Use of DALYs in economic analyses on interventions for infectious diseases: a systematic review.

A systematic literature review was performed on full economic evaluations of infectious disease interventions using disability-adjusted life years (DALY) as outcome measure. The search was limited to the period between 1994 and September 2011 and conducted in Medline, SciSearch and EMBASE databases. We included 154 studies, mostly targeting HIV/AIDS and malaria with most conducted for African countries (40%) and <10% in high-income countries. Third-payer perspective was applied in 29% of the studies, 25% used the societal perspective and 12% used both. Only 16% of the studies took indirect effects (i.e. herd immunity) of interventions into account. Intervention, direct healthcare and indirect non-healthcare costs were taken into account in respectively 100%, 81% and 36% of the studies. The majority of the studies followed the Global Burden of Disease method for DALY estimations, but most studies deviated from WHO cost-effectiveness guidelines. Better adherence to freely accessible guidelines will improve generalizability between full economic evaluations.

Time-dependent risk of developing distant metastasis in breast cancer patients according to treatment, age and tumour characteristics.

BACKGROUND: Metastatic breast cancer is a severe condition without curative treatment. How relative and absolute risk of distant metastasis varies over time since diagnosis, as a function of treatment, age and tumour characteristics, has not been studied in detail. METHODS: A total of 9514 women under the age of 75 when diagnosed with breast cancer in Stockholm and Gotland regions during 1990-2006 were followed up for metastasis (mean follow-up=5.7 years). Time-dependent development of distant metastasis was analysed using flexible parametric survival models and presented as hazard ratio (HR) and cumulative risk. RESULTS: A total of 995 (10.4%) patients developed distant metastasis; the most common sites were skeleton (32.5%) and multiple sites (28.3%). Women younger than 50 years at diagnosis, with lymph node-positive, oestrogen receptor (ER)-negative, >20 mm tumours and treated only locally, had the highest risk of distant metastasis (0-5 years' cumulative risk =0.55; 95% confidence interval (CI): 0.47-0.64). Women older than 50 years at diagnosis, with ER-positive, lymph node-negative and ≤20-mm tumours, had the same and lowest cumulative risk of developing metastasis 0-5 and 5-10 years (cumulative risk=0.03; 95% CI: 0.02-0.04). In the period of 5-10 years after diagnosis, women with ER-positive, lymph node-positive and >20-mm tumours were at highest risk of distant recurrence. Women with ER-negative tumours showed a decline in risk during this period. CONCLUSION: Our data show no support for discontinuation at 5 years of clinical follow-up in breast cancer patients and suggest further investigation on differential clinical follow-up for different subgroups of patients.

Age at first intercourse and HPV immunization.

The licence of the first human papillomavirus vaccine (HPV) has important implications for the most appropriate age for a mandatory immunization. In this paper data taken from a recent study show that more than 10% of the Italian women report having already had a sexual intercourse by the age of 15. There is thus sufficient evidence to recommend administration of the HPV vaccine to all girls by the age of 12.

[Risk management in health care systems: the new legislative orientations in medical civil responsibility]. / Risk management in sanità: i nuovi orientamenti legislativi sulla responsabilità civile in ambito medico.

The recent radical change in the relationships between physicians and patients has increased the frequency of malpractice. Consequently, on one hand, many physicians got used to avoiding any possible risk of denunciation by applying the so called "defensive medicine", while on the other hand, the insurance companies raised the prices of their premiums for policies concerning civil responsibility of health operators. In order to avoid this "vicious circle", some health structures created Units for the Risk Management related to malpractice, while others took advantage of the collaboration of Associations for Patients' Rights to create database about the most frequent medical mistakes. The need for a legislative change has been accepted by the Parliament which expects with the proposal n.108 (approved in spring 2002 by the Commission for Hygiene and Health of the Senate) to attribute the civil responsibility of the physicians to the hospitals (both private and public) for which they work, to constitute a Register of experts and to accelerate the legal disputes. The problem is complex and still to be solved, but it seems that time for a strong intervention in order to improve the situation has to come.

Impact of measles national vaccination coverage on burden of measles across 29 Member States of the European Union and European Economic Area, 2006-2011.

BACKGROUND: Challenges in reaching good vaccination coverage against measles emerged in several European Union/European Economic Area Member States (EU/EEA MS) leading to progressive accumulation of susceptible individuals and outbreaks. The Burden of Communicable Diseases in Europe (BCoDE) project developed a methodology for measuring the burden of communicable diseases expressed in Disability-Adjusted Life Years (DALYs) in the EU/EEA MS. The aim of this study was to compare national vaccination coverage and burden of measles across EU/EEA MS. METHODS: Country-specific data on measles national vaccination coverage 2006-2011 from 29 EU/EEA MS (MCV1) were retrieved from Centralized Information System for Infectious Diseases (CISID). DALYs were calculated for each country separately using a disease progression model with a single input parameter (annual measles incidence, adjusted for under-estimation). A software application was used to compute estimated DALYs according to country-specific and year-specific population age-distributions (data retrieved from Eurostat). Log-linear mixed-effect regression modeling approach was used to investigate a linear relation between natural logarithm-transformed DALYs and coverage. RESULTS: The reported annual vaccination coverage ranged from 72.6% to 100%. The estimated national annual burden ranged from 0 to 30.6 DALYs/100,000. Adjusting for year, there was a significant negative relationship between coverage and burden. For a given country there was a decrease in log-transformed DALYs/100,000 of 0.025 (95% confidence interval: -0.047 to -0.003) for every percentage increase in vaccination coverage. The largest effect of calendar time on estimated burden of measles was observed for the year 2011, the smallest was for the year 2007. CONCLUSIONS: This study shows that the degree of success of national measles vaccination programs, when measured by the coverage obtained, is significantly associated with overall impact of measles across EU/EEA MS. In EU/EEA MS each percentage point increase in national vaccination coverage seems to lead to early significant reduction of overall burden of measles.

Assessment of the first HPV vaccination campaign in two northern Italian health districts.

From December 2008 the Italian region of Lombardy started offering the vaccine against HPV to all schoolgirls aged 12. Many topics like knowledge, organization and acceptability should be addressed. This study investigated the compliance to the first vaccination campaign in two suburbs of Milan and assessed the knowledge about HPV and cervical cancer among the mothers of the recipients and the opinions of the healthcare professionals about the campaign by using anonymous multiple choice questionnaires. Knowledge about HPV among mothers went from 63% to 76% after vaccination. Healthcare professionals gave an average grading of 5.7 (scale 1-10) about organization and management of the campaign. Coverage of the immunization campaign was quite poor: after the first round only 55.3% got vaccinated with the first dose. Knowledge of mothers of the recipients is still to improve, particularly among immigrants and less educated. It is necessary to implement information campaigns to improve knowledge about HPV and the acceptability of the new vaccine.

Study of the biological and prognostic significance of the antigen CaMBr8 on breast carcinoma.

We previously reported that the expression on the primary tumour of the antigen CaMBr8 was related to a short survival, attributable either to higher tumour aggressiveness or a poor response to oophorectomy. To further verify the CaMBr8 prognostic value, we analysed retrospectively 862 breast cancer patients with a 19 year follow-up. In this series, CaMBr8 expression was found to be associated to some negative prognostic factors (premenopausal status, lymphnode invasion, a high number of mitosis and HER-2/neu oncoprotein expression), but had no influence on the patients' survival. Direct association with a poor prognosis was only evident in patients with lobular or mixed breast carcinoma, which however represent only a small fraction of the total breast cancers. Another possibility was that CaMBr8 could identify a subgroup of patients which did not respond to hormone therapy. To verify this hypothesis we evaluated on a second series of 116 patients the relationship between CaMBr8 expression and hormone-receptor levels. A negative association emerged which was also observed in vitro in the human breast cancer line MCF-7 treated with Sodium Butyrate, a differentiation inducer, which reduced hormone-receptor levels and increased CaMBr8 expression. In conclusion, the longer survival of CaMBr8 negative tumour patients observed in the initial study, was probably related to a better response to oophorectomy, due to the hormone-receptor level of their tumours.

Glycolipids carrying Le(y) are preferentially expressed on small-cell lung cancer cells as detected by the monoclonal antibody MLuC1.

The monoclonal antibody MLuC1, which reacts strongly with a high percentage of small-cell lung cancers (SCLC), as well as with various human carcinomas, has been used to immunochemically characterize the recognized epitope (CaMLuC1). To this aim 3 different approaches were adopted: (1) immunoblotting/immunostaining of extracts from various tumor-cell lines; (2) inhibition of binding by purified oligosaccharides; (3) direct binding to oligosaccharide-protein conjugates. All of these experiments indicate that CaMLuC1 is present on the Le(y) blood-group structure heterogeneously expressed on various glycoproteins and glycolipids. The expression of the glycoconjugates carrying Le(y) was then analyzed on breast and lung cancers and on their normal counterparts. Our overall results suggest that SCLC produce Le(y)-active glycolipids in higher amounts compared to other tumors of the same or of a different oncotype, as well as normal lung cells, thus indicating an SCLC-specific modification of the glycosylation pathways.