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Increased Persistence (increased + persistence)
Selected AbstractsLoss of RD1 contributed to the attenuation of the live tuberculosis vaccines Mycobacterium bovis BCG and Mycobacterium microtiMOLECULAR MICROBIOLOGY, Issue 3 2002Alexander S. Pym Summary Although large human populations have been safely immunized against tuberculosis with two live vaccines, Mycobacterium bovis BCG or Mycobacterium microti, the vole bacillus, the molecular basis for the avirulence of these vaccine strains remains unknown. Comparative genomics has identified a series of chromosomal deletions common to both virulent and avirulent species but only a single locus, RD1, that has been deleted from M. bovis BCG and M. microti. Restoration of RD1, by gene knock-in, resulted in a marked change in colonial morphology towards that of virulent tubercle bacilli. Three RD1-encoded proteins were localized in the cell wall, and two of them, the immunodominant T-cell antigens ESAT-6 and CFP-10, were also found in culture supernatants. The BCG::RD1 and M. microti::RD1 knock-ins grew more vigorously than controls in immunodeficient mice, inducing extensive splenomegaly and granuloma formation. Increased persistence and partial reversal of attenuation were observed when immunocompetent mice were infected with the BCG::RD1 knock-in, whereas BCG controls were cleared. Knocking-in five other RD loci did not affect the virulence of BCG. This study describes a genetic lesion that contributes to safety and opens new avenues for vaccine development. [source] Treatment with inhaled corticosteroids in asthma is too often discontinued,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 4 2008Nancy S. Breekveldt-Postma PhD Abstract Purpose To study persistence with inhaled corticosteroids (ICS) and its determinants in asthma-patients. Methods From the PHARMO database, asthma-patients (age,<,35 years) with a first dispensing for ICS in 1999,2002 and,,,2 dispensings in the first year were included. Persistence during the first year was defined as the number of days from start to time of first failure to continue renewal of the initial ICS. Potential determinants of persistence were assessed at ICS-start and 1 year before. Results The study-cohort included 5563 new users of single ICS and 297 of fixed-combined ICS. Less than 10% of patients using single ICS and 15% of patients using fixed-combined ICS were persistent at 1 year. Similar persistence-rates were observed when stratified for age (children/adolescents: 0,18 years and adults: 19,34 years). Increased persistence with single ICS was observed with the type of ICS (budesonide), prescriber (specialist), prior use of long-acting beta-agonists, previous hospitalization for asthma, metered-dose inhaler, low starting-dose and once-daily dosing regimen at start. Persistence with fixed combined ICS-treatment increased with younger age and was decreased in patients having high starting-dose of ICS and prior use of antibiotics. Conclusion New users of both single and fixed combined ICS have alarming low persistence rates with ICS-treatment in the first year of follow-up. Persistence was mainly related to patient factors, such as severity of disease, and to treatment-related factors, such as once-daily dosing frequency. Copyright © 2008 John Wiley & Sons, Ltd. [source] The economic consequences of noncompliance in cardiovascular disease and related conditions: a literature reviewINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2008N. Muszbek Summary Objectives:, To review studies on the cost consequences of compliance and/or persistence in cardiovascular disease (CVD) and related conditions (hypertension, dyslipidaemia, diabetes and heart failure) published since 1995, and to evaluate the effects of noncompliance on healthcare expenditure and the cost-effectiveness of pharmaceutical interventions. Methods:, English language papers published between January 1995 and February 2007 that examined compliance/persistence with medication for CVD or related conditions, provided an economic evaluation of pharmacological interventions or cost analysis, and quantified the cost consequences of noncompliance, were identified through database searches. The cost consequences of noncompliance were compared across studies descriptively. Results:, Of the 23 studies identified, 10 focused on hypertension, seven on diabetes, one on dyslipidaemia, one on coronary heart disease, one on heart failure and three covered multiple diseases. In studies assessing drug costs only, increased compliance/persistence led to increased drug costs. However, increased compliance/persistence increased the effectiveness of treatment, leading to a decrease in medical events and non-drug costs. This offset the higher drug costs, leading to savings in overall treatment costs. In studies evaluating the effect of compliance/persistence on the cost-effectiveness of pharmacological interventions, increased compliance/persistence appeared to reduce cost-effectiveness ratios, but the extent of this effect was not quantified. Conclusions:, Noncompliance with cardiovascular and antidiabetic medication is a significant problem. Increased compliance/persistence leads to increased drug costs, but these are offset by reduced non-drug costs, leading to overall cost savings. The effect of noncompliance on the cost-effectiveness of pharmacological interventions is inconclusive and further research is needed to resolve the issue. [source] The dynamics of unattached benthic macroalgal accumulations in the Swan,Canning EstuaryHYDROLOGICAL PROCESSES, Issue 13 2001Helen Astill Abstract It has been suggested that macroalgal accumulations may impact on benthic nutrient cycling by promoting remineralization of sedimentary nutrients, otherwise inaccessible, and act as sinks/sources for dissolved nutrients in the water column. However, little consideration has been given to the time taken for these impacts to occur, and if accumulations persist long enough in a region for impacts to occur. In this study, accumulations were characterized seasonally, according to biomass, height relative to water depth, and organic content of the underlying sediment, from November 1996 to August 1997, in the Swan,Canning Estuary. Persistence of accumulations was measured from late summer to mid-winter in 1997, by tagging individual plants and recording the time tagged plants persisted at 10 sites. In summer 1998, physicochemical profiles of accumulations were measured over 24 h, at two locations: one with relatively low sediment organic content (SOCn) (1·5% LOI) and one with relatively high SOC (6% LOI). Accumulations rarely exceeded 25 cm in height, regardless of water column depth, and ranged between 100 and 500 g dwt m,2. Macroalgae persisted between one week, in relatively well-flushed regions, to one month in areas with poor flushing. Over the entire diurnal period, almost 100% of incident light was attenuated at the bottom of all accumulations. Dissolved oxygen levels at the bottom of accumulations were generally depressed, particularly at night, with hypoxia (1 mg l,1) recorded at the high SOC site at 03 : 00 h. No significant differences in FRP concentrations (approximately 30,60 µg l,1) were recorded between sites, or within accumulation profiles. Ammonium levels were greatly raised inside accumulations at the high SOC site by 03 : 00 h (10 and 300 µg l,1, inside and outside, respectively). The results show that, where SOC is high, conditions within accumulations are affected. Impacts occurred within 24 h; well within the period for which accumulations persist. These results also indicate that regulation of hydrological regimes in estuarine systems may result in increased persistence of macroalgal accumulations, and associated water quality problems. Copyright © 2001 John Wiley & Sons, Ltd. [source] |