Indications for Systemic Fluoroquinolone Therapy in Europe and Prevalence of Primary-Care Prescribing in France, Germany and the UK:Descriptive Population-Based Study

BACKGROUND AND OBJECTIVES: In the USA the benefit-risk profile of fluoroquinolones for treating patients with acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, and uncomplicated urinary tract infections (uUTIs) is considered unfavorable. However, the number of fluoroquinolone products in the EU indicated and prescribed for these infections is uncertain. The objective of this study was to provide data on indications for fluoroquinolones in Europe and examine the prevalence of prescribing in France, Germany and the UK.METHODS: Descriptive analysis of indications for systemic fluoroquinolone antibiotics across the European Economic Area (EEA) and descriptive analysis of systemic fluoroquinolone antibiotic prescribing in France, Germany and UK electronic health records (2000-2015).RESULTS: All EEA countries had fluoroquinolone products indicated for acute sinusitis, acute bronchitis, or uUTIs, with differences in the number of products between countries for: acute sinusitis (19.5-51.9%), acute bronchitis (22.2-73.4%), and uUTIs (52.0-89.1%). The prevalence of fluoroquinolone prescribing for the treatment of respiratory tract infections (RTIs) appeared to fall with time in all countries and for UTI in France and UK only. Changes were greatest in the UK. In France, Germany, and the UK, respectively: acute sinusitis accounted for 29.5, 20.6, and 40.7% of all oral fluoroquinolone prescriptions for upper RTIs; acute bronchitis accounted for 63.0, 83.0, and 89.9% of all fluoroquinolone prescriptions for lower RTIs; uUTIs accounted for 83.3, 89.9, and 32.2% of all fluoroquinolone prescriptions for UTIs.CONCLUSION: Large numbers of fluoroquinolone products in Europe are listed for the treatment of milder infections such as acute bronchitis, acute sinusitis and uUTIs. Among the countries assessed, fluoroquinolones were commonly prescribed for these conditions and potentially should lead to a review of therapeutic guidelines.</p

The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes

Organisms have evolved to survive rigorous environments and are not prepared to thrive in a world of caloric excess and sedentary behavior. A realization that physical exercise (or lack of it) plays a pivotal role in both the pathogenesis and therapy of type 2 diabetes mellitus (t2DM) has led to the provocative concept of therapeutic exercise mimetics. A decade ago, we attempted to simulate the beneficial effects of exercise by treating t2DM patients with 3 weeks of daily hyperthermia, induced by hot tub immersion. The short-term intervention had remarkable success, with a 1 % drop in HbA1, a trend toward weight loss, and improvement in diabetic neuropathic symptoms. An explanation for the beneficial effects of exercise and hyperthermia centers upon their ability to induce the cellular stress response (the heat shock response) and restore cellular homeostasis. Impaired stress response precedes major metabolic defects associated with t2DM and may be a near seminal event in the pathogenesis of the disease, tipping the balance from health into disease. Heat shock protein inducers share metabolic pathways associated with exercise with activation of AMPK, PGC1-a, and sirtuins. Diabetic therapies that induce the stress response, whether via heat, bioactive compounds, or genetic manipulation, improve or prevent all of the morbidities and comorbidities associated with the disease. The agents reduce insulin resistance, inflammatory cytokines, visceral adiposity, and body weight while increasing mitochondrial activity, normalizing membrane structure and lipid composition, and preserving organ function. Therapies restoring the stress response can re-tip the balance from disease into health and address the multifaceted defects associated with the disease

Development and validation of Videogame Addiction Scale for Children (VASC)

The aim of the present study was to develop a valid and reliable Videogame Addiction Scale for Children (VASC). The data were derived from 780 children who completed the Videogame Addiction Scale (405 girls and 375 boys; 48.1% ranging in age from 9 to 12 years). The sample was randomly split into two different sub-samples (sample 1, n=400; sample 2, n= 380). Sample 1 was used to perform exploratory factor analysis (EFA) to define the factorial structure of VASC. As a result of EFA, a four-factor structure comprising 21 items was obtained and explained 55% of the total variance (the four factors being "self-control," "reward/reinforcement", "problems," and "involvement"). The internal consistency reliability of VASC has found 0.89. Confirmatory factor analysis (CFA) was performed to confirm the factorial structure obtained by EFA in the remaining half of sample (n= 390). The obtained fit indices from the CFA confirmed the structure of the EFA. The 21-item VASC has good psychometric properties that can be used among Turkish schoolchildren populations

Symmorphosis through dietary regulation: a combinatorial role for proteolysis, autophagy and protein synthesis in normalising muscle metabolism and function of hypertrophic mice after acute starvation

Animals are imbued with adaptive mechanisms spanning from the tissue/organ to the cellular scale which insure that processes of homeostasis are preserved in the landscape of size change. However we and others have postulated that the degree of adaptation is limited and that once outside the normal levels of size fluctuations, cells and tissues function in an aberant manner. In this study we examine the function of muscle in the myostatin null mouse which is an excellent model for hypertrophy beyond levels of normal growth and consequeces of acute starvation to restore mass. We show that muscle growth is sustained through protein synthesis driven by Serum/Glucocorticoid Kinase 1 (SGK1) rather than Akt1. Furthermore our metabonomic profiling of hypertrophic muscle shows that carbon from nutrient sources is being channelled for the production of biomass rather than ATP production. However the muscle displays elevated levels of autophagy and decreased levels of muscle tension. We demonstrate the myostatin null muscle is acutely sensitive to changes in diet and activates both the proteolytic and autophagy programmes and shutting down protein synthesis more extensively than is the case for wild-types. Poignantly we show that acute starvation which is detrimental to wild-type animals is beneficial in terms of metabolism and muscle function in the myostatin null mice by normalising tension production

Kelvin-Helmholtz instability in the presence of variable viscosity for mudflow resuspension in estuaries

The temporal stability of a parallel shear flow of miscible fluid layers of dif- ferent density and viscosity is investigated through a linear stability analysis and direct numerical simulations. The geometry and rheology of this Newto- nian fluid mixing can be viewed as a simplified model of the behavior of mud- flow at the bottom of estuaries for suspension studies. In this study, focus is on the stability and transition to turbulence of an initially laminar configuration. A parametric analysis is performed by varying the values of three control pa- rameters, namely the viscosity ratio, the Richardson and Reynolds numbers, in the case of initially identical thickness of the velocity, density and viscosity profiles. The range of parameters has been chosen so as to mimic a wide variety of real configurations. This study shows that the Kelvin-Helmholtz instability is controlled by the local Reynolds and Richardson numbers of the inflection point. In addition, at moderate Reynolds number, viscosity strat- ification has a strong influence on the onset of instability, the latter being enhanced at high viscosity ratio, while at high Reynolds number, the influ- ence is less pronounced. In all cases, we show that the thickness of the mixing layer (and thus resuspension) is increased by high viscosity stratification, in particular during the non-linear development of the instability and especially pairing processes. This study suggests that mud viscosity has to be taken into account for resuspension parameterizations because of its impact on the inflec- tion point Reynolds number and the viscosity ratio, which are key parameters for shear instabilities

How did smokers respond to standardised cigarette packaging with new, larger health warnings in the United Kingdom during the transition period?:A cross-sectional online survey

Introduction: In the United Kingdom, standardised packaging for cigarettes was phased in between May 2016 and May 2017. We assessed whether there was an association between using standardised packs and warning salience, thoughts about the risks of smoking, thoughts about quitting, and awareness and use of stop-smoking websites.Methods: We conducted a cross-sectional online survey with current smokers aged 16 and over (N = 1865) recruited in two regions of England between February-April 2017, when both standardised and fully-branded packs were on the market. Participants were asked about use of standardised packs, warning salience (noticing, reading closely), and whether the packs they were using increased thoughts of the risks of smoking and quitting. They were also asked about awareness of stop-smoking websites, source of awareness (including warnings on packs), and whether they had visited a stop-smoking website.Results: Most participants reported currently using standardised packs (76.4%), 9.3% were not currently using them but had previously used them, and 14.3% had never used them. Compared with never users, current users were more likely to have noticed the warnings on packs often/very often (AOR (95%CI) = 2.76 (2.10, 3.63)), read them closely often/very often (AOR(95%CI) = 2.16 (1.51, 3.10)), thought somewhat/a lot about the health risks of smoking (AOR(95%CI) = 1.92 (1.38, 2.68)), and thought somewhat/a lot about quitting (AOR(95%CI) = 1.90 (1.30, 2.77)). They were also more likely to have noticed a stop-smoking website on packs.Conclusions: Consistent with the broad objectives of standardised packaging, we found that it was associated with increased warning salience and thoughts about risks and quitting

Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy

The thymus is a central lymphoid organ with crucial role in generating T cells and maintaining homeostasis of the immune system. More than 30 peptides, initially referred to as “thymic hormones,” are produced by this gland. Although the majority of them have not been proven to be thymus-speciWc, thymic peptides comprise an eVective group of regulators, mediating important immune functions. Thymosin fraction Wve (TFV) was the Wrst thymic extract shown to stimulate lymphocyte proliferation and diVerentiation. Subsequent fractionation of TFV led to the isolation and characterization of a series of immunoactive peptides/polypeptides, members of the thymosin family. Extensive research on prothymosin (proT) and thymosin 1 (T1) showed that they are of clinical signiWcance and potential medical use. They may serve as molecular markers for cancer prognosis and/or as therapeutic agents for treating immunodeWciencies, autoimmune diseases and malignancies. Although the molecular mechanisms underlying their eVect are yet not fully elucidated proT and T1 could be considered as candidates for cancer immunotherapy. In this review, we will focus in principle on the eventual clinical utility of proT, both as a tumor biomarker and in triggering anticancer immune responses. Considering the experience acquired via the use of T1 to treat cancer patients, we will also discuss potential approaches for the future introduction of proT into the clinical setting

The timing of umbilical cord clamping at birth: physiological considerations

While it is now recognized that umbilical cord clamping (UCC) at birth is not necessarily an innocuous act, there is still much confusion concerning the potential benefits and harms of this common procedure. It is most commonly assumed that delaying UCC will automatically result in a time-dependent net placental-to-infant blood transfusion, irrespective of the infant’s physiological state. Whether or not this occurs, will likely depend on the infant’s physiological state and not on the amount of time that has elapsed between birth and umbilical cord clamping (UCC). However, we believe that this is an overly simplistic view of what can occur during delayed UCC and ignores the benefits associated with maintaining the infant’s venous return and cardiac output during transition. Recent experimental evidence and observations in humans have provided compelling evidence to demonstrate that time is not a major factor influencing placental-to-infant blood transfusion after birth. Indeed, there are many factors that influence blood flow in the umbilical vessels after birth, which depending on the dominating factors could potentially result in infant-to-placental blood transfusion. The most dominant factors that influence umbilical artery and venous blood flows after birth are lung aeration, spontaneous inspirations, crying and uterine contractions. It is still not entirely clear whether gravity differentially alters umbilical artery and venous flows, although the available data suggests that its influence, if present, is minimal. While there is much support for delaying UCC at birth, much of the debate has focused on a time-based approach, which we believe is misguided. While a time-based approach is much easier and convenient for the caregiver, ignoring the infant’s physiology during delayed UCC can potentially be counter-productive for the infant

Pulmonary hemodynamic responses to in utero ventilation in very immature fetal sheep

<p>Abstract</p> <p>Background</p> <p>The onset of ventilation at birth decreases pulmonary vascular resistance (PVR) resulting in a large increase in pulmonary blood flow (PBF). As the large cross sectional area of the pulmonary vascular bed develops late in gestation, we have investigated whether the ventilation-induced increase in PBF is reduced in immature lungs.</p> <p>Methods</p> <p>Surgery was performed in fetal sheep at 105 d GA (n = 7; term ~147 d) to insert an endotracheal tube, which was connected to a neonatal ventilation circuit, and a transonic flow probe was placed around the left pulmonary artery. At 110 d GA, fetuses (n = 7) were ventilated <it>in utero </it>(IUV) for 12 hrs while continuous measurements of PBF were made, fetuses were allowed to develop <it>in utero </it>for a further 7 days following ventilation.</p> <p>Results</p> <p>PBF changes were highly variable between animals, increasing from 12.2 ± 6.6 mL/min to a maximum of 78.1 ± 23.1 mL/min in four fetuses after 10 minutes of ventilation. In the remaining three fetuses, little change in PBF was measured in response to IUV. The increases in PBF measured in responding fetuses were not sustained throughout the ventilation period and by 2 hrs of IUV had returned to pre-IUV control values.</p> <p>Discussion and conclusion</p> <p>Ventilation of very immature fetal sheep <it>in utero </it>increased PBF in 57% of fetuses but this increase was not sustained for more than 2 hrs, despite continuing ventilation. Immature lungs can increase PBF during ventilation, however, the present studies show these changes are transient and highly variable.</p

Systemic Correlates of Angiographic Coronary Artery Disease

Coronary angiography allows a direct evaluation of coronary anatomy. The aim of the present investigation was to search for correlations between the magnitude of coronary artery disease, as assessed by angiography, and a number of systemic parameters. A group of 116 patients (80 male, 36 female) with coronary heart disease diagnosed by angiography, aged 62.0±10.5 years, was the subject of an observational study. Correlation and linear regression analysis using coronary artery disease burden (CADB - sum of the percentage of the luminal stenosis encountered in all the lesions of the coronary arterial trees) as dependent variable, and age, sex, plasma calcium, phosphorus, magnesium, glucose, HDL cholesterol, LDL cholesterol, triglycerides, uric acid, estimated glomerular filtration rate and body mass index as independent variables, were carried out. Significant correlation values versus CADB were seen with age (r 0.19, p 0.04), uric acid (r 0.18, p 0.048) and fasting plasma glucose (r 0.33, p<0.001). Linear regression analysis, yielding a global significance level of 0.002, showed a significant value for glucose (p 0.018) and for sex (0.008). In conclusion, among several systemic parameters studied, plasma glucose was found to be correlated to coronary artery atherosclerosis lesions