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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Methods: Attributes were defined from a literature search, clinician and patient interviews: shape, dose insertion, dose preparation, dose release, dose confirmation, dose counter and reusability. An online DCE was conducted in respondents with self-reported COPD stage 2–4 recruited through a panel. The study questionnaire included twelve choice scenarios per respondent and questions on patient characteristics, treatment and disease severity. Statistical analyses used a mixed logit regression model with random effects. Utility scores were estimated for four types of inhalers: Inhaler A – soft mist inhaler; Inhaler B – reusable soft mist inhaler; Inhaler C – multi-dose dry powder inhaler; and Inhaler D – single dose dry powder inhaler.
Results: The study was completed by 153 patients (50 females); respondents were 50.4?years old on average; 13 different inhaler devices were reported. The most preferred inhaler is L-shaped, has dose preparation with capsule insertion and a dose counter, and is reusable. Inhaler profiles A and B had the highest utilities (mean of 1.2533 and 0.9578 respectively) compared to inhaler C (0.6315) and D (0.2200).
Conclusions: This study showed statistically significant results that the strongest drivers of preference in French users of inhalation devices for COPD are shape, dose counter and reusability. Convenience-related characteristics are important to patients and should be taken into account by clinicians prescribing these devices. 相似文献
Purpose
To qualitatively and quantitatively compare unenhanced ultra-low-dose chest computed tomography (ULD-CT) acquired at 80 kVp and 135 kVp.Materials and methods
Fifty-one patients referred for unenhanced chest CT were prospectively included. There were 29 men and 22 women, with a mean age of 64.7 ± 11.6 (SD) years (range: 35–91 years) and a mean body mass index of 26.2 ± 6.3 (SD) (range: 17–54.9). All patients underwent two different ULD-CT protocols (80 kVp-40 mA and 135 kVp-10 mA). Image quality of both ULD-CT examinations using a 5-level scale as well as assessability of 6 predetermined lung parenchyma lesions were blindly evaluated by three radiologists and compared using a logistic regression model. Image noise of the two protocols was compared with Wilcoxon signed-rank test.Results
The mean dose-length product at 80 kVp and at 135 kVp were 14.7 ± 1.8 (SD) mGy.cm and 15.6 ± 1.9 (SD) mGy.cm, respectively (P < 0.001). Image noise was significantly lower at 135 kVp (58.9 ± 12.4) than at 80 kVp (74.7 ± 14.5) (P < 0.001). For all readers and for all examinations, the 135 kVp protocol yielded better image quality than 80 kVp protocol, with a mean qualitative score of 4.5 ± 0.7 versus 3.9 ± 0.8 (P < 0.001). The 135 kVp protocol was significantly more often of diagnostic quality than the 80 kvp protocol (92.3% versus 77.8%, respectively) (P < 0.001) and was less prone to image quality deterioration in obese patients. Parenchymal lesions were never better depicted on the 80 kVp protocol than with the 135 kVp protocol.Conclusion
Unenhanced chest ULD-CT should be acquired at a high kilovoltage and low current, such as 135 kVp-10 mA, over a low kilovoltage and high current protocol. 相似文献Patients and methods — All cemented stems with > 100 implantations were identified in the National Joint Registry of England and Wales from April 1, 2003 to September 31, 2013 and categorised as taper-slip or composite beam. Survival analyses using Kaplan–Meier and Cox regression were performed.
Results — We identified 292,987 cemented arthroplasties, of which 16% (47,586) were composite beam stems, with taper-slip stems making up the remainder (n = 245,401). There was a statistically significant increased chance of revision in the composite beam group compared with the taper-slip group (1.7% vs 1.3%, p < 0.001) but statistically no significant differences of survival estimates (p = 0.06). When the 2 groups were segregated to delineate the most implanted model in each category, the differences became more profound with the most implanted taper-slip stem (Exeter V40) showing statistically and clinically significant superior 8-year survival: 97.9% compared with 97.6% for all other taper-slip; 97.5% for the most implanted composite beam (Charnley cemented stem); and 97.7% for all other composite beam.
Interpretation — There was an increased incidence of revision for composite beam stems. The most implanted taper-slip stem demonstrated significant survival advantage vs. all other stems. 相似文献
Aims
To obtain an overview of the management and outcomes of children aged 18 years or younger diagnosed with differentiated thyroid carcinoma of follicular cell origin across the UK, by collecting and analysing data from the limited number of centres treating these patients. This multicentre data might provide a more realistic perspective than single-institution series.Materials and methods
Six centres submitted data extracted from historical records on patients aged 18 years or younger, diagnosed between 1964 and 2017. The univariate and multivariable Cox proportional hazard model was used to identify potential predictors of progression-free survival, using national data as a control.Results
Data on 166 patients were available for analysis. Females (74%) were predominant, and the age ranged from 3 to 19 years at diagnosis, mean 14.1 years. Nodal metastases were present in 51%; 12% had distant metastases. After surgery, 95% received radioactive iodine (39% on more than one occasion) and 4% received external beam radiotherapy. With a median follow-up duration of 5 years, 69% are alive with no evidence of disease; 20% are alive with a raised thyroglobulin level as the only evidence of residual disease; 6% have residual structural disease detectable on imaging; 2% have died, from cerebral metastases.Conclusion
Despite most patients having advanced disease at presentation, outcomes are very good. A national prospective registry should allow systematic collection of good-quality data and may facilitate research to further improve outcomes. 相似文献Introduction
Malignant pleural mesothelioma (MPM) is an uncommon cancer with a poor prognosis and heterogeneous survival. Surgery for MPM is offered in some specialist centers to highly selected patients. A previously described classification and regression tree (CART) model stratified survival in unselected MPM patients using routinely collected clinical data. This study aimed to examine the performance of this CART model on a highly selected surgical population.Methods
Data were collected from subjects undergoing cytoreductive surgery for MPM from specialist centers in Hyõgo, Japan, and Sydney, Australia, between 1991 and 2016. The CART model was applied using the combination of clinical variables to stratify subjects into risk groups (1 through 4); survival characteristics were then compared.Results
Two hundred eighty-nine cases were included (205 from Australia, 84 from Japan). Overall median survival was 34.6 (interquartile range: 17.5–56.1) months; median age was 63.0 (interquartile range: 57.0–67.8) years, and 83.0% (n = 240) were male. There were no clinically meaningful differences between the two cohorts. Survival across the four risk groups was significantly different (p < 0.0001); the model stratified survival well with a Harrell's concordance statistic of 0.62 (95% confidence interval: 0.57–0.66) at 36 months. The group with the longest survival (median, 82.5 months) had: no weight loss, hemoglobin > 153 g/L and serum albumin > 43 g/L at time of referral to the surgical center.Conclusions
Using routinely available clinical variables, the CART model was able to stratify surgical patients into risk groups with statistically different survival characteristics with fair to good performance. Presence of weight loss, anemia, and low albumin should confer caution when considering surgical therapy for MPM. 相似文献- Download : Download high-res image (134KB)
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