Efficacy and safety of ten day moxifloxacin 400 mg once daily in the treatment of patients with community-acquired pneumonia

AbstractCommunity-acquired pneumonia (CAP) remains a common and serious illness with approximately 2–4 million cases reported annually. Management of CAP is therapeutically challenging due to the increasing prevalence of penicillin- and macrolide-resistant pneumococci and β -lactamase producing Haemophilus influenzae, as well as the increased recognition of ‘atypical’ pathogens, such as Chlamydia pneumoniae and Mycoplasma pneumoniae, and the frequent need for empiric therapy.We aimed to evaluate the safety and efficacy of moxifloxacin in the treatment of patients with CAP. To do this we carried out a prospective, uncontrolled, non-blind, Phase III clinical trial, in 27 U.S. centers. Patients included in the study were over 18 years of age with signs and symptoms of CAP confirmed by evidence of a new or progressive infiltrate on chest radiograph. The intervention used was moxifloxacin 400 mg PO once daily for 10 days.Sputum samples were collected pretherapy for Gram stain and culture for typical organisms. Culture and serological testing for Chlamydia pneumoniae and Mycoplasma pneumoniae was also performed. Susceptibility to moxifloxacin was determined by disk diffusion and MIC. Clinical and bacteriological responses were determined at the end of therapy (0–6 days post-therapy), follow-up (14–35 days post-therapy) and overall (end of therapy plus follow-up). Analyses were performed on both valid for efficacy and intent-to-treat populations. The primary efficacy variable was overall clinical resolution.Of 254 patients enrolled in the Study, 196 patients were included in the efficacy analyses. The majority of patients were male (58%) and Caucasian (85%) with a mean age of 49 years (range: 18 to 85 years). Only 3% of patients were hospitalized pretherapy. The most common pretherapy organisms identified, by culture or serology, in the valid for efficacy population (i.e. 147 organisms among 116 patients), were: Chlamydia pneumoniae (n=63; 54%),Mycoplasma pneumoniae (n=29; 25%), Streptococcus pneumoniae (n=14; 12%) and Haemophilus influenzae (n=13; 10%). End of therapy, follow-up and overall clinical resolution rates for the valid for efficacy population were 94%, 93% and 93%, respectively. The 95% CI for the overall clinical resolution rate was 88·1%, 95·9%. The overall bacteriological response for patients diagnosed by culture or serological criteria, was 91% (95% CI=84%, 96%). For patients who only met serological criteria for infection, the overall bacteriological response was 94% (60/64). Bacterial response rates for the four most commonly isolated pathogens were: 89% (56/63) for C. pneumoniae, 93% (27/29) for M. pneumoniae, 93% (13/14) for S. pneumoniae and 85% (11/13) for H. influenzae. Drug-related adverse events were reported in 33% (85/254) of moxifloxacin-treated patients. Nausea (9%), diarrhea (6%) and dizziness (4%) were the most commonly reported adverse events.Atypical organisms were isolated in high frequency among patients with CAP. Moxifloxacin 400 mg once daily for 10 days was effective and well-tolerated in the treatment of these adult patients with CAP. Moxifloxacin offers an effective treatment alternative for CAP due to both typical and atypical bacterial pathogens

Observational Learning During Simulation-Based Training in Arthroscopy: Is It Useful to Novices?

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.OBJECTIVE: Observing experts constitutes an important and common learning experience for surgical residents before operating under direct guidance. However, studies suggest that exclusively observing experts may induce suboptimal motor learning, and watching errors from non-experts performing simple motor tasks may generate better performance. We investigated whether observational learning is transferrable to arthroscopy learning using virtual reality (VR) simulation. SETTING/DESIGN: In our surgical simulation laboratory, we compared students learning basic skills on a VR arthroscopy simulator after watching an expert video demonstration of VR arthroscopy tasks or a non-expert video demonstration of the same tasks to a Control group without video demonstration. Ninety students in 3 observing groups (expert, non-expert, and Control) subsequently completed the same procedure on a VR arthroscopy simulator. We hypothesized the non-expert-watching group would outperform the expert-watching group, and both groups to outperform the Control group. We examined performance pretest, posttest, and 1 week later. PARTICIPANTS: Participants were recruited from the final year of medical school and the very early first year of surgical residency training programs (orthopaedic surgery, urology, plastic surgery, and general surgery) at Western University (Ontario, Canada). RESULTS: All participants improved their overall performance from pretest to retention (p < 0.001). At initial retention testing, non-expert-watching group outperformed the other groups in camera path length p < 0.05 and time to completion, p < 0.05, and both the expert/non-expert groups surpassed the Control group in camera path length (p < 0.05). CONCLUSION: We suggest that error-observation may contribute to skills improvement in the non-expert-watching group. Allowing novices to observe techniques/errors of other novices may assist internalization of specific movements/skills required for effective motor performances. This study highlights the potential effect of observational learning on surgical skills acquisition and offers preliminary evidence for peer-based practice (combined non-experts and experts) as a complementary surgical motor skills training strategy.This project was supported by a Physicians׳ Services Incorporated (PSI) Foundation, Canada grant. Funds were used to pay for salary and employee benefits (LvE). The PSI Foundation did not play a role in the investigation

Gadobutrol-enhanced cardiac magnetic resonance imaging for detection of coronary artery disease

BACKGROUND: Gadolinium-based contrast agents were not approved in the United States for detecting coronary artery disease (CAD) prior to the current studies. OBJECTIVES: The purpose of this study was to determine the sensitivity and specificity of gadobutrol for detection of CAD by assessing myocardial perfusion and late gadolinium enhancement (LGE) imaging. METHODS: Two international, single-vendor, phase 3 clinical trials of near identical design, "GadaCAD1" and "GadaCAD2," were performed. Cardiovascular magnetic resonance (CMR) included gadobutrol-enhanced first-pass vasodilator stress and rest perfusion followed by LGE imaging. CAD was defined by quantitative coronary angiography (QCA) but computed tomography coronary angiography could exclude significant CAD. RESULTS: Because the design and results for GadaCAD1 (n = 376) and GadaCAD2 (n = 388) were very similar, results were summarized as a fixed-effect meta-analysis (n = 764). The prevalence of CAD was 27.8% defined by a ≥70% QCA stenosis. For detection of a ≥70% QCA stenosis, the sensitivity of CMR was 78.9%, specificity was 86.8%, and area under the curve was 0.871. The sensitivity and specificity for multivessel CAD was 87.4% and 73.0%. For detection of a 50% QCA stenosis, sensitivity was 64.6% and specificity was 86.6%. The optimal threshold for detecting CAD was a ≥67% QCA stenosis in GadaCAD1 and ≥63% QCA stenosis in GadaCAD2. CONCLUSIONS: Vasodilator stress and rest myocardial perfusion CMR and LGE imaging had high diagnostic accuracy for CAD in 2 phase 3 clinical trials. These findings supported the U.S. Food and Drug Administration approval of gadobutrol-enhanced CMR (0.1 mmol/kg) to assess myocardial perfusion and LGE in adult patients with known or suspected CAD

Geodemographic Patterns of Meat Expenditure in Great Britain

The future of the meat industry will require the management of important trade-offs between economic, environmental and health aspects of both humans and animals. Understanding the patterns and trends of meat expenditure and consumption is crucial for assessing the current resilience of the system and for economic, planning, health and environmental applications. Here, we show how the technique of geodemographic classification, combined with fine scale expenditure estimates can be used to explore temporal and spatial patterns of meat expenditure in Great Britain between 2008 and 2017. Whilst the expenditure patterns of some food categories such as sausages remained relatively consistent, others such as lamb show a trend towards a reduced proportion of expenditure and increased inequality of purchases. Short term changes in expenditure patterns also occurred, potentially due to product specific price variability, price elasticities or zoonotic disease scare. Environmental attitudes, financial constraints and the prominence of communities who do not eat meat for religious or cultural reasons are likely to be driving the differences between geodemographic groups. The methodology and results could be a valuable tool for policy makers in the meat industry and beyond

CDM primer An introduction and first-stop reference for designers on the Construction (Design &amp; Management) Regulations

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Urological Oncology 3-DAY VS 1-DAY OF XR CIPROFLOXACIN AS PROPHYLAXIS FOR PROSTATE NEEDLE BIOPSY Comparison of a 3-day with a 1-day regimen of an extended-release formulation of ciprofloxacin as antimicrobial prophylaxis for patients undergoing transrecta

RESULTS Of 497 patients enrolled, 247 were randomized to 1-day ciprofloxacin XR and 250 to the 3-day regimen. In the population valid for microbiological efficacy, the final assessment identified bacteriological success (primary efficacy endpoint) in more patients who had the 3-day regimen (98%) than in those who received the 1-day regimen (94.8%, 95% confidence interval, CI, − 6.1%, 0.8%), although the difference was not statistically significant. In this population, the clinical response at the final visit was 98.5% and 96.7% for patients receiving the 3-day and the 1-day regimens, respectively (95% CI − 5.2%, 0.8%). However, in the clinical efficacy population the clinical success rate was significantly greater for the 3-day (99.0%) than for the 1-day regimen (95.8%; 95% CI − 6.4%, − 0.3%). In a multivariate analysis, patients with diabetes mellitus and patients with a history of prostatitis had higher microbiological and clinical failure rates, respectively, than those without such conditions. For these patients, all failures occurred among those treated with the 1-day regimen. CONCLUSION As defined by bacteriological success in the population assessed for microbiological efficacy, prophylaxis with one dose of ciprofloxacin XR was statistically no worse than a 3-day regimen. However, in all efficacy analyses, bacteriological and clinical success rates were consistently lower for the 1-day than for the 3-day treatment. Thus, for selected patients undergoing TRNBP, there might be a role for 3-day preventive therapy with ciprofloxacin XR