Maria Lucia Specchia

Use of trastuzumab in HER2-positive metastatic breast cancer beyond disease progression: a systematic review of published studies

Aims and background Trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of ErbB, has determined clinical benefit for women affected by metastatic or early stage HER2-positive breast cancer and never previously treated with trastuzumab. Trastuzumab is generally used as first-line treatment of HER2+ metastatic breast cancer and is currently administered beyond progression even without clear evidence supporting such clinical practice. In fact, HER2-positive metastatic breast cancer has a high risk of progressing after first-line therapy, and second-line treatments vary. The aim of the study was to investigate by a systematic review the efficacy of trastuzumab-based treatments beyond progression in HER2-positive metastatic breast cancer. Materials and methods We performed a systematic review using Medline, Embase and Cochrane Library data bases and publications in principal meetings or congresses of oncology in Europe and America until September 2008. The main selection criterium was the reporting of time to progression, calculated from the start of each trastuzumab-based therapy to the date of progressive disease or death. Results Twelve studies were selected that included a total of 516 patients. The weighted mean time to progression was 23.66 weeks (standard deviation, 4.37) and the median was 26 weeks (range, 13–39). Interestingly, combined trastuzumab plus vinorelbine treatment showed a lower mean and median time to progression (20.59 and 19.57 weeks, respectively), whereas trastuzumab plus capecitabine yielded a mean time to progression of 30.33 weeks. Conclusions The added value of the present study has been to provide a quantitative summary measure of time to progression which can be used for comparisons between current and future available regimens.

An assessment of the effect of hepatitis B vaccine in decreasing the amount of hepatitis B disease in Italy

BackgroundHepatitis B (HBV) infection is an important cause of morbidity and mortality and it is associated to a higher risk of chronic evolution in infected children. In Italy the anti-HBV vaccination was introduced in 1991 for newborn and twelve years old children. Our study aims to evaluate time trends of HBV incidence rates in order to provide an assessment of compulsory vaccination health impact.MethodData concerning HBV incidence rates coming from Acute Viral Hepatitis Integrated Epidemiological System (SEIEVA) were collected from 1985 to 2006. SEIEVA is the Italian surveillance national system that registers acute hepatitis cases. Time trends were analysed by joinpoint regression using Joinpoint Regression Program 3.3.1 according to Kims method. A joinpoint represents the time point when a significant trend change is detected. Time changes are expressed in terms of the Expected Annual Percent Change (EAPC) with 95% confidence interval (95% CI).ResultsThe joinpoint analysis showed statistically significant decreasing trends in all age groups. For the age group 0–14 EAPC was -39.0 (95% CI: -59.3; -8.4), in the period up to 1987, and -12.6 (95% CI: -16.0; -9.2) thereafter. EAPCs were -17.9 (95% CI: -18.7; -17.1) and -6.7 (95% CI: -8.0; -5.4) for 15–24 and ≥25 age groups, respectively. Nevertheless no joinpoints were found for age groups 15–24 and ≥25, whereas a joinpoint at year 1987, before compulsory vaccination, was highlighted in 0–14 age group. No joinpoint was observed after 1991.DiscussionOur results suggest that the introduction of compulsory vaccination could have contribute partly in decreasing HBV incidence rates. Compulsory vaccination health impact should be better investigated in future studies to evaluate the need for changes in current vaccination strategy.

Economic impact of adult obesity on health systems: a systematic review

BACKGROUND Obesity represents an important public health issue. An assessment of its costs would be useful to provide recommendations for policy and decision-making strategies. The aims of our study were to carry out a systematic review to assess the economic burden of adult obesity in terms of direct and indirect costs and to perform a quality appraisal of the analysed studies. METHODS A literature search was carried out on PubMed, Scopus and Cochrane Library to retrieve cost-of-illness (COI) analyses focused on adult (aged 18 years or more) overweight or obese people and published up to 2013. COI analyses that considered direct and indirect costs were included. Each included manuscript was independently appraised by three groups of researchers on the basis of the British Medical Journal Drummonds checklist. RESULTS Approximately 2044 articles were initially retrieved, and 17 were included in the current review. The included studies showed a medium-high-quality level. The available studies seemed to be heterogeneous both in terms of methodology and results reporting. However, as many studies have been conducted from the payer perspective, just direct medical costs can be considered exhaustive. As only three studies included considered also indirect costs, there is no strong evidence to give a comprehensive picture of this phenomenon also from the societal perspective. CONCLUSION The review confirmed that obesity absorbs a huge amount of health-care resources. Further research is therefore needed to better understand the economic impact and to identify and promote public health strategies to tackle obesity.

The impact of electronic health records on healthcare quality: a systematic review and meta-analysis

OBJECTIVE To assess the impact of electronic health record (EHR) on healthcare quality, we hence carried out a systematic review and meta-analysis of published studies on this topic. METHODS PubMed, Web of Knowledge, Scopus and Cochrane Library databases were searched to identify studies that investigated the association between the EHR implementation and process or outcome indicators. Two reviewers screened identified citations and extracted data according to the PRISMA guidelines. Meta-analysis was performed using the random effects model for each indicator. Heterogeneity was quantified using the Cochran Q test and I2 statistics, and publication bias was assessed using the Eggers test. RESULTS Of the 23 398 citations identified, 47 articles were included in the analysis. Meta-analysis showed an association between EHR use and a reduced documentation time with a difference in mean of -22.4% [95% confidence interval (CI) = -38.8 to -6.0%; P < 0.007]. EHR resulted also associated with a higher guideline adherence with a risk ratio (RR) of 1.33 (95% CI = 1.01 to 1.76; P = 0.049) and a lower number of medication errors with an overall RR of 0.46 (95% CI = 0.38 to 0.55; P < 0.001), and adverse drug effects (ADEs) with an overall RR of 0.66 (95% CI = 0.44 to 0.99; P = 0.045). No association with mortality was evident (P = 0.936). High heterogeneity among the studies was evident. Publication bias was not evident. CONCLUSIONS EHR system, when properly implemented, can improve the quality of healthcare, increasing time efficiency and guideline adherence and reducing medication errors and ADEs. Strategies for EHR implementation should be therefore recommended and promoted.

CCR5 and CCR2 gene polymorphisms in hypertensive patients

Abstract Essential hypertension is a complex trait under polygenic control. Evidences suggests immune system involvement during pathogenesis. CC-chemokine receptor (CCR)5 and CCR2 are characterised by gene polymorphism. Variant alleles are derived from a deletion in the CCR5 gene (CCR5∆32) and a substitution mutation at the CCR2 locus (CCR264I). CCR polymorphic forms have been studied extensively as invasion cofactors for HIV-1, but they have also been implicated in immuno-related disorders. Here, we evaluate the allelic distribution of CCR5 and CCR2 genes in essential hypertension in a case-control study. Genotype frequency in a group of essential hypertensive patients (stage I-II; n=120) and a group of unrelated, healthy Caucasian subjects (n=340) is compared. CCR gene polymorphism is analysed by polymerase chain reaction and restriction enzyme digestion. A statistically significant difference was observed for CCR5 and CCR2 mutant alleles in essential hypertensive patients, compared with the controls (P=0.004 and P=0.003, respectively). CCR5∆32 and CCR264I alleles showed a 0.096 and 0.10 frequency among cases. To date, a role for the immune system in hypertension has not been clarified, nor has the predictive value of CCR polymorphisms.

Economic value of influenza vaccination.

Influenza epidemics are responsible for high mortality and morbidity rates in particular among elderly and high risk groups. This review is aimed at assessing the economic value of vaccination in these groups. A search of full economic evaluations of influenza vaccination in comparison with no interventions was performed on PubMed from January 1990 to May 2011. Only economic evaluations dealing with elderly and high risk groups were considered. The quality of selected articles was assessed through Drummond’s checklist. Sixteen cost-effectiveness analyses and four cost-benefit analyses were included: overall, the quality of studies was fairly good. The vaccination was demonstrated to be cost-effective or cost-saving in almost all studies, independently by the perspective and the type of analysis. Influenza vaccination is a worthwhile intervention from the pharmacoeconomic view-point, anyway a standardization of methods should be desirable in order to guarantee the comparability and transferability of results.

Health Technology Assessment of Belimumab: A New Monoclonal Antibody for the Treatment of Systemic Lupus Erythematosus

Objective. Systemic lupus erythematosus (SLE) is treated with anti-inflammatory and immunosuppressive drugs and off-label biologics. Belimumab is the first biologic approved after 50 years as an add-on therapy for active disease. This paper summarizes a health technology assessment performed in Italy. Methods. SLE epidemiology and burden were assessed using the best published international and national evidences and efficacy and safety of belimumab were synthesized using clinical data. A cost-effectiveness analysis was performed by a lifetime microsimulation model comparing belimumab to standard of care (SoC). Organizational and ethical implications were discussed. Results. Literature review showed that SLE affects 47 per 100,000 people for a total of 28,500 patients in Italy, 50% of whom are affected by active form of the disease despite SoC. These patients, if autoantibodies and anti-dsDNA positive with low complement, are eligible for belimumab. SLE determines work disability and a 2–5-fold increase in mortality. Belimumab with SoC may prevent 4,742 flares in three years being cost-effective with an incremental cost-effectiveness ratio of €32,859 per quality adjusted life year gained. From the organizational perspective, the development of clear and comprehensive clinical pathways is crucial. Conclusions. The assessment supports the use of belimumab into the SLE treatment paradigm in Italy.

The future of best investing in vaccines: the Health Technology Assessment approach.

Over the past two decades, scientific research has led to the development of a huge number of new health technologies, among which new vaccines. The decision process underlying the introduction of a new vaccine will be of particular concern in the future and a useful tool is needed to orientate decision makers towards better allocation of economic resources. Health Technology Assessment (HTA) is a multidisciplinary tool that aims to examine the clinical, economic, organizational, ethical, juridical, social and cultural implications of the introduction or the implementation of a specific technology; it could so represent an innovative and effective approach in order to support decision-making processes.

Extracorporeal Photopheresis for Second-Line Treatment of Chronic Graft-versus-Host Diseases: Results from a Health Technology Assessment in Italy

OBJECTIVES To develop a comparative, cost-effectiveness, and budget impact analysis of Therakos online extracorporeal photopheresis (ECP) compared with the main alternatives used for the treatment of steroid-refractory/resistant chronic graft-versus-host disease (cGvHD) in Italy. METHODS The current therapeutic pathway was identified by searching medical databases and from the results of a survey of practice in Italian clinical reference centers. A systematic review was performed to evaluate the efficacy and safety of second-line alternatives. Budget impact and cost-effectiveness analyses were performed from the Italian National Health Service perspective over a 7-year time horizon through the adaption of a Markov model. The following health states were considered: complete and partial response, stable disease, and progression. A discount rate of 3% was applied to costs and outcomes. RESULTS The most common alternatives used in Italy for the management of steroid-refractory/resistant cGvHD were ECP, mycophenolate, pentostatin, and imatinib. The literature review highlighted that complete and partial responses are higher with ECP than with the alternatives while serious adverse events are less common. The economic analysis showed that Therakos online ECP represents the dominating alternative, in that it delivers greater benefit at a lower cost. In fact, according to the alternatives considered, cost saving ranged from €3237.09 to €19,903.51 per patient with 0.04 to 0.21 quality-adjusted life-year gained. CONCLUSIONS Therakos online ECP should be considered an effective, safe, and cost-effective alternative in steroid-refractory/resistant cGvHD. There is inequality in access, and a dedicated reimbursement tariff, however, should be introduced to overcome these barriers.

Health inequalities: an analysis of hospitalizations with respect to migrant status, gender and geographical area

BackgroundThe quality of care includes several aspects which may be influenced by social-economic status.This study analyzes hospitalizations for several conditions, such as chronic diseases, cancer and appendectomy, in Italians and immigrant people living in Italy with the aim to evaluate possible inequalities in the quality of health care services due to migrant status, gender and geographical macro-areas (Northern, Central, Southern Italy).MethodsThe data source of hospital discharges for stroke, myocardial infarction, chronic liver disease, cervical cancer, mastectomy and appendectomy was the Ministry of Health. ICD 9 codes were used for data collection. Crude and standardized hospitalization rates per 100.000 were calculated. Italian resident population and an estimate of immigrants living in Italy were used as denominators while standardization was done with respect to the European population. The data we used covers the 2006–2008 period.ResultsImmigrants showed significantly higher hospitalization rates for stroke, cervical cancer and appendectomy and significantly lower hospitalization rates for chronic liver diseases and mastectomy. Males showed significantly higher hospitalization rates than females for myocardial infarction, chronic liver diseases and appendectomy. Notwithstanding, differences related to migrant status and gender varied according to geographical macro-area. With respect to that, Southern Italy showed significantly higher hospitalization rates for stroke, myocardial infarction and chronic liver diseases and significantly lower hospitalization rates for mastectomy and appendectomy.ConclusionsThe results of this study may reflect inequalities in the quality of health care, in particular in primary and secondary prevention, access to specialized care and inappropriateness, due to migrant status and gender. Also, differences between macro-areas suggest heterogeneities in the integration policies and the promotion of immigrants’ health. Research should be endorsed in this field in order to further describe inequalities and their reasons and in the light of supporting policies development.