Global Cross-Sectional Study Evaluating the Attitudes towards a COVID-19 Vaccine in Pregnant and Postpartum Women.

Pregnant and postpartum women have an increased risk of severe complications from COVID-19. Many clinical guidelines recommend vaccination of these populations, and it is therefore critical to understand their attitudes toward COVID-19 vaccines. We conducted a cross-sectional online survey in November 2020 of currently pregnant and ≤1-year postpartum women in Brazil, India, the United Kingdom (UK), and the United States (US) that assessed their openness to COVID-19 vaccines and reasons for vaccine hesitancy. Logistic regression analyses were conducted to evaluate openness to receiving a vaccine. Out of 2010 respondents, 67% were open to receiving a COVID-19 vaccine themselves. Among pregnant and postpartum participants, 72% and 57% were willing to receive a vaccine, respectively. Vaccine openness varied significantly by country: India (87%), Brazil (71%), UK (59%), and US (52%). Across all participants, among the 33% who were unsure/not open to receiving a COVID-19 vaccine, the most common reason cited was safety/side effect concerns (51%). Participants were similarly open to their children/other family members receiving a COVID-19 vaccine. Presence of a comorbidity, a positive COVID-19 test result, and pregnancy were all significantly associated with positive vaccine acceptance. Targeted outreach to address pregnant and postpartum women's concerns about the COVID-19 vaccine is needed.

Interest in Home Birth During the COVID-19 Pandemic: Analysis of Google Trends Data.

INTRODUCTION: Nearly all (94%-99%) pregnant persons in developed countries search for pregnancy-related information online. The advent of the novel coronavirus disease 2019 (COVID-19) and the associated restrictions in hospital policies may have pushed pregnant persons in the United States to consider giving birth at home to achieve their desired birth experience. METHODS: Google Trends is an open, rich source of real-time, anonymized, relative data on disease patterns and population behavior that provides data in the form of search volume index (SVI): the search volume for a queried term relative to overall search volume for a given time frame and geographic location. The SVI is normalized to a scale of 0 to 100. After the World Health Organization declared COVID-19 a pandemic on March 11, 2020, Google Trends was queried on February 21, 2021, for the search term home birth with location set to the United States and the time frame March 11, 2019 to February 21, 2021. RESULTS: The median SVI for home birth during nominally pre-COVID-19 baseline (weeks of March 17, 2019 to March 8, 2020) was relatively constant at 43 (range, 25-56) and increased sharply to 77 during the week of March 15, to 86 during the week of March 22, and peaked at 100 during the week of March 29, 2020. The SVI declined substantially in the following weeks but remained significantly elevated compared with baseline levels. During the approximate 2-year period of query, the states with the highest SVI values (≥80) were Arkansas, Washington, Montana, and Georgia. DISCUSSION: Interest in home birth spiked in the United States immediately after COVID-19 was declared a pandemic and remained significantly elevated thereafter. These results have implications for caregivers and health systems to ensure safe pregnancies and childbirths through the resolution of the ongoing pandemic.

Phase II open label pilot trial of aprepitant and palonosetron for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic FOLFOX chemotherapy for the treatment of colorectal cancer.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) causes significant morbidity among colorectal cancer patients, receiving fluorouracil, oxaliplatin, and leucovorin (FOLFOX) chemotherapy even with standard antiemetic prophylaxis. The purpose of this study is to determine if the addition of aprepitant to standard antiemetic therapy improves CINV in these patients. METHODS: Patients receiving FOLFOX for colorectal cancer were given antiemetic prophylaxis with aprepitant 125 mg orally on day 1 and 80 mg on days 2 and 3. Palonosetron 0.25 mg was given IV push on day 1 only. Dexamethasone 12 mg was administered orally on day 1 and 8 mg each morning on days 2 through 4. Assessments including emetic events, rescue doses, nutritional intake, and appetite were recorded in a patient diary which was returned to study personnel in the following cycle. RESULTS: Of the 53 patients screened, 50 were evaluable and had a complete dataset for cycle 1. For the first cycle, 74% of patients achieved a complete response (CR), 22% achieved a major response and 4% experienced treatment failure. The percentage of patients achieving a CR remained high throughout each cycle at 83, 83, and 86% for cycles 2, 3, and 4, respectively. Appetite and nutritional status remained largely unchanged throughout treatment. Adverse events occurring in more than 10% of patients included diarrhea (13.6%), fatigue (12.6%), and neutropenia (11%). CONCLUSIONS: Aprepitant added to standard antiemetic therapy appears to be an effective and safe regimen for prevention of CINV in patients receiving FOLFOX.

Efficacy Projection of Obiltoxaximab for Treatment of Inhalational Anthrax across a Range of Disease Severity.

Inhalational anthrax has high mortality even with antibiotic treatment, and antitoxins are now recommended as an adjunct to standard antimicrobial regimens. The efficacy of obiltoxaximab, a monoclonal antibody against anthrax protective antigen (PA), was examined in multiple studies conducted in two animal models of inhalational anthrax. A single intravenous bolus of 1 to 32 mg/kg of body weight obiltoxaximab or placebo was administered to New Zealand White rabbits (two studies) and cynomolgus macaques (4 studies) at disease onset (significant body temperature increase or detection of serum PA) following lethal challenge with aerosolized Bacillus anthracis spores. The primary endpoint was survival. The relationship between efficacy and disease severity, defined by pretreatment bacteremia and toxemia levels, was explored. In rabbits, single doses of 1 to 16 mg/kg obiltoxaximab led to 17 to 93% survival. In two studies, survival following 16 mg/kg obiltoxaximab was 93% and 62% compared to 0% and 0% for placebo (P = 0.0010 and P = 0.0013, respectively). Across four macaque studies, survival was 6.3% to 78.6% following 4 to 32 mg/kg obiltoxaximab. In two macaque studies, 16 mg/kg obiltoxaximab reduced toxemia and led to survival rates of 31%, 35%, and 47% versus 0%, 0%, and 6.3% with placebo (P = 0.0085, P = 0.0053, P = 0.0068). Pretreatment bacteremia and toxemia levels inversely correlated with survival. Overall, obiltoxaximab monotherapy neutralized PA and increased survival across the range of disease severity, indicating clinical benefit of toxin neutralization with obiltoxaximab in both early and late stages of inhalational anthrax.

Mechanism for Broadband White-Light Emission from Two-Dimensional (110) Hybrid Perovskites.

The recently discovered phenomenon of broadband white-light emission at room temperature in the (110) two-dimensional organic-inorganic perovskite (N-MEDA)[PbBr4] (N-MEDA = N(1)-methylethane-1,2-diammonium) is promising for applications in solid-state lighting. However, the spectral broadening mechanism and, in particular, the processes and dynamics associated with the emissive species are still unclear. Herein, we apply a suite of ultrafast spectroscopic probes to measure the primary events directly following photoexcitation, which allows us to resolve the evolution of light-induced emissive states associated with white-light emission at femtosecond resolution. Terahertz spectra show fast free carrier trapping and transient absorption spectra show the formation of self-trapped excitons on femtosecond time-scales. Emission-wavelength-dependent dynamics of the self-trapped exciton luminescence are observed, indicative of an energy distribution of photogenerated emissive states in the perovskite. Our results are consistent with photogenerated carriers self-trapped in a deformable lattice due to strong electron-phonon coupling, where permanent lattice defects and correlated self-trapped states lend further inhomogeneity to the excited-state potential energy surface.

THz-Pulse-Induced Selective Catalytic CO Oxidation on Ru.

We demonstrate the use of intense, quasi-half-cycle THz pulses, with an associated electric field component comparable to intramolecular electric fields, to direct the reaction coordinate of a chemical reaction by stimulating the nuclear motions of the reactants. Using a strong electric field from a THz pulse generated via coherent transition radiation from an ultrashort electron bunch, we present evidence that CO oxidation on Ru(0001) is selectively induced, while not promoting the thermally induced CO desorption process. The reaction is initiated by the motion of the O atoms on the surface driven by the electric field component of the THz pulse, rather than thermal heating of the surface.

Intense terahertz pulses from SLAC electron beams using coherent transition radiation.

SLAC has two electron accelerators, the Linac Coherent Light Source (LCLS) and the Facility for Advanced Accelerator Experimental Tests (FACET), providing high-charge, high-peak-current, femtosecond electron bunches. These characteristics are ideal for generating intense broadband terahertz (THz) pulses via coherent transition radiation. For LCLS and FACET respectively, the THz pulse duration is typically 20 and 80 fs RMS and can be tuned via the electron bunch duration; emission spectra span 3-30 THz and 0.5 THz-5 THz; and the energy in a quasi-half-cycle THz pulse is 0.2 and 0.6 mJ. The peak electric field at a THz focus has reached 4.4 GV/m (0.44 V/Å) at LCLS. This paper presents measurements of the terahertz pulses and preliminary observations of nonlinear materials response.

Comparison of the bacterial etiology of early-onset and late-onset ventilator-associated pneumonia in subjects enrolled in 2 large clinical studies.

BACKGROUND: Ventilator-associated pneumonia (VAP) is classified as early-onset or late-onset, in part, to identify subjects at risk for infection with resistant pathogens. We assessed differences in the bacterial etiology of early-onset versus late-onset VAP. METHODS: Subjects enrolled in 2004-2006 in 2 clinical studies of doripenem versus imipenem or piperacillin/tazobactam, with a diagnosis of VAP (n = 500) were included in the analysis. Subjects were classified by ventilator status: early-onset VAP (< 5 d of ventilation) or late-onset VAP (≥ 5 d of ventilation). Baseline demographics and bacterial etiology were analyzed by VAP status. RESULTS: Late-onset VAP subjects had higher Acute Physiology and Chronic Health Evaluation (APACHE II) scores (mean 16.6 versus 15.5, P = .008). There were no significant differences in Clinical Pulmonary Infection Score, sex, age, or presence of bacteremia between the groups. A total of 496 subjects had a baseline pathogen, and 50% of subjects in each group had ≥ 2 pathogens. With the exception of Staphylococcus aureus, which was common in early-onset VAP, the pathogens (including potentially multidrug-resistant (MDR) pathogens) isolated from early-onset versus late-onset VAP were not significantly different between groups. Acinetobacter baumannii or Pseudomonas aeruginosa with decreased susceptibility to any study drug was observed in early-onset and late-onset VAP subjects. CONCLUSIONS: There were no significant differences in the prevalence of potential MDR pathogens associated with early-onset or late-onset VAP, even in subjects with prior antibiotics. Empiric therapy for early-onset VAP should also include agents likely to be effective for potential MDR pathogens. Further prospective studies should evaluate microbiology trends in subjects with VAP.

Warfarin prophylaxis in patients after total knee or hip arthroplasty--international normalized ratio patterns and venous thromboembolism.

OBJECTIVE: Warfarin is frequently used for the prevention of venous thromboembolism (VTE) after total hip or knee arthroplasty (THA/TKA). The current study was conducted to determine the association between international normalized ratio (INR) levels and VTE outcomes. METHODS: Patients who received warfarin following THA/TKA were followed for up to 90 days using an electronic health record database. INR measurements were categorized based on American College of Chest Physicians (ACCP) guidelines. Cox proportional hazards models were used to compare the risk of VTE between patients with INR levels below and within the ACCP-recommended range in patients with ≥2 available INR level measurements. RESULTS: On or after Day 5, 33.3% and 28.6% of INR levels fell within the ACCP-recommended range for THA and TKA, respectively. VTE was diagnosed in 3% of each cohort. INR levels varied over time and were frequently below the ACCP-recommended range. Below-range INR levels were associated with greater risk of VTE in both THA (hazard ratio [HR]: 5.29; 95% CI: 2.64-10.61) and TKA (HR: 4.64; 95% CI: 2.59-8.29). CONCLUSIONS: In the current study, the majority of patients had INR levels below the ACCP-recommended range of 2.0-3.0 during warfarin exposure following orthopedic surgery. INR levels below 2.0 were associated with a four- to five-fold increase in the risk of VTE.

A clinical pathway for community-acquired pneumonia: an observational cohort study.

BACKGROUND: Six hospitals instituted a voluntary, system-wide, pathway for community acquired pneumonia (CAP). We proposed this study to determine the impact of pathway antibiotics on patient survival, hospital length of stay (LOS), and total hospital cost. METHODS: Data were collected for adults from six U.S. hospitals with a principal CAP discharge diagnosis code, a chest infiltrate, and medical notes indicative of CAP from 2005-2007. Pathway and non-pathway cohorts were assigned according to antibiotics received within 48 hours of admission. Pathway antibiotics included levofloxacin 750 mg monotherapy or ceftriaxone 1000 mg plus azithromycin 500 mg daily. Multivariable regression models assessed 90-day mortality, hospital LOS, total hospital cost, and total pharmacy cost. RESULTS: Overall, 792 patients met study criteria. Of these, 505 (64%) received pathway antibiotics and 287 (36%) received non-pathway antibiotics. Adjusted means and p-values were derived from Least Squares regression models that included Pneumonia Severity Index risk class, patient age, heart failure, chronic obstructive pulmonary disease, and admitting hospital as covariates. After adjustment, patients who received pathway antibiotics experienced lower adjusted 90-day mortality (p = 0.02), shorter mean hospital LOS (3.9 vs. 5.0 days, p < 0.01), lower mean hospital costs ($2,485 vs. $3,281, p = 0.02), and similar mean pharmacy costs ($356 vs. $442, p = 0.11). CONCLUSIONS: Pathway antibiotics were associated with improved patient survival, hospital LOS, and total hospital cost for patients admitted to the hospital with CAP.

Comparative antibiotic failure rates in the treatment of community-acquired pneumonia: Results from a claims analysis.

INTRODUCTION: Antibiotic treatment failure contributes to the economic and humanistic burdens of community-acquired pneumonia (CAP) by increasing morbidity, mortality, and healthcare costs. This study compared treatment failure rates of levofloxacin with those of other antibiotics in a large US sample. METHODS: Medical and pharmacy claims in the nationally representative SDI database were used to identify adults with a new outpatient diagnosis of CAP receiving a study antibiotic (levofloxacin, amoxicillin/clavulanate, azithromycin, moxifloxacin) between September 1, 2005 and March 31, 2008. Treatment failure was defined as ≥1 of the following events ≤30 days after index date: a refill for the index antibiotic after completed days of therapy, a different antibiotic dispensed >1 day after the index prescription, or hospitalization with a pneumonia diagnosis or emergency department visit >3 days postindex. Cohorts were propensity score matched for demographic and clinical characteristics. Treatment failure rates were compared between pairs of cohorts for the full sample and for high-risk patients (age ≥65 and/or on Medicaid). RESULTS: Among the 3994 study patients, the numbers of dispensed index prescriptions were 268 for amoxicillin/clavulanate, 1609 for azithromycin, 1460 for levofloxacin, and 657 for moxifloxacin. Unadjusted treatment failure rates for the sample were 20.8% for levofloxacin, 23.9% for amoxicillin/clavulanate, 23.9% for azithromycin, and 19.9% for moxifloxacin. For high-risk patients, unadjusted treatment failure rates were 19.1% for levofloxacin, 26.1% for amoxicillin/clavulanate, 26.3% for azithromycin, and 24.3% for moxifloxacin. Propensity score-matched treatment failure rates were significantly lower with levofloxacin than azithromycin (19.8% vs. 24.5%, odds ratio [OR] comparator vs. levofloxacin 1.38; 95% CI: 1.14, 1.67), a difference amplified in high-risk patients (19.0% vs. 26.4%, OR 1.61; 95% CI: 1.22, 2.13). No significant differences were observed for other paired comparisons. CONCLUSION: In a large US sample, treatment failure in CAP appeared to be less likely with quinolones (such as levofloxacin) than azithromycin, an effect particularly marked in high-risk patients (age ≥65 and/or on Medicaid).

Safety and efficacy of levofloxacin 750 mg for 2 weeks or 3 weeks compared with levofloxacin 500 mg for 4 weeks in treating chronic bacterial prostatitis.

OBJECTIVE: To compare the safety and efficacy of levofloxacin 750 mg QD for 2 weeks or levofloxacin 750 mg QD for 3 weeks to levofloxacin 500 mg QD for 4 weeks in treating chronic bacterial prostatitis (CBP). RESEARCH DESIGN AND METHODS: This was a randomized, multicenter, double-blind, noninferiority study. The primary efficacy end point was investigator assessment of clinical success in the modified intent-to-treat (mITT) population at post-therapy. National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) scores were utilized to evaluate subject-reported responses post-therapy. RESULTS: A total of 241 subjects were enrolled. At post-therapy (test of cure [TOC]), clinical success rates for levofloxacin-treated subjects (750 mg QD for 3 weeks [64.9%, 48/74]) were noninferior to 500 mg QD for 4 weeks (69.3%, 52/75: 95% CI, -19.5%, 10.6%). Success rates with levofloxacin 750 mg QD for 2 weeks (63.0%, 46/73) were not noninferior to therapy with levofloxacin 500 mg QD for 4 weeks (95% CI, -21.5%, 8.9%) at TOC. At 3 and 6 months post-therapy, clinical success rates were clinically higher for the 500-mg, 4-week treatment group, and statistical analysis demonstrated both groups were not noninferior to standard therapy with levofloxacin 500 mg (95% CI, -32.5%, -0.6% for both 750-mg groups at 6 months). NIH-CPSI scores showed similar trends. Overall, adverse event (AE) rates were similar for the three treatment groups; however, discontinuation of therapy due to AEs was higher with the 750-mg dose (p = 0.02, and p = 0.13 for 750 mg, 2 weeks and 750 mg, 3 weeks versus 500 mg for 4 weeks, respectively). The main limitation of this study was that no bacterial cultures were required. CONCLUSIONS: Higher doses for shorter durations were determined to be no worse than standard therapy with levofloxacin 500 mg for a longer duration at the TOC visit. However, at the 6-month follow-up visit, the levofloxacin 750-mg dose administered for either 2 weeks or 3 weeks was inferior to the standard therapy, suggesting that a longer duration of treatment may help extend the relapse-free interval in patients with CBP. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, nct00402688.

Hospital visits and costs following outpatient treatment of CAP with levofloxacin or moxifloxacin.

BACKGROUND: Hospital admissions (inpatient and emergency room) are a major source of medical costs for community-acquired pneumonia (CAP) initially treated in the outpatient setting. Current CAP treatment guidelines do not differentiate between outpatient treatment with levofloxacin and moxifloxacin. OBJECTIVE: Compare health care resource use and medical costs to payers for CAP outpatients initiating treatment with levofloxacin or moxifloxacin. RESEARCH DESIGN AND METHODS: CAP episodes were identified in the PharMetrics database between 2Q04 and 2Q07 based on: pneumonia diagnosis, chest X-ray and treatment with levofloxacin or moxifloxacin. Subsequent 30-day risk of pneumonia-related hospital visits and 30-day health care costs to payers for levofloxacin vs. moxifloxacin treatment were estimated after adjusting for pre-treatment demographics, health care resource use and pneumonia-specific risk factors using propensity score and exact factor matching. RESULTS: A total of 15,472 levofloxacin- and 6474 moxifloxacin-initiated CAP patients were identified. Among 6352 matched pairs, levofloxacin treatment was associated with a 35% reduction in the odds of pneumonia-related hospital visits (odds ratio = 0.65, P = 0.004), lower per-patient costs for pneumonia-related hospital visits (102 dollars vs. 210 dollars, P = 0.001), lower pneumonia-related total costs (medical services and prescription drugs, 363 dollars vs. 491 dollars, P < 0.001) and lower total costs (1308 dollars vs. 1446 dollars, P < 0.001) vs. moxifloxacin over the 30-day observation period. LIMITATIONS: Although observational analyses of claims data provide large sample sizes and reflect routine care, they do have several inherent limitations. Since randomization of subjects is not possible, adequate statistical techniques must be used to ensure that patient characteristics are well-balanced between treatment groups. In addition, data may be missing or miscoded. CONCLUSIONS: CAP outpatients initiated with levofloxacin generated substantially lower costs to payers compared to matched patients initiated with moxifloxacin. The cost savings for patients initiated with levofloxacin were largely attributable to reduced rates of pneumonia-related hospitalization or ER visits.

Cycle control with a 21-day compared with a 24-day oral contraceptive pill: a randomized controlled trial.

OBJECTIVE: To compare bleeding patterns between a 21/7-day triphasic norgestimate/ethinyl estradiol (E2) 25-microgram oral contraceptive pill (OCP) and a 24/4-day drospirenone/ethinyl E2 20-microgram OCP. METHODS: In a three-cycle, open-label, multicenter study, healthy, sexually active women were assigned randomly to a 21/7-day (norgestimate/ethinyl E2) or 24/4-day (drospirenone/ethinyl E2) OCP regimen. Randomization was stratified to assure a balanced distribution between regimens for "fresh starts" and "switchers." Bleeding data were collected daily using an interactive voice-response system. Bleeding was defined according to the 2007 U.S. Food and Drug Administration's Reproductive Health Drug Advisory Committee-endorsed criteria. RESULTS: Across the three cycles, the 21/7-day OCP group (n=165) reported fewer unscheduled bleeding days than did the 24/4-day OCP group (n=167) (mean 4.6 compared with 6.1 days, P=.003). Women using the 21/7-day OCP had significantly fewer episodes of unscheduled bleeding than did those using the 24/4-day OCP (mean 1.47 compared with 2.01, P=.001). Moreover, women using the 21/7-day OCP had a significantly lower absence of scheduled bleeding at each cycle (P<.001). Both regimens were well-tolerated. CONCLUSION: A 21-day norgestimate/ethinyl E2 25-microgram regimen results in less unscheduled bleeding and more scheduled bleeding than does a 24-day drospirenone/ethinyl E2 20-microgram regimen. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.ClinicalTrials.gov, NCT00745901. LEVEL OF EVIDENCE: I.

Meta-analysis of doripenem vs comparators in patients with pseudomonas infections enrolled in four phase III efficacy and safety clinical trials.

OBJECTIVE: Pseudomonas aeruginosa is a difficult-to-treat bacterial pathogen often isolated from patients with serious nosocomial infections. The goal of this analysis is to present the clinical and microbiologic effectiveness of doripenem in the treatment of infections due to P. aeruginosa. RESEARCH DESIGN AND METHODS: A meta-analysis was conducted on the subset of subjects enrolled in four randomized phase III clinical trials of doripenem in subjects with complicated intra-abdominal infections (cIAI) and nosocomial pneumonia/ventilator-associated pneumonia (NP/VAP) due to P. aeruginosa. Clinical and microbiologic success was determined by infection and across the two infections. RESULTS: Clinical success rates for modified intent-to-treat (mITT) subjects with P. aeruginosa in the cIAI and NP/VAP groups were 78.7% (37/47) and 59.6% (31/52), respectively, following treatment with doripenem versus 74.3% (26/35) and 32.8% (19/58), respectively, for subjects in the comparator groups (p < 0.05 for difference in success rates across infection types). Microbiologic eradication rates also favored doripenem, although the differences did not achieve statistical significance. The weighted difference (doripenem minus comparator) for the mITT population in clinical success rates between doripenem and the comparator agents was 16.0% (95% CI: 3.1%, 29.0%) and for microbiologic eradication rates was 9.1% (95% CI: -4.2%, 22.3%). The proportion of subjects reporting one or more treatment-emergent adverse events or serious adverse events was similar for doripenem and the comparator agents. Fourteen doripenem and 14 comparator subjects died during the study. Limitations of this retrospective meta-analysis also include the qualitative heterogeneity of the data, and a selected, narrow population of moderately ill clinical trial subjects included in the analysis. Due to limitations, these data may not be generalizable to all populations and should be considered hypothesis generating. CONCLUSION: The weighted difference in clinical success rates for subjects with cIAI and NP/VAP infections caused by P. aeruginosa was in favor of doripenem, with the relative benefit of doripenem compared with the comparator agents similar across the two infections.

Association between efficacy and body weight or body mass index for two low-dose oral contraceptives.

BACKGROUND: This analysis investigated the association of oral contraceptive efficacy with body weight and body mass index (BMI) for hypothesis-generating purposes. STUDY DESIGN: Data were from a randomized, parallel-group trial of 180/215/250 mcg of norgestimate (NGM)/25 mcg of ethinyl estradiol (EE) (given to 1671 women) and 1 mg of norethindrone acetate (NETA)/20 mcg of EE (given to 1139 women). Pregnancies were evaluated across BMI deciles and by BMI and body weight dichotomies. A Pearl index was calculated for each treatment group. The relative risk (RR) of pregnancy was calculated with a Cox proportional hazards model. RESULTS: The Pearl index for women who received NGM/EE was 2.36 [95% confidence interval (CI)=1.33-3.40]; for those who received NETA/EE, the Pearl index was 3.29 (95% CI=1.81-4.77). Consistent, weak positive associations between weight and pregnancy risk were found. Overall, for women with a BMI >or=25 kg/m(2) (compared with women with a BMI <25 kg/m(2)), the RR of pregnancy was 1.84 (95% CI=0.98-3.45); that for women who received NGM/EE was 1.39 (95% CI=0.57-3.40), whereas that for women who received NETA/EE was 2.49 (95% CI=1.01-6.13). For women with a body weight >or=70 kg (compared with women with a body weight <70 kg), the RR was 1.25 (95% CI=0.63-2.46); that for women who received NGM/EE was 1.41 (95% CI=0.56-3.54), whereas that for women who received NETA/EE was 1.12 (95% CI=0.40-3.12). CONCLUSION: Women in the higher body weight or BMI category showed a small increase in the risk of pregnancy with these oral contraceptives, but this increase was not statistically significant overall or for either formulation studied.

Levofloxacin versus azithromycin on the oropharyngeal carriage and selection of antibacterial- resistant streptococci in the microflora of healthy adults.

OBJECTIVE: To determine the proportion of subjects with oropharyngeal streptococci resistant to either levofloxacin or azithromycin prior to and during antibacterial exposure, and to follow temporal changes in the proportion of resistant and susceptible isolates through 6 weeks post-exposure. This randomized, open-label, single-center study is registered with ClinicalTrials.gov (identifier: NCT00821782). RESEARCH DESIGN AND METHODS: A total of 143 healthy volunteers (levofloxacin, n = 71; azithromycin, n = 72) without antibacterial exposure in the previous 90 days received either levofloxacin 750 mg once daily for 5 days or azithromycin 500 mg once daily on day 1 and 250 mg once daily on days 2 through 5. Oropharyngeal cultures were obtained pre-exposure, at day 5, and at 2, 4, and 6 weeks post-dosing. Bacterial strains were identified and the minimum inhibitory concentrations for levofloxacin and azithromycin were determined. RESULTS: At study entry 117 streptococci were isolated from 72 subjects randomized to azithromycin and 53 (45.3%) were azithromycin-resistant. None of the 121 streptococci isolated from 71 subjects randomized to.levofloxacin were colonized by a levofloxacin-resistant microorganism prior to dosing. At the end of dosing, the number of subjects with resistant streptococci (S. mitis, S. salivarius, S. sanguis, or alpha streptococcus species [spp.]) increased in azithromycin-exposed subjects and resistant isolates remained through 6 weeks post-dosing. In contrast, a small number of levofloxacin-resistant streptococci were observed at the end of dosing but decreased by week 2 post-dosing and continued to decrease through the 6-week evaluation period (p < 0.001 azithromycin vs. levofloxacin for S. mitis, S. salivarius, S. sanguis and alpha streptococcus spp. at week 6). Limitations of this study included the fact that, since previous antibiotic use was self-reported, genetic typing was not done. The results of this study may not be completely generalizable, because subjects in this study received study drug under directly-observed conditions, thus ensuring compliance. CONCLUSIONS: Both antibacterial agents were well tolerated. Levofloxacin 750 mg administered for 5 days was associated with less microbial resistance than that observed with azithromycin in healthy subjects.

Levofloxacin for the treatment of pneumonia caused by Streptococcus pneumoniae including multidrug-resistant strains: pooled analysis.

OBJECTIVE: To determine the clinical and microbiologic efficacy of levofloxacin for the treatment of subjects with pneumonia caused by multidrug-resistant (MDR) Streptococcus pneumoniae (MDRSP) and non-MDRSP strains. RESEARCH DESIGN AND METHODS: A pooled analysis was conducted using data from ten clinical studies in pneumonia: five comparative studies and five noncomparative studies conducted from 1992 to 2002. This analysis included data from levofloxacin-treated subjects with S. pneumoniae isolated at study entry. Susceptibility of S. pneumoniae isolated from subjects at study entry was determined against representative agents from five antimicrobial classes: tetracyclines, sulfonamides, second-generation cephalosporins, penicillins, and macrolides. Isolates were classified as MDRSP (based on resistance to two or more antimicrobial classes) or non-MDRSP (intermediate resistance or susceptible to all classes or resistant to 1 antimicrobial class). Clinical and microbiologic efficacy of levofloxacin (i.v., p.o., or i.v./p.o. for 5 to 14 days) in the microbiologically evaluable population was determined at post-therapy; a test for homogeneity of the odds ratio of the difference in clinical success for comparative versus noncomparative studies was performed. MAIN OUTCOME MEASURES AND RESULTS: The main outcome measures were clinical success rates and microbiologic eradication rates of 419 microbiologically evaluable levofloxacin-treated subjects with MDRSP or non-MDRSP. Clinical success rates were 96.3% (52/54) and 95.1% (347/365), respectively (difference -1.2; 95% confidence interval [CI]: -6.7, 4.3). Similarly, per pathogen microbiologic eradication rates for MDRSP and non-MDRSP were 96.3% (52/54) and 95.6% (350/366), respectively (difference -0.7; 95% CI: -6.1, 4.8). Study limitations include the use of data from comparative and noncomparative studies. A test for homogeneity of the odds ratios for clinical success in comparative versus noncomparative studies showed no significant difference (p = 0.27). CONCLUSIONS: These data support the use of levofloxacin for patients with community-acquired pneumonia caused by S. pneumoniae, including MDR strains.

Allodynia-associated symptoms, pain intensity and time to treatment: predicting treatment response in acute migraine intervention.

OBJECTIVE: To evaluate the relationship between treatment outcomes and allodynia-associated symptoms (AAS) at the time of treatment with almotriptan. METHODS: Analyses were performed with data collected prospectively from patients in 2 recently completed early intervention trials, AXERT Early miGraine Intervention Study (AEGIS) and AXERT 12.5 mg time vs Intensity Migraine Study (AIMS): 2-hour pain free, 2-hour pain relief (AEGIS only), sustained pain free (SPF), use of rescue medication, and median headache duration (AIMS only), in the presence and absence of pretreatment AAS, which was determined by responses to a questionnaire. Analyses were conducted to evaluate possible prognostic variables. RESULTS: The presence of pretreatment AAS did not have a significant effect on 2-hour pain-free, 2-hour pain-relief or SPF rates, use of rescue medication, or headache duration. Significant factors for most favorable outcomes (greater 2-hour pain-free, 2-hour pain-relief and SPF rates, less use of rescue medication, and shorter headache duration) included treatment with almotriptan 12.5 mg, treatment of mild or moderate headache pain, and treatment within 1 hour of headache onset. CONCLUSION: Almotriptan 12.5 mg was efficacious in providing 2-hour pain free, 2-hour pain relief, SPF, and reducing rescue medication use irrespective of the presence of AAS at the time of treatment. The most optimal efficacy outcomes occurred when patients treated migraine attacks early and before the onset of severe pain. The presence of AAS, which may indicate an early phase of allodynia, did not influence the efficacy of almotriptan therapy.

Scheduled and unscheduled bleeding patterns with two combined hormonal contraceptives: application of new recommendations for standardization.

OBJECTIVE: To reassess and compare cycle control attained with two combined hormonal contraceptives, norgestimate (NGM)/ethinyl estradiol (EE) 25 microg and norethindrone acetate (NETA)/EE 20 microg, by new general criteria recommendations for all combined hormonal contraceptives. DESIGN: Analysis of bleeding data for cycles 1-6 from a randomized, multicenter trial. SETTING: 221 North American centers. PATIENT(S): Healthy, sexually active women (18-45 years old). INTERVENTION(S): NETA/EE: 1 mg NETA/20 microg EE, days 1-21 of each cycle and 75 mg of ferrous fumarate, days 22-28; NGM/EE: triphasic NGM in 7-day increments (days 1-7: 180 microg; days 8-14: 215 microg; days 15-21: 250 microg) and 25 microg EE, placebo on days 22-28. MAIN OUTCOME MEASURE(S): Cycle control evaluated from patients' daily diaries. RESULT(S): For cycles 1-6, there was a statistically significant lower incidence of unscheduled bleeding/spotting with NGM/EE 25 microg (range 21.0%-34.4%) than with NETA/EE 20 microg (range 33.0%-46.6%). Of the women who had unscheduled bleeding/spotting, the mean number of days per cycle of bleeding/spotting was comparable. A statistically significant higher incidence of scheduled bleeding was seen with NGM/EE 25 microg (95.2%-97.5%) than with NETA/EE 20 microg (78.5%-84.2%). CONCLUSION(S): The NGM/EE 25 microg has a lower incidence and comparable length of unscheduled bleeding and a higher incidence of scheduled bleeding than NETA/EE 20 microg in this post hoc analysis.