Impact of the environment on the health: From theory to practice.

The Erice 56 Charter titled "Impact of the environment on the health: from theory to practice" was unanimously approved at the end of the 56th course of the "International School of Epidemiology and Preventive Medicine G. D'Alessandro" held from 3rd to November 7, 2019 in Erice - Sicily (Italy) and promoted by the Study Group of "Environment and Health" of the Italian Society of Hygiene, Preventive Medicine and Public Health. The course, that included lectures, open discussions and guided working groups, was aimed to provide a general training on epidemiological and toxicological aspects of the environmental health impact, to be used by public health professionals for risk assessment, without forgetting the risk communications. At the end of the course 12 key points were agreed among teachers and students: they underlined the need of specific training and research, in the perspective of "One Health" and "Global Health", also facing emerging scientific and methodological issues and focusing on communication towards stakeholders. This Discussion highlight the need to improve knowledge of Health and Environment topic in all sectors of health and environmental prevention and management.

Determinants of length of stay after cesarean sections in the Friuli Venezia Giulia Region (North-Eastern Italy), 2005-2015.

Since Italy has the highest cesarean section (CS) rate (38.1%) among all European countries, the containment of health care costs associated with CS is needed, along with control of length of hospital stay (LOS) following CS. This population based cross-sectional study aims to investigate LoS post CS (overall CS, OCS; planned CS, PCS; urgent/emergency CS, UCS), in Friuli Venezia Giulia (a region of North-Eastern Italy) during 2005-2015, adjusting for a considerable number factors, including various obstetric conditions/complications. Maternal and newborn characteristics (health care setting and timeframe; maternal health factors; child's size factors; child's fragility factors; socio-demographic background; obstetric history; obstetric conditions) were used as independent variables. LoS (post OCS, PCS, UCS) was the outcome measure. The statistical analysis was conducted with multivariable linear (LoS expressed as adjusted mean, in days) as well as logistic (adjusted proportion of LoS > 4 days vs. LoS ≤ 4 days, using a 4 day cutoff for early discharge, ED) regression. An important decreasing trend over time in mean LoS and LoS > ED was observed for both PCS and UCS. LoS post CS was shorter with parity and history of CS, whereas it was longer among non-EU mothers. Several obstetric conditions/complications were associated with extended LoS. Whilst eclampsia/pre-eclampsia and preterm gestations (33-36 weeks) were predominantly associated with longer LoS post UCS, for PCS LoS was significantly longer with birthweight 2.0-2.5 kg, multiple birth and increasing maternal age. Strong significant inter-hospital variation remained after adjustment for the major clinical conditions. This study shows that routinely collected administrative data provide useful information for health planning and monitoring, identifying inter-hospital differences that could be targeted by policy interventions aimed at improving the efficiency of obstetric care. The important decreasing trend over time of LoS post CS, coupled with the impact of some socio-demographic and obstetric history factors on LoS, seemingly suggests a positive approach of health care providers of FVG in decision making on hospitalization length post CS. However, the significant role of several obstetric conditions did not influence hospital variation. Inter-hospital variations of LoS could depend on a number of factors, including the capacity to discharge patients into the surrounding non-acute facilities. Further studies are warranted to ascertain whether LoS can be attributed to hospital efficiency rather than the characteristics of the hospital catchment area.

Author Correction: A Systematic Evaluation of Hospital Performance of Childbirth Delivery Modes and Associated Factors in the Friuli Venezia Giulia Region (North-Eastern Italy), 2005-2015.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Understanding Factors Leading to Primary Cesarean Section and Vaginal Birth After Cesarean Delivery in the Friuli-Venezia Giulia Region (North-Eastern Italy), 2005-2015.

Although there is no evidence that elevated rates of cesarean sections (CS) translate into reduced maternal/child perinatal morbidity or mortality, CS have been increasingly overused almost everywhere, both in high and low-income countries. The primary cesarean section (PCS) has become a major driver of the overall CS (OCS) rate, since it carries intrinsic risk of repeat CS (RCS) in future pregnancies. In our study we examined patterns of PCS, pl compared with planned TOLAC anned PCS (PPCS), vaginal birth after 1 previous CS (VBAC-1) and associated factors in Friuli Venezia Giulia (FVG), a region of North-Eastern Italy, collecting data from its 11 maternity centres (coded from A to K) during 2005-2015. By fitting three multiple logistic regression models (one for each delivery mode), we calculated the adjusted rates of PCS and PPCS among women without history of CS, whilst the calculation of the VBAC rate was restricted to women with just one previous CS (VBAC-1). Results, expressed as odds ratio (OR) with 95% confidence interval (95%CI), were controlled for the effect of hospital, calendar year as well as several factors related to the clinical and obstetric conditions of the mothers and the newborn, the obstetric history and socio-demographic background. In FVG during 2005-2015 there were 24,467 OCS (rate of 24.2%), 19,565 PCS (19.6%), 7,736 PPCS (7.7%) and 2,303 VBAC-1 (28.4%). We found high variability of delivery mode (DM) at hospital level, especially for PCS and PPCS. Breech presentation was the strongest determinant for PCS as well as PPCS. Leaving aside placenta previa/abuptio placenta/ante-partum hemorrhage, further significant factors, more importantly associated with PCS than PPCS were non-reassuring fetal status and obstructed labour, followed by (in order of statistical significance): multiple birth; eclampsia/pre-eclampsia; maternal age 40-44 years; placental weight 600-99 g; oligohydramios; pre-delivery LoS 3-5 days; maternal age 35-39 years; placenta weight 1,000-1,500 g; birthweight < 2,000 g; maternal age ≥ 45 years; pre-delivery LoS ≥ 6 days; mother's age 30-34 years; low birthweight (2,000-2,500 g); polyhydramnions; cord prolaspe; ≥6 US scas performed during pregnancy and pre-term gestations (33-36 weeks). Significant factors for PPCS were (in order of statistical significance): breech presentation; placenta previa/abruptio placenta/ante-partum haemorrhage; multiple birth; pre-delivery LoS ≥ 3 days; placental weight ≥ 600 g; maternal age  40-44 years; ≥6 US scans performed in pregnancy; maternal age ≥ 45 and 35-39 years; oligohydramnios; eclampsia/pre-eclampsia; mother's age 30-34 years; birthweight <2,000 g; polyhydramnios and pre-term gestation (33-36 weeks). VBAC-1 were more likely with gestation ≥ 41 weeks, placental weight <500 g and especially labour analgesia. During 2005-2015 the overall rate of PCS in FVG (19.6%) was substantially lower than the corresponding figure reported in 2010 for the entire Italy (29%) and still slightly under the most recent national PCS rate for 2017 (22.2%). The VBAC-1 rate on women with history of one previous CS in FVG was 28.4% (25.3% considering VBAC on all women with at least 1 previous CS), roughly three times the Italian national rate of 9% reported for 2017. The discrepancy between the OCS rate at country level (38.1%) and FVG's (24.2%) is therefore mainly attributable to RCS. Although there was a marginal decrease of PCS and PPCS crudes rates over time in the whole region, accompained by a progressive enhancement of the crude VBAC rate, we found remarkable variability of DM across hospitals. To further contain the number of unnecessary PCS and promote VBAC where appropriate, standardized obstetric protocols should be introduced and enforced at hospital level. Decision-making on PCS should be carefully scrutinized, introducing a diagnostic second opinion for all PCS, particularly for term singleton pregancies with cephalic presentation and in case of obstructed labour as well as non-reassuring fetal status, grey areas potentially affected by subjective clinical assessment. This process of change could be facilitated with education of staff/patients by opinion leaders and prenatal counseling for women and partners, although clinical audits, financial penalties and rewards to efficient maternity centres could also be considered.

A Systematic Evaluation of Hospital Performance of Childbirth Delivery Modes and Associated Factors in the Friuli Venezia Giulia Region (North-Eastern Italy), 2005-2015.

Cesarean sections (CS) have become increasingly common in both developed and developing countries, raising legitimate concerns regarding their appropriateness. Since improvement of obstetric care at the hospital level needs quantitative evidence, using routinely collected health data we contrasted the performance of the 11 maternity centres (coded with an alphabetic letter A to L) of an Italian region, Friuli Venezia Giulia (FVG), during 2005-15, after removing the effect of several factors associated with different delivery modes (DM): spontaneous vaginal delivery (SVD), instrumental vaginal delivery (IVD), overall CS (OCS) and urgent/emergency CS (UCS). A multivariable logistic regression model was fitted for each individual DM, using a dichotomous outcome (1 = each DM; 0 = rest of hospital births) and comparing the stratum specific estimates of every term with their respective reference categories. Results were expressed as odds ratios (OR) with 95% confidence intervals (95%CI). The Benjamini-Hochberg (BH) false discovery rates (FDR) approach was applied to control alpha error due to the large number of statistical tests performed. In the entire FVG region during 2005-2015, SVD were 75,497 (69.1% out of all births), IVD were 7,281 (6.7%), OCS were 26,467 (24.2%) and UCS were 14,106 (12.9% of all births and 53.3% out of all CS). SVD were more likely (in descending order of statistical significance) with: higher number of previous livebirths; clerk/employed occupational status of the mother; gestational age <29 weeks; placentas weighing <500 g; stillbirth; premature rupture of membranes (PROM). IVD were predominantly more likely (in descending order of statistical significance) with: obstructed labour, non-reassuring fetal status, history of CS, labour analgesia, maternal age ≥35 and gestation >40 weeks. The principal factors associated with OCS were (in descending order of statistical significance): CS history, breech presentation, non-reassuring fetal status, obstructed labour, multiple birth, placental weight ≥ 600 g, eclampsia/pre-eclampsia, maternal age ≥ 35 and oligohydramnios. The most important risk factors for UCS were (in descending order of statistical significance): placenta previa/abruptio placenta/ antepartum hemorrage; non-reassuring fetal status, obstructed labour; breech presentation; PROM, eclampsia/pre-eclampsia; gestation 33-36 weeks; gestation 41+ weeks; oligohydramnios; birthweight <2,500 g, maternal age ≥ 35 and cord prolapse. After removing the effects of all other factors, we found great variability of DM rates across hospitals. Adjusting for all risk factors, all hospitals had a OCS risk higher than the referent (hospital G). Out of these 10 hospitals with increased adjusted risk of OCS, 9 (A, B, C, D, E, F, I, J, K) performed less SVD and 5 (A, C, D, I, J) less IVD. In the above 5 centres CS was therefore probably overused. The present study shows that routinely collected administrative data provide useful information for health planning and monitoring. Although the overall CS rate in FVG during 2005-15 was 24.2%, well below the corresponding average Italian national figure (38.1%), the variability of DM rates across FVG maternity centres could be targeted by policy interventions aimed at reducing the recourse to unnecessary CS. In some clinical conditions such as obstructed labor, non-reassuring fetal status, breech presentation, history of CS, higher maternal age and multiple birth, consideration may be given to more conservative DM. The overuse of CS in nulliparas and repeat CS (RCS) should be carefully monitored and subject to audit.

The Use of Integra Dermal Regeneration Template Versus Flaps for Reconstruction of Full-Thickness Scalp Defects Involving the Calvaria: A Cost-Benefit Analysis.

BACKGROUND: INTEGRA® Dermal Regeneration Template is a well-known and widely used acellular dermal matrix. Although it helps to solve many challenging problems in reconstructive surgery, the product cost may make it an expensive alternative compared to other reconstruction procedures. This retrospective study aims at comparing INTEGRA-based treatment to flap surgery in terms of cost and benefit. PATIENTS AND METHODS: We considered only patients treated for scalp defects with bone exposure in order to obtain two groups as homogeneous as possible. We identified two groups of patients: 17 patients treated with INTEGRA and 18 patients treated with flaps. All patients were admitted in our institution between 2004 and 2010, and presented a defect of the scalp following trauma or surgery for cancer, causing a loss of the soft tissues of the scalp with bone exposure without pericranium. To calculate the cost in constant euros of each treatment, three parameters were evaluated for each patient: cost of the surgical procedure (number of doctors and nurses involved, surgery duration, anesthesia, material used for surgery), hospitalization cost (hospitalization duration, dressings, drugs, topical agents), and outpatient cost (number of dressing changes, personnel cost, dressings type, anti-infective agents). The statistical test used in this study was the Wilcoxon Mann-Whitney (α = 0.05). RESULTS: No significant difference was characterized between the two groups for gender, age, presence of diabetes, mean defect size, and number of surgical procedures. All patients healed with good quality and durable closure. The median total cost per patient was €11,121 (interquartile range (IQR) 8327-15,571) for the INTEGRA group and €7259 (IQR 1852-24,443) for the flap group (p = 0.34). A subgroup of patients (six patients in the INTEGRA group and five patients in the flap group) showing defects larger than 100 cm2 were considered in a second analysis. Median total cost was €11,825 (IQR 10,695-15,751) for the INTEGRA group and €23,244 (IQR 17,348-26,942) for the flap group. CONCLUSION: Both treatments led to a good healing of the lesions with formation of soft and resistant tissue. No significant difference was characterized between the two groups for days of hospitalization and costs. In cases of patients with defects larger than 100 cm2 for whom major surgery is needed, the treatment with INTEGRA seemed to be less expensive than the treatment with free flaps or pedicle flaps. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the A5 online Instructions to Authors. www.springer.com/00266 .

Neuropsychological assessment at school-age and prenatal low-level exposure to mercury through fish consumption in an Italian birth cohort living near a contaminated site.

The relative effects of prenatal and postnatal low-level mercury exposure and fish intake on child neurodevelopment are still controversial. Limited evidence is available from Mediterranean populations. In this prospective study, we measured the Verbal and Performance IQ in Italian children at school-age who were resident in an area declared as a National contaminated site because of mercury pollution, taking into account the possible beneficial effect of fish consumption and potential confounders. A mother-child cohort made up of 242 children was established at birth in Northeastern Italy in 2001. Their mothers were interviewed approximately 2 months after delivery to determine type, quantity, and origin of fish consumed during pregnancy and about a number of mother, child and family characteristics. Total mercury (THg) and methyl mercury (MeHg) were assessed in maternal hair and breast milk and in the child's hair. When children reached 7-9 years of age, 154 (63.6%) parents gave consent to participate in a follow-up evaluation. On that occasion, a child's hair sample was collected to determine the current concentration of THg, mothers were asked to complete a self-administered questionnaire, and children underwent neuropsychological testing. Verbal IQ, performance IQ and full scale IQ were measured by the Wechsler Intelligence Scale for Children (WISC III) administered by psychologists at school or local health centers. Demographic, socioeconomic and lifestyle information, medical information of the child's family and the child's dietary habits were collected using a questionnaire filled in by mothers. Multivariable linear regression models were used to evaluate the association between prenatal THg exposure through fish consumption of mothers in pregnancy and children's IQ after adjustment for possible confounders such as fish consumption of mothers in pregnancy, child's fish consumption at follow-up, child's birthweight, maternal cigarette smoking during pregnancy, house size and property place of residence during pregnancy and gender. THg in the child's hair at 7 years of age was fairly correlated with THg in maternal hair at delivery (rs=0.35; p<0.0001) and was strongly correlated with child's seafood consumption (rs=0.50, p<0.0001). No differences in maternal THg levels were found when comparing children with low or extremely low or high or extremely high scores vs others, considering separately full scale, verbal, and performance IQs. Children born from mothers with hair THg levels greater than or equal to 2000ng/g had full scale, verbal and performance IQs which were 4-5 points lower than children born from women with lower THg levels, but these differences were not statistically significant. Fresh fish intake of mothers in pregnancy was slightly positively associated with full scale and performance but not so with verbal IQs. Canned fish showed to be negatively associated with all the outcome variables. Unexpectedly, children born to mothers from one town showed IQ scores significantly lower than the other children; however, none of the many variables considered in these analyses could explain this result. The relatively low Hg levels found in the biological samples did not provide evidence of high and extensive Hg exposure in this population. Although THg levels in maternal and child's biological samples are correlated with fish consumption, the effects of THg and fish on neurological outcomes go in opposite directions. These results do not allow to develop recommendations regarding fish consumption in pregnancy but suggest that keeping THg hair levels<2000ng/g might be desirable.

Prognostic factors and outcome of Epstein-Barr virus DNAemia in high-risk recipients of allogeneic stem cell transplantation treated with preemptive rituximab.

AIMS AND METHODS: This study assessed incidence, predictive factors, and outcome of Epstein-Barr virus (EBV) DNAemia in 100 recipients of allogeneic hematopoietic stem cell transplant. A total of 68 patients received anti-thymocyte globulin before unrelated grafts. RESULTS: Cumulative incidence of high-load EBV DNAemia defined by levels >10,000 copies/mL was 14% at 12 months. In multivariate analysis, a CD4+ T-lymphocyte count >50 µL at day +30 was the only factor significantly associated with a reduced risk of high-load EBV DNAemia. Thirteen of 16 patients with high viral loads were preemptively treated with rituximab and achieved EBV DNA negativity. Three patients had already developed post-transplant lymphoproliferative disorder (PTLD) at the time of detection of high EBV DNA loads, and they obtained complete response after rituximab infusions and chemotherapy. Patients with high EBV DNA load had a significantly higher transplant-related mortality (TRM) compared with patients with negative or low viral load (54% vs. 16%, P = 0.009) and a trend to lower overall survival (55% vs. 29%, P = 0.060). CONCLUSION: We conclude that CD4+ cell count at day +30 is a predictive factor for EBV DNAemia and may help identify patients requiring closer monitoring. Although only 3% of patients progressed to PTLD and were all successfully managed, EBV reactivation was associated with higher TRM, mainly because of infections.