Elena Ricci

Reproductive factors and risk of uterine fibroids

We analyzed the relation between reproductive history and risk of uterine fibroids using data from a case-control study. Cases were 621 women with histologically confirmed diagnosis of uterine fibroids. Controls were 1,051 non-hysterectomized patients. Compared with nulliparae, parous women had a relative risk (RR) of fibroids of 0.5 [95% confidence interval (CI) = 0.4-0.6], and the risk declined with number of births. The risk of fibroids also decreased with number of induced abortions (RR = 0.8 and 0.6 for women reporting one or two or more abortions, respectively). A total of 24 cases (3.9%) and 19 controls (1.8%) reported a history of infertility (RR = 2.0; 95% CI = 1.1-3.7).

Probiotics reduce gut microbial translocation and improve adult atopic dermatitis.

Background: It has been suggested that probiotics modulate atopic dermatitis (AD) progression, but no data are actually available on their mechanisms of action and on their ability to act as immunomodulators in this pathology. Objective: The aim of this randomized double-blinded active treatment versus placebo study was to evaluate clinical efficacy of an intake of a combination of 2 probiotics (Lactobacillus salivarius LS01 and Bifidobacterium breve BR03) for the treatment of adult AD patients. Methods: Forty-eight patients were enrolled in the study (randomization ratio 2:1) and treated with a combination (LS01 and BR03) or placebo (maltodextrin) for 12 weeks. Clinical efficacy was assessed from baseline by changes in the SCORAD index and DLQ index improvement. Analysis on the gut permeability barrier, immunologic parameters, and changes in fecal microbiota and recovery of probiotics were performed at baseline, at the end of therapy, and 2 months later. Results: Patients receiving probiotics showed a significant improvement in clinical parameters (SCORAD, P<0.0001 and DLQ index, P=0.021) from baseline. The probiotics reduced microbial translocation (P=0.050), immune activation (P<0.001), improved T-helper cell (Th)17/regulatory T cell (Treg) (P=0.029) and Th1/Th2 (P=0.028) ratios. None of these changes were observed in the placebo group. Conclusions: Our results suggest that this specific mixture of probiotics (LS01 and BR03 strains) may induce beneficial effects for clinical and immunologic alterations in adult AD. This combination could be considered as adjuvant therapy for the treatment of AD in adult patients.

Identifying HIV patients with an unfavorable cardiovascular risk profile in the clinical practice: Results from the SIMONE study

OBJECTIVEnTo identify and characterize HIV-infected patients at higher cardiovascular risk in ordinary clinical settings.nnnDESIGNnMulticenter, nationwide cross-sectional study.nnnMETHODSnConsecutive HIV-patients, attending scheduled visits at facilities involved in the Italian coordination group for the study of allergies and HIV infection (CISAI), were included between February and April, 2005. Their 10-year probability of acute coronary events was calculated using the Framingham Risk Score (FRS) as well as 3 other cardiovascular algorithms (PROCAM, PROGETTO CUORE, SCORE); Metabolic Syndrome (MS) was diagnosed according to the National Cholesterol Education Program definitions. An estimated 10-year CVD >or=10% and/or MS led to the diagnosis of high CV risk. We compared selected clinical features between high- and low-risk patients.nnnRESULTSnA total of 1230 HIV infected patients (72% males, mean age of 43+/-9 years), 185 of whom treatment-naive, were evaluated. FRS gave the highest estimate of CV risk. The mean 10-year risk for acute coronary events according to FRS was 7.4+/-7.0. MS was present in 22% of the observed patients. Accordingly, 443 patients (36%) were classified at high risk. Twelve percent of the patients (n=142) had both a FRS >or=10% and a diagnosis of MS. The main single predictor of increased cardiovascular risk was smoking (60% of whole sample). A higher prevalence of clinically evident lipodystrophy and a higher CD4 T-cell counts were found both in patients with higher FRS and in patients with high FRS and MS (both p<0.001).nnnCONCLUSIONSnThe worst estimation of CV risk was obtained with the FRS algorithm. Clinical evidence of lipodystrophy and higher CD4 T-cell counts were closely associated to a worse cardiovascular risk profile.

Alcohol and endometrial cancer risk : findings from an Italian case-control study

Using data from a case-control study conducted in Northern Italy, we analyzed the relation between alcohol drinking and risk of endometrial cancer. Cases were 726 patients, < 75 years of age, admitted to the Ospedale Maggiore (including the 4 largest teaching and general hospitals in the Greater Milan area), the University Obstetrics and Gynecology Clinics, and the National Cancer Institute of Milan with histologically confirmed endometrial cancer. Controls were 2,123 nonhysterectomized patients, < 75 years of age, admitted for acute nongynecological non-hormone-related nonneoplastic conditions to the same network of hospitals where cases had been identified. When total consumption of all alcoholic beverages was considered, 68.2% of cases and 63.9% of controls were drinkers and 12% of cases and 9.3% of controls reported > or = 2 drinks/day. Considering total alcohol drinking, the relative risk for alcohol drinkers vs. nondrinkers was 1.3 (95% confidence interval 1.1-1.5), and the RR estimates for subsequent levels of intake were 1.1, 1.4, and 1.6 for women drinking > 0 < or = 1, > 1 < or = 2 drinks/day (chi 2(1) trend 11.33, p < 0.001). The estimates were similar when wine only (which represents the large majority of all alcohol intake in Italy) was considered, whereas data were less informative for beer and spirits intake only. No relation emerged between duration of alcohol consumption and risk of endometrial cancer. These findings suggest a potential link between alcohol drinking and endometrial cancer risk and are, in any case, inconsistent with a protective role of alcohol in endometrial carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Atherosclerosis is associated with multiple pathogenic mechanisms in HIV-infected antiretroviral-naive or treated individuals

Objectives:HIV-infected patients have a greater burden of sub-clinical and clinical atherosclerotic disease compared to the general population. The primary objective of this study was to compare the relative roles of inflammation, endothelial alterations, and metabolic factors in the induction and maintenance of atherosclerosis in antiretroviral therapy (ART)-treated or ART-naive patients. Design:Cross-sectional study; 79 HIV-infected patients (55 ART-treated and 24 naive individuals) were consecutively enrolled. In both groups, nearly 50% of the individuals had a high cardiovascular risk (Framingham value >20%). Methods:Echo-Doppler [intima–media thickness (IMT)], inflammatory, thrombophilic, endothelial, metabolic indexes, and cholesterol efflux molecules were evaluated. Multivariate analysis adjusted for age, CD4 nadir, BMI, and Framinghams score were used to analyze the results. Results:A complex pathogenesis drives atherogenesis in HIV infection. Thus, whereas inflammation could be responsible for this process in ART-naive individuals, metabolic factors [low-density lipoprotein (LDL), apolipoprotein B (ApoB), lipoprotein A] seem to play a more prevalent role in ART-treated patients. Notably, ABCA-1, an ATP-binding transporter cassette protein involved in cholesterol efflux, which is inhibited by Nef, is up-regulated in ART-treated individuals. Conclusion:Atherosclerosis in HIV infection results from the interaction of multiple factors: an inflammatory and HIV-driven disease could prevail in the absence of therapy; metabolic, non-inflammatory causes may be more important in patients undergoing therapy. Approaches to atherosclerotic disease in HIV infection should consider these differences.

Relations between cardiovascular risk estimates and subclinical atherosclerosis in naive HIV patients: results from the HERMES study.

Summary The aim of the study was to evaluate the cardiovascular risk factors associated with subclinical carotid atherosclerosis in antiretroviral therapy-naïve HIV-infected patients. The HERMES (HIV Exposure and Risk of Metabolic Syndrome) study enrolled therapy-naïve patients attending hospitals in the Italian coordination group for the study of allergies and HIV infection (CISAI [Coordinamento Italiano per lo Studio Allergia e Infezione da HIV]) in 2007. It was designed to identify metabolic syndrome (MS) and cardiovascular risk factors. The present analysis is a nested cross-sectional study with a subset of patients examined by carotid ultrasonography. Consecutive antiretroviral therapy-naïve HIV patients attending the facilities involved in the CISAI were included. Their 10-year probability of cardiovascular events was calculated using the Framingham Risk Score (FRS) and three other cardiovascular algorithms (the Global Framingham Risk Score – GFRS, ‘Progetto Cuore’ and ‘SCORE’). Vascular age was estimated using a new model derived from GFRS and was compared with chronological age. The diagnosis of MS was based on the National Cholesterol Education Programme and International Diabetes Federation (IDF) definitions. Subclinical atherosclerosis was determined as ultrasound carotid intima-media thickness >0.9 mm. Out of 140 patients enrolled in the HERMES study by the four centres participating in the nested study, a total of 72 (51.4%) subjects, with no overt cardiovascular disease, were examined using carotid ultrasonography. The median age was 40 years, 79.2% men. The vascular age was 7.6 years higher than the chronological age. The factors associated with subclinical atherosclerosis were age (P < 0.0001), vascular age (P = 0.0002), body mass index (P = 0.003), waist circumference (P = 0.0002), MS (IDF definition, P = 0.004) and all the cardiovascular (CV) models (FRS, P = 0.01, GFRS, P = 0.002, Progetto Cuore, P = 0.018, SCORE, P = 0.03). Independent of other significant factors, waist circumference was significantly associated with pathological results (P = 0.007). The GFRS (area under the receiver-operating characteristic curves, 0.78; P < 0.001) had slightly better predictive accuracy than the other three CV models (FRS, areas under the curve [AUC] = 0.71, P = 0.003; Progetto Cuore, AUC = 0.74, P = 0.0005; SCORE, AUC = 0.77, P < 0.0001); 55% of patients at intermediate risk (6–20%) had subclinical carotid lesions. Subclinical carotid lesions had a highly significant direct association with all the CV risk predictors. The GFRS and vascular age were highly predictive. We recommend a carotid ultrasonographic examination at least among HIV patients with GFRS >6% or with an elevated waist circumference.

Time since last use of oral contraceptives and risk of invasive cervical cancer

The time-risk relationship for the association between cervical cancer and oral contraceptives (OC) was examined using data on 592 cases of invasive cervical cancer aged 60 years or less and 616 controls with acute, non-gynaecological, non-hormone-related, non-neoplastic diseases. A total of 125 cases and 114 controls reported ever using OC and the multivariate odds ratio (OR) for ever versus never users was 1.21 (95% confidence interval (CI) 0.82-1.74). The risk of invasive cervical cancer was above unity in current users (OR 1.23) and in women who had stopped OC use less than 10 years before diagnosis, but not in those who had stopped their OC use > or = 10 years before (OR 0.85). Similarly, the OR was less for women who had started OC use 15 years or more previously than for more recent users. These data suggest that OCs may have a late stage (promoter) effect on cervical carcinogenesis and thus have public health implications, since the incidence of invasive cervical cancers is low at young ages, when OC use is more common and increases during middle age. The absence of a persisting risk is therefore of interest both for assessing individual risk and for its public health implications.

Temporal trends and determinants of peripartum hysterectomy in Lombardy, Northern Italy, 1996-2010

PurposeTo analyze the temporal trends of peripartum hysterectomy (PH) in the period 1996–2010 in Lombardy, Italy.MethodsUsing data from the Regional Database, PH ratios/1,000 deliveries were calculated from 1996 to 2010, in strata of age and mode of delivery among women resident in Lombardy, Italy. PH cases were identified searching the database for the ICD-9 and ICD-10 codes for subtotal and total hysterectomy. PH ratios/1,000 deliveries in strata of age, mode of delivery and calendar year were computed. Poisson’s regression analysis was used to test trend over time.ResultsA total of 905 PH and 1,289,163 deliveries were recorded between 1996 and 2010. The overall PH ratio was 0.70/1,000 deliveries. The PH ratio/1,000 deliveries increased over time, being 0.57 in 1996 and 0.88/1,000 deliveries in 2010 (Pxa0<xa00.0001). After including calendar year, mode of delivery and maternal age in the Poisson’s regression equation, no significant linear trend emerged in the PH ratio over time (Pxa0=xa00.28). Women who underwent cesarean section (CS) (CS vs. vaginal delivery: OR 5.66, 95xa0% CI 4.91–6.54) and older women were at increased risk of PH (maternal age ≥40 vs. <30xa0years: OR 5.66, 95xa0% CI 4.48–7.15). The frequency of intractable peripartum hemorrhage and placenta praevia/accreta, the main indications for PH, significantly increased over the study period.ConclusionsIn Lombardy, the PH ratio increased between 1996 and 2010. In our population, rising frequency of CS and older maternal age may explain this trend.

Hysterectomy rates for benign conditions are declining in Lombardy, Italy: 1996–2010

OBJECTIVEnTo analyse the hysterectomy rates (HR) temporal trends for gynecological benign conditions in Lombardy, Northern Italy.nnnSTUDY DESIGNnSince 1991, discharges from public or private hospitals have been registered in a standard form (Lombardy Region registry). Women aged ≥20 years, residing in Lombardy, who underwent hysterectomy for benign conditions, were included in the study. Admissions were codified according to the ICD-9 and ICD-10. HRs per 1000 women residing in Lombardy, of the same age class, were computed.nnnRESULTSnIn 1996-2010, 143,045 hysterectomies were performed for benign indications. HR showed a declining trend (average annual percent change (AAPC) -2.9), mainly due to the falling number of total abdominal hysterectomies (AAPC -5.3). The most remarkable decrease was seen in women aged 45-54 years (HR 8.05 in 1996 and 4.83 in 2010). Leiomyoma was the most frequent indication in women aged <55 years, whereas in older patients it was uterine prolapse.nnnCONCLUSIONSnIn 1996-2010, the frequency of hysterectomy in Lombardy fell markedly. This study confirms the declining trend in abdominal hysterectomies observed in most developed countries, though the surgical approaches to hysterectomy differ in different countries. In particular, in Lombardy the proportion of laparoscopically assisted vaginal hysterectomies, though increasing, is low.

Cost-Utility Analysis of Lopinavir/Ritonavir versus Atazanavir + Ritonavir Administered as First-Line Therapy for the Treatment of HIV Infection in Italy: From Randomised Trial to Real World

Objective To estimate the lifetime cost utility of two antiretroviral regimens (once-daily atazanavir plus ritonavir [ATV+r] versus twice-daily lopinavir/ritonavir [LPV/r]) in Italian human immunodeficiency virus (HIV)-infected patients naïve to treatment. Design With this observational retrospective study we collected the clinical data of a cohort of HIV-infected patients receiving first-line treatment with LPV/r or ATV+r. Methodology A Markov microsimulation model including direct costs and health outcomes of first- and second-line highly active retroviral therapy was developed from a third-party (Italian National Healthcare Service) payer’s perspective. Health and monetary outcomes associated with the long-term use of ATV+r and LPV/r regimens were evaluated on the basis of eight health states, incidence of diarrhoea and hyperbilirubinemia, AIDS events, opportunistic infections, coronary heart disease events and, for the first time in an economic evaluation, chronic kidney disease (CKD) events. In order to account for possible deviations between real-life data and randomised controlled trial results, a second control arm (ATV+r 2) was created with differential transition probabilities taken from the literature. Results The average survival was 24.061 years for patients receiving LPV/r, 24.081 and 24.084 for those receiving ATV+r 1 and 2 respectively. The mean quality-adjusted life-years (QALYs) were higher for the patients receiving LPV/r than those receiving ATV+r (13.322 vs. 13.060 and 13.261 for ATV+r 1 and 2). The cost-utility values were 15,310.56 for LPV/r, 15,902.99 and 15,524.85 for ATV+r 1 and 2. Conclusions Using real-life data, the model produced significantly different results compared with other studies. With the innovative addition of an evaluation of CKD events, the model showed a cost-utility value advantage for twice-daily LPV/r over once-daily ATV+r, thus providing evidence for its continued use in the treatment of HIV.