Giovanni Apolone

Overweight and obesity in Italian adults 2004, and an overview of trends since 1983

Objective:Overweight has been increasing in several developed countries over the last few decades. No update information on the issue is available for Italy.Design and setting:We conducted a computer assisted personal in-house interview survey in March–April 2004, on a sample of 2932 Italian individuals (1407 men and 1525 women) aged 18 years or over, representative of the general adult Italian population. Information on weight and height was self-reported.Results:Overall, 3.4% of the Italian adult population were underweight (<18.5 kg/m2, 0.9% of men and 5.8% of women), 31.3% were overweight (25.0–29.9 kg/m2, 38.4% of men, 24.7% of women), and 8.2% were obese (⩾30.0 kg/m2, 7.4% of men and 8.9% of women). Overweight or obesity was reported by 14.2% of subjects aged 18–24 years (20.6% of men and 7.6% of women). The highest proportions of overweight and obese subjects were in the 45–64 year age group for men (51.4% overweight, 10.0% obese) and in the ⩾65 year age group for women (38.8% overweight, 13.8% obese). Age- and sex-standardised prevalence of overweight or obesity was 36.0% for more educated subjects, and 54.0% for less educated ones. It was 32.3% in northern, 44.3% in central and 47.0% in southern Italy. Overweight increased from 1983 to the early 1990s, and levelled off thereafter. Prevalence of obesity remained around 8–9% across the last 20 years.Conclusions:Trends of overweight and obesity in Italy are more favourable than in several developed countries. Still, approximately 15 million of Italian adults are overweight and 4 million obese.

Metabolic syndrome, psychological status and quality of life in obesity: The QUOVADIS Study

Objective:We aimed to investigate the association of the clinical variables of the metabolic syndrome (MS) and psychological parameters on health-related quality of life (HRQL) in obesity. In particular, our aim was to investigate the relative impact of physical symptoms, somatic diseases and psychological distress on both the physical and the mental domains of HRQL.Design:Cross-sectional study.Subjects:A cohort of 1822 obese outpatients seeking treatment in medical centers.Measurements:HRQL was measured by the standardized summary scores for physical (PCS) and mental (MCS) components of the Short Form 36 Health Survey (SF-36). Patients were grouped according to tertiles of PCS and MCS. Metabolic and psychological profiles of PCS and MCS tertiles were compared by discriminant analysis.Results:The profile of metabolic and psychological variables was tertile-specific in 62.4 and 68.3% of patients in the lowest and highest tertiles of PCS, respectively, while concordance was low in the mid-tertile (32.8%). Concordance was very high in the lowest (74.4%) and in the highest (75.5%) tertiles of MCS, and was fair in the mid-tertile (53.2%). The main correlates of PCS were obesity-specific and general psychological well-being, BMI, body uneasiness, binge eating, gender and psychiatric distress. Only hypertension and hyperglycemia qualified as correlates among the components of MS. The components of MS did not define MCS.Conclusions:Psychological well-being is the most important correlate of HRQL in obesity, both in the physical and in the mental domains, whereas the features of MS correlate only to some extent with the physical domain of HRQL.

Clinical and psychological correlates of health-related quality of life in obese patients

BackgroundHealth-related quality of life (HRQL) is poor in obese subjects and is a relevant outcome in intervention studies. We aimed to determine factors associated with poor HRQL in obese patients seeking weight loss in medical units, outside specific research projects.MethodsHRQL, together with a number of demographic and clinical parameters, was studied with generic (SF-36, PGWB) and disease-specific (ORWELL-97) questionnaires in an unselected sample of 1,886 (1,494 women; 392 men) obese (BMI > 30 kg/m2) patients aged 20-65 years attending 25 medical units scattered throughout Italy. The clinics provide weight loss treatment using different programs. General psychopathology (SCL-90 questionnaire), the presence of binge eating (Binge Eating scale), previous weight cycling and somatic comorbidity (Charlsons index) were also determined. Scores on SF-36 and PGWB were compared with Italian population norms, and their association with putative determinants of HRQL after adjustment for confounders was assessed through logistic regression analysis.ResultsHRQL scores were significantly lower in women than in men. A greater impairment of quality of life was observed in relation to increasing BMI class, concurrent psychopathology, associated somatic diseases, binge eating, and weight cycling. In multivariate analysis, psychopathology (presence of previously-diagnosed mental disorders and/or elevated scores on SCL-90) was associated with lower HRQL scores on both psychosocial and somatic domains; somatic diseases and higher BMI, after adjustment for confounders, were associated with impairment of physical domains, while binge eating and weight cycling appeared to affect psychosocial domains only.ConclusionsPsychopathological disturbances are the most relevant factors associated with poor HRQL in obese patients, affecting not only psychosocial, but also physical domains, largely independent of the severity of obesity. Psychological/psychiatric interventions are essential for a comprehensive treatment of obesity, and to improve treatment outcome and to reduce the burden of disease.

Stopping a trial early in oncology: for patients or for industry?

BACKGROUND The aim of this study is to assess the use of interim analyses in randomised controlled trials (RCTs) testing new anticancer drugs, focussing on oncological clinical trials stopped early for benefit. MATERIALS AND METHODS All published clinical trials stopped early for benefit and published in the last 11 years, regarding anticancer drugs and containing an interim analysis, were assessed. RESULTS Twenty-five RCTs were analysed. The evaluation of efficacy was protocol planned through time-related primary end points, >40% of them overall survival. In 95% of studies, at the interim analysis, efficacy was evaluated using the same end point as planned for the final analysis. As a consequence of early stopping after the interim analysis, approximately 3300 patients/events across all studies were spared. More than 78% of the RCTs published in the last 3 years were used for registration purposes. CONCLUSION Though criticism of the poor quality of oncological trials seems out of place, unfortunately early termination raises new concerns. The relation between sparing patients and saving time and trial costs indicates that there is a market-driven intent. We believe that only untruncated trials can provide a full level of evidence which can be translated into clinical practice without further confirmative trials.

Construct Validity of the Short Form-36 Health Survey and Its Relationship with BMI in Obese Outpatients

Objective: To investigate the construct validity of the Short Form‐36 (SF‐36) Health Survey questionnaire in obese patients.

Are adaptive randomised trials or non-randomised studies the best way to address the Ebola outbreak in west Africa?

Summary The Ebola outbreak that has devastated parts of west Africa represents an unprecedented challenge for research and ethics. Estimates from the past three decades emphasise that the present effort to contain the epidemic in the three most affected countries (Guinea, Liberia, and Sierra Leone) has been insufficient, with more than 24 900 cases and about 10 300 deaths, as of March 25, 2015. Faced with such an exceptional event and the urgent response it demands, the use of randomised controlled trials (RCT) for Ebola-related research might be both unethical and infeasible and that potential interventions should be assessed in non-randomised studies on the basis of compassionate use. However, non-randomised studies might not yield valid conclusions, leading to large residual uncertainty about how to interpret the results, and can also waste scarce intervention-related resources, making them profoundly unethical. Scientifically sound and rigorous study designs, such as adaptive RCTs, could provide the best way to reduce the time needed to develop new interventions and to obtain valid results on their efficacy and safety while preserving the application of ethical precepts. We present an overview of clinical studies registered at present at the four main international trial registries and provide a simulation on how adaptive RCTs can behave in this context, when mortality varies simultaneously in either the control or the experimental group.

Surgery for oligometastatic non-small cell lung cancer: long-term results from a single center experience.

OBJECTIVE The role of surgery in the multimodal therapy for selected stage IV oligometastatic non-small cell lung cancer (NSCLC) is still a forum of open discussion. METHODS We have retrospectively analyzed the records of 53 patients with oligometastatic NSCLC who had been treated with curative intent in the period January 1997 to May 2010. RESULTS The mean age and the male/female ratio were 61 years and 32:21, respectively. A single metastatic lesion was present in 45 (84.9%) subjects, in 2 patients there were 2 different anatomic sites involved, and in 8 patients there were 2 metastases in the same site. The most common involved sites were brain (39), followed by adrenal gland (7), bone (3), vertebrae (3), liver (1), and contralateral supraclavicular lymph node (1). Distant disease was completely resected in 42 patients; 10 patients were treated with exclusive chemotherapy and/or radiotherapy and 1 with local laser therapy. Twenty-nine patients had been administered concurrent chemoradiation in a neoadjuvant setting before the surgical treatment at the lung or both sites (primary/distant). The pulmonary resection was complete (R0) in 42 patients (79.2%). Overall, 1- and 5-year survivals were 73.1% and 24%, respectively (median follow-up, 28 months). Median overall survival, local disease-free survival, and distant disease-free survival, estimated using the Kaplan-Meier method, were respectively 19, 72, and 12 months. After stepwise multivariate analysis, the weight loss (P<.001), the completeness of pulmonary resection (P=.0019), and, interestingly, the performance of a positron emission tomography-computed tomography scan in preoperative staging (P=.05) maintained their independent prognostic value as overall survival determinants. CONCLUSIONS Surgical treatment for selected stage IV NSCLC is feasible and safe. Furthermore, good survival can be expected in those patients in whom a complete resection of the primary tumor and radical control of the distant diseases are accomplished.

Illness awareness in terminal cancer patients: an Italian study

The amount and quality of information and awareness in cancer patients’ is a topic frequently debated, but few studies have focussed on terminal patients. This is the objective of the present study that involved two different palliative home-care units in Italy, which recruited 550 terminal cancer patients. Data from patients and their caregivers was prospectively collected with special attention to information patients were provided with when their cancer was diagnosed and patients’ awareness of their current health condition. In the case of the information, 67.0% of patients reported they were previously informed about their diagnosis, but only 58.0% seemed to be aware of their terminal condition. The comparison between the caregivers opinions about the level of information provided to the patients and their present awareness and what the patients really know about their own disease shows a high degree of correspondence. Some variables such as age and education level of patients were associated with patient’s awareness.

Role of combined 18F-FDG-PET/CT for predicting the WHO malignancy grade of thymic epithelial tumors: A multicenter analysis

INTRODUCTION To investigate the performance of combined (18)F-FDG-PET/CT as a predictor of the WHO-classification based malignancy grade in thymic epithelial tumors. METHODS From 05/06 to 02/12, the data of 47 patients with thymic epithelial tumors assessed by (18)F-FDG-PET/CT before being surgically treated were collected in 3 centers and retrospectively reviewed for the purposes of this study. The SUVmax and the SUVmax/T index (the ratio tumor-SUVmax to tumor-size) have been matched with specific subgroups of the WHO-classification: low-risk thymomas (types A-AB-B1), high-risk thymomas (types B2-B3) and thymic carcinomas (type C). RESULTS There were 22 men and 25 women (age range: 31-84 yrs). Mean tumor size was 44.7 ± 19.0 mm. The WHO-classification was: type-A #2, type-AB #11, type-B1 #9, type-B2 #9, type-B3 #9 and type-C #7. The SUVmax and the SUVmax/T were found to be predictive factors useful to distinguish thymomas from thymic carcinomas (SUVmax: area under ROC-curve: 0.955, p = 0.0045; SUVmax/T-size: area under ROC-curve: 0.927, p = 0.0022). Moreover, both parameters were found to be correlated with the WHO malignancy grade (low-risk thymomas; high-risk thymomas; thymic carcinoma), Spearman correlation coefficients being 0.56 (p < 0.0001) and 0.76 (p < 0.0001), respectively for the SUVmax and for the SUVmax/T index. In addition, the SUVmax is also significantly correlated with Masaoka stage (Spearman correlation coefficient: 0.30, p = 0.0436) CONCLUSIONS: A significant relationship was observed between (18)F-FDG-PET/CT findings and histologic WHO-classification for this cohort of thymic epithelial tumors. Thus, on the basis of these evidences, we infer that (18)F-FDG-PET/CT may be useful to predict histology and the WHO classes of risk.

A systems medicine clinical platform for understanding and managing non- communicable diseases

Non-Communicable Diseases (NCDs) are among the most pressing global health problems of the twenty-first century. Their rising incidence and prevalence is linked to severe morbidity and mortality, and they are putting economic and managerial pressure on healthcare systems around the world. Moreover, NCDs are impeding healthy aging by negatively affecting the quality of life of a growing number of the global population. NCDs result from the interaction of various genetic, environmental and habitual factors, and cluster in complex ways, making the complex identification of resulting phenotypes not only difficult, but also a top research priority. The degree of complexity required to interpret large patient datasets generated by advanced high-throughput functional genomics assays has now increased to the point that novel computational biology approaches are essential to extract information that is relevant to the clinical decision-making process. Consequently, system-level models that interpret the interactions between extensive tissues, cellular and molecular measurements and clinical features are also being created to identify new disease phenotypes, so that disease definition and treatment are optimized, and novel therapeutic targets discovered. Likewise, Systems Medicine (SM) platforms applied to extensively-characterized patients provide a basis for more targeted clinical trials, and represent a promising tool to achieve better prevention and patient care, thereby promoting healthy aging globally. The present paper: (1) reviews the novel systems approaches to NCDs; (2) discusses how to move efficiently from Systems Biology to Systems Medicine; and (3) presents the scientific and clinical background of the San Raffaele Systems Medicine Platform.