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E Paci

Publications and source records attributed to E Paci.

At least 73 records · Page 4Linked to original sources

Study design of randomized controlled clinical trials of breast cancer screening.

Evaluation of population screening must be based on a randomized clinical trial (RCT) with the study population randomized into two arms: an intervention group invited to screening and a control group not invited to screening. Reduced mortality in the intervention group is evidence of a benefit from screening. Individual randomization is the ideal, but cluster randomization is often used for logistical and ethical reasons. The use of volunteer subjects is methodologically acceptable, but results cannot be generalized. Seven RCTs of breast cancer screening by mammography have been carried out in the United States, Canada, Sweden, and Scotland. All the studies, except the Canadian, were designed to assess the effect of screening across a wide range of ages at entry. The question of the efficacy of breast cancer screening at younger ages (< 50 years) arose early, after the first results were reported. To address this question, basic elements of the screening protocol must be considered when interpreting the results; these are screening modality (e.g., mammography with or without physical examinations), interscreening interval, and number of screening rounds. This article examines the possible influence of these factors and reviews the design choices and the characteristics of the seven RCTs.

Adult↗

Intrinsic compressibility and volume compression in solvated proteins by molecular dynamics simulation at high pressure.

Constant pressure and temperature molecular dynamics techniques have been employed to investigate the changes in structure and volumes of two globular proteins, superoxide dismutase and lysozyme, under pressure. Compression (the relative changes in the proteins' volumes), computed with the Voronoi technique, is closely related with the so-called protein intrinsic compressibility, estimated by sound velocity measurements. In particular, compression computed with Voronoi volumes predicts, in agreement with experimental estimates, a negative bound water contribution to the apparent protein compression. While the use of van der Waals and molecular volumes underestimates the intrinsic compressibilities of proteins, Voronoi volumes produce results closer to experimental estimates. Remarkably, for two globular proteins of very different secondary structures, we compute identical (within statistical error) protein intrinsic compressions, as predicted by recent experimental studies. Changes in the protein interatomic distances under compression are also investigated. It is found that, on average, short distances compress less than longer ones. This nonuniform contraction underlines the peculiar nature of the structural changes due to pressure in contrast with temperature effects, which instead produce spatially uniform changes in proteins. The structural effects observed in the simulations at high pressure can explain protein compressibility measurements carried out by fluorimetric and hole burning techniques. Finally, the calculation of the proteins static structure factor shows significant shifts in the peaks at short wavenumber as pressure changes. These effects might provide an alternative way to obtain information concerning compressibilities of selected protein regions.

Muramidase↗

Dimer asymmetry in superoxide dismutase studied by molecular dynamics simulation.

Molecular dynamics (MD) simulations of 100 ps have been carried out to study the active-site behaviour of the Cu,Zn superoxide dismutase dimer (SOD) in water. The active site of each subunit was monitored during the whole simulation by calculating the distances between functional residues and the catalytic copper. The results indicate that charge orientation is maintained at each active site but the solvent accessibility varies. Analysis of the MD simulation, carried out by using the atomic displacement covariance matrix, has shown a different intra-subunit correlation pattern for the two monomers and the presence of inter-subunit correlations. The MD simulation presented here indicates an asymmetry in the two active sites and different dynamic behaviour of the two SOD subunits.

Animals↗

Assessment of the RSCL quality of life instrument during chemotherapy in an Italian setting.

Evaluation of the quality of life of oncological patients is now perceived as a major element of cancer treatment, and various instruments for measuring it have been proposed. However, whatever instrument is used must be capable of reflecting the different ways in which different contexts and cultures respond to cancer. We administered the Italian version of the Rotterdam Symptom Checklist (RSCL) to 60 patients with advanced disease attending five oncological centres in Romagna (central Italy). The RSCL was found to be able to measure both psychological and physical well-being and to detect a difference between patients on low/medium and those on high-burden chemotherapy. The Italian version of the RSCL is an adequate scale that is capable of capturing patient perceptions and could be used for monitoring the quality of life of Italian patients participating in clinical trials.

Adult↗

Sojourn time, sensitivity and positive predictive value of mammography screening for breast cancer in women aged 40-49.

BACKGROUND: In mammographic screening for breast cancer in women aged 40-49, previous studies have found very low estimates of sensitivity and predictive value. Methods of estimation have, however, used primitive models with relatively strong assumptions and less than full use of the data. METHODS: Here we estimate the underlying preclinical incidence, mean sojourn time, sensitivity and positive predictive value by a variety of methods in a randomized trial of mammographic screening (The Swedish Two-County Trial) and a service screening programme (The Florence Programme, 1975-1986) in women aged 40-49 years. RESULTS: In the Two-County study, sensitivity estimates ranged from 72-83% and predictive value from 39-89%. In the Florence programme, sensitivity estimates ranged from 69-85% and predictive value was uniformly estimated as 100%. CONCLUSIONS: The methods involving more explicit modelling of the disease process and fewer assumptions tended to find higher estimates of predictive value in the Two-County study. The results suggest that previously poor sensitivity and predictive value estimates may have been overpessimistic.

Adult↗

Liver. III: Gadolinium-based hepatobiliary contrast agents (Gd-EOB-DTPA and Gd-BOPTA/Dimeg).

Gd-EOB-DTPA and Gd-BOPTA/Dimeg are two paramagnetic contrast agents that are unlikely ECF contrast agents but that are selectively taken up by hepatocytes and yield a selective enhancement of the liver parenchyma on T1-weighted images. Gd-EOB-DTPA yields hepatocellular specific uptake within the biliary excretion rate of 50% of the injected dose. Gd-BOPTA/Dimeg is taken up by hepatocytes in a small portion (2%-4%); however, its high relaxivity provides a significant and sustained increase of signal intensity of the normal liver. Both compounds have demonstrated a safe pharmacologic and toxicologic profile on preclinical evaluation and phase I clinical trials. Preliminary results demonstrate that these contrast agents may improve the MR imaging capability to detect focal liver lesions, with a dramatic and selective increase of liver signal-to-noise ratio and lesion-liver contrast-to-noise ratio. The wide imaging window, allowed by the sustained enhancement achieved after injection also provides flexibility in selecting an imaging sequence.

Clinical Trials, Phase I as Topic↗

A model-based prediction of the impact on reduction in mortality by a breast cancer screening programme in the city of Florence, Italy.

The efficacy of breast cancer screening for women older than 50 years has been shown in several studies. Service screening is now ongoing or planned in several countries in Europe. MISCAN, a computer simulation programme, has been used to analyse data from the Florence District Programme (FDP) breast cancer experience. First, the model was fitted to the screening results for the period 1975-1986. A good correspondence between the model outcomes and the FDP results was achieved. It was then used to predict the impact on mortality of the new starting programme of the city of Florence (63,000 women, 50-69 years old). Assuming a 70% attendance rate, then for the city of Florence, 2563 screen-detected breast cancers are predicted for the period 1991-2020 out of the total number of 9095 breast cancers for all ages (28%). A total of 3720 deaths for breast cancer are expected without screening. An absolute reduction of 472 deaths (13%) is predicted for the whole population. The estimated number of years of life gained by screening until 2020 is 4354. Simulation by MISCAN has previously been a useful support tool for decision-making about screening. The present paper is the first based on a southern European experience. The possibility of applying MISCAN to predict the impact of a national programme in Italy is discussed.

Adult↗

Epidemiology and the Italian national health service.

The Italian national health services is under criticism. Although recent legislative changes are intended to introduce managed competition, there is no clear epidemiological view of the health care needs and priorities. Several inconsistencies and inequalities (particularly between the northern and the southern regions) are obvious, both in the health status of the population and in the provision of health care. Problems that should be addressed by future governments are: the uneven distribution of medical technology; the persistence of large inequalities, documented by outcomes such as rheumatic fever, between northern and southern regions; the large variability in clinical practices; the lack of an explicit policy as far as the diffusion of advanced technology is concerned; the ensuing "hidden" rationing; and the peculiar relationship between public and private health structures. Both the current ideological shift towards a market economy for health care and the traditional lack of epidemiological input in health care planning could threaten a rational approach to these problems.

Breast Neoplasms↗

Measurement of the costs in two mammographic screening programmes in the province of Florence, Italy.

OBJECTIVES: To estimate and to compare the cost per woman examined and per breast cancer detected in two mammographic screening programmes in the province of Florence. SETTING: Two ongoing, population based, mammographic screening programmes in the province of Florence. The first (district project) was started in the seventies in a rural area, whereas the second (city project) was started in the city at the end of 1990. METHODS: All relevant resources consumed by the programmes (costs) were listed and measured. The costs are related to 1993. The unit cost for each phase (recruitment, screening, assessment) of the screening process was estimated by dividing the total cost of the phase by the number of women examined. The cost per cancer detected was obtained by dividing the total cost of the programme by the number of cancers detected at screening. RESULTS: The costs per woman examined were $38.1 and $41.1 in the district and city programmes respectively. The cost per breast cancer detected was $7424 in the district programme and $5180 in the city programme. Staff accounted for more than 50% of the total cost. The unit cost in the screening phase was higher in the district programme, whereas it was lower in the assessment phase. CONCLUSIONS: Our results are consistent with, although slightly lower than, published estimates of the cost per woman screened. Important parameters for determining the efficiency of a mammographic screening programme are the compliance rate and the recall rate.

Breast Neoplasms↗

[Magnetic resonance arthrography in chondral disease of the knee].

The clinical usefulness of Magnetic Resonance Imaging (MRI) of the knee in the depiction of meniscal, ligament and tendon lesions is well known. In contrast, the role MRI plays in the diagnosis of chondromalacia remains debated, the gold standard being arthroscopy. A new technique, i.e., MR arthrography (MRA), has been recently proposed which consists of the intraarticular injection of a paramagnetic contrast agent (Gd-DTPA) during MRI. Thirty-one patients with clinically suspected chondromalacia of the knee were examined with MRA. The exams were performed with a 1T superconductive magnet and a dedicated coil. All the patients were examined before (baseline scans) and after paramagnetic contrast agent injection. MRA results were compared with arthrographic findings. Baseline MRI had 25% sensitivity, 77.9% specificity and 83% diagnostic confidence in the diagnosis of chondromalacia; these figures increased to 93%, 97.6% and 91.5% after contrast agent injection. This preliminary experience confirms MRA to be a useful tool in the diagnosis of chondral knee conditions.

Adult↗

[Letter].

Explore the source record for details and available documents.

Environmental Monitoring↗

[Effectiveness and monitoring of breast cancer screening programs].

Several experimental and non experimental studies have shown that mammography every 2-3 years can reduce mortality for breast cancer in women over 50 of about the 30%. On this basis, in the last few years several programmes, population-based, have been organised at Regional and National level in Europe. In this paper the main process indicators useful to assess early the impact of a screening programme are discussed. The proposal of a system for the programme evaluation is mainly based on the experience of the Two County Study, in Sweden, the most important randomised clinical trial in this field.

Adult↗

[Evaluation of the costs of mammographic screening program in the city of Florence].

This paper investigated differential direct costs determined by the difference between implementation of mammographic screening program for breast cancer detection in the city of Florence (PFD) and the "absence" of the PFD. The involved resources have been identified, quantified and evaluated. The results of the I round (1991/92) of the PFD involve the following different phases: invitations, mass screening, diagnostic assessment. Differential net costs aumonted to 780 million for total cost, and to 53,000 per screened woman. The PFD invited 27,325 women per year; at the I round, the PFD registered an attendance rate of 53.9% and a recall rate of 4.3%, with a total cost of about one thousand million and a cost per screened woman of about L. 64,000. Instead, economic results of alternative "absence" of screening registered a total cost of 170 million and a cost per screened woman of about L. 100,000. Costs for detected cancer amount about to 8.2 million for PFD and 5.7 million for "absence" of the Program. Sensitivity analysis has been performed texting the fundamental parameters of the PFD: attendance rate, recall rate and life time average of the investiments. The sensitivity analysis, performed on the PFD, registered a variation of total cost from 859 million to 1,216 million and a variation of the total cost per woman screened from L. 43,500 to L. 80,000. Sensitivity analysis results highlighted the fundamental role played by women's attendance and by the percentage of women recalled for diagnostic assessment.

Breast Neoplasms↗

Population-based breast cancer survival. Mammographic screening activities in central Italy.

BACKGROUND: The aim of this study was to evaluate the effect on 5-year survival of patients with invasive breast cancer relative to demographic and clinical variables (age, residence, and disease diffusion) and to early diagnostic procedures performed in the area. METHODS: The observed (Kaplan-Meier method) and relative 5-year survival in 1263 patients with invasive breast cancer in the Province of Florence, Italy, between 1985-1986 (source: Tuscany Cancer Registry) are presented. The results were compared with those of other European areas and of the Surveillance, Epidemiology, and End Results Program. The Cox model is used to evaluate the effects of age at diagnosis (5-year age groups), disease diffusion (localized, regional, distant, unspecified), residence (Municipality of Florence, screening area, other municipalities), and source of diagnosis (Center for the Study and Prevention of Cancer, hospitals) on observed survival. RESULTS: Observed 5-year survival was 68.4% (Kaplan-Meier method) and relative 5-year survival was 75.4%. Relative survival for patients younger than age 35 at diagnosis was high (82.3%); it decreased slowly from 80.5% in the group of patients 35-44 years of age, to 74.0% in those 65-74 years of age, and steeply decreased to 68.1% in those 75 years of age and older. Relative 5-year survival in Florence was lower only than that observed in Switzerland (Geneva) and in the USA (whites). Five-year prognosis was worse in women 70 years of age or older, in advanced stages, in residents of municipalities not involved in the screening program, and in cases diagnosed in hospitals. The gain in survival may be explained partially by lead-time effect and by length bias due to early diagnosis both in self-referred women and in screening-detected cases. In these cases, though, the better prognosis, although attenuated, persisted after adjustment by disease diffusion. CONCLUSIONS: The results suggest that the early diagnosis of breast cancer in self-referred women affects prognosis, at least concerning 5-year survival. Moreover, although lead-time effect and length bias cannot be excluded in this study, screening by personal invitation may reduce the disadvantage in the survival of patients with breast cancer often observed in rural areas.

Adult↗

What do Italian hospital physicians know about quality of life assessment in oncology?

AIMS: To assess the current level of information and use of quality of life assessment instruments by Italian physicians involved in oncologic patient care. METHODS: Specifically trained scientific representatives of a pharmaceutical company interviewed 2237 hospital physicians all over Italy. RESULTS: A total of 1390 physicians (62.1%) had some knowledge of quality of life assessment tools in oncology, but 364 of them (26.2%) were unable to recall the name of any instruments. The one that was most frequently recalled by the 1026 physicians who knew of the existence of one or more instruments was the Karnofsky Performance Status (KPS) (91%) followed by the Eastern Cooperative Oncology Group performance scale (ECOG) (35.5%) whereas the Quality of Life Index and Visual Analogue Scale were at the very bottom of the list (5.9% and 3.7%, respectively). Physician age and type of department were found to be strong predictors of knowledge of the instruments, which was greater among young physicians and those working in oncological departments. Of the physicians aware of the KPS, 56.6% used it, whereas the percentage of physicians using ECOG was higher (69.5%). CONCLUSIONS: The collected data indicate a poor knowledge of quality of life assessment instruments in Italian physicians. Most physicians tend to use so-called << objective >> instruments where the assessment is made by the physician and not by the patient (KPS, ECOG Quality of Life index), are practically unaware of the new generation of "subjective" self-rating instruments. The use of such instruments in particular might provide greater insights into the impact of the disease and related treatments on the quality of life of cancer patients.

Adult↗