Italian Journal of Public Health

Personalized health care: the hope beyond the hype

Stefania Boccia — Tue, 05 Mar 2024 00:00:00 +0000

Personalised healthcare can be defined as a customisation of the medical provision that accommodates individual differences in all stages in the process, from prevention, to diagnosis and treatment, to post-treatment follow-up. While the term personalized medicine...

Addressing the gap between genetics knowledge and clinical practice: a pilot study to implement genetics education among physicians in Italy

Walter Mazzuco, Walter Ricciardi, Stefania Boccia — Tue, 12 Mar 2024 00:00:00 +0000

As a result of large investments in basic science, the genomic discoveries have brought outstanding advances in understanding the molecular basis of human health. Hundreds of genes whose variations contribute to human diseases, or patients’ responses to drug treatments or even to vaccination have been discovered, laying the foundation for a paradigm shift in healthcare...

Ethical Implications and Legislative Control of Direct-to-Consumer Genetic Testing in Europe

John Shehata, Eva Kooijman , Carolina Ianuale — Tue, 12 Mar 2024 00:00:00 +0000

Since their first commercialization in 2007, the use of Direct To Consumer (DTC) genetic testing (GT) has rapidly increased. From the consumer viewpoint, the possibility to access genetic information without supervision of a medical doctor could allow for free choice and self-diagnosis (1), and in principle leads to an increased attention on...

Genetic and epigenetic interactions in adaptive thermogenesis pathways in association with obesity from a Public Health Genomics perspective

Caroline Brettfeld, Stephanie Englert, Eva Aumueller, Alexander G. Haslberger — Tue, 12 Mar 2024 00:00:00 +0000

Background: studying and apprehending the pathways and mechanisms by which overweight and obesity trigger complex disease progression is of prime importance for the development of therapy and prevention measures of this major public health burden. This review describes Single Nucleotide Polymorphisms (SNPs) and epigenetic methylation as well as histone modification in genes with relevance in adaptive thermogenesis and their possible role in the development of obesity. Epigenetic marks are discussed as solid biomarkers for gene-environment interactions.

Methods: a PubMed search on genetic and epigenetic variation of genes involved in adaptive thermogenesis was performed. The search included English publications between December 1996 and July 2010 reporting associations between SNPs and obesity in Caucasians. The search on epigenetic regulation was limited to DNA methylation and histone modifications. Genes that were found to be associated with the adaptive thermogenesis pathway included beta-3 adrenergic receptor (ADRB3), uncoupling protein 1 (UCP1), the transcription factors peroxisome proliferated activator receptor gamma (PPARγ), peroxisome proliferated activator receptor gamma co-activator 1 alpha (PGC1α), retinoid acid X receptor alpha (RXRα), CCAAT/enhancer-binding protein alpha (C/EBPα), fatty acid binding protein 4 (FABP4) and lipoprotein lipase (LPL).

Results: epigenetic studies are mainly discovery orientated and do not test hypotheses. However, SNPs as well as epigenetic mechanisms seem to regulate obesity and adaptive thermogenesis whereas genetic association studies are inconsistent.

Conclusions: the aim of this work was to confirm evidences on the contribution of genetic variations as well as epigenetic regulatory mechanisms of genes associated to obesity. The integration of epigenetic markers in epidemiologic research could help to unravel multi gene-environment interactions.

With this article we show the importance to introduce aspects of the epigenetic regulation in the assessment of obesity: We also discuss the benefits of including epigenomics as an integrative way to account for an individual’s environmental impact in public health policies.

Genetic prediction of common complex disorders assessed by next generation sequencing and genome wide analysis

Bruno Dallapiccola, Rita Mingarelli, Stefania Boccia — Mon, 31 Dec 2012 00:00:00 +0000

Insight into the biological make-up of complex disorders can improve their diagnosis, lead to the discovery of new targets for therapy, increase awareness of genome-environment interactions in health and disease, and open the door to predictive medicine. More than 1 600 genome-wide association studies (GWASs) have been published, and have identified thousands of polymorphisms associated with more than 250 common diseases or traits. However, for most of the genomic variants identified so far, only inconclusive associations with complex diseases have been reported and for many of them their predictive value reaches the same level as the traditional risk. The limited value of these results is probably due to regulatory elements in 2-3% of the encoding genome, whose function has only recently been partially decrypted. Nevertheless, genomic sequencing is an attractive tool for personalized medicine. During the last few years several commercial ventures have begun marketing GWASs directly to consumers for medical, genealogic, and even recreational purposes. Although these tests show promise for the future, consumers should be aware of the unreliability of most of their results at the present time. The development of methods integrating clinical and genetic data together with a better understanding of the heritability of complex diseases will be necessary in the endeavour to progress towards a personalized medicine. In order to achieve maximum benefits from GWASs while keeping the disadvantages to a minimum, guidelines will be necessary to manage the technical advances and to meet the challenges involved in the clinical application of whole genomic sequencing.

Cost saving and predictive factors of response to rituximab in rheumatoid arthritis, including the IL-6 promoter gene polymorphism

Tue, 12 Mar 2024 00:00:00 +0000

Background: to evaluate quality of life (QoL) and cost/utility when using predictors of response in a real-life cohort of rheumatoid arthritis (RA) patients treated with rituximab and followed for one year. A recently reported pharmacogenetic predictor of response was included.

Methods: this was a retrospective study in patients with established RA. The goal of this study was to understand the possible economic usefulness of the predictors of response in RA treated with rituximab. Information on QoL was collected at baseline, at month +6 and +12. Cost/QoL gained were also derived. Rheumatoid factor, number of TNF blockers previously failed (positive predictors) and the -174 CC interleukin-6 (IL-6) promoter genotype (negative predictor) were considered as predictive factors of response to rituximab.

Results: 66 patients (54 females, 12 males) with RA were treated with rituximab at standard regimen. Retreatment with rituximab was given at clinical relapse. Rituximab was generally used after failure of anti-TNFalpha agents (81.8%). 96 courses of rituximab were administered during 12 months. Cost/QoL gained was € 56 589.50 at month +12. Patients carrying predictors (≥2 out of 3) (28/66 patients) showed a cost/QoL gained of € 44 279.10 at month +12. Thirty-four courses of rituximab were administered in this group (1.21±0.42). Patients without predictors (≤1 out of 3) (38/66 patients) showed a cost/QoL gained of € 66 769.23 at month +12. 62 courses of rituximab were administered in this group (1.63±0.59). The number of courses of rituximab during one year significantly differed between the two groups (p=0.003).

Conclusion: predictors of response to rituximab selected those patients who need a lesser amount of rituximab during the first year after treatment. Cost/utility of rituximab in established RA may be optimized by using predictors of response, possibly including pharmacogenetic markers.

Time to revisit Geoffrey Rose: strategies for prevention in the genomic era?

Hilary Burton, Gurdeep S Sagoo, Paul Pharoah, Ron L Zimmern — Mon, 31 Dec 2012 00:00:00 +0000

Geoffrey Rose, in his article “Sick individuals and sick populations” highlighted the need to distinguish between prevention for populations and prevention for high risk individuals. In this article we revisit some of these concepts in light of the burgeoning literature on “personalised medicine” and of findings from our investigations into personalised cancer prevention as part of an EU research gene-environment study on hormone related cancers, the Collaborative Oncological Gene- environment Study (COGS). We suggest that Rose’s high risk strategy may be modified by segmenting the population by risk (in our example genetic risk) into a number of individual strata, to each of which differential interventions may be applied. We call this “stratified prevention”, and argue that such an approach will lead to consequential advantages in efficiency, effectiveness and harm minimisation.

Personalised Health Care, the need for reassessment. A HTA perspective far beyond cost-effectiveness

Iñaki Gutiérrez-Ibarluzea — Mon, 31 Dec 2012 00:00:00 +0000

Background: personalised health care has been claimed to play an outstanding role in the future health services. In fact, health care systems will have to face changes in their work flows and processes due to the implementation of personalised technologies. Health Technology Assessment provides information to decision makers at any level on the introduction and exclusion of health technologies from the health care systems.

Methods: the definition of Health Technology Assessment (HTA) and the concepts and questions raised in the EUnetHTA core model, were used as a framework to analyse the impact of these new services in health care provision.

Results: personalised health care services and products are health technologies, mainly diagnostics that have a broad impact in the health care systems. Although, safety, clinical effectiveness and economical aspects and consequences have been described, ethical, social and organisational issues raised questions that should be answered before considering their implementation in the health systems. Special attention should be paid on new requirements for regulation, data protection and the empowerment of citizen and health professionals.

Conclusions: the benefits and harms of personalised health-care technologies should be decided on a “case by case” rather than a “one size fits all” basis and has to be analysed under its many aspects. The combination of genetic, clinical and environmental factors is crucial for the correct understanding of personalised medicine and its implementation. Personalised health care will require a fine-tuned revision of existing HTA and Pharmacoeconomic’s guidelines to address its characteristics.

Personalization of antimicrobial dosing regimens: indicators of performance

Mon, 31 Dec 2012 00:00:00 +0000

Background: to assess the efficiency and effectiveness of the organizational system of a Clinical Pharmacological Service of an Italian tertiary care teaching hospital in providing advices (CPAs) to clinicians within timeframes useful for the personalization of antimicrobial dosing regimens in different patients’ populations according to the clinical benefit for patient care.

Methods: the frequency per week of the various typologies of CPA were defined on the basis of prior evaluations aimed at estimating the clinical benefit for patient care (high priority level, for antimicrobials used to treat acute infections in the critically ill patients; moderate priority level, for those used to treat cytomegalovirus infections in solid organ transplant recipients; mild priority level, for those used to treat chronic infections). The CPAs provided between December 2011and June 2012 represented the starting database. The measured turnaround time (TAT) of each CPA typology was used as an indicator of the performance of the organizational system according to a predefined scale (high, when within agreed timeframe; acceptable, when 1-2 days overdue; low, when > 2 days overdue).

Results: 6601 CPAs were provided (77.4% for AOUD and 22.6% for other hospitals), mainly for antimicrobials with high priority. The mean TAT was of < 24 hours for the CPAs provided 3 to 5 times per week, of < 48 hours for those provided 2 times per week, and of < 6 days for those provided once weekly or every over week. Overall, the performance was high, the percentage of overdue advices always less than 5%, irrespective of the CPA type.

Conclusions: our study confirms the suitability of the organizational system of our Service to provide a thousand per month TDM-based CPAs within timeframes clinically useful for the individualization of the dosing regimens of several antimicrobials.

Trends in treatment outcome of smear-positive pulmonary tuberculosis in Southeastern Nigeria, 1999 - 2008

Kingsley N. Ukwaja, Isaac Alobu, Ngozi A. Ifebunandu, Chijioke P. Osakwe — Mon, 31 Dec 2012 00:00:00 +0000

Background: the Directly Observed Treatment Short Course (DOTS) strategy was introduced into the tuberculosis control programme of Ebonyi, Southeastern, Nigeria in 1996. The impact of the programme on the treatment outcomes for smear-positive tuberculosis has not been assessed ever since. We assessed the trends in treatment outcome for new smear-positive pulmonary tuberculosis between 1999 and 2008.

Methods: we conducted a retrospective analysis of the Ebonyi state Ministry of Health quarterly smear-positive tuberculosis statistical returns. Patients were treated and treatment outcome categories computed according to the WHO/National Tuberculosis Control Programme’s guidelines. Chi-square for trends was used to determine significance.

Results: the number of smear-positive cases who registered for treatment fell from 1 361 patients in 1999 to 977 in 2008 (Trend χ2=349; P<0.001). The follow-up smear results at month two were not available for 16% of the patients in 1999; this unavailability decreased to 1.7% in 2008. The negative conversion rate at month two increased from 77.5% in 1999 to 95.9% in 2008 (Trend χ2=16.5; P<0.001). Treatment success rose from 74.9% in 1999 to 88.7% in 2008 (Trend χ2=12.8; P<0.001), whilst default rate declined from 12% to 4.3% (Trend χ2=55.6; P<0.001). Though decreasing (Trend χ2=4.64; P=0.031), the annual death rate remained at around 5% during the study period.

Conclusions: monitoring, supervision and home visits have improved, and our DOTS programme has achieved an 85% treatment success and declining default rates. However, with the current low case notification and high mortality rates, alternative mechanisms are needed to achieve global stop-TB targets in the State.

Low back pain among Kosovo power plant workers: a survey

Ardiana Murtezani, Zana Ibraimi, Ela Petrela, Merita Berisha, Teuta Osmani — Mon, 31 Dec 2012 00:00:00 +0000

Background: low back pain (LBP) has been identified as one of the most costly occupational illnesses among the worldwide working population. Objective: this study was designed to assess the prevalence of LBP among Kosovo power plant workers and to examine whether there was a correlation between age/job tenure and LBP.

Methods: a cross sectional questionnaire survey was carried out on 391 workers of the Kosovo Energy Corporation. Two hundred and six production workers (Group I) and 185 office workers (Group II) were included in the study. All the subjects were asked about LBP they had experienced in the previous year. Subjects with LBP then answered the questionnaire regarding the severity of LBP and functional disability caused by LBP. The severity of LBP was evaluated with a 10 mm visual analog scale (VAS). The Oswestry low back pain disability questionnaire (OSW) was used to measure functional disability.

Results: the prevalence of LBP was higher in Group I than in Group II (83.4%, 61.6%, respectively, p<0.001). The mean VAS and OSW score was higher in Group I than in Group II (p<0,001 vs. 0.016). There was a significant correlation of age (r= 0.249, p<0.01 and r= 0.155, p<0.05), and job tenure (r=0.245, p<0.01 and r=0.190, p<0.05) with VAS and OSW scores in blue collar workers with LBP. However, there was a statistically significant negative correlation found between job tenure and VAS and OSW scores of the office workers with LBP (p<0.05).

Conclusions: low back pain occurred at a high rate within this company. This study identified that age and job tenure correlated with the severity and functional disability of LBP among blue collar workers.

Caregiver burden from caring for impaired elderly: a cross-sectional study in rural Lower Egypt

Rasha Aziz Attia Salama, Faiza Ahmed Abou El-Soud — Mon, 31 Dec 2012 00:00:00 +0000

Background: increased life expectancy and an aging population have made home care for the elderly a major responsibility for families. Caring for a chronically ill or physically disabled person has been referred to as physically or emotionally stressful, placing the caregiver at a heightened risk of burden. This study aimed to identify factors related to caregiving burden among caregivers who care for their disabled older family members.

Methods: a cross sectional descriptive study was conducted from October 2008 to January 2009 in two randomly selected villages of Shebin El-Kom Menoufiya, Egypt. In an interview setting, questionnaires were used to collect the required data from 288 primary caregivers. Independent variables included the demographic characteristics of caregivers and care recipients, the severity of care recipients’ functional abilities, financial adequacy and caregivers’ degree of social support. Hierarchical regression was used to predict the levels of caregiver burden. The objective of the study was adequately explained to participants and their consent was obtained with assured confidentiality.

Results: caregivers who had little informal social support, inadequate financial resources and more caregiving hours were more likely to experience intense caregiving burden. Burden was also positively associated to the functional disabilities of care recipients and the degree of caregiver burnout. The results of this study indicated that the female spouse was the most common caregiver within the sample, which indicates that cultural norms in Egypt still affect caregiving burden.

Conclusions: identifying predictors of caregiver burden promotes a more comprehensive understanding of burden experiences when caring for older adults, and this may help prevent their deterioration to burn out syndrome

Beliefs on and attitude toward doping use among athletes: an Italian survey

Mon, 31 Dec 2012 00:00:00 +0000

Background: data on the prevalence of use, beliefs and attitude towards doping substances and practices among Italian athletes are scarce.

Methods: we interviewed 508 Italian athletes in sports facilities, using an anonymous structured questionnaire to collect information on the athletes’ beliefs about the role in performance and side effects of selected doping practices and substances, the reasons for use, obstacles in obtaining drugs, responsibility in the decision, changes in use in recent years, and anti-doping controls.

Results: among the athletes, 88.2% believed that supplements were effective to improve performance and 4.8% that they were potentially dangerous. They believed that 87.0% of top-level athletes frequently use supplements, namely 69.1% anti-inflammatories and 56.9% creatine. Doping was widespread in the opinion of 87.4% of athletes, and 45.3% thought it was used at all competition levels. Among those interviewed, 43.9% reported that athletes and coaches together were responsible for use, and 25.2% that it was easy to obtain substances. Lastly, 34.8% believed that doping use increased during 2002-05, and 54.7% thought that anti-doping controls should be more frequent.

Conclusions: this survey indicates that athletes believe that doping (mainly supplement use) is widespread at all competition levels, that athletes are aware of the seriousness of adverse effects and ask for more severe control and emphasis on potential dangers in the press.

Pinpointing outliers in experimental data: the Hat matrix in Anova for fixed and mixed effects models

Annalisa Orenti, Giuseppe Marano, Patrizia Boracchi, Ettore Marubini — Mon, 31 Dec 2012 00:00:00 +0000

The Hat (H) matrix and in particular the elements of its principal diagonal (leverages) have a paramount importance in multiple regression analysis in order to pinpoint possible outliers and/or influential points as components of several regression diagnostics. This note presents some features of the H matrix and residuals for ANOVA models of experimental designs. For fixed effects models, the values of the elements of H are discussed in completely randomized, randomized complete block and Latin squares designs. The increasing complexity of the design structure leads to different patterns, with increasing values of the corresponding leverages (hii). For mixed effects models, developments on leverage and residuals for marginal and conditional estimates are illustrated. The application of H matrix and residuals in fixed effects and mixed effects model is shown in a worked example. It is concluded that for H matrix in mixed models, an important role is played by the values of the variances of the random effects and the error term, and, consequently, by their method of estimation. Marginal and conditional studentized residuals provide different information about the data, and thus should be both used for model checking.

Power estimation for multiple co-primary endpoints: a comparison among conservative solutions

Antonio Lucadamo, Nadia Accoto, Daniele De Martini — Mon, 31 Dec 2012 00:00:00 +0000

The problem of estimating the power of the multivariate Intersection Union test (IUT) is studied. Four classical parametric solutions and a bootstrap non-parametric one, providing statistical lower bounds (i.e. one directional confidence intervals) for the power, are considered. The performances of these techniques in several bivariate IUT settings are compared through a simulation study. All solutions are biased, since their actual coverage probabilities are higher than the nominal one. The bootstrap solution shows the smallest bias, and the variability of its estimates is the lowest. Moreover, the bias of the bootstrap solution reduces faster than those of the other techniques when the pilot sample size, or the correlation, or the rate between the two non-centrality parameters increases. Also, the non-parametric bootstrap solution can be improved by calibration, with a considerable bias reduction.

High Dimensional Regression on Serum Analytes

Yuanzhang Li, Emanuel Schwarz, Sabine Bahn, Robert Yolken, David W Niebuhr — Mon, 31 Dec 2012 00:00:00 +0000

Regression of high dimensional data is particularly difficult when the number of observations is limited. Principal Component Analysis, canonical correlation analysis and factor analysis are commonly used methods to reduce data dimensions, but usually cannot find the most significant linear combination. The goal is usually to find a particular partition of the space X consisting of all independent factors. In this paper, we propose an approach to high dimensional regression for applications where N>K or N<K, where N is the sample size, k is the dimension of space X. The approach starts by finding the most significant linear combination and one of the most insignificant directions to decompose the sample space into two subspaces and reduce the dimension. Further, we examine the contributions of individual variables to those most significant vectors by the coefficients of the combinations to reduce the total number of variables in the selected space without losing the power of the prediction. We use the proposed approach to determine the potential association of 51 serum analytes with schizophrenia using data derived from a case control study (n=208). Numerical results demonstrate that the proposed approach can significantly improve dimension reduction.

“Successes and failures of health policy in Europe over four decades. Diverging trends, converging challenges”. Edited by Johan Mackenbach and Martin McKee.

Stefania Boccia, Walter Ricciardi — Mon, 31 Dec 2012 00:00:00 +0000

The volume represents one of a series of books produced by the European Observatory on Health Systems and Policies, and it is directed to public health practitioners, health policy makers, and public health scientists both in Europe and elsewhere. It aims to depict...

Giulio Alfredo Maccacaro

Roberto Bucci, Serena Traglia — Mon, 31 Dec 2012 00:00:00 +0000

Giulio Alfredo Maccacaro was a biometrist, a scientist using statistical methods to calculate the laws and phenomena of the biological system. Well known in the international arena, he...