Comparison of the safety and efficacy of a fixed-dose combination regimen and separate formulations for pulmonary tuberculosis treatment

OBJECTIVES: Fixed-dose combination formulations, which simplify the administration of drugs and prevent the development of drug resistance, have been recommended as a standard anti-tuberculosis treatment regimen. However, the composition and dosage recommendations for fixed-dose combination formulations differ from those for separate formulations. Thus, questions about the effectiveness and side effects of combination formulations remain. The aim of this study was to compare the safety and efficacy of these two types of anti-tuberculosis regimens for pulmonary tuberculosis treatment. METHOD: A prospective, randomized controlled study was conducted using the directly observed treatment short-course strategy. Patients were randomly allocated to one of two short-course regimens. One year after completing the treatment, these patients’ outcomes were analyzed. ClinicalTrials.gov: NCT00979290. RESULTS: A total of 161 patients were enrolled, 142 of whom were evaluable for safety assessment. The two regimens had a similar incidence of adverse effects. In the per-protocol population, serum bilirubin concentrations at the peak level, at week 4, and at week 8 were significantly higher for the fixed-dose combination formulation than for the separate formulations. All patients had negative sputum cultures at the end of the treatment, and no relapse occurred after one year of follow-up. CONCLUSIONS: In this randomized study, transient higher serum bilirubin levels were noted for the fixed-dose combination regimen compared with the separate formulations during treatment. However, no significant difference in safety or efficacy was found between the groups when the directly observed treatment short-course strategy was used

Influence of Step Length and Cadence on the Sharing of the Total Support Moments Between the Lower Limbs During Level Walking

The current study aimed to investigate the effects of walking speed on the inter-limb sharing of whole body support in terms of total support moments (Ms) during walking. A multiple linear regression model was conducted to explore the relationship between gait speed in terms of step length and cadence, and the difference of the first and second peaks of the Ms (DMs) during walking. The DMs were found to increase with either increased step length or cadence. Walking with greater speed relied more on the leading limb to provide support for the forward progression of the body. In addition, variations of gait speed parameters affected the load-sharing pattern between the lower limbs during weight transfer of walking. Gait speed parameters have to be taken as covariates when analysing the coordination of the kinetics between lower limbs

Concurrent Use in Taiwan of Chinese Herbal Medicine Therapies among Hormone Users Aged 55 Years to 79 Years and Its Association with Breast Cancer Risk: A Population-Based Study

Background. The purpose of the present study was to analyze the concurrent use of Chinese herbal products (CHPs) among women aged 55 to 79 years who had also been prescribed hormonal therapies (HT) and its association with breast cancer risk. Methods. The use, frequency of service, and CHP prescribed among 17,583 HT users were evaluated from a random sample of 1 million beneficiaries from the National Health Insurance Research Database. A logistic regression method was used to identify the factors that were associated with the coprescription of a CHP and HT. Cox proportional hazards regressions were performed to calculate the hazard ratios (HRs) of breast cancer between the TCM nonusers and women who had undergone coadministration of HT and a CHP or CHPs. Results. More than one out of every five study subjects used a CHP concurrently with HT (CHTCHP patients). Shu-Jing-Huo-Xie-Tang was the most commonly used CHP coadministered with HT. In comparison to HT-alone users, the HRs for invasive breast cancer among CHTCHP patients were not significantly increased either in E-alone group or in mixed regimen group. Conclusions. The coadministration of hormone regimen and CHPs did not increase the risk of breast cancer

A Cascaded Approach for ultraly High Performance Lesion Detection and False Positive Removal in Liver CT Scans

Liver cancer has high morbidity and mortality rates in the world. Multi-phase CT is a main medical imaging modality for detecting/identifying and diagnosing liver tumors. Automatically detecting and classifying liver lesions in CT images have the potential to improve the clinical workflow. This task remains challenging due to liver lesions' large variations in size, appearance, image contrast, and the complexities of tumor types or subtypes. In this work, we customize a multi-object labeling tool for multi-phase CT images, which is used to curate a large-scale dataset containing 1,631 patients with four-phase CT images, multi-organ masks, and multi-lesion (six major types of liver lesions confirmed by pathology) masks. We develop a two-stage liver lesion detection pipeline, where the high-sensitivity detecting algorithms in the first stage discover as many lesion proposals as possible, and the lesion-reclassification algorithms in the second stage remove as many false alarms as possible. The multi-sensitivity lesion detection algorithm maximizes the information utilization of the individual probability maps of segmentation, and the lesion-shuffle augmentation effectively explores the texture contrast between lesions and the liver. Independently tested on 331 patient cases, the proposed model achieves high sensitivity and specificity for malignancy classification in the multi-phase contrast-enhanced CT (99.2%, 97.1%, diagnosis setting) and in the noncontrast CT (97.3%, 95.7%, screening setting)

The Strange Parton Distribution of the Nucleon: Global Analysis and Applications

The strangeness degrees of freedom in the parton structure of the nucleon are explored in the global analysis framework, using the new CTEQ6.5 implementation of the general mass perturbative QCD formalism of Collins. We systematically determine the constraining power of available hard scattering experimental data on the magnitude and shape of the strange quark and anti-quark parton distributions. We find that current data favor a distinct shape of the strange sea compared to the isoscalar non-strange sea. A new reference parton distribution set, CTEQ6.5S0, and representative sets spanning the allowed ranges of magnitude and shape of the strange distributions, are presented. Some applications to physical processes of current interest in hadron collider phenomenology are discussed.Comment: 19 pages; revised version submitted to JHE

Increased Risk for Invasive Breast Cancer Associated with Hormonal Therapy: A Nation-Wide Random Sample of 65,723 Women Followed from 1997 to 2008

BACKGROUND: Hormonal therapy (HT) either estrogen alone (E-alone) or estrogen plus progesterone (E+P) appears to increase the risk for breast cancer in Western countries. However, limited information is available on the association between HT and breast cancer in Asian women characterized mainly by dietary phytoestrogens intake and low prevalence of contraceptive pills prescription. METHODOLOGY: A total of 65,723 women (20-79 years of age) without cancer or the use of Chinese herbal products were recruited from a nation-wide one-million representative sample of the National Health Insurance of Taiwan and followed from 1997 to 2008. Seven hundred and eighty incidents of invasive breast cancer were diagnosed. Using a reference group that comprised 40,052 women who had never received a hormone prescription, Cox proportional hazard models were constructed to determine the hazard ratios for receiving different types of HT and the occurrence of breast cancer. CONCLUSIONS: 5,156 (20%) women ever used E+P, 2,798 (10.8%) ever used E-alone, and 17,717 (69%) ever used other preparation types. The Cox model revealed adjusted hazard ratios (HRs) of 2.05 (95% CI 1.37-3.07) for current users of E-alone and 8.65 (95% CI 5.45-13.70) for current users of E+P. Using women who had ceased to take hormonal medication for 6 years or more as the reference group, the adjusted HRs were significantly elevated and greater than current users and women who had discontinued hormonal medication for less than 6 years. Current users of either E-alone or E+P have an increased risk for invasive breast cancer in Taiwan, and precautions should be taken when such agents are prescribed

GenEpi: gene-based epistasis discovery using machine learning.

BackgroundGenome-wide association studies (GWAS) provide a powerful means to identify associations between genetic variants and phenotypes. However, GWAS techniques for detecting epistasis, the interactions between genetic variants associated with phenotypes, are still limited. We believe that developing an efficient and effective GWAS method to detect epistasis will be a key for discovering sophisticated pathogenesis, which is especially important for complex diseases such as Alzheimer's disease (AD).ResultsIn this regard, this study presents GenEpi, a computational package to uncover epistasis associated with phenotypes by the proposed machine learning approach. GenEpi identifies both within-gene and cross-gene epistasis through a two-stage modeling workflow. In both stages, GenEpi adopts two-element combinatorial encoding when producing features and constructs the prediction models by L1-regularized regression with stability selection. The simulated data showed that GenEpi outperforms other widely-used methods on detecting the ground-truth epistasis. As real data is concerned, this study uses AD as an example to reveal the capability of GenEpi in finding disease-related variants and variant interactions that show both biological meanings and predictive power.ConclusionsThe results on simulation data and AD demonstrated that GenEpi has the ability to detect the epistasis associated with phenotypes effectively and efficiently. The released package can be generalized to largely facilitate the studies of many complex diseases in the near future