receptor–positive breast cancer, increasing age was associated with a higher disease-specific mortality.

Objective To examine the risk of intussusception following pentavalent rotavirus vaccine (RV5) in US infants.

Design, Setting, and Patients This cohort study included infants 4 to 34 weeks of age, enrolled in the Vaccine Safety Datalink (VSD) who received RV5 from May 2006-February 2010. We calculated standardized incidence ratios (SIRs), relative risks (RRs), and 95% confidence intervals for the association between intussusception and RV5 by comparing the rates of intussusception in infants who had received RV5 with the rates of intussusception in infants who received other recommended vaccines without concomitant RV5 during the concurrent period and with the expected number of intussusception visits based on background rates assessed prior to US licensure of the RV5 (2001-2005).

Main Outcome Measure Intussusception occurring in the 1- to 7-day and 1- to 30-day risk windows following RV5 vaccination.

Results During the study period, 786 725 total RV5 doses, which included 309 844 first doses, were administered. We did not observe a statistically significant increased risk of intussusception with RV5 for either comparison group following any dose in either the 1- to 7-day or 1- to 30-day risk window. For the 1- to 30-day window following all RV5 doses, we observed 21 cases of intussusception compared with 20.9 expected cases (SIR, 1.01; 95% CI, 0.62-1.54); following dose 1, we observed 7 cases compared with 5.7 expected cases (SIR, 1.23; 95% CI, 0.5-2.54). For the 1- to 7-day window following all RV5 doses, we observed 4 cases compared with 4.3 expected cases (SIR, 0.92; 95% CI, 0.25-2.36); for dose 1, we observed 1 case compared with 0.8 expected case (SIR, 1.21; 95% CI, 0.03-6.75). The upper 95% CI limit of the SIR (6.75) from the historical comparison translates to an upper limit for the attributable risk of 1 intussusception case per 65 287 RV5 dose-1 recipients.

Conclusion Among US infants aged 4 to 34 weeks who received RV5, the risk of intussusception was not increased compared with infants who did not receive the rotavirus vaccine.

Objectives To determine the accuracy of clinical symptoms and signs to diagnose infection in chronic wounds and to determine whether there is a preferred noninvasive method for culturing chronic wounds.

Data Sources We searched multiple databases from inception through November 18, 2011, to identify studies focusing on diagnosis of infection in a chronic wound.

Study Selection Original studies were selected if they had extractable data describing historical features, symptoms, signs, or laboratory markers or were radiologic studies compared with a reference standard for diagnosing infection in patients with chronic wounds. Of 341 studies initially retrieved, 15 form the basis of this review. These studies include 985 participants with a total of 1056 chronic wounds. The summary prevalence of wound infection was 53%.

Data Extraction Three authors independently assigned each study a quality grade, using previously published criteria. One author abstracted operating characteristic data.

Data Synthesis An increase in the level of pain (likelihood ratio range, 11-20) made infection more likely, but its absence (negative likelihood ratio range, 0.64-0.88) did not rule out infection. Other items in the history and physical examination, in isolation or in combination, appeared to have limited utility when infection was diagnosed in chronic wounds. Routine laboratory studies had uncertain value in predicting infection of a chronic wound.

Conclusions The presence of increasing pain may make infection of a chronic wound more likely. Further evidence is required to determine which, if any, type of quantitative swab culture is most diagnostic.