Comparison of baseline patient characteristics in Italian oncology drug monitoring registries and clinical trials: a real-world cross-sectional study.

Background: Generalizability of registrative clinical trials to real-world clinical practice is influenced by comparability of patients in the two settings. We compared characteristics of cancer patients in registrative trials with real-world clinical practice in Italy. Methods: Data on age, sex and performance status (PS) were derived from web-based monitoring registries developed by Italian Medicines Agency (AIFA) and corresponding registrative trials reported in the European Public Assessment Reports (EPAR) of European Medicines Agency (EMA). Weighted means were calculated in registries and trials and differences were described. Multivariate analysis was performed using Principal Component Analysis and Cluster Analysis. Findings: From January, 2013 to April, 2023, 419,461 unique pairs of patients and therapeutic indications were recorded in 129 AIFA registries. Within 140 related trials, 87,452 patients had been enrolled. Median age and rate of elderly (≥65 years old) patients were higher in monitoring registries than in clinical trials [mean difference of median age 5.3 years, p < 0.001; mean difference of elderly rate 17.17% (95% CI 1.06, 1.48)]. Overall, rate of female patients was not different between registries and trials [mean difference -0.55% (95% CI -1.06, -0.05)]. Mean rate of patients with deteriorated PS was low both in trials (3.1%) and in registries (4.3%) with a mean difference of 1.27% (95% CI 1.06, 1.48). Two clusters were identified with multivariate analysis: one including more registries (higher median age and elderly rate, lower female rate, higher rate of deteriorated patients), the other more trials (lower median age and elderly rate, higher female rate, lower rate of deteriorated patients). Interpretation: This study supports that cancer patients enrolled in trials do only partially represent those who have been treated in Italy in clinical practice. Inclusiveness of registrative trials should be increased to ensure generalizability of results to real-world population. Funding: Partially supported by Italian Ministry of Health.

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.

Investigating the synergistic interaction of diabetes, tobacco smoking, alcohol consumption, and hypercholesterolemia on the risk of pancreatic cancer: a case-control study in Italy.

The aims of the present research are to investigate the possible predictors of pancreatic cancer, in particular smoking status, alcohol consumption, hypercholesterolemia, and diabetes mellitus, in patients with histologically confirmed pancreatic carcinoma and to examine the synergism between risk factors. A case-control study (80 patients and 392 controls) was conducted at the Teaching Hospital "Agostino Gemelli" in Rome. A conditional logistic regression was used for the statistical analysis and results were presented as odds ratio (OR) and 95% confidence intervals (95% CI). We also investigated the possible interactions between risk factors and calculated the synergism index (SI). The multivariate analysis revealed that hypercholesterolemia and alcohol consumption resulted in important risk factors for pancreatic cancer even after the adjustment for all variables (OR: 5.05, 95% CI: 2.94-8.66; OR: 2.25, 95% CI: 1.30-3.89, resp.). Interestingly, important synergistic interactions between risk factors were found, especially between ever smoking status and alcohol consumptions (SI = 17.61) as well as alcohol consumption and diabetes (SI = 17.77). In conclusion, the study confirms that hypercholesterolemia and alcohol consumption represent significant and independent risk factors for pancreatic cancer. Moreover, there is evidence of synergistic interaction between diabetes and lifestyle factors (drinking alcohol and eating fatty foods).

The prevention of postmenopausal osteoporotic fractures: results of the Health Technology Assessment of a new antiosteoporotic drug.

OBJECTIVE: The Health Technology Assessment (HTA) approach was applied to denosumab in the prevention of osteoporotic fractures in postmenopausal women. METHOD: Epidemiological, clinical, technical, economic, organizational, and ethical aspects were considered. Medical electronic databases were accessed to evaluate osteoporosis epidemiology and therapeutical approaches. A budget impact and a cost-effectiveness analyses were performed to assess economic implications. Clinical benefits and patient needs were considered with respect to organizational and ethical evaluation. RESULTS: In Italy around four millions women are affected by osteoporosis and have a higher risk for fractures with 70,000 women being hospitalized every year. Bisphosphonates and strontium ranelate are recommended as first line treatment for the prevention of osteoporotic fractures. Denosumab is effective in reducing vertebral, nonvertebral, and hip/femoral fractures with an advantage of being administered subcutaneously every six months. The budget impact analysis estimated a reduction in costs for the National Health Service with the introduction of denosumab. Furthermore, the economic analysis demonstrated that denosumab is cost-effective in comparison to oral bisphosphonates and strontium ranelate. Denosumab can be administered in outpatients by involving General Practitioners in the management. Ethical evaluation is positive because of its efficacy and compliance. CONCLUSION: Denosumab could add value in the prevention of osteoporotic fractures.

Epidemiology of home injuries: a large observational study among adult mothers in Italy.

AIMS: The aims of the study were to describe the epidemiology of home injuries (HI) among Italian students' mothers and to identify the possible predictors of having HI. METHODS: An anonymous questionnaire was used in several Italian schools. In order to identify predictors of having HI, a multivariate analysis was performed. RESULTS: In our sample (3,610 women), the prevalence of HI was 18%; 6.2% of the interviewed had a severe HI. The multivariate analyses showed that increasing age, to spend more than 13 hours a day at home and to be housewife are risk factors for having HI. CONCLUSIONS: This study reports a high prevalence of HI, highlighting an urgent need for undertaking interventions to develop an adequate culture of safety and prevention.

Antiplatelet/anticoagulant agents and chronic subdural hematoma in the elderly.

BACKGROUND AND PURPOSE: In the last decade there has been an increasing use of antiplatelet/anticoagulant agents in the elderly. The aim of the study was to evaluate the association between exposure to anticoagulant/antiplatelet therapy and chronic subdural haematoma-CSDH. METHODS: Single institution case-control study involving 138786 patients older than 60 years who visited our academic tertiary care Emergency Department from January 1st 2001 to December 31st 2010. 345 patients with CSDH (cases) were identified by review of ICD-9 codes 432.1 and 852.2x. Case and controls were matched with a 1:3 ratio for gender, age (± 5 years), year of admission and recent trauma. A conditional logistic model was built. A stratified analysis was performed with respect to the presence (842 patients) or absence (536 patients) of recent trauma. RESULTS: There were 345 cases and 1035 controls. Both anticoagulant and antiplatelet agents were associated with an increased risk of CSDH with an OR of 2.46 (CI 95% 1.66-3.64) and 1.42 (CI 95% 1.07-1.89), respectively. OR was 2.70 (CI 95% 1.75-4.15), 1.90 (CI 95% 1.13-3.20), and 1.37(CI 95% 0.99-1.90) for patients receiving oral anticoagulants, ADP-antagonists, or Cox-inhibitors, respectively. History of recent trauma was an effect modifier of the association between anticoagulants and CSDH, with an OR 1.71 (CI 95% 0.99-2.96) for patients with history of trauma and 4.30 (CI 95% 2.23-8.32) for patients without history of trauma. CONCLUSIONS: Anticoagulant and antiplatelet therapy have a significant association with an increased risk of CSDH. This association, for patients under anticoagulant therapy, appears even stronger in those patients who develop a CSDH in the absence of a recent trauma.

A pilot survey on the quality of life in respiratory rehabilitation carried out in COPD patients with severe respiratory failure: preliminary data of a novel Inpatient Respiratory Rehabilitation Questionnaire (IRRQ).

BACKGROUND: Measuring the state of health is a method for quantifying the impact of an illness on the day-to-day life, health and wellbeing of a patient, providing a quantitative measure of an individual's quality of life (QoL). QoL expresses patient point of view by a subjective dimension and can express the results of medical intervention. Pulmonary rehabilitation is an essential component in the management of COPD patients, and measuring QoL has become a central focus in the study of this disease.Although nowadays several questionnaires for measuring the QoL in COPD patients are available, there are no questionnaires specifically developed for evaluating QoL in COPD patients undergoing respiratory rehabilitation.The aim of this study was to develop a novel questionnaire for the QoL quantification in COPD patients undergoing in-patient pulmonary rehabilitation program. METHODS: The questionnaire, administered to COPD patients undergoing long-term oxygen therapy into a respiratory rehabilitation ward, was developed by a simple and graphic layout to be administered to elderly patients. It included one form for admission and another for discharge. It included only tips related to the subjective components of QoL that would be relevant for patient, although likely not strictly related to the respiratory function.A descriptive analysis was performed for the socio-demographic characteristics and both the non-parametric Wilcoxon T-test and the Cronbach's alpha index were calculated for evaluating the sensitivity of the questionnaire to the effects of respiratory rehabilitation and for identifying its consistency. RESULTS: The physical and psychological condition of the 34 COPD patients improved after the rehabilitative treatment and this finding was detected by the questionnaire (overall improvement: 14.2±2.5%), as confirmed by the non-parametric Wilcoxon test (p<0.01). The consistency detected by the Cronbach's alpha was good for both the questionnaire at admission and at discharge (0.789±0.084 and 0.784±0.145, respectively), although some items did not adequately measure the intended outcome. CONCLUSIONS: This proposed questionnaire represents a substantial innovation compared to previous methods for evaluating the QoL, since it has been specifically designed for hospitalized COPD patients undergoing respiratory rehabilitation with serious respiratory deficiency, allowing to effectively determining the QoL in these patients.

[EpiInfo as a research and teaching tool in epidemiology and statistics: strengths and weaknesses]. / EpiInfo come strumento per la ricerca e per la didattica dell'epidemiologia e della statistica: punti di forza e di debolezza.

EpiInfo is a free software developed in 1988 by the Centers for Disease Control and Prevention (CDC) in Atlanta to facilitate field epidemiological investigations and statistical analysis. The aim of this study was to assess whether the software represents, in the Italian biomedical field, an effective analytical research tool and a practical and simple epidemiology and biostatistics teaching tool. A questionnaire consisting of 20 multiple-choice and open questions was administered to 300 healthcare workers, including doctors, biologists, nurses, medical students and interns, at the end of a CME course in epidemiology and biostatistics. Sixty-four percent of participants were aged between 26 and 45 years, 52% were women and 73% were unmarried. Results show that women are more likely to utilize EpiInfo in their research activities with respect to men (p = 0.023), as are individuals aged 26-45 years with respect to the older and younger age groups (p = 0.023) and unmarried participants with respect to those married (p = 0.010). Thirty-one percent of respondents consider EpiInfo to be more than adequate for analysis of their research data and 52% consider it to be sufficiently so. The inclusion of an EpiInfo course in statistics and epidemiology modules facilitates the understanding of theoretical concepts and allows researchers to more easily perform some of the clinical/epidemiological research activities.

PTPN22 and myasthenia gravis: replication in an Italian population and meta-analysis of literature data.

Polymorphisms in PTPN22 are associated with many autoimmune diseases; while rs2476601 is supposed to play a major role, other experimental data suggest that rs2488457 may be even more important. Results in myasthenia gravis are controversial. In 356 Italian myasthenic patients and 439 controls genotyped for both polymorphisms, we found that rs2476601 was not associated with myasthenia, presence of autoantibodies, thymus pathology, sex or onset age unlike previous studies on other European populations (confirmed by the present meta-analysis). On the other hand, while rs2488457 was not associated with myasthenia or thymus pathology, we found a correlation of rs2488457 with low autoantibody titers and a trend of association with a less severe disease. Both polymorphisms were in tight linkage disequilibrium in controls, not in patients. Our results suggest that SNPs in this gene different from rs2476601, and/or epigenetic interactions, could play a greater role.

Prevalence of influenza vaccination among nurses and ancillary workers in Italy: systematic review and meta analysis.

INTRODUCTION: 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. RESULTS: 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%). DISCUSSION: 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. METHODS: Research was conducted using medical database Scopus, PubMed, the search engine Google Scholar and ISI web of knowledge, and was concluded February 1st 2011.

Clinical accuracy of midnight salivary cortisol measured by automated electrochemiluminescence immunoassay method in Cushing's syndrome.

BACKGROUND: The diagnosis of Cushing's syndrome (CS) represents a challenge for endocrinologists. Several screening tests are used, but none of them seems to be the gold standard for the diagnosis. The aim of this study was to confirm the diagnostic value of salivary cortisol (SC) as a first-level screening test and to evaluate the clinical performance of a electrochemiluminescence immunoassay (ECLIA) method. METHODS: In 33 patients with a strong clinical suspicion of CS, we evaluated urinary free cortisol, circadian rhythm plasma cortisol (PC) and morning PC after low-dose dexamethasone suppression test (LDDST). At the same sampling times, we evaluated SC analysed by the same automated method. Correlation studies were evaluated by Spearman index (significance P < 0.05). RESULTS: On the basis of biochemical results CS was confirmed in 21/33. SC was significantly correlated to PC at 12:00 and 23:00. Thus, we chose 8.3 nmol/L as midnight SC cut-off value with 100% sensitivity and 97.4% specificity. The cut-off chosen after LDDST was 1.7 nmol/L (100% sensitivity and 72% specificity). CONCLUSION: SC assay showed a good clinical accuracy and the ECLIA method can be used in clinical routine to obtain fast results easily.

Intrafamilial transmission of hepatitis C virus in Italy: a systematic review.

BACKGROUND: Hepatitis C virus (HCV) transmission is mainly due to parenteral exposure; however, in absence of such risk factor, there are reports of intrafamilial spread of HCV and observational studies suggest an increased risk for households of infected subjects. The aim of our study was to systematically review and meta-analyse studies about HCV prevalence among households of HCV patients in Italy. METHODS: PubMed and Embase were searched to identify Italian studies about HCV intrafamilial transmission. Keywords used were: 'HCV', 'Hepatitis C', 'intrafamilial', 'family' and 'Italy'. Selected studies were reviewed to assess the quality and meta-analysed using StatsDirect software. RESULTS: 25 studies were selected. The pooled overall prevalence was 9% (95% CI 7.1% to 11.1%). The highest pooled prevalence was found among sexual partners of index cases: 14.7% (95% CI 10.7% to 19.2%) globally and 9.9% (95% CI 3.6% to 18.8%) and 17.6% (95% CI 12.1% to 24%) in northern and central-southern regions, respectively. The meta-analysis of high-quality studies yielded the lowest HCV prevalence. CONCLUSION: To be a HCV patient household is a risk factor for HCV and counselling for these households should be provided.

[Prevalence of domestic accidents amongst mothers of elementary and middle school children in Sardinia (Italy)]. / Indagine epidemiologica sugli incidenti domestici in Sardegna. Uno studio di prevalenza tra le madri degli alunni delle scuole di I e II grado.

A study was performed to examine the epidemiology of domestic accidents in Sardinia (Italy). A questionnaire was administered to mothers of public school students attending elementary and middle classes during the 2006-2007 school year. Overall 2.075 mothers (59,3% of eligible mothers) participated in the study, 400 (19,3%) of whom declared having had a domestic accident during the previous year. The most frequent lesions were those of the upper (58%) and lower (24%) extremities. Geographical origin and school attended by the student were both found to be statistically associated with domestic accidents.