Toxoplasmosis and knowledge: what do the Italian women know about?

Toxoplasmosis is a worldwide zoonotic infectious disease caused by Toxoplasma gondii. This infection is estimated to affect about a third of the world's population. The aim of this study was to evaluate the knowledge of Italian women about toxoplasmosis and its forms of transmission, clinical manifestations, diagnosis and prevention through two different modalities (e-research and traditional research). In a cross-sectional study, 808 Italian women were interviewed, using a self-administered questionnaire, through two different modalities: an e-research or web survey and a traditional paper research and 84% reported to have heard about toxoplasmosis, but from most of the sample, it resulted that the knowledge of the protozoan disease was superficial and incomplete.The assessment of the dimensionality related to the toxoplasmosis knowledge's instrument showed that the scale is composed by two stable and reliable factors which explain 58.6% of the variance: (a) the basic knowledge (α = 0.83), which explains the 45.2% of the variance and (b) the specialist knowledge (α = 0.71), which explains the 13.4% of the variance. The variance and the multiple linear regression data analysis showed significant predictors of correct basic knowledge of toxoplasmosis: the highest age, the highest degree of study, to have previously contracted illness or to know someone who had contracted it, to be working or to be housewives. In conclusion, this study showed limited awareness of toxoplasmosis and suggested the implementation of effective education and learning programs. The results also showed that online data collection, in academic research, might be a valid alternative to more traditional (paper-and-pencil) surveys.

Trends in overall survival and costs of multiple myeloma, 2000-2014.

Little real-world evidence is available to describe the recent trends in treatment costs and outcomes for patients with multiple myeloma (MM). Using the Truven Health MarketScan Research Databases linked with social security administration death records, this study found that the percentage of MM patients using novel therapy continuously increased from 8.7% in 2000 to 61.3% in 2014. Compared with MM patients diagnosed in earlier years, those diagnosed after 2010 had higher rates of novel therapy use and better survival outcomes; patients diagnosed in 2012 were 1.25 times more likely to survive 2 years than those diagnosed in 2006. MM patients showed improved survival over the study period, with the 2-year survival gap between MM patients and matched controls decreasing at a rate of 3% per year. Total costs among MM patients have increased in all healthcare services over the years; however, the relative contribution of drug costs has remained fairly stable since 2009 despite new novel therapies coming to market. Findings from this study corroborate clinical data, suggesting a paradigm shift in MM treatment over the past decade that is associated with substantial survival gains. Future studies should focus on the impact on specific novel agents on patients' outcomes.

Predicting imminent risk for fracture in patients aged 50 or older with osteoporosis using US claims data.

UNLABELLED: Patient characteristics contributing to imminent risk for fracture, defined as risk of near-term fracture within the next 12 to 24 months, have not been well defined. In patients without recent fracture, we identified factors predicting imminent risk for vertebral/nonvertebral fracture, including falls, age, comorbidities, and other potential fall risk factors. PURPOSE: Several factors contribute to long-term fracture risk in patients with osteoporosis, including age, bone mineral density, and fracture history. Some patients may be at imminent risk for fracture, defined here as a risk of near-term fracture within 12-24 months. Many patient characteristics contributing to imminent risk for fracture have not been well defined. This case-control study used US commercial and Medicare supplemental insured data for women and men without recent fracture to identify factors associated with imminent risk for fracture. METHODS: Patients included were aged ≥50 with osteoporosis, had a vertebral or nonvertebral fracture claim (index date; fracture group) or no fracture claim (control group) from January 1, 2006, to September 30, 2012, continuously enrolled and without fracture in the 24 months before index. Potential risk factors during the period before fracture were assessed. RESULTS: Using data from 12 months before fracture, factors significantly associated with imminent risk for fracture were previous falls, older age, poorer health status, specific comorbidities (psychosis, Alzheimer's disease, central nervous system disease), and other fall risk factors (wheelchair use, psychoactive medication use, mobility impairment). Similar findings were observed with data from 24 months before fracture. CONCLUSIONS: In patients with osteoporosis and no recent fracture, falls, older age, poorer health status, comorbidities, and other potential fall risk factors were predictive of imminent risk for fracture. Identification of factors associated with imminent risk for vertebral/nonvertebral fracture may help identify and risk stratify those patients most in need of immediate and appropriate treatment to decrease fracture risk.

Teriparatide treatment patterns in osteoporosis and subsequent fracture events: a US claims analysis.

UNLABELLED: The objective of this study was to describe the risk of fragility-related fractures in the 2 years following teriparatide initiation. In an administrative claims analysis of over 11,407 patients, approximately one in eight patients had a new or recurrent fragility-related fracture in the 2 years following teriparatide initiation. INTRODUCTION: The objective of this study was to describe the risk of fragility-related fractures in the 2 years following the initiation of teriparatide in a real-world setting. METHODS: This retrospective study used data from the 2002 to 2011 MarketScan® Commercial and Medicare Supplemental Databases to identify patients 50 years and older with a diagnosis of osteoporosis (ICD-9-CM code 733.0x) who were initiating teriparatide. Patients were required to have continuous medical and pharmacy benefit coverage for the 12 months prior to and 24 months following teriparatide initiation (index event). Teriparatide treatment patterns (persistence and adherence) were described, as was the use of antiresorptive therapy. The primary study outcome was the presence of a new or recurring fragility fracture following the initiation of teriparatide. RESULTS: A total of 11,407 patients met the study criteria (mean age = 69.5, standard deviation = 10.6 years; 92.0% female). One in four (25.6%) patients had fragility fracture claims in the year prior to teriparatide initiation, of which 64.0% were on existing antiresorptive therapy. Overall, 13.4% (n = 1527) of patients had a new or recurrent fracture during the 2-year follow-up period. Forty-eight percent of patients on teriparatide treatment were considered persistent; fragility fractures were more common among patients nonpersistent with teriparatide (15.2%) than among those persistent with teriparatide (11.4%). A higher fracture rate (35.7%) was observed in the cohort with previous fragility fracture then those without pre-index fractures (24%). CONCLUSION: More than 13.4% of patients had new or recurrent fragility-related fractures during the 2 years following the initiation of teriparatide; these fractures were more in common in patients with pre-existing fractures and the patients who were nonpersistent with teriparatide.

Direct medical care costs among pegylated interferon plus ribavirin-treated and untreated chronic hepatitis C patients.

BACKGROUND: Hepatitis C virus (HCV) is a common and expensive infectious disease. The current standard of care for HCV infection, pegylated interferon with ribavirin (PEG-RBV), is costly and has a significant adverse event profile. AIM: To quantify the direct economic burden of HCV infection and PEG-RBV treatment for HCV. METHODS: Using a large administrative claims database, we evaluated the medical and prescription drug costs of patients with HCV from 2002 to 2007. A cohort of patients with PEG-RBV was 1:1 propensity score-matched to a cohort of untreated HCV patients. Multivariate models adjusted for demographic and clinical characteristics in evaluating the effect of PEG-RBV treatment on direct medical expenditure. RESULTS: The matched analysis included 20,002 patients. PEG-RBV-treated patients had higher total direct medical costs ($28,547 vs. $21,752; P < 0.001), outpatient pharmacy costs ($17,419 vs. $2,900; P < 0.001), and outpatient physician visit costs ($894 vs. $787; P < 0.001), but lower inpatient costs ($3,942 vs. $9,543; P < 0.001) and emergency room costs ($366 vs. $505; P < 0.001). After multivariate adjustment, PEG-RBV use was associated with an additional $9,423 in total direct medical costs and an additional $12,244 in HCV-related total medical costs. CONCLUSION: Total HCV-related medical costs are higher for treated than untreated patients, driven mostly by higher outpatient pharmacy costs, which outweigh higher HCV-related inpatient costs incurred by untreated patients.

Development of a refractory gastro-oesophageal reflux score using an administrative claims database.

BACKGROUND: Approximately one-third of gastro-oesophageal reflux disease (GERD) patients demonstrate refractory symptoms following treatment with proton pump inhibitor (PPI) therapy. AIM: To develop a refractory GERD score that can be applied to predict patients' healthcare utilisation. METHODS: We enrolled adults (≥18 years) with a diagnosis of GERD. Refractory GERD was evaluated on an 8-point scale where 1 point was given for each of the following criteria: doubling, addition, or switching of GERD medication dose, receipt of a GERD-related endoscopic procedure or surgery, or ≥3 GERD-related outpatient visits. Refractory GERD was defined as the presence of two or more points. RESULTS: A total of 135,139 GERD patients (44% male) were analysed with a mean (±s.d.) age of 52.9 ± 15 years. The mean overall refractory GERD score was 1.12 ± 1.2 (range 0-8 on an 8-point scale); 31% of patients had refractory GERD with a mean score of 2.56 ± 0.82. Among patients with refractory GERD, 31% doubled their GERD medication, 28% added a new GERD medication, 60% switched GERD medications, 54% had a GERD-related procedure and 1% had a GERD-related surgery. Patients with refractory GERD were more likely to be female (59% vs. 55%, P < 0.001) and had a higher co-morbidity score (0.78 vs. 0.56, P < 0.001). The overall mean costs for refractory patients during the study period were significantly higher compared with treatment-responsive patients ($18,088 ± $36,220 vs. $11,044 ± $22,955, P < 0.001). CONCLUSIONS: Refractory GERD was present in approximately one-third of the GERD patients. We created a GERD refractory score that could define need for increased anti-reflux therapy and predict higher healthcare resource utilisation.

Correlation between vancomycin MIC values and those of other agents against gram-positive bacteria among patients with bloodstream infections caused by methicillin-resistant Staphylococcus aureus.

An increase in the distribution of vancomycin MIC values among methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) isolates has been noted. It is postulated that the shift in vancomycin MIC values may be associated with a concurrent rise in the MIC values of other anti-MRSA agents. Scant data are available on the correlation between vancomycin MIC values and the MIC values of other anti-MRSA agents. This study examined the correlation between vancomycin MIC values and the MIC values of daptomycin, linezolid, tigecycline, and teicoplanin among 120 patients with bloodstream infections caused by MRSA at a tertiary care hospital between January 2005 and May 2007. For each included patient, the MIC values of the antibiotics under study were determined by the Etest method and were separated into the following two categories: day 1 (index) and post-day 1 (subsequent). For subsequent isolates, the MIC values for each antibiotic from the post-day 1 terminal isolate were used. Among the index isolates, there was a significant correlation (P value, <0.01) between the MIC values for vancomycin and daptomycin and between the MIC values for vancomycin and teicoplanin. The MIC values for daptomycin were significantly correlated with linezolid, tigecycline, and teicoplanin MIC values. Among the 48 patients with subsequent isolates, vancomycin MIC values were significantly correlated with MIC values for daptomycin, linezolid, and teicoplanin (rho value of >or=0.38 for all comparisons). This study documented an association between vancomycin MIC values and the MIC values of other anti-MRSA antibiotics among patients with bloodstream infections caused by MRSA primarily treated with vancomycin.

The wheat and barley vernalization gene VRN3 is an orthologue of FT.

Winter wheat and barley varieties require an extended exposure to low temperatures to accelerate flowering (vernalization), whereas spring varieties do not have this requirement. In this study, we show that in these species, the vernalization gene VRN3 is linked completely to a gene similar to Arabidopsis FLOWERING LOCUS T (FT). FT induction in the leaves results in a transmissible signal that promotes flowering. Transcript levels of the barley and wheat orthologues, designated as HvFT and TaFT, respectively, are significantly higher in plants homozygous for the dominant Vrn3 alleles (early flowering) than in plants homozygous for the recessive vrn3 alleles (late flowering). In wheat, the dominant Vrn3 allele is associated with the insertion of a retroelement in the TaFT promoter, whereas in barley, mutations in the HvFT first intron differentiate plants with dominant and recessive VRN3 alleles. Winter wheat plants transformed with the TaFT allele carrying the promoter retroelement insertion flowered significantly earlier than nontransgenic plants, supporting the identity between TaFT and VRN-B3. Statistical analyses of flowering times confirmed the presence of significant interactions between vernalization and FT allelic classes in both wheat and barley (P < 0.0001). These interactions were supported further by the observed up-regulation of HvFT transcript levels by vernalization in barley winter plants (P = 0.002). These results confirmed that the wheat and barley FT genes are responsible for natural allelic variation in vernalization requirement, providing additional sources of adaptive diversity to these economically important crops.

CD11b expression identifies CD8+CD28+ T lymphocytes with phenotype and function of both naive/memory and effector cells.

A previously unreported CD8(+)CD28(+)CD11b(+) T cell subset occurs in healthy individuals and expands in patients suffering from primary viral infections. In functional terms, these cells share the features of naive/memory CD8(+)CD28(+)CD11b(-) and terminally differentiated effector CD8(+)CD28(-)CD11b(+) subpopulations. Like CD28(-) cells, CD28(+)CD11b(+) lymphocytes have the ability to produce IFN-gamma, to express perforin granules in vivo, and to exert a potent cytolytic activity. Moreover, these cells can respond to chemotactic stimuli and can efficiently cross the endothelial barrier. In contrast, like their CD11b(-) counterpart, they still produce IL-2 and retain the ability to proliferate following mitogenic stimuli. The same CD28(+)CD11b(+) subpopulation detected in vivo could be generated by culturing naive CD28(+)CD11b(-) cells in the presence of mitogenic stimuli following the acquisition of a CD45RO(+) memory phenotype. Considering both phenotypic and functional properties, we argue that this subset may therefore constitute an intermediate phenotype in the process of CD8(+) T cell differentiation and that the CD11b marker expression can distinguish between memory- and effector-type T cells in the human CD8(+)CD28(+) T cell subset.

High-level expression of chromosomally encoded SHV-1 beta-lactamase and an outer membrane protein change confer resistance to ceftazidime and piperacillin-tazobactam in a clinical isolate of Klebsiella pneumoniae.

We describe Klebsiella pneumoniae 15571, a clinical isolate resistant to ceftazidime MIC = 32 microg/ml) and piperacillin-tazobactam (MICs = 1,024 and 128 microg/ml). K. pneumoniae 15571 expresses a single beta-lactamase with a pI of 7.6. However, when cloned in a high-copy-number vector in Escherichia coli, this bla(SHV-1) gene did not confer resistance to ceftazidime, a spectrum consistent with the nucleotide sequence, which was nearly identical to those of previously described bla(SHV-1) genes. Outer membrane protein (OMP) analysis of K. pneumoniae 15571 revealed a decrease in the quantity of a minor 45-kDa OMP in comparison to that in K. pneumoniae 44NR, a low-level ampicillin-resistant strain that also expresses a chromosomally determined bla(SHV-1). Crude beta-lactamase enzyme extracts from K. pneumoniae 15571 produced roughly 200-fold more beta-lactamase activity than K. pneumoniae 44NR. Northern hybridization analysis revealed that this difference was explainable by quantifiable differences in transcription of the bla(SHV-1) gene in the two strains. Primer extension analysis of bla(SHV-1) mRNA from K. pneumoniae 15571 and 44NR indicated that the transcriptional start sites were identical in the two strains. DNA sequencing of the promoter regions upstream of the of bla(SHV-1) open reading frames in the two K. pneumoniae strains revealed an A-->C change in the second position of the -10 region in K. pneumoniae 44NR compared to that in 15571. Site-directed mutagenesis of the cloned K. pneumoniae 15571 bla(SHV-1), in which the A in the second position of the 15571 -10 region was changed to a C, resulted in a substantial lowering of the MIC of ampicillin. When the levels of beta-lactamase enzyme expression in E. coli were compared, the bla(SHV-1) downstream of the altered -10 region produced 17-fold less beta-lactamase enzyme. These results indicate that elevated levels of ceftazidime resistance can result from a combination of increased enzyme production and minor OMP changes and that levels of chromosomally encoded SHV-1 beta-lactamase production can vary substantially with a single-base-pair change in promoter sequence.

Enterococcal transposon Tn5384: evolution of a composite transposon through cointegration of enterococcal and staphylococcal plasmids.

Mechanisms for the possible transfer of antimicrobial resistance genes between staphylococci and enterococci remain poorly defined. We have previously reported the transfer between Enterococcus faecalis strains of a multiresistance chromosomal element (beta-lactamase positive and resistance to erythromycin, gentamicin, mercuric chloride, streptomycin, and tetracycline) which we have tentatively designated Tn5385. Tn5385 is a composite of several smaller transposable elements, including Tn5384, a 26-kb composite transposon conferring resistance to erythromycin, gentamicin, and mercuric chloride. Analyses of 7 kb within Tn5384 and flanking sequences within the larger element revealed sequences characteristic of staphylococcal beta-lactamase and small, mobilizable plasmids flanking a region with a sequence identical to those of the replication genes previously described for enterococcal and streptococcal broad-host-range plasmids. These diverse regions are linked by insertion sequences IS256 and IS257 in a manner which suggests a series of cointegration events as the genesis of the current relationship. Taken together, these data suggest that Tn5384 and the larger element within which it is incorporated (Tn5385) evolved at least in part as a result of cointegration between an enterococcal broad-host-range plasmid and staphylococcal beta-lactamase and small mobilizable plasmids. These results implicate broad-host-range plasmids in the transfer of resistance determinants from staphylococci to enterococci.

Sequences found on staphylococcal beta-lactamase plasmids integrated into the chromosome of Enterococcus faecalis CH116.

We have previously reported the presence of the staphylococcal beta-lactamase gene in chromosomes of Enterococcus faecalis strains CH19 and CH116. CH116 also harbors a 26-kb mobile element, designated Tn5384, which confers resistance to erythromycin and gentamicin. Sequence analysis of the rightmost 9 kb of Tn5384 indicates that this element lies immediately upstream of the beta-lactamase determinant in E. faecalis CH116. This 9-kb region consists of sequences highly homologous to those previously described in staphylococcal beta-lactamase plasmids, including a beta-lactamase transposon indistinguishable from Tn552, an open reading frame encoding a deduced amino acid sequence 94% identical to a previously described potential staphylococcal invertase, an intact copy of staphylococcal insertion-like element IS257, and the major portion of the staphylococcal organomercurial lyase (merB) gene. These data are consistent with the hypothesis that several of the resistance genes encoded within the large transferable region of the CH116 chromosome were originally components of a staphylococcal beta-lactamase plasmid.