Paolo Castiglia

Efficacy, safety and tolerability of linezolid containing regimens in treating MDR-TB and XDR-TB : systematic review and meta-analysis

Linezolid is used off-label to treat multidrug-resistant tuberculosis (MDR-TB) in absence of systematic evidence. We performed a systematic review and meta-analysis on efficacy, safety and tolerability of linezolid-containing regimes based on individual data analysis. 12 studies (11 countries from three continents) reporting complete information on safety, tolerability, efficacy of linezolid-containing regimes in treating MDR-TB cases were identified based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Meta-analysis was performed using the individual data of 121 patients with a definite treatment outcome (cure, completion, death or failure). Most MDR-TB cases achieved sputum smear (86 (92.5%) out of 93) and culture (100 (93.5%) out of 107) conversion after treatment with individualised regimens containing linezolid (median (inter-quartile range) times for smear and culture conversions were 43.5 (21–90) and 61 (29–119) days, respectively) and 99 (81.8%) out of 121 patients were successfully treated. No significant differences were detected in the subgroup efficacy analysis (daily linezolid dosage ≤600 mg versus >600 mg). Adverse events were observed in 63 (58.9%) out of 107 patients, of which 54 (68.4%) out of 79 were major adverse events that included anaemia (38.1%), peripheral neuropathy (47.1%), gastro-intestinal disorders (16.7%), optic neuritis (13.2%) and thrombocytopenia (11.8%). The proportion of adverse events was significantly higher when the linezolid daily dosage exceeded 600 mg. The study results suggest an excellent efficacy but also the necessity of caution in the prescription of linezolid.

Multiple sclerosis epidemiology in Sardinia : evidence for a true increasing risk

Objectives– To update prevalence and incidence rates of MS among Sardinians. Materials and methods– The present work is a “spider” kind of population based survey, conducted over the interval 1968–97, on patients with MS (Poser criteria) living in the province of Sassari, Northern Sardinia (454,904 population). Results– A crude total prevalence rate of 144.4 per 100,000, an onset‐adjusted prevalence rate of 149.7 per 100,000 and an average annual incidence rate of 8.2 for the period 1993–7 were found. Conclusion– Repeated epidemiological assessments of MS in Sardinia over decades have shown that the island is at high risk for MS. The present work highlights that MS incidence in Sardinia has been increasing over time. Although a substantial and widely spread improvement in MS case ascertainment can be postulated as the reason for such observations, a comparison between our data and those recently reported from a more industrialized province in Northern Italy seems to prove an at least partially real increase in MS risk among Sardinians and favours the hypothesis of a MS “Sardinian focus” as related to its latitude.

Italian multicenter study on infection hazards during dental practice: Control of environmental microbial contamination in public dental surgeries

BackgroundThe present study assessed microbial contamination in Italian dental surgeries.MethodsAn evaluation of water, air and surface microbial contamination in 102 dental units was carried out in eight Italian cities.ResultsThe findings showed water microbial contamination in all the dental surgeries; the proportion of water samples with microbial levels above those recommended decreased during working. With regard to Legionella spp., the proportion of positive samples was 33.3%. During work activity, the index of microbial air contamination (IMA) increased. The level of microbial accumulation on examined surfaces did not change over time.ConclusionThese findings confirm that some Italian dental surgeries show high biocontamination, as in other European Countries, which highlights the risk of occupational exposure and the need to apply effective measures to reduce microbial loads.

Multiple sclerosis distribution in northern Sardinia Spatial cluster analysis of prevalence

Background: A heterogeneous geographic distribution of MS has been reported among different ethnic groups, and also within small communities. Epidemiologic studies conducted over the past two decades using repeated assessments clearly show that Sardinia is at high risk for MS, with a prevalence of 150 per 100,000 in 1997. Objective: To present spatial analysis of the disease prevalence to disclose possible “hot” or “cold” spots of disease, further allowing correlations with risk factors. Methods: A spatial analysis of the whole province of Sassari, in northern Sardinia, at a microgeographic level (i.e., in the 89 administrative communes and 6 linguistic areas) was conducted. Because of the small number of cases per commune and to overcome random variability, a hierarchical Bayesian approach was adopted. The distribution of prevalent cases by commune of residence on December 31, 1997 and from age 5 to 15 years was analyzed. Results: A clustering pattern was found in the southwestern communes of the province based on geographic distribution by both prevalence and residence at age 5 to 15 years. A west-to-east gradient also was observed. Conclusions: This study highlights a hot spot of MS in the southwestern part of Sassari province, bordering with the commune of Macomer, where MS was once hypothesized as having occurred as an epidemic. Interestingly, these areas of MS clustering comprise the Common Logudorese linguistic domain. The Catalan area, linguistically and genetically distant from the remaining Sardinian domains, does not show such high estimates. Because MS is not a single-source infectious disease, this study may help test the hypothesis that a widely and evenly spread environmental (infectious?) agent may produce disease in subgroups of genetically more susceptible individuals in areas at higher inbreeding rates, wherein a disease mode of inheritance could be better investigated.

Multiple sclerosis complexity in selected populations: the challenge of Sardinia, insular Italy

Several lines of evidence indicate a genetic contribution to multiple sclerosis (MS) both in terms of predisposition to the disease and of immunological mechanisms which are known to play crucial roles in MS pathogenesis. The presence of high‐ and low‐risk areas for MS in neighbouring regions supports the theory that MS predisposition is influenced by a complex interaction of genetic and environmental factors. Therefore, the use of genetically homogeneous and geographically isolated populations becomes an increasing requirement to reduce biasing biological variables. Sardinians fulfil these conditions well because of their different phylogeny from Europeans and the unique selective pressures which shaped their genome. Sardinians display amongst the highest MS prevalence rates world‐wide and increasing MS incidence rates over time. Also, MS in Sardinia is linked to distinct human leucocyte antigen (HLA) alleles and associated to different patterns of cytokine production from lymphoid cells of different HLA subtypes. In this context, recent findings and future perspectives on the peculiarities of Sardinian MS concerning genetic, immunological and epidemiological aspects are presented. So far, our results indicate that variations at the level of territorial distribution and HLA‐association are present which render MS heterogeneous even in this ethnically homogeneous population.

National pathfinder survey on children's oral health in Italy: pattern and severity of caries disease in 4-year-olds.

This paper describes the dental health status of Italian 4-year-olds in 2004/2005 and analyzes the association between caries in preschool children and some background characteristics in children and parents. Caries was recorded according to WHO criteria. 5,538 subjects were examined. Information on the children’s and their parents’ social, behavioral, ethnic and demographic status was obtained through a series of closed questions. Bivariate analysis was performed to investigate the association between caries and background characteristics. The probability of being an extra zero for the dmfs index was estimated via the zero-inflated negative binomial regression model (ZINB). 78.4% (95% CI = 77.2–79.6) of the children were caries-free. The national mean dmfs index was 1.36 (95% CI = 1.15–1.57), ranging from 1.22 (95% CI = 1.03–1.42) in the Italian North-East to 1.73 (95% CI = 0.83–2.63) in the South section. Significant bivariate associations between caries experience and risk factors were observed for parents’ nationality (not Italian vs. Italian: p < 0.001), parents’ educational levels (low vs. high: p < 0.001), preterm birth (yes vs. no: p = 0.011), prolonged breastfeeding (≤13 months vs. >13 months: p = 0.038) and early tooth eruption (<6 months as reference: p = 0.004). Multivariable analysis (ZINB) showed that children with a low caries risk level had a higher probability of being an extra zero; in particular, children from fathers with a high educational level showed a probability of being an extra zero of 0.22. The results suggest a need to plan preventive programs to reduce oral health disparities among Italian preschool children, based on educational intervention with parents and children concerning oral health and caries prevention.

National Pathfinder Survey of 12-Year-Old Children’s Oral Health in Italy

No recent data on the experience of caries among Italian 12-year-olds are available. In 2004, an epidemiological survey called ‘National Pathfinder among Children’s Oral Health in Italy’ was promoted and carried out. This study reports the actual oral health status of Italian 12-year-olds according to gender, residence area and geographical distribution. Clinical examinations were carried out from March 2004 to April 2005, according to WHO criteria, and included dental caries (decay at the dentinal lesion level) and Community Periodontal Index (CPI). 5,342 children (2,670 males, 2,672 females) were examined by 7 ad hoc calibrated raters. Dental caries experience was found in 43.1% (95% CI 41.8–44.4%) of the study population. The mean DMFT score was 1.09 (95% CI 0.98–1.21). Significant differences (p < 0.05) were observed among geographical sections for DT, FT and DMFT. An inverse relationship was observed between mean DMFT and gross national product per capita (p < 0.001). Gingival bleeding was observed in 23.8% of children, while 28.7% had calculus. Significant differences in CPI scores among sections were found throughout the sample in both males and females (p < 0.001). Over the past two decades, mean DMFT fell from over 5 to its present level, halving every decade; consequently, the recorded level of dental caries has become aligned with that in other Western European countries. Nevertheless, differences in DMFT values remain between children from different socioeconomic backgrounds.

Usefulness of magnetic resonance in patients with invasive cancer eligible for breast conservation: a comparative study.

BACKGROUND The role of magnetic resonance imaging (MRI) in newly detected breast cancer remains controversial. We investigated the impact of preoperative MRI on surgical management of infiltrating breast carcinoma (IBC). METHODS We reviewed data of 237 patients with IBC who were suitable for breast-conserving surgery (BCS) between 2009 and 2011. Of these patients, 109 underwent preoperative MRI (46%; MRI group) and 128 did not (54%; no-MRI group). We analyzed MRI-triggered changes in surgical plan and compared differences in rates of positive margins and mastectomy. RESULTS Tumor size was larger in the MRI group (16.8 mm vs. 13.9 mm; P < .001). MRI changed the initial surgical planning in 18 of 109 patients (16.5%) because of detection of larger tumor diameter requiring wider resection (8 patients [7.3%]) or additional malignant lesions in the ipsilateral (9 patients [8.2%]) or contralateral breast (1 patient [0.9%]). MRI-triggered treatment changes included mastectomy (n = 12), wider excision (n = 5), and contralateral BCS (n = 1). Reoperation rates for positive margins after BCS appeared higher in the no-MRI group (4.1% vs. 8.6%), but the difference missed statistical significance (P = .9). Overall mastectomy rates were higher in the MRI group (13.7% vs. 7.0%; P < .05). The likelihood of having a change of treatment resulting from MRI was significantly higher for patients with tumors > 15 mm and for those with positive lymph nodes. CONCLUSION Lymph node positivity and tumor size > 15 mm may predict an MRI-triggered change in surgical plan. Preoperative MRI resulted in higher mastectomy rates justified by biopsy-proven additional foci of carcinoma and did not significantly reduce reoperation rates for positive margins.

Diet and nutrients are contributing factors that influence blood cadmium levels.

Studies suggested the intake of Cd from diet can be approximately equivalent to that from smoking. Moreover, a mutual metabolic influence between Cd and nutrients has been reported. The purpose of this study was to evaluate the relationship between blood cadmium concentration (BCdC) and food consumption, nutrients intake (Ca, Fe, Zn, vitamin C, and vitamin D), tobacco smoking, and some other variables (age, body mass index, and residence) in 243 adults living in the Italian island of Sardinia (Sassari Province). Specifically, we hypothesized that offal consumption contributes to Cd intakes and blood levels. The BCdC was quantified by graphite furnace atomic absorption spectrometry, and information on personal data was collected through questionnaires. Smoke significantly contributed to the BCdC (P < .001). Nonsmoker subjects who eat offal showed significantly higher BCdC (P = .04). Moreover, slightly higher BCdCs were also observed in nonsmoker subjects who eat rice, fish, and bread. The BCdC positively correlated with age of subjects (r = 0.144; P = .025) and offal daily intake in nonsmokers (r = 0.393; P < .001). The intake of Ca was negatively correlated (r = -0.281; P = .001) with the BCdC in females. The multiple linear regression analysis showed smoking > consumption of offal > body mass index ≈ age as the most important risk factors for the BCdC in the selected population.

Sexual behaviour and risk factors for the acquisition of human papillomavirus infections in young people in Italy: suggestions for future vaccination policies

BackgroundHuman Papillomavirus (HPV) is the most common sexually transmitted infection. The main risk factors correlated with HPV infection are: early sexual debut, the number of partners, frequency and type of sexual contact and partner’s sexual histories.We surveyed sexual habits among young people in order to provide information that might orient decision-makers in adopting HPV multi-cohort vaccination policies.MethodsWe administered a questionnaire to students (14–24 years old) in five Italian cities.Results7298 questionnaires were analyzed (4962 females and 2336 males); 55.3% of females (95% CI 53.9–56.7) and 52.5% of males (95% CI 50.5–54.5) reported regular sexual activity. The mean age at sexual debut was 15.7 ± 1.6 and 15.6 ± 1.6 for females and males, respectively, and the median age was 16 for both sexes.With regard to contraceptive use during the last year, 63.6% of males and 62.8% of females responded affirmatively; 42.6% of males and 42.8% of females used condoms.ConclusionThe results reveal precocious sexual activity among respondents, with the mean age at first intercourse declining as age decreases. Condom use proved to be scant. Considering lifestyle-related risk factors, males appear to have a higher probability of acquiring HPV infection than females.These data support the importance of promoting multi-cohort HPV vaccination strategies for females up to 25 years of age. It is essential to improve vaccination coverage through different broad-spectrum strategies, including campaigns to increase awareness of sexually transmitted diseases and their prevention.