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Introduction

There is an urgent need for new anti-tuberculosis (TB) drugs and optimization of current TB treatment. Moxifloxacin and linezolid are valuable options for the treatment of drug-resistant TB; however, it is crucial to find a dose at which these drugs not only show high efficacy but also suppress the development of further drug resistance.

Methods

Activity of moxifloxacin and linezolid against Mycobacterium tuberculosis was studied in the hollow-fiber infection model system in log-phase growth under neutral pH and slow growth in an acidic environment. Doses that achieved maximum bacterial kill while suppressing the emergence of drug resistance were determined. Through Monte Carlo simulations the quantitative output of this in vitro study was bridged to the human patient population to inform optimal dosage regimens while accounting for clinical minimum inhibitory concentration (MIC) distributions.

Results and Discussion

Moxifloxacin activity was significantly decreased in an acidified environment. The loss of activity was compensated by accumulation of the drug in TB lung lesions; therefore, moderate efficacy can be expected. Moxifloxacin 800 mg/day is the dose that most likely leads to resistance suppression while exerting maximum bacterial kill. Linezolid demonstrated very good activity even at a reduced pH. Linezolid 900 mg once-daily (QD) is likely to achieve a maximum killing effect and prevent the emergence of drug resistance; 600 mg QD in a robust drug regimen may have similar potential.  相似文献   
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ObjectiveShared decision-making exists to reconcile healthcare practitioners’ responsibilities to respect patients’ autonomy whilst ensuring well-made decisions. Patients sometimes make unprompted requests for procedures that carry medical and other risks, such as risk-reducing mastectomy (RRM). Faced with pre-formed decisions into which they have had little input, it is unclear how practitioners can reconcile respecting autonomy with ensuring well-made decisions.MethodsQualitative study of linked patient-practitioner interviews in a breast unit in North-West England. We examined how 10 practitioners addressed 19 patients’ unprompted requests for RRM.ResultsPractitioners empathised with patients’ distress about cancer risk, regarded RRM as legitimate to help, but were wary of choices made ‘emotionally’. Practitioners did not seek to establish whether choices were well-made but, instead, ‘warranted’ patients by satisfying themselves that patients were ‘sensible’ and ‘informed’ decision-makers, and thus their decisions could be trusted. Practitioners provided information, and tested patients’ resolve by delaying decisions and presenting ‘what if’ scenarios depicting failure or harm from RRM.ConclusionPatients who present emotionally and with resolution can receive RRM without evidence of a well-made decision.Practice Implications: Argumentation theory proposes an ethically robust and clinically practicable approach, whereby practitioners elicit, examine and, where appropriate, challenge arguments underpinning patients’ decisions.  相似文献   
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Effects of temperature (25 and 37 degrees C), pH (4.9-10.5), and CaF2 on CaHPO4.2H2O (DCPD) hydrolysis were studied in a pH-stat. Octa-calcium phosphate (OCP) was the product at pH 6.2-6.8 and 25-37 degrees C; thermodynamically stable apatitic compounds were formed at higher pH and/or higher temperature. In the presence of CaF2, apatite was the product, its crystallinity improved, and the fluoride content increased as pH of the reaction decreased. The results demonstrate the remarkable ability of fluoride to promote the hydrolysis of an acidic calcium phosphate, DCPD, to apatite.  相似文献   
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BACKGROUND: This article is the first of two that focus on recent changes in the funding of dental services in the United States. METHODS: This study is based on analyses of data regarding dental expenditures among children 2 to 17 years of age from the 1987 National Medical Expenditure Survey and the 1996 Medical Expenditure Panel Survey. Both of these surveys were designed to produce national estimates of annual medical expenditures in the United States. RESULTS: Overall, real per capita dental expenditures among 2- to 17-year-old children who had had a dental visit fell from $578.05 in 1987 to $498.57 in 1996. Large increases per patient were reported for the poorest children, while decreases were reported for children from families with higher incomes. CONCLUSIONS: Much of the increase from 1987 to 1996 in dental expenditures among economically disadvantaged children who had had a dental visit was due to an increase in care provided by dentists that was not reimbursed. PRACTICE IMPLICATIONS: More needs to be done to increase the number of economically disadvantaged children who visit a dentist. All segments of society must cooperate to achieve this result.  相似文献   
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The effect of chewing gum use on in situ enamel lesion remineralization.   总被引:1,自引:0,他引:1  
Two independent cross-over studies investigated the possibility of enhanced early enamel lesion remineralization with the use of chewing gum. The first study involved a sorbitol-containing chewing gum, and the second, which had an identical protocol, tested a sucrose-containing chewing gum. In each study, 12 volunteers wore in situ appliances on which were mounted enamel sections containing artificial caries lesions. Subjects brushed twice daily for two min with a 1100-ppm-F (NaF) dentifrice (control and test) and in the test phase chewed five sticks of gum per day for 20 min after meals and snacks. Microradiographs of the enamel lesions were made at baseline and at the end of the seven-week experimental period. In the sugar-free gum study, the weighted mean total mineral loss (delta z) difference [(wk7-wk0) x (-1)] was 788 vol.% min. x micron for the gum, corresponding to remineralization of 18.2%, vs. the control value of 526 vol.% min. x micron, 12.1% remineralization (p = 0.07). There were no significant differences for the surface-zone (p = 0.20) and lesion-body (p = 0.28) values. In the sucrose-containing gum study, the delta z difference was 743 vol.% min. x micron for the gum, corresponding to a remineralization of 18.3%, vs. the control value of 438 vol.% min. x micron, 10.8% remineralization (p = 0.08). The surface-zone values were not significantly different (p = 0.55). For the lesion body, however, the sucrose-containing gum value of 6.11 vol.% min. was significantly different (p = 0.01) from that of the control (2.81 vol.% min.).  相似文献   
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Mucormycosis of the mandible   总被引:1,自引:0,他引:1  
A case of mucormycosis of the mandible and adjacent soft tissue is presented. The rampant osteomyelitis that developed over a two-month period shows the necessity of early medical and surgical intervention. The management of these patients includes aggressive medical management of underlying problems, high-dose amphotericin B administration, and early surgical debridement of all involved tissues.  相似文献   
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