Treatment plan comparison in acute and chronic respiratory tract diseases : an observational study of doxophylline vs. theophylline

BACKGROUND: The main objective of this article is to estimate the global cost related to the use of the two drugs (associated drugs, specialist visits, hospital admissions, plasma drug monitoring). METHODS: The drug prescriptions were extracted from the Information System of the Pharmaceutical Prescriptions of the Marche Region for each ATC code in the years 2008-2012 and the number of patients per year and other outcomes measure were obtained. RESULTS: 13,574 patients were treated with theophylline and 19,426 patients with doxophylline. The number of patients treated was approximately 5,000 per year. Co-prescription with other drugs, use of corticosteroids, mean number of visits and hospital admissions (per 100 patients) were lower for doxophylline vs theophylline (1.55vs5.50, 0.3vs0.7, 2.05vs3.73 and 1.57vs3.3 respectively). The annual mean cost per patient was €187.4 for those treated with doxophylline and €513.5 for theophylline. CONCLUSIONS: In our study, doxophylline resulted to be associated with a reduction of the overall cost

The actinobacterial transcription factor RbpA binds to the principal sigma subunit of RNA polymerase

RbpA is a small non-DNA-binding transcription factor that associates with RNA polymerase holoenzyme and stimulates transcription in actinobacteria, including Streptomyces coelicolor and Mycobacterium tuberculosis. RbpA seems to show specificity for the vegetative form of RNA polymerase as opposed to alternative forms of the enzyme. Here, we explain the basis of this specificity by showing that RbpA binds directly to the principal σ subunit in these organisms, but not to more diverged alternative σ factors. Nuclear magnetic resonance spectroscopy revealed that, although differing in their requirement for structural zinc, the RbpA orthologues from S. coelicolor and M. tuberculosis share a common structural core domain, with extensive, apparently disordered, N- and C-terminal regions. The RbpA-σ interaction is mediated by the C-terminal region of RbpA and σ domain 2, and S. coelicolor RbpA mutants that are defective in binding σ are unable to stimulate transcription in vitro and are inactive in vivo. Given that RbpA is essential in M. tuberculosis and critical for growth in S. coelicolor, these data support a model in which RbpA plays a key role in the σ cycle in actinobacteria

Fetal heart rate and fetal heart rate variability in Lipizzaner broodmares

Monitoring fetal heart rate (FHR) and fetal heart rate variability (FHRV) helps to understand and evaluate normal and pathological conditions in the foal. The aim of this study was to establish normal heart rate reference values for the ongoing equine pregnancy and to perform a heart rate variability (HRV) time-domain analysis in Lipizzaner mares. Seventeen middle- and late-term (days 121–333) pregnant Lipizzaner mares were examined using fetomaternal electrocardiography (ECG). The mean FHR (P = 0.004) and the standard deviation of FHR (P = 0.012) significantly decreased during the pregnancy. FHR ± SD values decreased from 115 ± 35 to 79 ± 9 bpm between months 5 and 11. Our data showed that HRV in the foal decreased as the pregnancy progressed, which is in contrast with the findings of earlier equine studies. The standard deviation of normal-normal intervals (SDNN) was higher (70 ± 25 to 166 ± 108 msec) than described previously. The root mean square of successive differences (RMSSD) decreased from 105 ± 69 to 77 ± 37 msec between the 5th and 11th month of gestation. Using telemetric ECG equipment, we could detect equine fetal heartbeat on day 121 for the first time. In addition, the large differences observed in the HR values of four mare-fetus pairs in four consecutive months support the assumption that there might be ‘high-HR’ and ‘low-HR’ fetuses in horses. It can be concluded that the analysis of FHR and FHRV is a promising tool for the assessment of fetal well-being but the applicability of these parameters in the clinical setting and in studs requires further investigation

Eosinophils Target Therapy for Severe Asthma: Critical Points

Asthma is a chronic and heterogeneous disease, which is defined as severe disease whenever it requires treatment with a high dose of inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming ‘‘uncontrolled’’ or if it remains ‘‘uncontrolled’’ despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma, which is characterized by sputum eosinophilia, associated with mild to moderate increase in blood eosinophil count, frequently adult-onset, and associated with chronic rhinosinusitis with nasal polyps in half of the cases. Eosinophilic asthma is driven by T2 inflammation, characterized, among the others, by interleukin-5 production. IL-5 plays a key role in the differentiation, survival, migration, and activation of eosinophils, and it has become an appealing therapeutic target for eosinophilic asthma. In recent years two monoclonal antibodies (mepolizumab and reslizumab) directed against IL-5 and one monoclonal antibody directed against the alpha-subunit of the IL-5 receptor (benralizumab) have been developed. All these IL-5 target drugs have been shown to reduce the number of exacerbation in patients with severe asthma selected on the basis of peripheral blood eosinophil count. There are still a number of unresolved issues related to the anti-IL5 strategy in eosinophilic asthma, which are here reviewed. These issues include the effects of such therapy on airway obstruction and asthmatic symptoms, the level of baseline eosinophils that predicts a response to treatment, the relationship between blood and airway eosinophilia, and, perhaps most importantly, how to elucidate the pathogenetic role played by eosinophils in the individual patient with severe eosinophilic asthma

ANALYSIS OF LIFE INSURANCE INVESTMENT COMPOSITION

Economic recession and global mettle down have brought the question of insurance company investment to the forefront. Growing attention has shifted to the pattern of investments by the insurance and question of how to evaluate such investments. The aim of this research is to evaluate investment compositions which are made by life insurance companies in Indonesia, as well as to know the effects on the performance of Insurance companies

Transabdominal ultrasonographic evaluation of fetal well-being in the late-term mare and cow

In the equine practice, attempts have been made to examine the fetus in the second and third trimester of pregnancy but all of the available methods have limitations. Until now, transabdominal ultrasonography has been regarded as the most informative examination. This method allows us to measure fetal heart rate, fetal activity as well as the quality and quantity of the fetal fluids. A modified biophysical profile for horses was used by several researchers in the USA from the 1990s as a gold standard. However, it is not sensitive enough and, in the authors’ experience, professionals can face difficulties during its application (e.g. for measuring aortic diameter and fetal breathing movements). In cows, this method was first used for this purpose by a Canadian research group in 2007. They reported that transabdominal ultrasound was promising but showed low sensitivity in this species. The present studies show that birth weight cannot be predicted from fetal aortic diameter measurement in cows as suggested by other researchers. Transabdominal ultrasound needs special equipment (2–3.5 MHz convex transducer) and basic ultrasonographic knowledge; however, we suggest that in most cases it can be performed with the dam placed in a stock and without shaving the examination area. The method provides useful information within 30–40 minutes, enabling the examiner to determine whether or not the fetus is alive and to recognise placentitis or twins. This technique also allows measuring the combined thickness of the uteroplacental unit, and the authors’ ongoing study showed higher normal values in Lipizzaner mares compared to values in other breeds. In conclusion, with the help of advanced techniques, simple and low-cost methods should be developed for the evaluation of the pregnant dam and its fetus to assess fetal viability in the veterinary practice