Although a relationship between marital status and mortality has long been recognized, no summary estimates of the strength of the association are available. A meta-analysis of cohort studies was ...conducted to produce an overall estimate of the excess mortality associated with being unmarried in aged individuals as well as to evaluate whether and to what degree the effect of marriage differs with respect to gender, geographical/cultural context, type of non-married condition and study methodological quality. All included studies were published after the year 1994, used multivariate analyses and were written in English. Pooling 53 independent comparisons, consisting of more than 250,000 elderly subjects, the overall relative risk (RR) for married versus non-married individuals (including widowed, divorced/separated and never married) was 0.88 (95% Confidence Interval: 0.85–0.91). This estimate did not vary by gender, study quality, or between Europe and North America. Compared to married individuals, the widowed had a RR of death of 1.11 (1.08–1.14), divorced/separated 1.16 (1.09–1.23), never married 1.11 (1.07–1.15). Although some evidence of publication bias was found, the overall estimate of the effect of marriage was robust to several statistical approaches and sensitivity analyses. When the overall meta-analysis was repeated with an extremely conservative approach and including eight non-significant comparisons, which were initially excluded because of data unavailable, the marriage protective influence remained significant, although the effect size was reduced (RR=0.94; 0.92–0.95). Despite some methodological and conceptual limitations, these findings might be important to support health care providers in identifying individuals “at risk” and could be integrated into the current programs of mortality risk estimation for the elderly.
Vascular endothelial growth factor (VEGF), an angiogenic factor produced in response to ischemic injury, promotes vascular permeability (VP). Evidence is provided that Src kinase regulates ...VEGF-mediated VP in the brain following stroke and that suppression of Src activity decreases VP thereby minimizing brain injury. Mice lacking pp60c-src are resistant to VEGF-induced VP and show decreased infarct volumes after stroke whereas mice deficient in pp59c-fyn, another Src family member, have normal VEGF-mediated VP and infarct size. Systemic application of a Src-inhibitor given up to six hours following stroke suppressed VP protecting wild-type mice from ischemia-induced brain damage without influencing VEGF expression. This was associated with reduced edema, improved cerebral perfusion and decreased infarct volume 24 hours after injury as measured by magnetic resonance imaging and histological analysis. Thus, Src represents a key intermediate and novel therapeutic target in the pathophysiology of cerebral ischemia where it appears to regulate neuronal damage by influencing VEGF-mediated VP.
Objectives. Haemophilia A is a congenital disorder of coagulation that mainly affects males and causes a considerable use of resources, especially when hemophilic patients are treated with ...prophylaxis. The aim of the present review was to discuss and appraise the methodological aspects and results of published economic evaluations of haemophilia A treatments in the last decade. Methods. The literature search, performed by consulting four engines, covered studies published between 2002 and 2014. Full economic evaluations published in English language were identified and included in the review. A quality assessment of the studies was also carried out based on Drummond’s checklist. Results. After careful evaluations of the identified records, 5 studies were reviewed. Primary and secondary prophylaxis resulted cost-effective compared to on-demand therapy: the ICER of primary prophylaxis ranged from €40.236 to €59.315/QALY gained, while the ICER of secondary prophylaxis was €40.229/QALY gained. Furthermore, 60% were high quality and 40% were medium quality studies. Conclusions. The review underlines the cost-effectiveness of prophylaxis versus on-demand treatment and the different methodological approaches applied. Further economic evaluations are required with models that reflect the clinical reality and consumption of resources in each country.
Summary Influenza H5N1 is thought to be a likely causative agent for a future human influenza pandemic. Several types of H5N1 vaccine have been tested, including different doses and adjuvants, and a ...meta-analysis is needed to identify the best formulation. We searched Medline, Embase, the Cochrane Library, and other online databases to February, 2009, in any language for randomised trials comparing different H5N1 vaccines with or without placebo in healthy adults. Primary outcomes were seroconversion, seroresponse, or both according to haemagglutination–inhibition and microneutralisation. Secondary outcomes were adverse events. Because of the large number of compared formulations, multiple-treatments meta-analysis was used for primary outcomes. Direct-comparison meta-analyses were also done. We included 13 trials, which assessed 58 groups. With non-aluminium adjuvant, sufficiently high immunogenicity (greater than 70%) was achieved even at 12 μg or less (given as two doses of 6 μg or less), and higher doses did not provide major improvements. Immunogenicity for non-adjuvanted and aluminium-adjuvanted formulations increased with increasing dose, but was not sufficiently high. No serious vaccine-related adverse events were reported across 9600 participants. Currently, H5N1 influenza vaccines with non-aluminium adjuvants might represent the best available option in a pandemic. Large-scale studies are needed to verify the high immunogenicity of non-aluminium-adjuvanted vaccines that use very low doses of antigen.
Bispecific antibodies (BsAbs) target multiple epitopes on the same molecular target or different targets. Although interest in BsAbs has persisted for decades, production of stable and active BsAbs ...has hindered their clinical evaluation. Here, we describe the production and characterization of tetravalent IgG-like BsAbs that combine the activities of allosteric and competitive inhibitors of the type-I insulin-like growth factor receptor (IGF-1R). The BsAbs, which were engineered for thermal stability, express well, demonstrate favorable biophysical properties, and recognize both epitopes on IGF-1R. Only one BsAb with a unique geometry, denoted BIIB4-5scFv, was capable of engaging all four of its binding arms simultaneously. All the BsAbs (especially BIIB4-5scFv) demonstrated enhanced ligand blocking over the single monoclonal antibodies (mAbs), particularly at high ligand concentrations. The pharmacokinetic profiles of two IgG-like BsAbs were tested in nude mice and shown to be comparable with that of the parental mAbs. The BsAbs, especially BIIB4-5scFv, demonstrated an improved ability to reduce the growth of multiple tumor cell lines and to inhibit ligand-induced IGF-1R signaling in tumor cells over the parental mAbs. BIIB4-5scFv also led to superior tumor growth inhibition over its parental mAbs in vivo. In summary, BsAbs that bridge multiple inhibitory mechanisms against a single target may generally represent a more effective strategy for intervention in oncology or other indications compared with traditional mAb therapy.
The epidermal growth factor receptor (EGFR) and the type I insulin-like growth factor receptor (IGF-1R) are two cell surface receptor tyrosine kinases known to cooperate to promote tumor progression ...and drug resistance. Combined blockade of EGFR and IGF-1R has shown improved anti-tumor activity in preclinical models. Here, we report the characterization of a stable IgG-like bispecific antibody (BsAb) dual-targeting EGFR and IGF-1R that was developed for cancer therapy. The BsAb molecule (EI-04), constructed with a stability-engineered single chain variable fragment (scFv) against IGF-1R attached to the carboxyl-terminus of an IgG against EGFR, displays favorable biophysical properties for biopharmaceutical development. Biochemically, EI-04 bound to human EGFR and IGF-1R with sub nanomolar affinity, co-engaged the two receptors simultaneously, and blocked the binding of their respective ligands with similar potency compared to the parental monoclonal antibodies (mAbs). In tumor cells, EI-04 effectively inhibited EGFR and IGF-1R phosphorylation, and concurrently blocked downstream AKT and ERK activation, resulting in greater inhibition of tumor cell growth and cell cycle progression than the single mAbs. EI-04, likely due to its tetravalent bispecific format, exhibited high avidity binding to BxPC3 tumor cells co-expressing EGFR and IGF-1R, and consequently improved potency at inhibiting IGF-driven cell growth over the mAb combination. Importantly, EI-04 demonstrated enhanced in vivo anti-tumor efficacy over the parental mAbs in two xenograft models, and even over the mAb combination in the BxPC3 model. Our data support the clinical investigation of EI-04 as a superior cancer therapeutic in treating EGFR and IGF-1R pathway responsive tumors.
Italian Ministry of Health, recommends vaccination for seasonal influenza to all healthcare workers (HCW), particularly to nurses who have an important interaction with patients. The aim of this ...study is to conduct a systematic review in order to estimate the pooled prevalence of influenza vaccinations among nurses and ancillary workers in Italy and analyse the enhancing and hindering factors.
The review was performed using 15 articles, six containing the prevalence of vaccination for nurses and ancillary workers, while the others qualitative analysis. In all the selected articles the score calculation has been carried out by using a protocol for observational studies. The nurses and ancillary workers pooled proportion of influenza vaccination was respectively 13.47% (95%CI 9.58-17.90%) and 12.52% (95%CI 9.97-15.31%).
The Italian mean of influenza vaccination prevalence appear low if compared to other European countries, ranging from 15% to 29% in Countries such as UK, Germany, France. This situation of weakness should be seen as an opportunity to improve the vaccination rate for seasonal influenza significantly This should be done by intervening on the category which affirms caring less. In fact, this category has a priority to receive vaccination, due to their numbers and closer contact to patients.
Research was conducted using medical database Scopus, PubMed, the search engine Google Scholar and ISI web of knowledge, and was concluded February 1st 2011.
Objectives. To assess the influence of sociodemographic factors on smoking habits in Italy and if an interaction exists between these variables. Methods. Data from the national survey “Health ...Conditions and Healthcare Services Use” in 2005 were used. The independent association between tobacco smoking and sociodemographical variables was assessed using logistic regression analysis. Interactions between variables were investigated calculating the synergism index (SI). Results. Sample population consists of 109.829 subjects (over 15 years). 21.9% are current and 21.8% are former smokers. Current smokers are mostly 45–54-years old males, from Central Italy, unemployed, divorced or separated but having a good health status without chronic medical conditions. Ever smokers are mostly 45–54 years old males, from Northeast Italy, unemployed, with chronic conditions. People with a university degree and with a good household income have the lowest OR for both conditions. A synergistic effect was found between marital status and educational level (for ever smokers SI = 1.96; for current smokers SI = 1.67). Conclusions. Smoking is prevalent in lower socioeconomic groups and there is the strong need to increase social, economic and cultural capital in order to reduce it.
The aim of this study was to quantify the level of health related quality of life and burnout in a call centers sample of precarious workers.
An observational study was carried out in Italy. A ...self-reported anonymous questionnaire was administered to temporary workers in order to estimate burn-out and quality of life levels.
227 questionnaires were collected. 78% of the sample was female and the mean age was 35.48 years (SD=9.91). Among the participants, 40% were smokers, 42% regularly drinkers, 65% changed the body weight (more than 5 kg, in 1 year). The mental component score (MCS) was significantly better in subject that have a regularly life style, for example in those no change their body weight (p=0.001), sleep more than 7 hours (p=0.018) and followed a diet (p=0.035). The DP (depersonalization) is significant higher in former smokers (p=0.031), in underweight subjects (p=0.025) and in the group that have a precarious employment of over 2 years (p=0.013).
This investigation shows that in this particular category of atypical workers depressive symptoms and quality of life were lower than the general population. It is important to underline that the interpretation of the results is limited partly by the observational character of the study.
We evaluated the concentration and congener distribution of seven “target” polychlorinated biphenyls (PCBs) present in water collected in different aquaculture farms of the Mediterranean area, ...commercial feeds, and farmed seafood. PCBs were present in feed and in tissues of all the analysed organisms at levels ranging from 1.96 ng g⁻¹ to 124.00 ng g⁻¹ wet weight, and in 10.5% of the water samples, at levels from under detection limit to 33.0 ng l⁻¹ with total PCB concentrations significantly higher in samples from the Tyrrhenian Sea than the Adriatic Sea. PCB congener distribution in tissues resembled that of feed, suggesting that commercial feed is an important source of PCBs. The estrogenicity of organic extracts of the samples was also evaluated by using an in vitro yeast reporter assay. Estrogenic activity higher than 10% of the activity induced by 10 nM 17 β-estradiol was observed in 20.0% of seafood samples and 15.8% of water samples. Seafood and water samples from the Tyrrhenian Sea were more frequently estrogenic than the Adriatic ones (16.45 versus 4.08%). A significant correlation of total PCB concentrations on biological activity was observed for sea bass and mussels from the Adriatic Sea (p < 0.045 and p < 0.04, respectively), and for sea bass of the Tyrrhenian Sea (p = 0.05). These results indicate the need of an integral approach in the exposure assessment to potential toxic compounds for human via food.
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