Ten-year experience with pharmacogenetic testing for DPYD in a national cancer center in Italy: Lessons learned on the path to implementation.

Background: Awareness about the importance of implementing DPYD pharmacogenetics in clinical practice to prevent severe side effects related to the use of fluoropyrimidines has been raised over the years. Since 2012 at the National Cancer Institute, CRO-Aviano (Italy), a diagnostic DPYD genotyping service was set up. Purpose: This study aims to describe the evolution of DPYD diagnostic activity at our center over the last 10 years as a case example of a successful introduction of pharmacogenetic testing in clinical practice. Methods: Data related to the diagnostic activity of in-and out-patients referred to our service between January 2012 and December 2022 were retrieved from the hospital database. Results: DPYD diagnostic activity at our center has greatly evolved over the years, shifting gradually from a post-toxicity to a pre-treatment approach. Development of pharmacogenetic guidelines by national and international consortia, genotyping, and IT technology evolution have impacted DPYD testing uptake in the clinics. Our participation in a large prospective implementation study (Ubiquitous Pharmacogenomics) increased health practitioners' and patients' awareness of pharmacogenetic matters and provided additional standardized infrastructures for genotyping and reporting. Nationwide test reimbursement together with recommendations by regulatory agencies in Europe and Italy in 2020 definitely changed the clinical practice guidelines of fluoropyrimidines prescription. A dramatic increase in the number of pre-treatment DPYD genotyping and in the coverage of new fluoropyrimidine prescriptions was noticed by the last year of observation (2022). Conclusion: The long path to a successful DPYD testing implementation in the clinical practice of a National Cancer Center in Italy demonstrated that the development of pharmacogenetic guidelines and genotyping infrastructure standardization as well as capillary training and education activity for all the potential stakeholders are fundamental. However, only national health politics of test reimbursement and clear recommendations by drug regulatory agencies will definitely move the field forward.

The phytoremediation of an organic and inorganic polluted soil: A real scale experience.

A phytoremediation process with horse manure, plants (Populus alba, Cytisus scoparius, Paulownia tomentosa) and naturally growing vegetation was carried out at a real-scale in order to phytoremediate and functionally recover a soil contaminated by metals (Zn, Pb, Cd, Ni, Cu, Cr), hydrocarbons (TPH) and polychlorobiphenyls (PCB). All the plants were effective in two years in the reclamation of the polluted soil, showing an average reduction of about 35%, 40%, and 70% in metals, TPH and PCB content, respectively. As regards the plants, the poplar contributed the most to organic removal. In fact, its ability to take up and detoxify organic pollutants is well known. Paulownia tomentosa, instead, showed high metal removal. The Cytisus scoparius was the least effective plant in soil decontamination. The recovery of soil functionality was followed by enzyme activities, expressing the biochemical processes underway, and nutrient content useful for plant growth and development. Throughout the area, an enhancement of metabolic processes and soil chemical quality was observed. All the enzymatic activities showed a general increase over time (until 3-4 fold than the initial value for urease and ß-glucosidase). Moreover, Cytisus scoparius, even though it showed a lower decontamination capability, was the most effective in soil metabolic stimulation.

Reed bed systems for sludge treatment: case studies in Italy.

In recent years, reed bed systems (RBSs) have been widely considered as a valid technology for sludge treatment. In this study are presented results about sludge stabilization occurring within beds in four RBSs, situated in Tuscany (Italy). The results showed that stabilization of the sludge over time occurred in all RBSs, as shown by the low content of water-soluble carbon and dehydrogenase activity, which measures indirectly the overall microbial metabolism, and by the re-synthesis of humic-like matter highlighted by the pyrolytic indices of mineralization and humification. Results about heavy metal fractionation, an appropriate technique to estimate the heavy metal bioavailability and sludge biotoxicity, showed that the process of sludge stabilization occurring in RBSs retains metals in fractions related to the stabilized organic matter, making metals less bioavailable. Moreover, the concentrations of various toxic organic compounds were below the limit of concentration suggested by the European Union's Working Document on Sludge, for land application. The effectiveness of the stabilization processes in RBs was hence clearly proven by the results that measured mineralization and humification processes, and by the low levels of bioavailable heavy metals and toxic organic compounds in stabilized sludges.

Biochemical activity and chemical-structural properties of soil organic matter after 17 years of amendments with olive-mill pomace co-compost.

This study evaluates soil fertility, biochemical activity and the soil's ability to stabilize organic matter after application of composted olive-mill pomace. This organic amendment was applied in two different olive groves in southern Spain having different soil typologies (carbonated and silicic). Olive grove soils after 17 years of organic management with application of olive-mill pomace co-compost were of higher quality than those with conventional management where no co-compost had been applied. The main chemical parameters studied (total organic carbon, total nitrogen, available phosphorus, exchangeable bases, cation exchange capacity, total extractable carbon (TEC), and humic-to-fulvic acids ratio), significantly increased in soils treated with the organic amendment. In particular, the more resistant pool of organic matter (TEC) enhanced by about six and eight fold in carbonated and silicic soils, respectively. Moreover, the amended silicic soils showed the most significant increases in enzyme activities linked to C and P cycles (ß-glucosidase twenty-five fold higher and phosphatase seven fold higher). Organic management in both soils induced higher organic matter mineralization, as shown by the higher pyrrole/phenol index (increasing 40% and 150% in carbonated and silicic soils, respectively), and lower furfural/pyrrole index (decreasing 27% and 71% in carbonated and silicic soils, respectively). As a result of mineralization, organic matter incorporated was also more stable as suggested by the trend of the aliphatic/aromatic index (decreasing 36% and 30% in carbonated and silicic soils, respectively). Therefore, management system and soil type are key factors in increasing long-term C stability or sequestration in soils. Thus application of olive-oil extraction by-products to soils could lead to important mid-to -long-term agro-environmental benefits, and be a valuable alternative use for one of the most widespread polluting wastes in the Mediterranean region.

Phytoremediation of dredged marine sediment: monitoring of chemical and biochemical processes contributing to sediment reclamation.

In this study, a pilot phytoremediation experiment was performed to treat about 80 m(3) of silty saline sediments contaminated by heavy metals and organic compounds. After preliminary mixing with a sandy soil and green compost application, three different plant treatments [Paspalum vaginatum (P); P. vaginatum + Spartium junceum (P + S); P. vaginatum + Tamarix gallica (P + T)] were compared to each other and to an unplanted control (C) in order to evaluate the plant efficiency in remediating and ameliorating agronomical and functional sediment properties. The experiment was monitored for one year after planting by taking sediment samples at two depths and performing several chemical and biochemical analyses. After one year, the increase in hydrolytic enzyme and dehydrogenase activities indicated the stimulation of sediment functionality. Additionally, the availability of energy sources derived from organic matter application and plant-root activity promoted the formation of a stable organic matter fraction. Finally, P + S and P + T were also effective in decontaminating polluted marine sediments from both organic (total petroleum hydrocarbons, TPH) and inorganic (heavy metal) pollutants.

Factors controlling carbon metabolism and humification in different soil agroecosystems.

The aim of this study was to describe the processes that control humic carbon sequestration in soil. Three experimental sites differing in terms of management system and climate were selected: (i) Abanilla-Spain, soil treated with municipal solid wastes in Mediterranean semiarid climate; (ii) Puch-Germany, soil under intensive tillage and conventional agriculture in continental climate; and (iii) Alberese-Italy, soil under organic and conventional agriculture in Mediterranean subarid climate. The chemical-structural and biochemical soil properties at the initial sampling time and one year later were evaluated. The soils under organic (Alberese, soil cultivated with Triticum durum Desf.) and nonintensive management practices (Puch, soil cultivated with Triticum aestivum L. and Avena sativa L.) showed higher enzymatically active humic carbon, total organic carbon, humification index (B/E(3)s), and metabolic potential (dehydrogenase activity/water soluble carbon) if compared with conventional agriculture and plough-based tillage, respectively. In Abanilla, the application of municipal solid wastes stimulated the specific ß-glucosidase activity (extracellular ß-glucosidase activity/extractable humic carbon) and promoted the increase of humic substances with respect to untreated soil. The evolution of the chemical and biochemical status of the soils along a climatic gradient suggested that the adoption of certain management practices could be very promising in increasing SOC sequestration potential.

Prevalence of hemostatic disorders in adolescents with abnormal uterine bleeding.

STUDY OBJECTIVE: To evaluate the incidence of hemostatic disorders in a population of adolescents with various patterns of abnormal uterine bleeding (AUB). DESIGN: Retrospective observational study. SETTING: University hospital. PARTICIPANTS: One hundred thirteen adolescents with AUB; mean age at menarche and mean age at the onset of symptoms 12 ± 1.2 years and 13.5 ± 2.8 years, respectively. MAIN OUTCOME MEASURES: Data on menstrual history, bleeding symptoms, co-existing medical conditions, and medical therapies were assessed. All patients were screened for hemostatic disorders with laboratory testing. The incidence of the disorders was calculated. Subjects were further divided in 2 groups based on whether the AUB started in the first 2 years from menarche (group 1) or later (group 2). A statistical analysis was performed using a chi-square test to compare incidence of hemostatic disorders between the groups. RESULTS: One hundred thirteen adolescents with AUB were identified. Overall, 54 (47.8%) patients had some underlying hemostatic disorder, of which a platelet dysfunction was the most common (17.7%). Von Willebrand disease was detected in 13.3% of cases and a deficiency of a coagulation factor in 12.4%. In 7.1% of patients an isolated increase of bleeding time was observed. When divided in 2 groups, 44.2% of patients in group 1 and 59.2% in group 2 had a coagulation disorders, with no statistically significant difference between the 2 groups (P = .17). CONCLUSION: AUB in adolescents is frequently associated with an underlying disorder of hemostasis, most commonly a platelet function disorder. The results highlight the importance of screening for coagulation disorders in adolescents with AUB, independently from the gynecologic age at onset.

Decontamination and functional reclamation of dredged brackish sediments.

The continuous stream of sediments, dredged from harbors and waterways for keeping shipping traffic efficiency, is a considerable ongoing problem recognized worldwide. This problem gets worse as most of the sediments dredged from commercial ports and waterways turn out to be polluted by a wide range of organic and inorganic contaminants. In this study, phytoremediation was explored as a sustainable reclamation technology for turning slightly-polluted brackish dredged sediments into a matrix feasible for productive use. To test this possibility, a phytoremediation experimentation was carried out in containers of about 0.7 m(3) each, filled with brackish dredged sediments contaminated by heavy metals and hydrocarbons. The sediments were pre-conditioned by adding an agronomic soil (30 % v/v) to improve their clayey granulometric composition, and by topping the mixture with high quality compost (4 kg m(-2)) to favour the initial adaptation of the selected vegetal species. The following plant treatments were tested: (1) Paspalum vaginatum, (2) Phragmites australis, (3) Spartium junceum + P. vaginatum, (4) Nerium oleander + P. vaginatum, (5) Tamarix gallica + P. vaginatum, and (6) unplanted control. Eighteen months after the beginning of the experimentation, all the plant species were found in healthy condition and well developed. Throughout the whole experiment, the monitored biological parameters (total microbial population and dehydrogenase activity) were generally observed as constantly increasing in all the planted sediments more than in the control, pointing out an improvement of the chemico-physical conditions of both microorganisms and plants. The concentration decrease of organic and inorganic contaminants (>35 and 20 %, respectively) in the treatments with plants, particularly in the T. gallica + P. vaginatum, confirmed the importance of the root-microorganism interaction in activating the decontamination processes. Finally, the healthy state of the plants and the sediment characteristics, approaching those of an uncontaminated natural soil (technosoil), indicated the efficiency and success of this technology for brackish sediments reclamation.

In situ phytoremediation of a soil historically contaminated by metals, hydrocarbons and polychlorobiphenyls.

In the past several years, industrial and agricultural activities have led to serious environmental pollution, resulting in a large number of contaminated sites. As a result, much recent research activity has focused on the application of bioremediation technologies as an environmentally friendly and economically feasible means for decontamination of polluted soil. In this study horse manure and Populus nigra (var. italica) (HM + P treatment) have been used, at real scale level, as an approach for bioremediation of a soil historically contaminated by metals (Pb, Cr, Cd, Zn, Cu and Ni) and organic contaminants, such as polychlorobiphenyls and petroleum hydrocarbon. After one year, the HM + P phytotreatment was effective in the reclamation of the polluted soil from both organic and inorganic contaminants. A reduction of about 80% in total petroleum hydrocarbon (TPH), and 60% in polychlorobiphenyls (PCBs) and total metals was observed in the HM + P treatment. In contrast, in the horse manure (HM) treatment, used as control, a reduction of only about 30% of TPH was obtained. In order to assess both effectiveness and evolution of the remediation system to a biologically active soil ecosystem, together with the pollution parameters, the parameters describing the evolution of the soil functionality (enzymatic activities and protein SDS-PAGE pattern) were investigated. A stimulation of the metabolic soil processes (increase in dehydrogenase activity) was observed in the HM + P compared to the HM treatment. Finally, preliminary protein SDS-PAGE results have permitted the identification of proteins that have been recovered in the HM + P soil with respect to the HM; this may become a basic tool for improving the biogeochemical status of soil during the decontamination through the identification of microbial populations that are active in soil decontamination.

Pollutant monitoring in sludge treatment wetlands.

Phragmites australis for sludge dewatering and stabilization processes have been widely proved. The presence of reeds, indeed, efficiently allows solids dewatering and organic matter stabilization in order to obtain a stabilised product that can be suitable for land application, even if its environmental impact has to be considered. The actual revision of the European Union's Working Document on Sludge (2000), in fact, seems to be addressed to detect two principal categories of pollutants in sludge for agricultural use: heavy metals and toxic organic compounds. In this study are presented results about sludge stabilization and monitoring of heavy metal fractionation and organic compounds in four urban wastewater treatment plants managed by Acque S.p.A., (Tuscany, Italy). To evaluate the process of sludge stabilization parameters were determined that highlight the biochemical and chemico-structural properties of sludge organic matter. The results showed that stabilization of the sludge over time occurred as shown by the low content of water soluble carbon and dehydrogenase activity, and by the re-synthesis of humic-like matter highlighted by the pyrolytic indices of mineralization and humification. Results about fractionation showed that heavy metals were retained in fractions related to the stabilized organic matter. Moreover, toxic organic compounds showed a drastic reduction at the end of the monitoring period.

Phytotreatment of sludges (Phragmites australis) for their reuse in the environment.

The aim of this study is the evaluation of the agronomic characteristics acquired by a phytotreated sludge coming from a wastewater treatment plant (WWTP) located in Tuscany (central Italy). The chemical characterization showed values which are within the Italian legislation limits for mixed composts. From an agronomic point of view, the sludge did not present a level of phytotoxicity, as shown by the germination index (GI% = 77). Furthermore, pathogen compounds are inexistent (Escherichia coli < 1,000 CFU/g). Different substrates (obtained by mixing the sludge with sandy agronomic soil - 0.5% w/w, 1% w/w, 2.5% w/w and 5% w/w) were prepared in order to evaluate the best mixture performance in terms of water retention capacity and plant growth. No significant differences were observed for all sludge mixtures. Different plants were tested in plots (Lepidium sativum, Cucumis sativus and Avena sativa). The best plant adaptation, measured as dry biomass production, was observed for Avena sativa. The results obtained underlined that the phytotreatment of sludge can bring about the transformation of sewage sludges into organic products that are reusable in agriculture, if previously mixed with other appropriate materials and taking into account their heavy metal content.

Hydraulic and biochemical analyses on full-scale sludge consolidation reed beds in Tuscany (Italy).

The management of sewage sludge has recently become one of the most significant challenges in wastewater management. Reed bed systems appear to be an efficient and economical solution for sludge management in small wastewater treatment plants. Four years ago, one of the holding companies for water and wastewater in central Italy adopted this technology in 6 wastewater treatment plants. Hydraulic and biochemical analyses were performed on the most representative site to asses the behaviour of reed beds with regard to dewatering, mineralization and humification of disposed sludge. Moreover, daily water content analysis were performed in the interval between subsequent sludge loadings. Results indicated a decrease of sludge volume by about 93% on a yearly basis. Biochemical analysis highlighted that mineralization processes decrease over time due to a rapid decrease of microbial activity and labile substrates, such as DHase enzyme and water-soluble carbon and ammonium, respectively. Moreover, a significant interrelationship between the parameters linked with mineralization was found: after two years of operation, the process of mineralization of organic matter is still predominant in the humification of organic matter. Daily water content data were used to define a semi empirical equation describing the dynamics of the dewatering process. Overall, the use of sludge reed beds resulted feasible, ecologically sustainable and cost-effective.

Post-load insulin resistance is an independent predictor of hepatic fibrosis in virus C chronic hepatitis and in non-alcoholic fatty liver disease.

BACKGROUND: Insulin resistance is a significant risk factor for hepatic fibrosis in patients with both non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC), either directly or by favouring hepatic steatosis. Several methods are available to assess insulin resistance, but their impact on this issue has never been evaluated. AIMS: To determine the relative contribution of steatosis, metabolic abnormalities and insulin resistance, measured by different basal and post-load parameters, to hepatic fibrosis in CHC and in NAFLD patients. METHODS: In 90 patients with CHC and 90 pair-matched patients with NAFLD, the degree of basal insulin resistance (by the homeostasis model assessment, (HOMA)) and post-load insulin sensitivity (by the oral glucose insulin sensitivity (OGIS) index) was assessed, together with the features of the metabolic syndrome according to Adult Treatment Panel III definition. Data were correlated with hepatic histopathology. RESULTS: The prevalence of basal insulin resistance (HOMA values >75th percentile of normal) was 23.3% in CHC patients and 57.8% in NAFLD, but it increased to 28.8 and 67.8% when measured by post-load insulin resistance (OGIS <25th percentile). In a multivariate model, after adjustment for age, gender and body mass index, OGIS was a predictor of severe fibrosis in CHC and in NAFLD patients, independently of steatosis. An OGIS value below the cut-off of the 25th percentile increased the likelihood ratio of severe fibrosis by a factor of 1.5-2 and proved to be a more sensitive and generally more specific test than HOMA-R for the identification of subjects with severe fibrosis both in NAFLD and in CHC. CONCLUSIONS: Post-load insulin resistance (OGIS <9.8 mg/kg/min) is associated with severe hepatic fibrosis in both NAFLD and CHC patients, and may help identify subjects at risk of progressive disease.

Oral terbinafine in the treatment of multi-site seborrhoic dermatitis: a multicenter, double-blind placebo-controlled study.

Seborrheic dermatitis (SD) is a common disorder for which no satisfactory curative treatment exists. Preliminary studies suggest that terbinafine may be effective. The efficacy and tolerability of oral terbinafine was evaluated in multi-site SD in a randomized, double-blind, placebo-controlled study. For this purpose, 174 adult patients with SD lesions involving >or=3 skin areas, each causing >or=2 moderate/severe symptoms according to a pre-defined clinical score, were classified according to the localization of lesions: patients with lesions predominantly involving non-exposed skin areas, such as scalp and hairline and sternum and/or interscapular area (Population A, n=83) or patients with lesions in exposed sites, mainly the face (Population B, n=91). Patients were randomized to oral terbinafine (250 mg/day ) (n=86) or matching placebo (n=88), each given for 6 weeks. Primary efficacy variable was the response rate, defined as >or=50% decrease in baseline total clinical score without rescue medication intake after 6 weeks of treatment. The main secondary assessments were: subject's global assessment of relief and proportion of patients satisfied with treatment. Recurrence rate was assessed in responder patients during a 4-week treatment-free period. In Population A the response rate after 6 weeks of treatment was significantly higher with terbinafine (70% vs 45.4%; p=0.03) and so was the proportion of patients who reported relief (75% vs 41%; p=0.007) and who were satisfied (66% vs 40%; p=0.02). No significant differences were recorded in Population B. Adverse events occurred in 11.5% of terbinafine patients and 8% of placebo patients. One patient discontinued treatment with terbinafine because of adverse events (mild tachycardia and insomnia). In conclusion, our results show that terbinafine is significantly more effective than placebo in reducing the severity of SD lesions in nonexposed sites. Clinical trials comparing terbinafine to standard treatment regimens in different types of patients with SD are warranted.

Gastric emptying and intragastric balloon in obese patients.

BACKGROUND: Intragastric balloons have been proposed to induce weight loss in obese subjects. The consequences of the balloon on gastric physiology remain poorly studied. We studied the influence of an intragastric balloon on gastric emptying in obese patients. PATIENTS AND METHODS: 12 patients were included in the study, with BMI (mean +/- SD) of 38.51 +/- 4.32 kg/m2. The balloon was inserted under light anaesthesia and endoscopic control, inflated with 700 ml saline, and removed 6 months later. Body weight and gastric emptying (T1/2 and T lag) using 13C-octanoic acid breath test were monitored before balloon placement, during its permanence and 2 months after removal. RESULTS: Mean weight loss was: 6.2 +/- 2.3 kg after one month; 12.4 +/- 5.8 kg after 3 months; 14.4 +/- 6.6 kg after 6 months and 10.1 +/- 4.3 kg two months after BIB removal. Gastric emptying rates were significantly decreased in the first periods with balloon in place, and returned to pre-implantation values after balloon removal. T1/2 was: 87 +/- 32 min before BIB positioning, 181 +/- 91 min after 1 month, 145 +/- 99 min after 3 months, 104 +/- 50 min after 6 months and 90 +/- 43 min 2 months after removal. T lag was 36 +/- 18 min before BIB positioning, 102 +/- 82 min after 1 month, 77 +/- 53 min after 3 months, 59 +/- 28 min after 6 months and 40 +/- 21 min. 2 months after removal. CONCLUSIONS: BIB in obese patients seems to be a good help in following the hypo caloric diet, especially during the first three months when the gastric emptying is slower and the sense of repletion is higher. After this period gastric emptying starts to return to normal and the stomach adapts to BIB loosing efficacy in weight loss.

Anti-human versus anti-guinea pig tissue transglutaminase antibodies as the first-level serological screening test for coeliac disease in the general population.

BACKGROUND: So far the reliability of the anti-guinea pig and anti-human tissue transglutaminase antibodies for the coeliac disease diagnosis has been evaluated in selected groups of patients. AIM: To compare the diagnostic accuracy of anti-human versus anti-guinea pig tissue transglutaminase in the coeliac disease screening of the general population. SUBJECTS: Two healthy Italian populations living in Marche region and in Western Sardinia. METHODS: Both anti-guinea pig and anti-human tissue transglutaminase were determined using an enzyme-linked immunosorbent assay-based commercially available kit (Eu-tTG, Eurospital, Trieste, Italy). RESULTS: During the period 1999-2001, 3541 subjects (1500 from "continental" Italy and 2041 from Sardinia) were screened for coeliac disease using both anti-guinea pig and anti-human tissue transglutaminase as first-level tests. Both these tests were negative in 3439/3541 sera, while 29 resulted positive for both of them and 73 showed discordant results. Overall, 50 intestinal biopsies were performed in 22, 21 and 7 subjects with positivity to both screening tests, to anti-guinea pig and to anti-human tissue transglutaminase alone, respectively. A coeliac disease diagnosis was made in 25 subjects giving an overall prevalence of 1:126 individuals. The anti-tissue transglutaminase specificity and sensitivity were 98 and 92% for guinea pig and 99.6 and 96% for human tissue transglutaminase, respectively. CONCLUSIONS: The anti-human tissue transglutaminase test should definitely replace the anti-guinea pig-derived one as first-level screening tool for identifying all subjects who need the second-level investigations (small intestinal biopsy).

Long term efficacy, safety, and tolerabilitity of low daily doses of isosmotic polyethylene glycol electrolyte balanced solution (PMF-100) in the treatment of functional chronic constipation.

AIMS: To assess the long term therapeutic effectiveness, safety, and tolerability of low daily doses of isosmotic PEG electrolyte solutions (PMF-100) administered for a six month period for the treatment of functional constipation, in a double blind, placebo controlled, parallel group study. METHODS: After an initial four week run in period with PMF-100 (250 ml twice daily; PEG 14.6 g twice daily), 70 patients suffering from chronic constipation (58 females, aged 42 (15) years) with normalised bowel frequency (>3 bowel movements (bm)/week) were randomly allocated to receive either PMF-100 or placebo, contained in sachets (one sachet in 250 ml of water twice daily) for 20 weeks. Patients were assessed at four week intervals, and reported frequency and modality of evacuation, laxative use, and relevant symptoms on a diary card. At weeks 1, 12, and 24, a physical examination and laboratory tests were performed. RESULTS: Complete remission of constipation was reported by a significantly (p<0.01) higher number of patients treated with PMF-100 compared with placebo at each four week visit. At the end of the study, 77% of the PMF-100 group and 20% of the placebo group were asymptomatic. Compared with placebo, patients treated with PMF-100 reported hard/pellety stools and straining at defecation less frequently, a significantly higher bowel frequency (week 12: 7. 4 (3.1) v 4.3 (2.5) bm/week, 95% CI 1.64, 4.42; week 24: 7.4 (3.2) v 5.4 (2.1) bm/week, 95% CI 0.13,3.93), reduced consumption of laxative/four weeks (week 12: 0.7 (2.7) v 2.2 (3.3), 95% CI -2.29, 0. 03; week 24: 0.2 (0.8) v 1.4 (2), 95% CI -2.07, -0.023), reduced mean number of sachets used (week 12: 33 (13) v 43 (12), 95% CI -17. 24, 4.56; week 24: 33 (13) v 44 (12), 95% CI -19.68, -2.24), and reduced number of drop outs for therapy failure (16 v 3; p<0.005). Adverse events, physical findings, laboratory values, palatability, and overall tolerance of the solutions did not differ between groups. CONCLUSIONS: Administration of small daily doses of isosmotic PEG electrolyte balanced solutions was effective over a six month period for the treatment of functional constipation. A mean daily dose of approximately 300 ml of PEG solution (PEG 17.52 g) appeared to be safe, well tolerated, and devoid of significant side effects.

Determinants of age at menopause in Italy: results from a large cross-sectional study. ICARUS Study Group. Italian Climacteric Research Group Study.

OBJECTIVE: To identify the determinants of age at menopause in an Italian population, using data from the Italian Climacteric Research Group Study (ICARUS). METHODS: ICARUS is a prospective study of the effect of menopause on women's health that has been running in menopause clinics throughout Italy since 1995. A total of 4300 women with spontaneous menopause, aged 55 years or more and observed for the first time at the participating centres are included in the present analysis. RESULTS: The mean age at menopause in the total population was 50.9 years. After taking into account potential covariates, the women reported smoking, had a slightly lower mean age at menopause than non smokers 50.4 versus 50.9 years; P = 0.01. The mean age at menopause in nulliparae was 50.0 years, and, respectively 50.4, 50.6, 50.9, 51.2 and 50.9 years in those reporting 1, 2, 3, 4 and 5 or more births (P < 0.01). A low body mass index and an early age at menarche were associated with early menopause in the crude analysis, but these associations disappeared after taking into account the confounding factors. CONCLUSIONS: This study offers an estimate of the mean age at menopause of women attending menopause clinics in Italy, on the basis of the data obtained from a large sample. It also indicates that smoking and nulliparity are associated with early menopause.

Cost analysis of an Italian ICU.

BACKGROUND: Cost reduction is an important issue in medicine today, especially when considering ICUs, since they account for a large percentage of all hospital expenditure. Through a retrospective analysis of the data regarding the expenses incurred during the years 1996-97, we have been able to evaluate the total costs of our ICU and the influence that each component had on the final costs, thus gathering the necessary information for the improvement of the unit itself. METHODS: Retrospective analysis of a 5-bedded multidisciplinary ICU activity over a two-year period (1996-1997). Cost-related data have been supplied by the Hospital Administration as to wages, infrastructures, equipment buying and maintenance; by Hospital Pharmacy as to drugs and devices supplies; and by Laboratory and Radiology as to diagnostic investigations. RESULTS: According to our experience, physicians and non-medical staff account for more than 50% of the total expenditure--the latter slightly prevailing. Furthermore, we have assessed that the cost distribution is hardly comparable to that reported by other authors. CONCLUSIONS: It is useful to analyse the total distribution and to evaluate their nature only to gain the necessary data that will lead to a more effective management of the unit. Nevertheless, this methodology is valid within the cost analysis of our ICUs but the ICUs of other countries show great differences in the way they are structured and some of the use more reliable activity-based costing methodology.

Sociodemographic and clinical factors associated with HRT use in women attending menopause clinics in Italy.

OBJECTIVE: The aim of this analysis is to find any association between the use of hormone replacement therapy (HRT) and sociodemographic and clinical factors among women attending 54 menopause clinics in Italy. METHODS: The analysis includes data relating to 17,851 women who attended one of 54 menopause clinics in Italy for general gynecological evaluations and counselling between 1995 and 1997. The characteristics of women reporting ever HRT use were compared with those of never users. The odds ratios (ORs) of HRT use were computed in relation to selected reference categories, together with their 95% confidence intervals (CIs). RESULTS: Of the 17,851 women interviewed, 8539 reported ever HRT use. The mean age of the never and ever HRT users was 52.8 years and 53.7 years, respectively. Higher education was associated with an increased frequency of HRT use: in comparison with women reporting no or primary-/middle-school education, the OR of HRT use of women reporting a high-school diploma or university degree was 1.3 (95% CI 1.1-1.6). HRT use tended to be less frequently reported with increasing body mass index (BMI): in comparison with women whose BMI was < 23.4 kg/m2, the OR of HRT use in those with a BMI of 23.4-26.1 kg/m2 and > or = 26.2 kg/m2 was 0.8 (95% CI 0.8-0.9) and 0.6 (95% CI 0.5-0.7), respectively. Among the postmenopausal women, those who had undergone surgical menopause had an OR of HRT use of 1.3 (95% CI 1.2-1.4). A history of breast cancer was associated with a lower frequency of HRT use (OR 0.3, 95% CI 0.2-0.4). Likewise, a history of thromboembolic disease (OR 0.5, 95% CI 0.4-0.7) or myocardial infarction (OR 0.7, 95% CI 0.6-0.9) was associated with a lower frequency of HRT use. CONCLUSIONS: In our study population, the variable most closely related to HRT use was education/social class, thus underlining the impact of information campaigns on HRT and women's health. Among the medical determinants, our analysis indicates that a history of myocardial infarction, thromboembolic disease or breast cancer is associated with less frequent use of HRT.