Abstract: OBJECTIVE: The study aimed to compare the efficacy of the Osservatorio Epidemiologico sulla Sincope nel Lazio (OESIL) risk score, San Francisco Syncope Rule, and clinical judgment in assessing the short-term prognosis of syncope. METHODS: We studied 488 patients consecutively seen for syncope at the emergency department of 2 general hospitals between January and July 2004. Sensitivity, specificity, predictive values, and likelihood ratios for short-term (within 10 days) severe outcomes were computed for each decision rule and clinical judgment. Severe outcomes comprised death, major therapeutic procedures, and early readmission to hospital. RESULTS: Clinical judgment had a sensitivity of 77%, a specificity of 69%, and would have admitted less patients (34%, P < .05 vs decision rules). The OESIL risk score was characterized by a sensitivity of 88% and a specificity of 60% (admission 43%). San Francisco Syncope Rule sensitivity was 81% and specificity was 63% (admission 40%). According to both clinical rules, no discharged patient would have died. With combined OESIL risk score and clinical judgment, the probability of adverse events was 0.7% for patients with both low risk scores, whereas that for both high risk scores was roughly 16%. CONCLUSION: Because of a relatively low sensitivity, both risk scores were partially lacking in recognizing patients with short-term high-risk syncope. However, the application of the decision rules would have identified all patients who subsequently died, and OESIL risk score and clinical judgment combined seem to improve the decision-making process concerning the identification of high-risk patients who deserve admission.
Abstract: BACKGROUND: In the era of screening colonoscopy, assessment of operator competence is warranted. AIM: To evaluate feasibility of a computer simulator (CS) use for assessment of competence in colonoscopy by investigating performance of expert endoscopists at CS. SUBJECTS: Twenty expert endoscopists involved in screening colonoscopy. METHODS: Experts returned a questionnaire regarding personal practice (duration of activity, number of colonoscopies in the last year and assistance by a nurse) and performances (percentage of caecal intubation and polyp detection rate). One easy and one difficult colonoscopy were proposed at CS in randomized order. RESULTS: Participation rate was 75%. Caecal intubation rate in clinical practice was more than 90% for all experts. At CS, time to caecal intubation and number of attempts for ileal intubation were significantly lower during easy versus difficult colonoscopy (P<0.01 for both items); interestingly, percentage of mucosa explored was higher (P<0.05) during the difficult simulation. Withdrawal time >/=6 min was achieved by 40 and 33% of experts during the easy and difficult simulation, respectively. Independent of simulation difficulty, time with loop was lower (P<0.05) for experts using hands-free insertion (n = 8) compared with those using nurse assistance in their clinical practice (n = 7). No correlation was found between scores at CS and performance in clinical practice. CONCLUSION: Scores at CS are sensitive to the rate of technical difficulty and nurse assistance during daily practice. Withdrawal time is often shorter than required for high accuracy in polyp detection. CS could be a well-accepted tool for assessment of competence.
Abstract: BACKGROUND: Long-term follow-up studies of achalasia after pneumatic dilation, mostly retrospective, have shown variable results. AIM: To examine the outcome of achalasia after pneumatic dilation using a prospective follow-up programme. METHODS: One or two dilations (first dilation treatment) in 77 patients to achieve stable (>1 year) remission and patients followed up with yearly clinical and manometric assessments. Endoscopy, pH monitoring and barium swallow were also performed. RESULTS: A total of 69 patients achieved stable remission and were followed up for 5.6 years (3-10.7) [median (IQ range)], whereas six patients underwent cardiomyotomy and two experienced a perforation. Twelve of the 69 patients relapsed after 2.6 years (1.7-5.1): nine of 12 underwent one to two further dilations. Six-year remission rate (by Kaplan-Meyer estimates) was 82% after first dilation treatment and 96% after all dilations. Continuous antisecretory treatment was clinically needed in 16%, oesophagitis present in 7% and reflux pathological in 28% of the patients. Beneficial effects of dilation on oesophageal motility and on diameter of the oesophageal body at barium swallow were maintained during follow-up. CONCLUSIONS: A management strategy including sessions of pneumatic dilation until stable remission and a standardized follow-up is highly successful in the long term. Gastro-oesophageal reflux is clinically relevant in a minority of patients.
Abstract: The aim of the present study was to compare the characteristics of patients referred to our heart failure outpatient clinic with those of patients enrolled in clinical trials on heart failure pharmacological treatment. Thus, we estimated the proportion of patients admitted to our heart failure outpatient clinic who would have been included in randomized controlled trials evaluating the effects of medical treatments on heart failure mortality, published over a 10 years period (1993-2003). Sixteen studies (n = 45276) and 299 consecutive outpatients, were included. On average, only 34% of the outpatients would have been included in at least one of the 16 trials (8-71%). The main reasons for exclusion were: NYHA class (70% were in NYHA class II), ejection fraction (29% had EF > 35%), co-morbidity (51% had co-morbidity, mainly renal failure, COPD, and disthyroidism), age (22% were older than 80 years), and occurrence of a recent acute event (50% experienced an ischemic coronary syndrome, revascularization, pulmonary edema, or stroke in the prior 6 months). These results underline the crucial role of patient selection in clinical trials, raising uncertainties about the complete applicability of trial results to clinical practice.
Abstract: One group of six male control rats [21 months old] and one group of six male rats of the same age, singularly stored in a cage, and treated with acetyl-l-carnitine-HCl (ALCAR: 60 mg/kg/day/p.o.) for six months were tested in the spatial learning/memory Morris maze-water task and for atrophy and cell loss in seven myelo- and cytostructurally defined basal forebrain (BF) cholinergic regions [Gritti et al., 1993 J Comp Neurol 329: 438-457]. Coronal sections 25 mum thick were cut through the BF regions and processed every 200 mum for choline acetyltransferase (ChAT) immunohistochemistry. The ALCAR-treated rats had significantly shorter exit times on the Morris maze-water task test than the control rats (ANOVA-enzyme: F(1,39)=112.5, P=0.0001; sessions: F(3,39)=10.41, P=0.0001; interaction: F(3,39)=5.09, P=0.0044). Degenerative morphological changes in the BF ChAT-positive cells were observed in the control rats, but not in the treated animals, in: the diagonal band of Broca, the magnocellular preoptic nucleus, the olfactory tubercle, the substantia innominata, and the globus pallidus (ANOVA-enzyme: F(1,2)=14, P=0,0003; structures: F(6,7)=4, P=0,0018; interaction: F(6,7)=3, P=0,0043). In the diagonal band of Broca (P<0.0494) and in the magnocellular preoptic nucleus (P<0.0117) there were significantly fewer ChAT-positive neurons in the aged control rats than in the ALCAR-treated rats. These results demonstrate that in rats aged from 15 to 21 months ALCAR treatment significantly attenuated spatial learning/memory impairment on the Morris maze-water task and also importantly reduced the degeneration in size and number of cholinergic cells in the BF.
Abstract: OBJECTIVES: Whether the duration of maintenance treatment with azathioprine (AZA) affects the outcome of ulcerative colitis (UC) is unclear. We investigated clinical outcomes and any predictive factors after withdrawal of AZA in UC. METHODS: In this multicenter observational retrospective study, 127 Italian UC patients, who were in steroid-free remission at the time of withdrawal of AZA, were followed-up for a median of 55 months or until relapse. The frequency of clinical relapse or colectomy after AZA withdrawal was analyzed according to demographic, clinical, and endoscopic variables. RESULTS: After drug withdrawal, a third of the patients relapsed within 12 months, half within 2 years and two-thirds within 5 years. After multivariable analysis, predictors of relapse after drug withdrawal were lack of sustained remission during AZA maintenance (hazard ratio, HR 2.350, confidence interval, CI 95% 1.434-3.852; P=0.001), extensive colitis (HR 1.793, CI 95% 1.064-3.023, P=0.028 vs. left-sided colitis; HR 2.024, CI 95% 1.103-3.717, P=0.023 vs. distal colitis), and treatment duration, with short treatments (3-6 months) more disadvantaged than >48-month treatments (HR 2.783, CI 95% 1.267-6.114, P=0.008). Concomitant aminosalicylates were the only predictors of sustained remission during AZA therapy (P=0.009). The overall colectomy rate was 10%. Predictors of colectomy were drug-related toxicity as the cause of AZA withdrawal (P=0.041), no post-AZA drug therapy (P=0.031), and treatment duration (P<0.0005). CONCLUSIONS: Discontinuation of AZA while UC is in remission is associated with a high relapse rate. Disease extent, lack of sustained remission during AZA, and discontinuation due to toxicity could stratify relapse risk. Concomitant aminosalicylates were advantageous. Prospective randomized controlled trials are needed to confirm whether treatment duration is inversely associated with outcome.
Abstract: OBJECTIVES: Several studies have investigated, with conflicting results, the risk factors for reoperation in Crohn's disease (CD) patients. CARD15 gene variants have been identified as a major genetic risk factor for CD patients and associated with ileal disease, stenosis, and risk of surgery. However, data regarding the association between these variants and the need for reoperation are very few and conflicting. This study evaluated the risk factors of reoperation, including CARD15 gene variants. METHODS: A total of 253 consecutive CD patients, recruited in four Italian tertiary-care inflammatory bowel disease (IBD) referral centers, who had submitted to surgery for CD, were included in the study. Clinical characteristics of CD patients, time and main indications for surgery, type of operation, postoperative therapy, and time to second surgery were recorded. CARD15 gene variants were determined by DNA sequencing analysis in each center. Factors related to surgical recurrence, including CARD15 variants, were estimated by Cox proportional hazard regression. RESULTS: In all, 89 patients (35.1%) showed at least one surgical recurrence. Reoperation was significantly correlated with stenosis as indications at initial surgery only. CARD15 variants were found in 36.0% of patients, but did not correlate significantly with the demographic and clinical characteristics of the patients, rate of first surgical recurrence, and time to second operation. CARD15 variants did not significantly affect the reoperation rate, irrespective of indications for surgery. CONCLUSIONS: Reoperation for CD is correlated with stenosis at initial surgery, but not with CARD15 gene variants. This finding does not justify more aggressive prophylactic therapy on the basis of CARD15 genotype.
Abstract: Cytokine production, immune activation, T lymphocytes maturation, and serum IL-7 concentration were examined in 24 youngsters with Down syndrome and no acquired diseases (healthy Down syndrome [12 prepubertal, 13 pubertal]) and 42 age- and gender-matched controls (20 prepubertal, 22 pubertal). Results showed that a complex immune and impairment is present in healthy individuals with Down syndrome in whom interferon gamma, interleukin (IL) IL-10 production, as well as serum IL-7 concentrations and activation markers-bearing T lymphocytes were significantly augmented. Additionally, a complex skewing of post-thymic lymphocyte maturation pathways was observed in patients: significant reduction of CD4+ and CD8+ naive (RA+CCR7+) lymphocytes, significant increase of CD4+ and CD8+ central memory (RA-CCR7+), and terminally differentiated (TD) (RA+CCR7-) lymphocytes.
Abstract: Liver disease may alter the pharmacokinetics of antiretrovirals and produce changes in plasma protein binding. The aim was to evaluate the pharmacokinetics of total and unbound lopinavir (LPV) in HIV-infected patients with and without hepatitis C virus (HCV) coinfection. Fifty-six HIV+ patients receiving lopinavir/ritonavir (LPV/r) (group I = 24 controls; II = 23 HIV/HCV-coinfected; III = 9 cirrhotic HIV/HCV-coinfected) were included. Total (n = 56) and unbound (n = 36) LPV pharmacokinetic parameters were determined at steady-state using validated high-performance liquid chromatography with ultraviolet detection and high-performance liquid chromatography-tandem mass spectrometry methods, respectively. Pharmacokinetic parameters (plasma concentration just before drug administration, peak concentrations in plasma, times to maximum plasma concentration, areas under the plasma concentration-time curve from 0 to 12 hours, and CL/F/kg) of both total and unbound LPV were calculated by standard noncompartmental methods and differences among groups evaluated (Kruskal-Wallis test).LPV apparent oral clearance normalized to body weight (median, interquartile range) was 55 (40-68), 59 (44-69), and 71 (53-78) mL/h/kg for groups I, II, and III, respectively (II vs. I, P = 0.52; III vs. I, P = 0.16). The areas under the plasma concentration-time curve from 0 to 12 hours were 110.4 (80.9-135.2), 103.4 (85.5-131.3), and 92.8 (87.4-116.3) microg h/mL for groups I, II, and III, respectively (II vs. I, P = 0.68; III vs. I, P = 0.71). Chronic liver impairment produced a slight, although not significant, decrease in plasma protein binding. The free-fraction of LPV increased ( approximately 21%) from 0.97% (0.80-1.06) in HIV+/HCV- patients to 1.18% (0.89-1.65) in HIV/HCV+ cirrhotic patients. The apparent oral clearance of unbound LPV (CLu/F/kg) in cirrhotic patients did not change significantly, supporting the concept that the clearance of unbound LPV in liver disease is not affected after being inhibited by low-dose ritonavir co-administration.LPV total and unbound pharmacokinetics were not affected by hepatic impairment, suggesting that no adjustment of LPV/r dose is required for HIV/HCV-coinfected patients with and without cirrhosis and moderate impairment of liver function.
Abstract: BACKGROUND: Mesenteric adipose tissue hypertrophy is a frequent sonographic finding in Crohn's disease (CD). This study assessed its sonographic prevalence, the correlation with the degree of clinical or biochemical activity of the disease, and its impact on disease outcome in CD patients. METHODS: In all, 185 consecutive CD patients underwent bowel ultrasound to assess the presence of mesenteric fat tissue alteration as well as thickness and echopattern of the bowel wall, site and extent of CD, and presence of stenosis, fistulas, and abscesses. Clinical and biochemical parameters of disease activity were also assessed. Multiple logistic regression analysis was used to identify variables related to mesenteric adipose tissue alteration. RESULTS: Mesenteric adipose tissue alteration, detected in 88 (47.6%) patients, showed a significant correlation both with clinical and biochemical CD activity and with internal fistulas, bowel wall thickness, and length of thickened bowel wall. Logistic regression analysis showed that internal fistulas (odds ratio [OR] = 13.5), thickened bowel wall (OR = 7.6), C-reactive protein (OR = 6.1), CD Activity Index (CDAI) (OR = 3.1), and length of diseased bowel walls (OR = 2.6) were significantly associated with mesenteric adipose tissue alteration. Of the 111 patients with quiescent CD, 22 showed mesenteric adipose tissue hypertrophy. These patients did not show increased risk of relapse compared with quiescent patients without mesenteric fat alteration. CONCLUSIONS: Mesenteric adipose tissue alteration is correlated with biochemical and clinical activity of CD and with internal fistulas and increased bowel wall thickness. In quiescent CD, mesenteric hypertrophy does not appear to be a risk factor of relapse.
Abstract: OBJECTIVE: We sought to assess short- and long-term prognosis of syncope and associated risk factors. BACKGROUND: Syncope is a common clinical event, but our knowledge of its short-term outcome is largely incomplete. Further, it is unknown whether hospital admission might positively affect a patient's syncope prognosis. METHODS: We screened 2,775 consecutive subjects who presented for syncope at 4 emergency departments between January and July 2004. Short- and long-term severe outcomes (i.e., death and major therapeutic procedures) and related risk factors were compared in all enrolled patients arrayed according to hospital admission or discharge. RESULTS: A total of 676 subjects were included in the study. Forty-one subjects (6.1%) experienced severe outcomes (5 deaths, 0.7%; 36 major therapeutic procedures, 5.4%) in the 10 days after presentation. An abnormal electrocardiogram, concomitant trauma, absence of symptoms of impending syncope, and male gender were associated with short-term unfavorable outcomes. Long-term severe outcomes were 9.3% (40 deaths, 6.0%; 22 major therapeutic procedures, 3.3%), and their occurrence was correlated with an age >65 years, history of neoplasms, cerebrovascular diseases, structural heart diseases, and ventricular arrhythmias. Short-term major therapeutic procedures were more common (p < 0.05) in subjects who had been admitted to hospital (13.3%) than in discharged (1.6%), whereas mortality was similar. One-year mortality was greater (p < 0.05) in admitted (14.7%) than in discharged (1.8%) patients. CONCLUSIONS: Risk factors for short- and long-term adverse outcomes after syncope differed. Hospital admission favorably influenced syncope short term prognosis. Instead, 1-year mortality was unaffected by hospital admission and related to comorbidity.
Abstract: ABSTRACT: BACKGROUND: In an effort to ensure that all physicians have access to valid and reliable evidence on drug effectiveness, the Italian Drug Agency sponsored a free-access e-learning system, based on Clinical Evidence, called ECCE. Doctors have access to an electronic version and related clinical vignettes. Correct answers to the interactive vignettes provide Continuing Medical Education credits. The aims of this trial are to establish whether the e-learning program (ECCE) increases physicians' basic knowledge about common clinical scenarios, and whether ECCE is superior to the passive diffusion of information through the printed version of Clinical Evidence. DESIGN: All Italian doctors naïve to ECCE will be randomised to three groups. Group one will have access to ECCE for Clinical Evidence chapters and vignettes lot A and will provide control data for Clinical Evidence chapters and vignettes lot B; group two vice versa; group three will receive the concise printed version of Clinical Evidence. There are in fact two designs: a before and after pragmatic trial utilising a two by two incomplete block design (group one versus group two) and a classical design (group one and two versus group three). The primary outcome will be the retention of Clinical Evidence contents assessed from the scores for clinical vignettes selected from ECCE at least six months after the intervention. To avoid test-retest effects, we will randomly select vignettes out of lot A and lot B, avoiding repetitions. In order to preserve the comparability of lots, we will select vignettes with similar, optimal psychometric characteristics. TRIAL REGISTRATION: ISRCTN27453314.
Abstract: BACKGROUND: Two Pneumocystis jiroveci independent genomic regions, internal transcribed spacer (ITS) 1 and ITS2, and dihydropteroate synthase (DHPS) gene have been used for typing a cohort of HIV-infected Italian patients with P jiroveci pneumonia (PcP). METHODS: Bronchoalveolar lavage samples isolated from 207 HIV-infected adults were ITS and DHPS genotyped by DNA sequencing and by restriction fragment length polymorphism analysis, respectively. Mutant DHPS samples were cloned and ITS typed. Data on severity, treatment, and outcome of PcP were obtained by chart review. RESULTS: High diversity with 46 different ITS genotypes was observed. At the DHPS locus, 9.1% of samples analyzed were found to be mutated. A correlation was observed between DHPS mutants and greater severity of PcP, as defined by higher lactate dehydrogenase (P = 0.015) and need for intubation (P = 0.002), and worse outcomes, as defined by failure of sulfa treatment (P = 0.04), death, and/or relapse of PcP (P = 0.008). There was a significant difference in ITS genotype patterns between DHPS wild-type and mutants (P = 0.028). CONCLUSIONS: The present data suggest the absence of a correlation between P jiroveci ITS types and specific clinical characteristics. DHPS mutations correlate with possible failure of anti-P jiroveci sulfa therapy, and a trend of association is shown between DHPS mutations and some clinical PcP features.
Abstract: OBJECTIVES: To estimate the relative efficiency of transmission of different HIV-1 drug-resistance mutations from patients failing treatment, considered as potential transmitters (PTs), to seroconverters (SCs). DESIGN: Ecological cross-sectional study. METHODS: HIV-1 protease and reverse transcriptase (RT) sequence data, obtained from 155 SCs and 2,690 PTs at the Department of Molecular Biology of the University of Siena, Italy, in the period 1997-2004 were used. The efficiency of transmission was studied by odds ratio (OR) analysis and evaluation of 95% confidence intervals (95% CIs). For mutations not detected in viruses from SCs, a binomial probability model was used, assuming P-values <0.05 as indicative of a negative selection at transmission. RESULTS: The overall prevalence of drug mutations associated with nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs) and protease inhibitors (PIs) was 13.2%, 4.6% and 2.0% in SCs, and 69.9%, 27.6% and 33.7% in PTs, respectively. Among RT mutations present both in PTs and SCs, M1841/V and T215F/Y had the lowest relative efficiency of transmission, whereas V1181, Y181C/I and K219E/Q showed the highest relative efficiency. Of the three major protease mutations that could be evaluated by this approach, M46l/L had a lower rate of transmission than 184V and L90M. Among the mutations not detected in viruses from SCs, the RT E44D, V1081, Q151M and Y188C/H/L, and the protease D30N, G48V and V82A/F/S/T substitutions appeared to be negatively selected. CONCLUSIONS: The transmission rate of drug-resistant HIV-1 variants may be differentially affected by the mutational pattern. The binomial model enabled to evaluate the negative selection against specific substitutions. Given the low prevalence of some resistance mutations in SCs, very large data sets are required to evaluate the potential selection of such mutations.
Abstract: OBJECTIVES: To identify predictive factors for moderate/severe liver fibrosis and to analyse fibrosis progression in paired liver biopsies from HIV-positive patients with chronic hepatitis C virus (HCV) infection. METHODS: HIV/HCV coinfected patients followed at the 2nd Department of Infectious Diseases of L. Sacco Hospital in Milan, Italy, with at least one liver biopsy specimen were retrospectively evaluated. RESULTS: A total of 110 patients were enrolled in the study. In a univariate analysis, predictive factors of Ishak-Knodell stage > or =3 were a history of alcohol abuse [odds ratio (OR) 3.6, P=0.004], alanine aminotransferase level >100 IU/L at biopsy (OR 2.4, P=0.05), necro-inflammatory grade > or =9 (OR 37.14, P<0.0001) and CD4 count <350 cells/microL at nadir (OR 5.3, P=0.05). In a multivariate analysis, age >35 years (OR 3.19, P=0.04) and alcohol abuse (OR 4.36, P=0.002) remained independently associated with Ishak-Knodell stage. Paired liver biopsies were available in 36 patients; 18 showed an increase of at least one stage in the subsequent liver biopsy. Either in a univariate or in a multivariate analysis, a decrease of CD4 cell count of more than 10% between two biopsies (OR 6.85, P=0.002) was significantly associated with liver fibrosis progression. CONCLUSION: Our findings highlight the relevance of encouraging a withdrawal of alcohol consumption in people with chronic HCV infection and of carrying out close follow-up of patients, especially if they are more than 35 years old. It is therefore mandatory to evaluate HIV/HCV coinfected patients for anti-HCV treatment and to increase CD4 cell count through antiretroviral therapy in order to reduce the risk of fibrosis progression and to slow the evolution of liver disease.
Abstract: BACKGROUND AND AIM: In patients with chronic liver disease, the accuracy of ultrasound scan (US), spiral computed tomography (CT), magnetic resonance imaging (MRI), and alpha-fetoprotein (AFP) in diagnosing hepatocellular carcinoma (HCC) has never been systematically assessed, and present systematic review was aimed at this issue. METHODS: Pertinent cross-sectional studies having as a reference standard pathological examinations of the explanted liver or resected segment(s), biopsies of focal lesion(s), and/or a period of follow-up, were identified using MEDLINE, EMBASE, Cochrane Library, and CancerLit. Pooled sensitivity, specificity, and likelihood ratios (LR) were calculated using the random effect model. Summary receiver operating characteristic (SROC) curve and predefined subgroup analyses were made when indicated. RESULTS: The pooled estimates of the 14 US studies were 60% (95% CI 44-76) for sensitivity, 97% (95% CI 95-98) for specificity, 18 (95% CI 8-37) for LR+, and 0.5 (95% CI 0.4-0.6) for LR-; for the 10 CT studies sensitivity was 68% (95% CI 55-80), specificity 93% (95% CI 89-96), LR+ 6 (95% CI 3-12),and LR- 0.4 (95% CI 0.3-0.6); for the nine MRI studies sensitivity was 81% (95% CI 70-91), specificity 85% (95%CI 77-93), LR+ 3.9 (95%CI 2-7), and LR- 0.3 (95% CI 0.2-0.5). The sensitivity and specificity of AFP varied widely, and this could not be entirely attributed to the threshold effect of the different cutoff levels used. CONCLUSIONS: US is highly specific but insufficiently sensitive to detect HCC in many cirrhotics or to support an effective surveillance program. The operative characteristics of CT are comparable, whereas MRI is more sensitive. High-quality prospective studies are needed to define the actual diagnostic role of AFP.
Abstract: BACKGROUND: Chronic hepatitis C is common and aggressive in HIV-positive patients, so the development of a well-tolerated HCV therapy is a priority. We evaluated the efficacy and safety of pegylated interferon alpha2b (PEG-IFN) plus ribavirin (RBV) versus PEG-IFN monotherapy in HIV/HCV-coinfected patients undergoing highly active antiretroviral therapy (HAART), and analysed the predictive factors of response. METHODS: An Italian, multicentre, open-label trial including 135 coinfected patients, randomized to PEG-IFN 1.5 microg/kg/week plus RBV 400 mg twice daily (n=69, arm A) or PEG-IFN 1.5 microg/kg/week (n=66, arm B) for 48 weeks. We assessed the predictive values of early virological response (EVR) at week 8 (HCV-RNA drop >2 log10 compared with baseline or undetectable levels) on sustained virological response (SVR). RESULTS: Fifty-five patients (28 from arm A and 27 from arm B) completed 48 weeks of therapy. At the end of treatment, 20/28 patients in arm A and 11/27 in arm B had HCV-RNA <50 IU/ml. In a per-protocol analysis, SVR was reached by 54% of patients in arm A (genotype 2-3, 11/16; genotype 1-4, 4/12) and 22% in arm B (genotype 2-3, 3/15; genotype 1-4, 3/12). In an intention-to-treat analysis, the SVR was 22% in arm A (genotype 2-3, 11/32; genotype 1-4, 4/37) versus 9% in arm B (genotype 2-3, 3/32; genotype 1-4, 3/34). The best predictors of SVR were the use of combination therapy, infection with HCV genotype 3 versus genotype 1, and EVR at week 8. Thirty patients (15 from arm A and 15 from arm B) dropped out of the trial prematurely due to side effects. The positive predictive value of EVR at week 8 was 65%, the negative predictive value was 86%. CONCLUSIONS: PEG-IFN plus RBV can be considered a solid option for the treatment of HIV/HCV-coinfected patients. The key to successfully improving efficacy is strong compliance through strict overall patient monitoring, in order to best manage drug toxicity. EVR assessment at week 8 may become a useful stategy in the management of therapy.
Abstract: PURPOSE: To evaluate the accuracy of ultrasonography (US) in the detection of Crohn disease in adults by systematically reviewing both cohort studies (those including patients whose clinical characteristics were consistent with those caused by an inflammatory bowel disease) and case-control studies (those in which patients with Crohn disease were compared with patients with other bowel diseases or healthy control subjects). MATERIALS AND METHODS: The MEDLINE, EMBASE, and Cochrane Library databases were used to retrieve all the cross-sectional studies that assessed the diagnostic accuracy of US against that of one of several predefined reference standards (ie, radiologic, endoscopic, or histologic findings). The studies that fulfilled the inclusion criteria were identified, and their methodological quality was evaluated. Of the 2860 primary studies identified, two case-control and five cohort series fulfilled the inclusion criteria. Statistical analysis was performed by using the summary receiver operating characteristic (SROC) model. RESULTS: The ranges of US sensitivity and specificity for the diagnosis of Crohn disease reported for the included series were 75%-94% and 67%-100%, respectively; the heterogeneity of these values prevented the calculation of a cumulative value. The SROC curve revealed a clear cutoff effect that depended on the chosen bowel wall thickness threshold. Sensitivity and specificity of 88% and 93%, respectively, were achieved when a bowel wall thickness threshold greater than 3 mm was used, and sensitivity and specificity of 75% and 97%, respectively, were achieved when a threshold greater than 4 mm was used. CONCLUSION: US examination seems appropriate for confirming or excluding Crohn disease as a diagnosis in a clinical context characterized by a pretest probability of Crohn disease that ranges from 12% to about 60%. In particular, for Crohn disease limited to the ileum, US may represent a valid alternative to the small-bowel series, while for colonic involvement US may be useful in ruling out the diagnosis.
Abstract: OBJECTIVES: To evaluate the risk factors for lopinavir/ritonavir (LPV/r)-related liver enzyme elevation (LEE) in HIV antiretroviral-experienced patients. METHODS: An open prospective observational study was carried out to analyse the incidence and time of LEE development during LPV/r treatment, and to determine whether LEE development was correlated with epidemiological, clinical and biochemical data, immune and virological profiles, concomitant hepatic diseases, antiretroviral therapy, or histological and ultrasonography liver examination results. A diagnosis of LEE was considered when LEE symptoms occurred after LPV/r introduction and was confirmed by a second control within 2 weeks. RESULTS: A total of 782 HIV-positive outpatients have been enrolled in six different Infectious Diseases Departments in Northern Italy since August 2000. Of these patients, 71 (9.1%) developed LEE within 115+/-85 days (mean+/-standard deviation); 13 of these subjects discontinued LPV/r and four were hospitalized. Of the patients with LEE, 74.6% and 25.4% had grade 2 and > or =3 toxicity, respectively. No correlation between LEE and sex, baseline CD4 cell count, viral load, HIV stage, triglyceride values, histological and ultrasonography liver examination results, nevirapine use, or increase in CD4 cell count was observed. Higher baseline alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) values (P < 0.0001 and P=0.004, respectively), younger age (P=0.008), previous hepatitis B virus (HBV) infection (P=0.012), efavirenz use (P=0.04), and hepatitis C virus (HCV) and/or HBV coinfection (P < 0.0001, relative risk 4.78) were significantly related to LEE. No correlations between LEE and the same risk factors as investigated in the whole study population were found in subgroups of patients with HCV and/or HBV infection. CONCLUSIONS: HCV and HBV testing and measurement of baseline ALT values are essential for screening subjects at risk of LEE before starting LPV/r. Strict monitoring of clinical and biochemical parameters should be performed in these patients.
Abstract: OBJECTIVE: To evaluate the prevalence of HIV-related central nervous system (CNS) lesions (HIV-encephalitis and/or HIV-leukoencephalopathy: HIV-E/L) with and without concomitant opportunistic diseases in a large autopsy series, and to correlate it with the changes in antiretroviral treatment that have occurred since the beginning of the epidemic. METHODS: We reviewed 1597 consecutive autopsies of HIV-positive patients performed between 1984 and 2000, and divided into four time periods on the basis of the therapeutic regimens available: 1984-1987, no therapy; 1988-1994, monotherapy (zidovudine); 1995-1996, dual combination therapy with nucleoside reverse transcriptase inhibitors (NRTI); and 1997-2000, triple combination therapy including two NRTI and at least one protease inhibitor or non-NRTI. The data concerning the treatment actually received were collected only for the patients who died during the last period. The chi -test was used to assess the significance of the differences in prevalence. RESULTS: The CNS of 1210 patients (76%) was affected by opportunistic diseases, HIV-related lesions or both. The prevalence of HIV-related lesions in the four periods was respectively 54%, 32%, 18% and 15%; this reduction was statistically significant (P < 0.000001). During the last period, however, differences in HIV-E/L between treated and untreated patients were not statistically significant, although there were fewer than expected cases among the treated patients (six instead of eight) and more than expected among the untreated patients (10 instead of eight). CONCLUSIONS: These neuropathological data from a large autopsy series confirm clinical observations concerning the efficacy of antiretroviral treatment in reducing the frequency of HIV-related CNS lesions in AIDS patients.
Abstract: The aim of this study was to evaluate sensitivity and specificity of in situ hybridization (ISH) using peptide nucleic acid (PNA) probes and tyramide-based amplification for the differentiation between Mycobacterium tuberculosis (MTB) and mycobacteria other than tuberculosis (MOTT) on formalin-fixed, paraffin-embedded tissue samples. We performed ISH simultaneously with both probes on 86 specimens from different organs: 70 obtained at autopsy and 16 by biopsy, all with a histologic evidence of mycobacterial infection confirmed by Ziehl-Neelsen-positive staining. Taking culture as the "gold standard," the sensitivity and the specificity of the MTB probe were 100% (41/41) and 95% (38/40), respectively. In only 2 cases ISH failed to identify mycobacteria. Culture results were not available in 3 cases. We propose ISH as a relatively simple and rapid method to differentiate mycobacteria on formalin-fixed, paraffin-embedded specimens (it is more specific than usual histologic stains) and as an alternative to polymerase chain reaction, allowing the morphologic evaluation of positive bacilli.
Abstract: The authors enrolled 1,029 patients with CD4 counts </= 200/microL and no CNS AIDS-defining events (CNS-AIDS) between January 1993 and December 1998. The primary end point was the first appearance of CNS-AIDS. Three different periods and different antiretroviral regimens were considered. During the median follow-up of 329 days, 144 patients (9.5%) developed CNS-AIDS. The independent predictors were CD4 counts and therapy. All regimens decreased the risk of CNS-AIDS. Highly active antiretroviral therapy led to a 95% risk reduction in comparison with untreated patients.
Abstract: BACKGROUND: H. pylori CagA seropositivity has been recently associated with ischaemic heart disease. OBJECTIVE: To evaluate whether H. pylori virulence has any effect on certain circulating coagulation factors and on markers of systemic inflammation in healthy individuals. DESIGN: Prospective cohort study. SETTING: Haematology and gastroenterology unit at a university teaching hospital. SUBJECTS: A total of 494 consecutive asymptomatic blood donors attending a blood bank. MEASUREMENTS: Blood analysis for haemostatic factors, lipids concentrations, inflammatory parameters as well as determination of anti H. pylori IgG and CagA reactivity by ELISA assayes. RESULTS: The overall prevalence of H. pylori infection was 53%; 56% of H. pylori positive sera expressed CagA reactivity. CagA seropositive subjects did not differ significantly from CagA negative or H. pylori negative subjects in values for lipids, haemostatic factors, or inflammatory parameters. CONCLUSIONS: CagA seropositivity is not associated with increased systemic inflammation or with raised concentrations of haemostatic factors - predictors of ischaemic heart disease - in healthy individuals.
Abstract: BACKGROUND: To evaluate the prevalence and endoscopic grade of reflux oesophagitis (RO) and to correlate them to symptoms and to a list of risk factors including age, sex, weight, smoking, alcohol, work, hiatus hernia. METHODS: This study was carried out in Roccacorga (LT), a little town of 3435 inhabitants in central Italy. The sample totalled 1084 volunteers, aged over 18 years old and enlisted in opened cohort. After filling in the questionnaire, all the patients were subjected to esophagogastroduodenoscopy without eating for at least six hours and diazepam pretreated (10 mg ev). Three biopsies were routine performed on the 3 biopsies on distal esophagous wall. The RO range was evaluated according to the Savary-Miller classification. RESULTS: The RO was found in 443 patients (188 M, 42%; 255 F, 58%) (p<0.0002), a large number of asymptomatic patients (39%). The prevalence of hiatus hernia was 7.2%, RO associated in 60.3% (p<0005). The prevalence of associated gastroduodenal injuries was pointed out (p<0.03). Patients affected only by RO were mostly female (p<0.02). Precancerous esophagous were 0,37%. CONCLUSIONS: According to this study the RO diagnosed through endoscopy is much more prevalent than supposed, especially among females and it affects a younger age than reported (31-50 years). Smoking and alcohol are among male risk factors, while, in female, agricultural works, weight and hormonal state could have a leading role (p=NS).
Abstract: OBJECTIVE: Determination of the urinary levels of 2.5-hexanedione (2,5-HD) was performed in subjects belonging to the Italian general population to define the reference value for this metabolite. MATERIALS AND METHODS: Urine samples were collected from 123 healthy Italian subjects who had not been occupationally exposed to n-hexane or methyl-n-butyl ketone (60 men and 63 women; 53 living in urban areas and 70 living in rural areas; 36 smokers and 87 nonsmokers; 65 aged above 35 years and 58 aged below 35 years). The determinations were performed by a gas chromatography method using a flame ionization detector (FID). A quality-control step was realized by analysis of 78 of these samples by high-performance liquid chromatography (HPLC) with UV detection. RESULTS AND DISCUSSION: The distribution of 2,5-HD concentration was log-normal and the corresponding centiles at the 95% confidence interval were as follows: the 50th centile, 0.270 mg/l for men and 0.191 mg/l for women; the 75th centile, 0.352 and 0.330 mg/l, respectively, for men and women; and the 95th centile, 0.762 and 0.582 mg/l, respectively, for men and women. The reference value, calculated as the upper unilateral 95% tolerance interval at 95% of confidence, was 0.795 mg/l for men and 0.627 for women.
Abstract: OBJECTIVE: To report the results of the second phase of a pilot study of an Italian national external quality evaluation program (EQA) aimed at assessing whether participation in the first phase had increased the reliability and accuracy of diagnoses and to what extent. STUDY DESIGN: In the second phase, two sets of cervical smears (similar to the ones examined in the first phase) were circulated among the 14 participating cytologic laboratories throughout Italy. Responses were recorded on a standardized form. Participants were asked to judge the adequacy of each smear and to formulate a diagnosis. They were also asked to recommend management of the patient on the basis of the smear report and to evaluate the degree of diagnostic difficulty of each slide. The results were discussed in workshops, and it was possible to reach a consensus diagnosis on 37 of 40 smears. In the statistical analysis, new indices of diagnostic variability were developed and calculated; a gross index of agreement, unweighted and weighted kappas, analysis of exchangeability, sensitivity and specificity were also estimated. RESULTS: The results of the second phase are similar to those of the first phase and no substantial improvement in accuracy and little reduction in variability were observed. The interventions carried out in this study (discussion between representatives of laboratories of diagnostic differences and reassessment of the most controversial slides) were aimed at increasing consensus among the participating pathologists but were insufficient to change the diagnostic routines in their laboratories. CONCLUSION: It may be advisable to promote two kinds of interlaboratory quality programs with two separate but integrated components: (1) a core component with slides having clear-cut diagnoses, and (2) a continuing education component.
Abstract: OBJECTIVES: The paper describes the results of a polycentric study for the assessment of reference values of urinary chromium (U-Cr) in the Italian population. METHOD: A total of 890 subjects (58.3% males and 41.7% females) were selected on the basis of standardized criteria in eight different areas of Italy. Urinary chromium was determined on morning spot samples collected using standardized procedures. The U-Cr was determined independently by three laboratories using an Electrothermic atomization-Atomic Absorption Spectrometry (ETA-AAS) method with a detection limit of 0.05 microgram/l, adopting-for the statistical analysis-the median value of the results of the three laboratories. The between-laboratories within-subjects standard deviation was 0.049 microgram/l. Due to the high proportion (approx, 28%) of undetectable chromium levels, the geometric mean (GM) and geometric standard deviation (GSD) were estimated using a procedure of linear interpolation. The analysis of the effects of some variables (sex, age, center, residence, smoking and drinking habits) on the U-Cr values, was also performed, by multiple regression analysis after logarithmic transformation, using GM and SD. RESULTS: The reference value of U-Cr was of 0.08 microgram/l as an estimated GM, whereas the expected distribution ranged from not detectable (nd) (95% CI = nd-0.06) to 0.24 microgram/l (95th percentile; 95% CI = 0.20-0.31). Among the variables studied, only geographical area and sex significantly influenced the U-Cr levels. In subjects selected in the provinces of Bari and Venice values of U-Cr were significantly lower than those determined in subjects residing in other areas. CONCLUSIONS: From our investigation the reference values for U-Cr were lower than those obtained in previous investigations. In addition it confirms a further reduction in U-Cr levels following the previous decline reported in the 1970s and 1980s. In over 20 years U-Cr values in the general population dropped from values greater than 1 microgram/l to values between 0.5 and 0.2 microgram/l. The reasons of this progressive decline cannot be attributed in our opinion to a reduced intake of the metal, but mainly to the improvement in analytical instrumentation and methods. A further decrease may be ascribed to a more accurate definition of the reference groups and to a better control of pre-analytical factors. Considering that the reference values for U-Cr are much lower than those determined some decades ago, toxicological studies in order to verify the significance of biological limit values currently suggested for chromium seem to be necessary.
Abstract: OBJECTIVES: To assess reliability and accuracy of cervical smear diagnoses, to evaluate the effectiveness of the participation in a programme of slide exchange in increasing reliability and to re-examine the agreement in discriminating between CIN 2 and CIN 3 (merged in High grade SIL in the Bethesda System). SETTING: 15 laboratories participating on a voluntary basis throughout Italy, for a period of 1 year. METHOD: Phase one: circulation of 40 slides including all main diagnostic categories; discussion of results by representatives of participating centres. Phase two: circulation of another 40 similar slides. For each slide, not only a diagnosis but also recommendations for further examinations and a judgment on diagnostic difficulty were asked. Common measures of reliability and accuracy and (the latter only for slides on which a consensus diagnosis was reached corresponding to the histological diagnosis) were calculated; three new indices of diagnostic variability were also computed. RESULTS: Consensus diagnosis among representatives of participating laboratories on about 90% of the slides was reached both in the first and in the second phase. On 3 slides it was impossible to reach a consensus diagnosis even among external referees. In both phases, the study showed a marked variability among diagnoses, recommendations and judgment on diagnostic difficulty and, on some slides, a worrying lack of reliability in the determination of precancerous lesions. The agreement on discrimination between CIN 1 and CIN 2 was low, but it was slightly better between CIN 2 and CIN 3. No significant relationship between accuracy and workload was found. External quality control or better said, continuous quality improvement activities are essential but should be conducted in a more systematic way with greater involvement of cytotechnicians.
Abstract: BACKGROUND: Although a reduced prevalence of Helicobacter pylori infection has been observed in inflammatory bowel disease (IBD) patients, the clinical significance of H. pylori infection in this setting remains unknown. The aim of this study was, therefore, to evaluate the prevalence of H. pylori infection in a large series of IBD patients and the frequency of gastroduodenal lesions in those who agreed to undergo upper GI endoscopy. METHODS: Two hundred and sixteen consecutive IBD patients (123 with Crohn's disease (CD) and 93 with ulcerative colitis (UC)) had their anti-H. pylori IgG titres measured. Two hundred and sixteen blood donors matched for age, sex, place of birth in Italy, and socioeconomic status served as controls. All patients were offered the possibility of undergoing endoscopy with antral and corpus biopsies regardless of their H. pylori status. RESULTS: The overall seroprevalence of H. pylori infection was 48% in IBD patients versus 59% in the control group (P < 0.05), with a significantly lower frequency in CD versus UC patients (41% versus 56%). After adjustment for age, education, and socioeconomic status CD remained associated with a significantly lower risk of H. pylori infection. Previous therapy with sulphasalazine but not with 5-aminosalicylic acid or with steroids/immunosuppressants was associated with a reduced risk of H. pylori infection both in CD and UC patients. One hundred and eighty-nine patients (110 with CD and 79 with UC) underwent endoscopy; the prevalence of peptic ulcer was similar in both groups (5.5% in CD and 5.1% in UC patients); however, 11 more CD patients had gastroduodenal ulcers that were interpreted as CD-related; 7 of these patients had never had foregut symptoms. Two CD patients had granulomatous gastritis at histology, and another 16 patients with CD had H. pylori-negative gastritis. CONCLUSIONS: IBD patients have a reduced prevalence of H. pylori infection as compared with matched healthy controls; this appears mostly attributable to a reduced frequency of H. pylori colonization in CD patients. Previous use of sulphasalazine is associated with a reduced risk of infection both in CD and UC patients. Of CD patients 10% have a gastroduodenal localization of their disease, which is often asymptomatic. Of CD patients 15% also have H. pylori-negative gastritis at histology.
Abstract: The efficacy of 4 commercial cleansing products was tested with 3 colouring agents widely used in the dyeing industry in a randomised double blind trail involving 8 workers each time. A between-detergents statistically significant difference was observed; the interaction (detergents x colouring agents) was significant. The efficacy of type A detergent was higher for type I-III dyers, while the efficacy of type C detergent, which widely used was lowest.
Abstract: This paper reports results of a first phase of a pilot study to assess and improve quality of diagnoses in cervical cytological laboratories located throughout Italy. It represents the first phase of an External Quality Assurance programme (EQA). In the first phase, two sets of cervical smears representing a range of diagnoses were circulated among participating laboratories. Responses were recorded on a standardized form. Participants were asked to assess the adequacy of the smear and formulate a diagnosis. They were also asked to recommend management of the patient on the basis of the smear report and judge the degree of diagnostic difficulty of each slide. Crude index of agreement, unweighted and weighted kappas, diagnostic specific kappas, sensitivity and specificity as well as clinical indices of variability were calculated. In the second phase, two additional sets of slides were circulated after discussion of the first phase. There was striking variability between laboratories, both in terms of diagnoses offered and recommendations for management on individual slides. Assessment of the degree of difficulty of each slide was also very variable. Discrimination between CINII and CINIII was poor, confirming the choice of merging these two categories in the Bethesda classification. However, discrimination between CINI and CINII was also unsatisfactory. The results were discussed in workshops and it was possible to reach a consensus diagnosis in 35 of 40 smears. This study confirms the need for external quality control programmes.
Abstract: Reference values for blood-cadmium levels (B-Cd) are available for only a limited number of geographical areas and for particular population strata (sex, age, smoking habits). This paper, in agreement with the TRACY guidelines, describes and discusses the criteria used to rank published papers on reference values for cadmium retrieved by Medline and Toxline between 1976 and 1991. The TRACY criteria deal with the grading of published papers in terms of their suitability for calculating provisional reference values. Only four out of 18 papers were considered suitable for the TRACY project. The four articles were finally used via meta-analysis to provide provisional reference values for smokers and non-smokers. The comparison of results obtained using published statistics and individual data is used to discuss the appropriateness of meta-analysis in the case of cadmium. Due to the availability of large enough studies and to the clear differences across countries, the suitability of a compound upper reference limit to B-Cd levels seems limited.
Abstract: Over the period 1980-1990, 2024 workers in ceramic plants in the Emilia-Romagna region, Italy were evaluated for exposure to noise and hearing loss. Data collected by the National Health Service Local of Occupational and Preventive Medicine Units were used. In a relatively young population (34.8 years mean age, 8.98 years s.d.) exposed for not too long to > 90 dBA noise levels (87.2 for less than 4 years) a statistically significant effect of exposure was found only on the audiometric frequency of 6 kHz (95% confidence interval for mean hearing loss for 1 year exposure to > 90 dBA: 0.05-0.72 dB). An initial isolated loss at the audiometric frequency of 6 kHz was found to be significantly associated with (was a prognostic indicator of) a subsequent impairment at 4 kHz.
Abstract: A total of 942 workers of 13 dyeing and printing factories in the area of Como (N. Italy) were examined in order to detect skin complaints on the hands and forearms. Of these, 868 were eligible for and consented to participate in a controlled and randomized experiment aimed at assessing the efficacy of using barrier creams in practical circumstances. 657 workers underwent all three control examinations arranged over about one year. In the randomized group for treatment with barrier creams the cumulative incidence of objective skin lesions was significantly lower than in the group in which no particular recommendation of use was made (44.5% versus 54.4% positive for objective examination in at least one of the three control examinations after recruitment: 95% confidence limits of the difference between 2%-17% percentages; 39.9% versus 47.0% in subjects who were negative at the recruitment examination, 59.0% versus 76.8% in subjects who were positive at the recruitment examination). The use of a hydrocarbon cream was significantly more effective than using a silicone cream (95% confidence limits of the differences of cumulative incidences: -10.9% +20.7% comparing silicone creams with non-treatment; 2.8%-20.2% comparing hydrocarbon creams with non-treatment).
Abstract: We investigated the role of urinary testosterone levels as a marker of risk of recurrent disease in 113 operable breast cancer patients (70 premenopausal, 43 postmenopausal). Twenty-four-hour urine collections for testosterone measurement were obtained before surgical treatment, between 20-40 days thereafter, and then every 6 months for 5 years. The cutoff values to separate 'high testosterone (A+)' from 'normal testosterone (A-)' were 8.0 micrograms/24 h in premenopause and 4.9 micrograms/24 h in postmenopause. Urinary testosterone levels were considered high when they exceeded the cutoff value in at least 2 of the first 3 measurements (pretreatment, post-treatment, 6 months) of each patient. According to the aforementioned criterion, 33 patients (29.2%) had high testosterone levels, which were associated to axillary node involvement in 16 patients. Thirteen of the latter relapsed during the 5-year follow-up period (5/7 in premenopause, 8/9 in postmenopause). Relapse-free survival (RFS) curves were drawn only for node-positive patients owning to the small number of recurrences observed in the node-negative group. In premenopausal node-positive patients, RFS was significantly different for patients presenting high and normal urinary testosterone levels (77% vs 28%, respectively; logrank test, p < 0.006). In postmenopausal node-positive patients, RFS was also different between the two groups (54% vs 11% in 'high' and 'normal' excretors, respectively) but the difference was not statistically significant. The present findings suggest that urinary testosterone is a prognostic indicator of early breast cancer recurrence in node-positive patients.
Abstract: Health education represents a fundamental tool in the prevention of occupational diseases. For lead-exposed workers, work practices, personal hygiene, and life habits are certainly influences in the amount of the metal absorbed in the body. This study evaluated the effectiveness of a health education program in 50 workers exposed to inorganic lead employed in seven small factories. The study was performed in 3 phases over one year. Before the program, blood lead levels were measured, and a questionnaire was administered in order to evaluate the baseline knowledge of the workers about lead poisoning and its prevention. After the health education program, the blood lead levels decreased (from 38.2 to 32.3 micrograms/dl) and the questionnaire scores improved in a highly significant manner (p < 0.001). These results were obtained both in the short (4 months) and in the medium term (1 year). The reduction of blood lead concentrations seemed to be due to changes in hygienic behaviors and life habits, such as alcohol consumption or cigarette smoking, probably induced by an increase in specific knowledge about the prevention of lead damages.
Abstract: A study was made of 3,368 workers in 36 ceramic plants in the Scandiano area (Reggio Emilia, Italy) during the year 1990; 403 had an accident during the observation period. The incidence and severity of the accident were correlated to age, job (low, intermediate, high accident risk), duration of employment as at 1.1.1990 (> 24, 12-24, > 24, 12-24, < 12 months, engaged during 1990). Logistic regression analysis, survival analysis and RIDIT analysis were performed using GLIM and EGRET statistical packages. Risk: ORs for intermediate and high-risk jobs vs low-risk jobs were 1.3 (1.0-1.7 95% confidence limits) and 1.7 (1.3-2.3), respectively, adjusted for duration of employment; ORs for the 12-24, < 12 months, engaged during 1990 categories vs the > 24 months category were 1.5 (1.1-2.0), 1.7 (1.3-2.2), 2.1 (1.6-2.8) respectively. Severity: the mean RIDIT of the > 44-year-old vs < 30-year-old workers was 0.6 (0.53-0.67).
Abstract: An investigation on the health effects of occupational exposure to motor vehicle exhaust and environmental pollutants was carried out on traffic wardens in Milan (Italy). Randomized samples of 292 traffic wardens (exposed group) and 60 hospital staff members (control group) underwent a physical examination and laboratory tests. No significant difference was observed between the exposed and control groups as regards general morbidity, apart from musculo-skeletal disorders in females. The mean blood lead level (PbB) among traffic wardens was 15.2 micrograms/dl compared with 11.7 in control (p less than 0.01). The carboxyhaemoglobin concentration (COHb) in traffic wardens at the beginning of the shift was 2.8% for smokers and 1.2% for non-smokers (3.0% and 0.9% respectively in controls). At the end of the shift COHb in the exposed group was 4.3% for smokers and 2.5% for non-smokers (p less than 0.01). PbB was significantly correlated (r = 0.17) with Median Nerve Motor Conduction Velocity (NCV) in the exposed but not in the control group. The same pattern was observed for the correlation of PbB and Systolic Blood Pressure (SBP) (r = -0.24). COHb was significantly correlated with HDL cholesterol (r = -0.20) in the exposed group only. It is questionable whether very low PbB levels can affect NCV and SBP directly or rather whether PbB, as well as COHb, should be regarded as tracers of exposure to those urban pollutants leading also to cardiovascular and nervous disorders.
Abstract: In the present study, a definition of the reference values of blood cadmium (Cd-B) and urinary cadmium (Cd-U) was attempted, adopting the same methodology as that used for Hg-B by ICOH and IUPAC. Papers published from 1976 onwards were reviewed. The majority of the studies were concerned with the formation of control groups for toxicological and epidemiological investigations rather than with the definition of reference values. Since the number of subjects for whom data on cadmium were available was small, only the data on Cd-B were considered. After evaluation, only four studies were found to be suitable for the establishment of tentative reference values for Cd-B. It is essential in all such studies to check the statistical and analytical methods for correctness, and the case-list must be selected taking smoking into account as the main interfering factor. It was found that Cd-B values show less dispersion when geometric means and standard geometric deviations are used instead of arithmetic means and standard deviations.
Abstract: This paper deals with some basic statistical issues arising from biological monitoring. Data description, Gaussianity tests, outlier identification, parametric and non-parametric estimates of fractiles and their standard errors, and parametric estimate of the one tail upper side tolerance interval are treated and exemplified using two data sets. Sample size and power determination are considered in terms of the cut-off point of the diagnostic quantitative test.
Abstract: The precision of the Ballard scale for assessing gestational age (GA) was evaluated in a consecutive sample of 227 preterm and/or low-birth-weight neonates. Each newborn was rated independently by two neonatologists and the difference in GA estimation between them was computed. The estimated precision was not high, the 95% tolerance interval estimate being as large as 7.4 weeks. The precision of the neurologic and physical parts of the scale was poorer than that of the complete scale (95% of differences less than 10.5 and 9.2 weeks respectively), and more influenced by the type of delivery. These findings are not unexpected from statistical theory, and cast doubts on the use of only the physical part of the Ballard scale in assessing GA, since greater accuracy could be accompanied by reduced precision.
Abstract: By undertaking to act as 'medico necroscopo' (the medical doctors in charge of authorizing every burial) in the Unità Socio-Sanitaria Locale (USSL) 70, a region containing 92,500 inhabitants, we were able to collect over a four-year period (1985-88) information on 3371 deaths among residents of the area. Of these, 68.1% died at home, 12.6% in hospital with no autopsy, 9.5% in hospital with an autopsy and 9.8% outside of the USSL region. For the analysis, age, sex and leading cause of death were considered as explanatory variables and place of death and proportion of autopsied cases as the response variables. The factors found to be associated with deaths occurring in hospital were non-neoplastic (particularly cardiovascular and digestive) pathological conditions in patients under the age of 60. People with malignant neoplasms usually died at home, especially when they had a gastric or breast cancer. Factors associated with autopsy were: death at a young age, short length of hospitalization and death from a cardiovascular disease. Sex did not appear to play a direct role in selection for necropsy. Our results indicate that, in our and similar regions, the cases selected for autopsy form a subset that is so specific that any extrapolation to the total deceased population is misleading.
Abstract: Statistical aspects of tolerance intervals estimation are considered and tolerance coefficients for unilateral and central intervals are derived for normally distributed biological variables. The difference between confidence and tolerance interval is explained and application to biological and environmental monitoring, as well as applications to reference values estimation, are exemplified. Tables of unilateral and central coefficients are also produced and reported for different sample dimensions, confidence, and tolerance levels.
Abstract: A panel review of histologic specimens was carried out as part of a multi-centre case-control study of gastric cancer (GC) and diet. Comparisons of diagnoses of 100 GCs by six pathologists revealed agreement in histologic classification for about 70-80% of the cancers. Concordance was somewhat higher when using the Lauren rather than the Ming or World Health Organization classification systems. Histologic types from reading biopsy tissue agreed with those derived from surgical specimens for 65-75% of the 100 tumours. Intra-observer agreement in histologic classification, assessed by repeat readings up to 3 years apart by one pathologist, was 95%. The findings indicate that, although overall concordance was good, it is important to standardise diagnoses in multi-centre epidemiologic studies of GC by histologic type.
Abstract: A sample of high school students in grade 9 and 13 (14-15 and 18-19 years old respectively) in Brescia, North Italy, were interviewed to assess the relationship of smoking habit with attitudes, knowledge, behavioural and socio-environmental factors among adolescents. The associations between smoking habit, considered as a dichotomous response variable, and the other variables were assessed by estimating the prevalence ratios. The following variables were found to be associated with the students' smoking: best friend and/or partner smoking, sibling smoking, alcohol drinking and the students' judgement of the health risks of smoking. Although no conclusion can be drawn on the causal relationship of these associations due to the cross-sectional design of the survey, these findings suggest that social environment influences adolescents' smoking more than family life does. Furthermore, the knowledge of the health risks of smoking was not associated to adolescents' smoking.
Abstract: Since the 1986, the National Institute for Occupational Accident Insurance (INAIL) provides each single Region with the occupational accident data on magnetic support. This strengthens the need to critically evaluate the most commonly used risk indicators. In this paper we discuss advantages and limits of the usual frequency and severity measures; the formulae for the standard errors are also given. A method proposed by I. Bross (1958), the RIDIT Analysis, is considered and exemplified. The appealing properties of this method ask for a more extensive application in this field.
Abstract: We evaluated the chelation test in 38 subjects exposed to lead or with suspected lead exposure, comparing the values of lead excretion at the 3rd h (PbU EDTA/3-h) and at the 24th h (PbU EDTA/24-h) after EDTA administration. Good correlation exists between PbU EDTA/3-h and PbU EDTA/24-h (r = .86) and between them and the main biological indicators of dose and effect of lead. When a second chelation test was performed in 15 subjects, a slightly better r coefficient (.93) was observed between the two tests, without reaching statistical significance. It seems difficult, in terms of the type of exposure that we considered, to use the 3-h test, on an individual basis, to predict the PbU EDTA/24-h values.
Abstract: The paper describes the methods currently used for numerical synthesis of statistical data. A review is made of the main properties of the various statistical indices required to describe the central tendency, dispersion and shape of distribution of values. Mode, median, arithmetic mean, harmonic and geometric mean, range, quantiles and standard deviation, asymmetry and kurtosis indices are described and discussed using data drawn from practical experience. Special attention is paid to the errors most frequently incurred using these methods. An appendix supplies details of some of the mathematical properties of the operators described.
Abstract: The quality of the certificates of death for 2429 cases, all the residents died at home in the USL 70 during the period 1.8.83-31.12.87, was evaluated thanks to the necroscopic activity of the Legnano's Hospital pathologist. All the information, oral or written, available about each case was used to check the family doctor's certificate. Any correction to the certificate was discussed with the certifier. During the period a gradual and progressive reduction of error in the statement of the underlying cause of death was shown. The improvement comes out using different quality indicators.
Abstract: This is the second part of an introduction to probability calculation and covers basic concepts such as conditional and simple probabilities and independent events and also a definition of two fundamental laws, those of addition and multiplication, which permit a correct combination of probabilities. Explanation of probability concepts and ideas is illustrated with the aid of examples from the field of screening tests. Bayes theorem is derived by applying the addition and multiplication laws to conditional and simple probabilities.
Abstract: This is the first of a series of articles on probability calculation, consisting of a simple introduction to the definitions of probability. A brief historical background explains some of the reasons for the delay in the development of probability calculation and recalls the main problems that had to be faced, the solution of which marked the birth of the theory of probability. Classical, frequentist and subjective approaches are addressed and their relative merits and weaknesses are discussed.
Abstract: This article discusses the feasibility of fitting a straight line to the reciprocal serum creatinine (1/SCr) values obtained from 32 patients with IgA mesangial nephropathy and established renal insufficiency. Three models were tested for fit: linear, logarithmic and quadratic. The decline of renal function, once renal failure has been established, is neither constant nor regular in all patients with this fairly well-diagnosed glomerular disease. Therefore we cannot rely on simple mathematical models to compare sequences of serum creatinine values or to forecast decline in renal function in patients with IgA nephropathy.
Abstract: Estrogen (ER) and progesterone receptor (PgR) status was determined in 41 women with operable endometrial cancer before and after administration of tamoxifen (TAM). The first sample was obtained by hysteroscopy to ensure a precise biopsy of neoplastic tissue; the second was done on the surgical specimen. PgR content was significantly increased after TAM treatment and this data was compared with the degree of tumor differentiation.
Abstract: One hundred and twenty Pap-smears were examined by 3 cytotechnologists on two occasions in the Legnano Hospital Cytologic Center. A 10-category classification system was used. Chance-adjusted overall and category-specific agreement was estimated (Cohen's unweighted kappa-statistics) within and between cytotechnologists. Mean K for the Center, weighted for precision, was 0.432, S.E. 0.029 (between cytotechnologists). The most reproducible categories (between cytotechnologists) were "9: malignant cells" (K = 0.683) and "1: normal" (K = 0.533); the least reproducible categories were "4: endocervical metaplastic cells" (K = 0.024) and "8: severe squamous dysplasia CIN III" (K = 0.227).
Abstract: A total of 3357 women (88.1% married, 82.0% parous) were examined at least once in the mass-screening program carried out by the Legnano Hospital Screening Center in Nerviano (a small town near Milan with 15,600 inhabitants) in 1974, 1977 and 1980. Married women with visible portio and adequate smear were 2758: a visibly healthy cervix was found only in 1143 subjects (41.4%). A total of 1516 married women were examined at least in 2 consecutive campaigns: 1279 (84.4%) reported "no gynecologic treatment in the previous 5 years" at the first campaign, and 899 (59.3%) reported "no gynecologic treatment in the previous 3 years" at their second one. Of 350 women with "medical lesions" and 525 with "surgical lesions" recorded at the first visit, 111 (31.7%) and 232 (44.2%) reported, respectively, a "medical treatment" or a "surgical treatment" at the second visit. In women with "medical lesions" at the first visit, at the second visit a healthy cervix was found in 66.2% of the treated women and in 72.6% of the untreated patients. In those with "surgical lesions" a healthy cervix was successively found in 91.6% of treated and in 40.7% of the untreated patients.
Abstract: Both in animals and in man the inhalation of CS2 vapor induces a chronic polyneuropathy with primary lesions in the axons of peripheral nerves. Since it was reported in several studies that the administration of gangliosides improves nerve regeneration and the functional recovery of nerves damaged by section as well as cryodegeneration, a study was undertaken to evaluate the effects of bovine-brain gangliosides administration on the experimental CS2 neuropathy in the rat. One hundred and fifty male rats were intoxicated with CS2 by a discontinuous inhalation exposure to 700 ppm for 12 weeks until a clear neuropathy developed. Thereafter the animals were subdivided at random into five groups and treated in different ways: 10 mg/kg BW gangliosides, 0.5 mg/kg gangliosides, 0.5 mg/kg vitamin B1, and 1 mg/kg vitamin B6, physiological solution, and controls without any treatment. The recovery from neuropathy was controlled for 18 weeks of treatment and assessed periodically by means of clinical, electromyographic, and morphological examination. The results of morphological studies showed more pronounced regeneration activity in the rats treated with the high dose of gangliosides than in all others, while no differences among the groups could be observed as far as clinical and neurophysiological parameters are concerned. The mechanism supporting this ganglioside-induced effect has so far not been ascertained, and further studies on this subject are in progress.
