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71.

Background

Physicians treating nonvalvular atrial fibrillation (AF) assess stroke and bleeding risks when deciding on anticoagulation. The agreement between empirical and physician-estimated risks is unclear. Furthermore, the association between patient and physician sex and anticoagulation decision-making is uncertain.

Methods

We pooled data from 2 national primary care physician chart audit databases of patients with AF (Facilitating Review and Education to Optimize Stroke Prevention in Atrial Fibrillation and Coordinated National Network to Engage Physicians in the Care and Treatment of Patients with Atrial Fibrillation Chart Audit) with a combined 1035 physicians (133 female, 902 male) and 10,927 patients (4567 female and 6360 male).

Results

Male physicians underestimated stroke risk in female patients and overestimated risk in male patients. Female physicians estimated stroke risk well in female patients but underestimated the risk in male patients. Risk of bleeding was underestimated in all. Despite differences in risk assessment by physician and patient sex, > 90% of patients received anticoagulation across all subgroups. There was modest agreement between physician estimated and calculated (ie, CHADS2 score) stroke risk: Kappa scores were 0.41 (0.35-0.47) for female physicians and 0.34 (0.32-0.36) for male physicians.

Conclusions

Our study is the first to examine the association between patient and physician sex influences and stroke and bleeding risk estimation in AF. Although there were differences in agreement between physician estimated stroke risk and calculated CHADS2 scores, these differences were small and unlikely to affect clinical practice; further, despite any perceived differences in the accuracy of risk assessment by sex, most patients received anticoagulation.  相似文献   
72.

Background and aims

It is not known whether non alcoholic fatty liver disease (NAFLD) is a risk factor for diabetes in non obese, non centrally-obese subjects. Our aim was to investigate relationships between fatty liver, insulin resistance and a biomarker score for liver fibrosis with incident diabetes at follow up, in subjects who were neither obese nor centrally-obese.

Methods and results

As many as 70,303 subjects with a body mass index (BMI) < 25 kg/m2 and without diabetes were followed up for a maximum of 7.9 years. At baseline, fatty liver was identified by liver ultrasound, insulin resistance (IR) by homeostatic model assessment of insulin resistance (HOMA-IR) ≥2.0, and central obesity by waist circumference (waist circumference ≥90 cm (men) and ≥85 cm (women). The Fibrosis-4 (FIB-4 score) was used to estimate extent of liver fibrosis. Cox proportional hazards models adjusted for confounders were used to estimate hazard ratios (aHRs) for incident diabetes. As many as 852 incident cases of diabetes occurred during follow up (median [IQR] 3.71 [2.03] years). Mean ± SD BMI was 22.8 ± 1.8 and 21.7 ± 2.0 kg/m2 in subjects with and without diabetes at follow up. In subjects without central obesity and with fatty liver, aHRs (95% CI) for incident diabetes at follow up were 2.17 (1.56, 3.03) for men, and 2.86 (1.50,5.46) for women. Similar aHRs for incident diabetes occurred with fatty liver, IR and the highest quartile of FIB-4 combined, in men; and there was a non significant trend toward increased risk in women.

Conclusions

In normal weight, non-centrally obese subjects NAFLD is an independent risk factor for incident diabetes.  相似文献   
73.
Wistar Audiogenic Rat (WAR) strain is an animal model for epilepsy studies, the chronic multifactorial disease that affects millions of people worldwide. The animals of this strain are genetically predisposed to sound-induced seizures, called audiogenic seizures, and have been used for many years in studies to understand the mechanisms involved in the epilepsies and their neuropsychiatric comorbidities, as well as the screening of potential anti-convulsant agents. Nevertheless, little is known about the reproductive characteristics of these animals. The main goal of this study was to characterize the female reproductive performance and the fetal growth of WARs in comparison to the Wistar rats, obtaining important information for physiology and behavioral studies, as well as for the preservation of the strain. The results indicated few differences between WAR and Wistar regarding the female reproductive performance. There was no significant difference in the number of pregnant females by mating, number of live births per female, number of cells per blastocyst, and several characteristics related to reproductive performance, such as pre- and post-implantation losses. However, significant differences were observed in birth weight and weight gain until weaning, with WAR animals presenting a body weight below Wistar at birth and reduced body weight gain during the lactation period. In addition, the WAR females showed lower body weight on the day 20 of pregnancy and a larger number of corpora lutea, when compared with those of Wistar animals. Thus, we conclude that although Wistar and WAR strains have few differences in their reproductive performance, which might impact future physiological life challenges or others experimentally induced procedures, it still is a very viable strain regarding reproduction.

Abbreviations: CONCEA: National Council for the Control of Animal Experimentation; GEPR: genetically epilepsy-prone rats; WAR: Wistar Audiogenic Rat.  相似文献   

74.
BackgroundThe efficacy of ticagrelor in the long-term post–ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain.ObjectivesThe purpose of this study was to evaluate the efficacy of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy.MethodsThis international, multicenter, randomized, open-label with blinded endpoint adjudication trial enrolled 3,799 patients (age <75 years) with STEMI receiving fibrinolytic therapy. Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg daily thereafter). The key outcomes were cardiovascular mortality, myocardial infarction, or stroke, and the same composite outcome with the addition of severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events at 12 months.ResultsThe combined outcome of cardiovascular mortality, myocardial infarction, or stroke occurred in 129 of 1,913 patients (6.7%) receiving ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio: 0.93; 95% confidence interval: 0.73 to 1.18; p = 0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio: 0.88; 95% confidence interval: 0.71 to 1.09; p = 0.25). The rates of major, fatal, and intracranial bleeding were similar between the ticagrelor and clopidogrel groups.ConclusionAmong patients age <75 years with STEMI, administration of ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel. (Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis [TREAT]; NCT02298088)  相似文献   
75.

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   
76.

Purpose

The purpose of this study was to assess the potential of a deep learning model to discriminate between benign and malignant breast lesions using magnetic resonance imaging (MRI) and characterize different histological subtypes of breast lesions.

Materials and methods

We developed a deep learning model that simultaneously learns to detect lesions and characterize them. We created a lesion-characterization model based on a single two-dimensional T1-weighted fat suppressed MR image obtained after intravenous administration of a gadolinium chelate selected by radiologists. The data included 335 MR images from 335 patients, representing 17 different histological subtypes of breast lesions grouped into four categories (mammary gland, benign lesions, invasive ductal carcinoma and other malignant lesions). Algorithm performance was evaluated on an independent test set of 168 MR images using weighted sums of the area under the curve (AUC) scores.

Results

We obtained a cross-validation score of 0.817 weighted average receiver operating characteristic (ROC)-AUC on the training set computed as the mean of three-shuffle three-fold cross-validation. Our model reached a weighted mean AUC of 0.816 on the independent challenge test set.

Conclusion

This study shows good performance of a supervised-attention model with deep learning for breast MRI. This method should be validated on a larger and independent cohort.  相似文献   
77.
Background and purpose — 1 in 5 patients are dissatisfied following unicompartmental or total knee arthroplasty (UKA or TKA). This may be partly explained by failing to return to desired activity post-arthroplasty. To facilitate return to desired activity, a greater understanding of predictors of return to desired activity in UKA and TKA patients is needed. We compared rates of return to desired activity 12 months following UKA vs. TKA, and identified and compared predictors of return to desired activity 12 months following UKA vs. TKA.

Patients and methods — Patients were prospectively recruited from 2 hospitals prior to undergoing UKA or primary TKA. Patients reported preoperatively the activity/activities that were limited due to their knee that they wished to return to after arthroplasty. At 12-months postoperatively, patients reported whether they had returned to these activities (‘return to desired activity’). Preoperative predictors evaluated were age, sex, BMI, education, comorbidities, pain expectations, Oxford Knee Score (OKS), UCLA Activity Score, and EQ-5D. Generalized linear models assessed the relationship between potential predictors and return-to-desired-activity.

Results — The response rate of all patients eligible for 12-month follow-up was 74%. TKA patients (n = 575) were older (mean (SD) 70 (9) vs. 67 (10)) with a greater BMI (31 (6) vs. 30 (5)) than patients undergoing UKA (n = 420). 75% of UKA and 59% of TKA patients returned to desired activity. TKA patients had a greater risk of non-return to desired activity than patients undergoing UKA (risk ratio (95% CI) 1.5 (1.2–1.8)). Predictors of non-return to desired activity following UKA were worse OKS (0.96 (0.93–0.99)), higher BMI (1.04 (1.01–1.08)), and worse expectations (1.9 (1.2–2.8)). Predictors of non-return to desired activity following TKA were worse EQ-5D (0.53 (0.33–0.85)) and worse OKS (0.98 (0.96–1.0)).

Interpretation — UKA patients were more likely to return to desired activity than TKA patients. Predictors of return to desired activity differed following UKA and TKA. Optimizing selection of arthroplasty procedure based on patient characteristics and targeting predictors of poor outcome may facilitate return to desired activity with potential to enhance postoperative satisfaction.  相似文献   

78.
79.

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   
80.
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