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.

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.

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.

Comparison of a transdermal contraceptive patch vs. oral contraceptives on hemostasis variables.

PURPOSE: The aim of this study was to compare effects of the transdermal contraceptive patch, a desogestrel/ethinyl estradiol (EE)-containing, monophasic combination oral contraceptive (COC) and a levonorgestrel/EE-containing, triphasic COC on hemostasis variables. STUDY DESIGN: This was a randomized, open-label study of 104 young women who received six cycles of treatment. Blood was collected at baseline and on treatment; changes by Day 20/Cycle 6 in baseline hemostasis markers [prothrombin fragment 1+2 (F 1+2), plasmin-plasmin inhibitor complex (PAP) and fibrin degradation products (D-dimer)] were assessed. RESULTS: All contraceptives induced similar increases in F 1+2 and D-dimer. Patch-induced PAP increases were less than with the monophasic and similar to the triphasic COC. Decreases in protein S and increases in sex hormone-binding globulin were greater with the patch than with either COC. Patch-induced increases in activated protein C resistance were greater than with the triphasic and similar to the monophasic COC. CONCLUSION: These contraceptives appeared to accelerate baseline procoagulation processes to a similar extent and to change coagulation potency variables differently.

Topiramate for the treatment of binge eating disorder associated with obesity: a placebo-controlled study.

BACKGROUND: In a single-center, placebo-controlled study, topiramate reduced binge eating and weight in patients with binge eating disorder (BED) and obesity. The current investigation evaluated the safety and efficacy of topiramate in a multicenter, placebo-controlled trial. METHODS: Eligible patients between 18 and 65 years with >or= 3 binge eating days/week and a body mass index (BMI) between 30 and 50 kg/m2 were randomized. RESULTS: A total of 407 patients enrolled; 13 failed to meet inclusion criteria, resulting in 195 topiramate and 199 placebo patients. Topiramate reduced binge eating days/week (-3.5 +/- 1.9 vs. -2.5 +/- 2.1), binge episodes/week (-5.0 +/- 4.3 vs. -3.4 +/- 3.8), weight (-4.5 +/- 5.1 kg vs. .2 +/- 3.2 kg), and BMI (-1.6 +/- 1.8 kg/m2 vs. .1 +/- 1.2 kg/m2) compared with placebo (p < .001). Topiramate induced binge eating remission in 58% of patients (placebo, 29%; p < .001). Discontinuation rates were 30% in each group; adverse events (AEs) were the most common reason for topiramate discontinuation (16%; placebo, 8%). Paresthesia, upper respiratory tract infection, somnolence, and nausea were the most common AEs with topiramate. CONCLUSIONS: This multicenter study in patients with BED associated with obesity demonstrated that topiramate was well tolerated and efficacious in improving the features of BED and in reducing obesity.

Effects of low-dose oral contraceptives on body weight: results of a randomized study of up to 13 cycles of use.

OBJECTIVE: To compare the effect of 2 oral contraceptives (OCs) on body weight. STUDY DESIGN: A randomized, parallel-group, multicenter study of 1,723 women taking an OC with norgestimate (NGM) 180/215/250 microg/ethinyl estradiol (EE) 25 microg vs. 1,171 women taking on OC with norethindrone acetate 1 mg/EE 20 microg for 6-13 cycles was performed. Body weight changes between baseline and cycle 6 and baseline and cycle 13 were analyzed. Analysis included not only changes in mean body weight but also the distribution of changes that were within 5% of baseline weight, 5-10% of baseline weight and > 10% of baseline weight. Only the 10% change was felt to be clinically significant. RESULTS: The distribution of body weight changes did not statistically differ between the 2 OC groups for any parameter measured. The mean weight change after 6 months for the NGM/EE and norethindrone acetate/EE groups was +0.71 kg and +0.57 kg, respectively. At 13 cycles for the NGM/EE and norethindrone acetate/ EE groups, the mean body weight change was +0.93 kg and +0.62 kg, respectively. Only 0.3% of subjects in both OC groups experienced a 10% change in weight. CONCLUSION: Use of OCs does not substantially affect body weight for most women.

Levofloxacin 750 mg QD for five days versus amoxicillin/clavulanate 875 mg/125 mg BID for ten days for treatment of acute bacterial exacerbation of chronic bronchitis: a post hoc analysis of data from severely ill patients.

This post hoc analysis of data from a previous randomized, blinded, multicenter, parallel, noninferiority study assessed the bacterial etiology, symptom resolution, and tolerability of severe acute bacterial exacerbation of chronic bronchitis (ABECB) patients treated with either levofloxacin 750 mg QD for 5 days or amoxicillin/clavulanate 875 mg/125 mg BID for 10 days. Severe ABECB was defined as ABECB and forced expiratory volume in 1 second (FEV(1)) <50% of the predicted value, or (FEV(1)) of 50% to 65% of the predicted value plus comorbidities, or > or =4 exacerbations per year. A total of 369 patients were included in the intent-to-treat (ITT) population (187 treated with levofloxacin and 182 treated with amoxicillin/clavulanate), and 175 patients were microbiologically assessable (MA) (86 treated with levofloxacin and 89 treated with amoxicillin/clavulanate). In the ITT population, the mean age was 58.7 years, 49.1 % were male, and 48.2% were current smokers. At the on-treatment visit, a significantly higher proportion of MA patients in the levofloxacin group resolved purulent sputum production (57.5% vs 35.6%; P < 0.006), sputum production (65.4% vs 45.3%; P < 0.013), and cough (60.0% vs 44.0%; P < 0.045), compared with the amoxicillin/clavulanate group. However, no significant between-group differences were observed at posttreatment. A total of 341 pathogens were isolated, of which 143 (41.9%) were traditional ABECB flora, 181 (53.1%) were other gram-negative organisms, and 17 (5.0%) were gram-positive organisms. Overall susceptibility of the pathogens was 97.1% for levofloxacin and 90.6% for amoxicillin/clavulanate (P < 0.001). The prevalence of treatment-emergent adverse events was 42.1 % in patients who received levofloxacin and 48.6 % in those who received amoxicillin/clavulanate (95% CI,-4.0 to 17.0).

Extended use of transdermal norelgestromin/ethinyl estradiol: a randomized trial.

OBJECTIVE: To compare bleeding profiles and satisfaction among women using a norelgestromin/ethinyl estradiol (E2) transdermal contraceptive patch in an extended regimen to those among women using a traditional 28-day patch regimen. METHODS: Healthy, regularly menstruating women (N = 239) were randomly assigned (2:1 ratio) to receive the norelgestromin/ethinyl E2 transdermal patch in an extended regimen (weekly application for 12 consecutive weeks, 1 patch-free week, and 3 more consecutive weekly applications, n = 158) or a cyclic regimen (4 consecutive cycles of 3 weekly applications and 1 patch-free week, n = 81). Subjects recorded bleeding data daily and completed satisfaction questionnaires. Subjects and investigators provided overall assessments of the regimens. RESULTS: Extended use of the norelgestromin/ethinyl E2 transdermal patch resulted in fewer median bleeding days (6 compared with 14, P < .001), bleeding episodes (1 compared with 3, P < .001), and bleeding or spotting episodes (2 compared with 3, P < .001) compared with cyclic use during days 1-84; median numbers of bleeding or spotting days were similar between regimens (14 compared with 16, P = .407) during this time. Extended use delayed median time to first bleeding to 54 days compared with 25 days with cyclic (P < .001). Subjects were highly satisfied with both regimens. Although not statistically significant, slightly more adverse events were reported with the extended than with the 28-day regimen. CONCLUSION: Compared with cyclic use, extended use of the norelgestromin/ethinyl E2 transdermal patch delayed menses and resulted in fewer bleeding days. This regimen may represent a useful alternative for women who prefer fewer episodes of withdrawal bleeding.

Contraceptive efficacy, compliance and beyond: factors related to satisfaction with once-weekly transdermal compared with oral contraception.

OBJECTIVE: To investigate contraceptive efficacy, compliance and user's satisfaction with transdermal versus oral contraception (OC). STUDY DESIGN: Randomized, open-label, parallel-group trial conducted at 65 centers in Europe and South Africa. One thousand four hundred and eighty-nine women received a contraceptive patch (n = 846) or an OC (n = 643) for 6 or 13 cycles. RESULTS: Overall/method-failure Pearl Indices were 0.88/0.66 with the patch and 0.56/0.28 with the OC (p = n.s.). Compliance was higher at all age groups with the patch compared to the OC. Significantly more users were very satisfied with the contraceptive patch than with the OC. The percentage of patch users being very satisfied increased with age whereas it did not in the OC group. Likewise, improvements of premenstrual symptoms as well as emotional and physical well-being increased with age in the patch-group in contrast to the OC group. Ratings of satisfaction with the study medication correlated weakly with emotional (r = 0.33) and physical well-being (r = 0.39) as well as premenstrual symptoms (r = 0.30; p < 0.001). CONCLUSION: Contraceptive efficacy of the patch is comparable to OC, but compliance is consistently better at all age groups. Higher satisfaction with the patch at increasing age may be attributed to improvements in emotional and physical well-being as well as reduction of premenstrual symptoms.

Contraceptive efficacy and cycle control with the Ortho Evra/Evra transdermal system: the analysis of pooled data.

OBJECTIVE: To present efficacy and cycle control data pooled from three pivotal studies of the contraceptive patch (Ortho Evra/Evra). DESIGN: Three multicenter, open-label, contraceptive studies that included up to 13 treatment cycles. SETTING: 183 centers. PATIENT(S): 3,319 women. INTERVENTION(S): Three consecutive 7-day patches (21 days) with 1 patch-free week per cycle. MAIN OUTCOME MEASURE(S): Contraceptive efficacy and cycle control. RESULT(S): Overall and method failure life-table estimates of contraceptive failure through 13 cycles were 0.8% (95% CI, 0.3%-1.3%) and 0.6% (95% CI, 0.2%-0.9%), respectively. Corresponding Pearl indices were 0.88 (95% CI, 0.44-1.33) and 0.7 (95% CI, 0.31-1.10). Contraceptive failure among women with a body weight < 90 kg (<198 lb) was low and uniformly distributed across the weight range. A subgroup of women with body weight > or = 90 kg (> or = 198 lb) may have increased risk of pregnancy. The incidence of breakthrough bleeding was low and decreased over time. CONCLUSION(S): In contraceptive patch users, the overall annual probability of pregnancy was 0.8% and the method failure probability was 0.6%. The efficacy of the patch was high and similar across age and racial groups. Among women < 90 kg (<198 lb), contraceptive failure was low and uniformly distributed across the range of body weights. In women > or = 90 kg (> or = 198 lb), contraceptive failures may be increased. Efficacy and cycle control have been shown to be comparable to an established oral contraceptive.

Integrated summary of Ortho Evra/Evra contraceptive patch adhesion in varied climates and conditions.

OBJECTIVE: To assess the adhesive reliability of the contraceptive patch (Ortho Evra/Evra). DESIGN: Pooled data of 3,319 women from three contraceptive studies of up to 13 treatment cycles; a subset of 325 women of the pooled data from warm and humid climates; and 30 women from a three-period, crossover exercise study. SETTING: 184 centers. PATIENT(S): 3,349 healthy women. INTERVENTION(S): In the contraceptive studies, each treatment cycle consisted of three consecutive 7-day patches (21 days) followed by one patch-free week. During each treatment period in the exercise study, women wore the patch for 7 days and participated in one of six activities (normal activity, excluding bathing; sauna; whirlpool; treadmill; cool-water immersion; or a combination of activities) each day at a supervised health center. MAIN OUTCOME MEASURE(S): Patch adhesion. RESULT(S): In the contraceptive studies, 4.7% of patches were replaced because they fell off (1.8% [1,297 of 70,552 patches]) or became partly detached (2.9% [2,050 of 70,552 patches]); patch replacement rates in centers from a warm, humid climate were 1.7% (85 of 4,877 patches) and 2.6% (128 of 4,877 patches), respectively. Only one of 87 patches (1.1%) completely detached in the exercise study. CONCLUSION(S): The reliability of adhesion of the contraceptive patch is excellent and consistent across all studies; only 1.8% and 2.9% of patches required replacement due to complete or partial detachment, respectively. Heat, humidity, and exercise do not affect adhesion.

A comparative and pooled analysis of the safety and tolerability of the contraceptive patch (Ortho Evra/Evra).

OBJECTIVE: To review the safety and tolerability of the contraceptive patch (Ortho Evra/Evra) versus a standard oral contraceptive (Triphasil) and to present the pooled safety and tolerability of the patch across three pivotal studies. DESIGN: Three open-label, contraceptive studies of up to 13 treatment cycles. SETTING: 183 centers. PATIENT(S): Comparative study (812 patch, 605 oral contraceptive); pooled analysis (3,330 patch). INTERVENTION(S): The patch regimen was three consecutive 7-day patches (21 days) followed by 1 patch-free week per cycle; the oral contraceptive was dosed according to the U.S. physician package insert. MAIN OUTCOME MEASURE(S): Adverse events, laboratory tests, vital signs, and body weight. RESULT(S): The incidence of most events was similar between the patch and oral contraceptive groups, with the exception of a higher incidence of application site reactions, breast discomfort (cycles 1 and 2 only), and dysmenorrhea in the patch group. Pooled analysis demonstrated that most application site reactions (92%) and breast symptoms (86%) were mild or moderate in severity, and <2% of participants discontinued the patch because of either event. Only 7 (0.2%) participants experienced a serious adverse event classified as possibly, probably, or likely related to the patch. The mean change in body weight from baseline to the end of treatment was an increase of 0.3 kg. CONCLUSION(S): Overall, the contraceptive patch is well tolerated and has a side effect profile similar to an established oral contraceptive.

Assessment of compliance with a weekly contraceptive patch (Ortho Evra/Evra) among North American women.

OBJECTIVE: To determine compliance with the contraceptive patch (Ortho Evra/Evra) overall and by age among women in North America and to compare rates of perfect use with those of an established oral contraceptive. DESIGN: Data were pooled for three contraceptive studies in which women participated for up to 13 cycles; the subset of centers in North America was used in this analysis. SETTING: 76 North American centers. PATIENT(S): Healthy women 18-45 years of age. INTERVENTION(S): In all studies, the patch regimen was three consecutive 7-day patches (21 days) followed by 1 patch-free week per cycle. MAIN OUTCOME MEASURE(S): Perfect use for the patch or oral contraceptive, defined as 21 consecutive days of drug-taking followed by a 7-day drug-free period; for contraceptive patch users, no patch could be worn for more than 7 days. Oral contraceptives were used according to package labeling. RESULTS: For all contraceptive patch users in North America (n = 1,785), perfect use was consistent across age groups. The percentage of cycles with perfect use of the patch ranged within age groups from 88.1% to 91.0%. In the comparative study conducted only in North America, perfect use was also consistent across age groups for the patch (n = 812), but rates of perfect use for the oral contraceptive (n = 605) differed significantly by age. CONCLUSION(S): Age did not affect compliance with the patch among all North American women studied. In a comparative study of women at North American centers, compliance with the weekly contraceptive patch was significantly better than with an established oral contraceptive. The contraceptive patch is uniformly easy to use across all ages.

Ortho Evra/Evra versus oral contraceptives: follicular development and ovulation in normal cycles and after an intentional dosing error.

OBJECTIVE: To compare the effects of the contraceptive patch to oral contraceptives (OCs) on follicular size and incidence of ovulation in normal cycles and after dosing errors. DESIGN: Randomized, open-label. SETTING: Twelve centers. PATIENT(S): One hundred twenty-four ovulatory women. INTERVENTION(S): Subjects received either the patch (groups 1 and 2) or one of three OCs. Correct dosing occurred in cycles 1, 2, 3, and 5. The following dosing errors were planned during cycle 4, a shortened 10-day cycle: [1] patch group 1 subjects wore one patch for 10 consecutive days; [2] for patch group 2 and OC subjects, 7 dosing days were followed by 3 drug-free days. MAIN OUTCOME MEASURE(S): Follicular size, as determined at each cycle by the maximum mean follicular diameter. RESULT(S): After a 3-day dosing error, follicular size was significantly smaller in the patch group (mean, 7.0 mm) vs. each OC group (range of means, 11.8-17.1 mm). Similar results were seen after proper dosing. The incidence of ovulation was significantly lower for the patch users than for women using OCs. CONCLUSION(S): Follicular size and incidence of ovulation were significantly reduced among contraceptive patch users compared with women using OCs in normal cycles and after planned dosing errors.

The impact of improved compliance with a weekly contraceptive transdermal system (Ortho Evra) on contraceptive efficacy.

OBJECTIVE: The contraceptive efficacy of perfect dosing cycles and imperfect dosing cycles has not been described previously. Method compliance determines the proportion of perfect and imperfect dosing cycles, and together can form the basis for evaluating differences in efficacy based on differences in compliance. MATERIALS AND METHODS: The transdermal contraceptive delivery system (Ortho Evra) has been studied in a North American randomized trial vs. an oral contraceptive (OC) and in total has been evaluated in 3319 women in contraceptive clinical trials. This article explores the impact of perfect vs. imperfect compliance with the contraceptive method on contraceptive efficacy. Previously published data for a transdermal system (Patch, n = 812) and OC (Triphasil, n = 605) users from the North American comparative study were reanalyzed to determine the effect of imperfect use on the contraceptive efficacy of the different methods. RESULTS: Contraceptive efficacy was significantly better (p = 0.007) in cycles with perfect dosing (Pearl Index = 0.83) compared to those with imperfect dosing (Pearl Index = 6.32) for both methods. This difference is homogeneous (p = 0.62) across the Patch and OC groups. Pooled data for all Patch users confirm that perfect dosing cycles are associated with significantly better efficacy than imperfect dosing cycles (p = 0.047). In addition, compliance did not vary by age in the pooled Patch data, which are in agreement with the previously published Patch data from the comparative study. In the comparative study, the percentage of cycles with perfect dosing was significantly higher with the Patch than with the OC (88.7% vs. 79.2%, p < 0.001), and was consistently high in all age groups (range, 89.6-91.8%). By contrast, among OC users, the percentage of cycles with perfect dosing increased with increasing age (p < 0.001) from 67.7% in users aged 18-20 years to more than 80% in those aged 30 years and older. CONCLUSION: In conclusion, deviations from perfect use (whether corrected or not) of a transdermal contraceptive system and of an OC increase contraceptive failures by approximately 5-10-fold when compared to perfect use. The weekly change schedule of the transdermal contraceptive delivery system is associated with a significantly greater proportion of cycles in which there is perfect dosing compared to an OC.

Transdermal contraceptive patch delivering norelgestromin and ethinyl estradiol. Effects on the lipid profile.

OBJECTIVE: To evaluate the metabolic impact on lipids of a contraceptive patch that delivers norelgestromin (primary active metabolite of norgestimate) and ethinyl estradiol to the systemic circulation as compared with a placebo patch. STUDY DESIGN: In this randomized, double-blind trial, healthy women received the contraceptive patch (n = 99) or placebo patch (n = 47) for up to 9 cycles. Fasting blood samples were obtained at baseline and cycles 3, 6 and 9 for determining the serum lipid profile. RESULTS: At cycles 3, 6 and 9, mean increases from baseline in high-density lipoprotein (HDL) cholesterol, HDL3 cholesterol, total cholesterol and total triglycerides, and mean decreases in calculated (Friedewald) low-density lipoprotein (LDL)/HDL were observed in the contraceptive patch group (all P < .05 vs. placebo except for total cholesterol at cycle 6). Mean changes in HDL2 and calculated LDL cholesterol were minimal and comparable between treatments. Mean body weight increased from baseline to the end of treatment by 0.8 and 0.6 kg in the 2 groups, respectively; this difference was not significant. CONCLUSION: The lipid changes seen with the contraceptive patch are consistent with those of oral contraceptives containing norgestimate and ethinyl estradiol.

Cycle control, tolerability, and satisfaction among women switching from 30-35 microg ethinyl estradiol-containing oral contraceptives to the triphasic norgestimate/25 microg ethinyl estradiol-containing oral contraceptive Ortho Tri-Cyclen LO.

OBJECTIVE: To determine cycle control, tolerability, and satisfaction among women (aged 18-45) switching from oral contraceptives (OCs) containing 30-35 microg ethinyl estradiol (EE) to Ortho Tri-Cyclen LO (norgestimate 180/215/250 microg/EE 25 microg) and Loestrin Fe 1/20 (norethindrone acetate 1 mg/EE 20 microg). DESIGN: A subset of patients from a study comparing Ortho Tri-Cyclen LO (N = 864) with Loestrin Fe 1/20 (N = 565) was analyzed. The subset was defined as those who had taken a 30-35 microg EE-containing OC within 60 days of study start. The total number of cycles of exposure for the subset was 6,054 for Ortho Tri-Cyclen LO and 3,814 for Loestrin Fe 1/20. Additional analyses evaluated switchovers from Ortho Tri-Cyclen to Ortho Tri-Cyclen LO (N = 111). MAIN OUTCOME MEASURES: Cycle control was assessed by daily diary cards reporting the frequency, severity, and duration of bleeding/spotting. Discontinuation rates due to adverse events (AEs) were considered to reflect tolerability. Satisfaction was evaluated by questionnaire. RESULTS: The proportion of cycles in which subjects experienced breakthrough bleeding and/or spotting was significantly lower with Ortho Tri-Cyclen LO than Loestrin Fe 1/20. Discontinuations due to AEs and serious AEs were comparable for Ortho Tri-Cyclen LO (3.4% and 0.6%, respectively) and Loestrin Fe 1/20 (3.2% and 0.7%, respectively). More women on Ortho Tri-Cyclen LO versus Loestrin Fe 1/20 were very or somewhat satisfied at Cycle 6 (86% vs. 81.1%; P < 0.05) and last visit (81.6% vs. 78.1%; P < 0.05). At Cycle 6, 89.3% of Ortho Tri-Cyclen to Ortho Tri-Cyclen LO switchovers were very or somewhat satisfied, and 72.6% desired to continue taking Ortho Tri-Cyclen LO after study conclusion. Conclusions-Switchovers from OCs containing 30-35 microg EE to Ortho Tri-Cyclen LO had excellent cycle control and tolerability, and were satisfied.

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.

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).