High-Sensitivity Cardiac Troponin and the Management of Congenital Heart Disease in Newborns and Infants.

BACKGROUND: Early cardiac interventions in newborns and infants suspected for congenital heart disease (CHD) decrease morbidity and mortality. After updating current evidence on the use of cardiac troponins (cTn) in the context of CHD for risk stratification at early ages, we discuss relevant issues, starting from the evidence that only the measurement of the cTnT form is useful in this population. CONTENT: In newborns/infants with CHD, the cTnT concentration increase is correlated with: (a) cardiac stress and hemodynamic parameters, but not with the type of CHD; (b) volume overload/right ventricular pressure overload; (c) postoperative hypoperfusion injury and mortality; and (d) effects of cardioprotective strategies. For infants with CHD, high-sensitivity cTnT (hs-cTnT) concentrations >25 ng/L are an independent predictor of poor outcomes. Transitioning from cTnT to hs-cTnT in newborns/infants improves the identification of: (a) physiopathological mechanisms and factors that increased hs-cTnT early after birth; (b) myocardial injury, even when subclinical; (c) identification of patients requiring immediate therapeutic interventions; and (d) 99th percentile upper reference limits (URLs). However, no reliable URLs are currently available to allow the detection of myocardial injury associated with CHD in newborns/infants. SUMMARY: Additional data evaluating the clinical value of hs-cTnT in the risk stratification of newborns/infants with CHD who may suffer myocardial injury is needed. Validating the measurement, possibly in amniotic fluid samples, and improving the interpretation of hs-cTnT concentrations in the prenatal period, at birth and within 1 year of age are crucial to change CHD mortality/morbidity trends in the pediatric population.

Public health indicators for cerebral palsy: A European collaborative study of the Surveillance of Cerebral Palsy in Europe network.

BACKGROUND: Public health indicators (PHIs) play an increasingly important role in health policy decision-making. Although cerebral palsy (CP) is the commonest physical disability in children, its impact at population level has not been systematically measured so far. OBJECTIVES: We aimed to propose six PHIs for CP designed to annually document the extent of CP and effectiveness of perinatal organisation, the burden of this condition, access to health services and preventive health strategies in the post-neonatal period and to report on the latest updated estimations using population-based data routinely collected by European CP registries. METHODS: The study included children with CP born between 2002 and 2011. Harmonised data (number of cases, functional profile, imaging) were extracted from the Surveillance of Cerebral Palsy in Europe (SCPE) database. Eligibility criteria for analyses were applied separately for each indicator by selecting registries, birth years and CP cases. Current estimates were based on the last 3 birth years, while trends were reported over a 10-year period. All analyses were descriptive. Sensitivity analyses were carried out to examine the stability of the results using various thresholds of percentages of missing values. RESULTS: Analyses were performed on a total of 8621 children with CP from 12 to 17 SCPE registries. A decreasing prevalence of pre/perinatal CP overall, as well as in preterm and full-term-born children, was observed. The burden of the condition was strongly dependent on CP subtype and the presence of associated impairments. Access to brain imaging ranged from 80% to 100% depending on registries. The overall prevalence of post-neonatally acquired CP was approximately 0.8 per 10,000 live births over the study period. CONCLUSIONS: Population-based CP registries can provide data that are relevant for generating key outcomes of interest at the population level, thus potentially contributing to improving public health policies for children with disabilities.

Epidemiology of Pierre-Robin sequence in Europe: A population-based EUROCAT study.

BACKGROUND: Pierre Robin sequence (PRS) is a rare congenital anomaly. Respiratory disorders and feeding difficulties represent the main burden. OBJECTIVE: The aim of this study was to investigate the epidemiology of PRS using a cohort of cases from EUROCAT, the European network of population-based registries of congenital anomalies. METHODS: We analysed cases of PRS born in the period 1998-2017 collected by 29 population-based congenital anomaly registries in 17 different countries. We calculated prevalence estimates, prenatal detection rate, survival up to 1 week, and proportions of associated anomalies. The effect of maternal age was tested using a Poisson regression model. RESULTS: Out of 11 669 155 surveyed births, a total of 1294 cases of PRS were identified. The estimate of the overall prevalence was 12.0 per 100 000 births (95% CI 9.9, 14.5). There was a total of 882 (68.2%) isolated cases, and the prevalence was 7.8 per 100 000 births (95% CI 6.7, 9.2). A total of 250 cases (19.3%) were associated with other structural congenital anomalies, 77 cases (6.0%) were associated with chromosomal anomalies and 77 (6.0%) with genetic syndromes. The prenatal detection rate in isolated cases was 12.0% (95% CI 9.8, 14.5) and increased to 16.0% (95% CI 12.7, 19.7) in the sub-period 2008-2017. The prevalence rate ratio of non-chromosomal cases with maternal age ≥35 was higher than in cases with maternal age <25 for total (PRR 1.26, 95% CI 1.05, 1.51) and isolated cases (PRR 1.33, 95% CI 1.00, 1.64). Survival of chromosomal cases (94.2%) and multiple anomaly cases (95.3%) were lower than survival of isolated cases (99.4%). CONCLUSIONS: This epidemiological study using a large series of cases of PRS provides insights into the epidemiological profile of PRS in Europe. We observed an association with higher maternal age, but further investigations are needed to test potential risk factors for PRS.

Spectrum of congenital anomalies among VACTERL cases: a EUROCAT population-based study.

BACKGROUND: The VACTERL (Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula, Renal anomalies, Limb abnormalities) association is the non-random occurrence of at least three of these congenital anomalies: vertebral, anal, cardiac, tracheo-esophageal, renal, and limb anomalies. Diagnosing VACTERL patients is difficult, as many disorders have multiple features in common with VACTERL. The aims of this study were to clearly outline component features, describe the phenotypic spectrum among the largest group of VACTERL patients thus far reported, and to identify phenotypically similar subtypes. METHODS: A case-only study was performed assessing data on 501 cases recorded with VACTERL in the JRC-EUROCAT (Joint Research Centre-European Surveillance of Congenital Anomalies) central database (birth years: 1980-2015). We differentiated between major and minor VACTERL features and anomalies outside the VACTERL spectrum to create a clear definition of VACTERL. RESULTS: In total, 397 cases (79%) fulfilled our VACTERL diagnostic criteria. The most commonly observed major VACTERL features were anorectal malformations and esophageal atresia/tracheo-esophageal fistula (both occurring in 62% of VACTERL cases), followed by cardiac (57%), renal (51%), vertebral (33%), and limb anomalies (25%), in every possible combination. Three VACTERL subtypes were defined: STRICT-VACTERL, VACTERL-LIKE, and VACTERL-PLUS, based on severity and presence of additional congenital anomalies. CONCLUSION: The clearly defined VACTERL component features and the VACTERL subtypes introduced will improve both clinical practice and etiologic research.

Epidemiology of achondroplasia: A population-based study in Europe.

Achondroplasia is a rare genetic disorder resulting in short-limb skeletal dysplasia. We present the largest European population-based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. All cases of achondroplasia notified to 28 EUROCAT registries (1991-2015) were included in the study. Prevalence, birth outcomes, prenatal diagnosis, associated anomalies, and the impact of paternal and maternal age on de novo achondroplasia were presented. The study population consisted of 434 achondroplasia cases with a prevalence of 3.72 per 100,000 births (95%CIs: 3.14-4.39). There were 350 live births, 82 terminations of pregnancy after prenatal diagnosis, and two fetal deaths. The prenatal detection rate was significantly higher in recent years (71% in 2011-2015 vs. 36% in 1991-1995). Major associated congenital anomalies were present in 10% of cases. About 20% of cases were familial. After adjusting for maternal age, fathers >34 years had a significantly higher risk of having infants with de novo achondroplasia than younger fathers. Prevalence was stable over time, but regional differences were observed. All pregnancy outcomes were included in the prevalence estimate with 80.6% being live born. The study confirmed the increased risk for older fathers of having infants with de novo achondroplasia.

Fall prevention: is the STRATIFY tool the right instrument in Italian Hospital inpatient? A retrospective observational study.

BACKGROUND: Although several risk assessment tools are in use, uncertainties on their accuracy in detecting fall risk already exist. Choosing the most accurate tool for hospital inpatient is still a challenge for the organizations. We aimed to retrospectively assess the appropriateness of a fall risk prevention program with the STRATIFY assessment tool in detecting acute-care inpatient fall risk. METHODS: Number of falls and near falls, occurred from January 2014 to March 2015, was collected through the incident reporting web-system implemented in the hospital's intranet. We reported whether the fall risk was assessed with the STRATIFY assessment tool and, if so, which was the judgement. Primary outcome was the proportion of inpatients identified as high risk of fall among inpatients who fell (True Positive Rate), and the proportion of inpatients identified as low-risk that experienced a fall howsoever (False Negative Rate). Characteristics of population and fall events were described among subgroups of low risk and high risk inpatients. RESULTS: We collected 365 incident reports from 40 hospital units, 349 (95.6%) were real falls and 16 (4.4%) were near falls. The fall risk assessment score at patient's admission had been reported in 289 (79%) of the overall incident reports. Thus, 74 (20.3%) fallers were actually not assessed with the STRATIFY, even though the majority of them presented risk recommended to be assessed. The True Positive Rate was 35.6% (n = 101, 95% CI 30% - 41.1%). The False Negative Rate was 64.4% (n = 183, 95% CI 58.9%-70%) of fallers, nevertheless they incurred in a fall. The STRATIFY mean score was 1.3 ± 1.4; the median was 1 (IQQ 0-2). CONCLUSIONS: The prevention program using only the STRATIFY tool was found to be not adequate to screen our inpatients population. The incorrect identification of patients' needs leads to allocate resources to erroneous priorities and to untargeted interventions, decreasing healthcare performance and quality.

Epidemiology of Serratia marcescens infections in NICU of a Teaching and Research Hospital in Northern Italy.

BACKGROUND: Serratia marcescens (Sm) is a known cause of infection and colonization in neonates receiving intensive care. The aim of this study was to identify the risk factors for colonization and infection with Sm in Neonatal Intensive Care Unit (NICU) of a tertiary care Hospital. METHODS: A case-control study was conducted from January to December 2011 in neonates admitted to the NICU. Cases are patients with a microbiologically confirmed infection or colonization, controls were randomly chosen among patients admitted to the same NICU. RESULTS: Globally, 39 acquired infections or colonizations were identified. Among factors related to pregnancy, only premature delivery was independently associated to the risk of infection; as well as mechanical ventilation and catheterization for parenteral nutrition, considering indwelling devices. Prolonged administration with antibiotics were also related to the risk of infection. Among Sm strains which have been tested to antibiotics, all have been resistant to amoxicillin/clavulanic acid and to colistin. CONCLUSIONS: This study confirms the association between Sm infection or colonization and low gestational age. Invasive medical devices and medications, strictly necessary in care-support of preterm neonates, are likely related to Sm infection too. Preventive control strategies are expected to be effective in the control of Sm spread in NICUs.

Maternal age and the prevalence of congenital heart defects in Europe, 1995-2015: A register-based study.

BACKGROUND: Evidence on the direction and strength of association between maternal age and the prevalence of congenital heart defects (CHD) in different age group categories is conflicting. Some studies have illustrated different trends with an increase in prevalence in younger and older age groups while other studies have reported a linear relationship. Given the increase in maternal age over recent years, it is important to study the CHD prevalence by maternal age. OBJECTIVES: To examine the association between maternal age and the prevalence of CHD in Europe between 1995 and 2015 using population-based data from 24 registries belonging to the European Surveillance of Congenital Anomalies (EUROCAT) network. METHODS: Associations over time of all nonsyndromic CHD according to maternal age category and for three CHD severity groupings (severity group I: very severe; severity group II: severe; severity group III: less severe) were examined using Bayesian multilevel Poisson regression modeling. Further subgroup analyses were undertaken within four maternal age-bands: ≤24, 25-29, 30-34 and 35-44 years. Descriptive summaries are also presented. RESULTS: There were 51,608 nonsyndromic CHD cases in Europe over the 20-year study period. Total prevalence for all CHD combined was increased for younger mothers (≤24 years) and for mothers 35-44 years of age when compared with mothers aged 25-29 years (reference group) (IRR: 1.05, 95% CI: 1.02, 1.07). The total prevalence was increased for severity group I (very severe) only for younger mothers compared to those aged 25-29 years (IRR: 1.14, 95% CI: 1.04, 1.23). We found an increased prevalence of the following CHD subtypes: double outlet right ventricle (IRR:1.33, 95% CI: 1.09, 1.60), hypoplastic left heart syndrome (IRR: 1.18, 95% CI: 1.05, 1.32), hypoplastic right heart syndrome (IRR: 1.41, 95% CI: 1.05, 1.84), atrioventricular septal defect (IRR: 1.15, 95% CI: 1.01, 1.32), coarctation of aorta (IRR: 1.15, 95% CI: 1.03, 1.28) and atrial septal defect (IRR: 1.08, 95% CI: 1.02, 1.13). For older mothers (35-44 years) compared to the reference category, we observed an increased risk in the prevalence for severity group II (IRR: 1.09, 95% CI: 1.03, 1.14), severity group III (IRR: 1.05, 95% CI: 1.01, 1.08) and an increased prevalence of the CHD subtypes: Pulmonary valve stenosis (IRR: 1.22, 95% CI: 1.09, 1.34), ASD (IRR: 1.07, 95% CI: 1.02, 1.13), CoA (IRR: 1.18, 95% CI: 1.06, 1.32) and Tetralogy of Fallot (IRR: 1.14, 95% CI: 1.01, 1.28). Finally, for all age categories compared to the reference category, different associations of ASD and an increased prevalence of CoA was also observed. CONCLUSIONS: Based on data for cases of CHD from 24 European population-based registries, evidence of a positive association between maternal age and the total prevalence of CHD for younger (≤24 years old) and older (35-44 years old) mothers was observed. The results suggest that young maternal age (≤24 years old) is a factor associated with severe CHD phenotypes while a positive association between advanced maternal age (35-44 years old) and mild CHD phenotypes was observed.

Prevalence of congenital heart defects in Europe, 2008-2015: A registry-based study.

BACKGROUND: The total prevalence of congenital heart defects (CHDs) varies by populations and over time. Studies that examine trends in the prevalence of CHD in different regions may shed light on our understanding of the occurrence of CHD and the impact of different risk factors. OBJECTIVES: To examine trends in total and live birth prevalence of nonsyndromic CHD in Europe between the years 2008 and 2015 and to investigate if the decreasing trend reported by previous studies is continuing. METHODS: Cases of CHD delivered between January 1, 2008 and December 31, 2015 notified to 25 population-based EUROCAT (European Surveillance of Congenital Anomalies) registries in 14 countries, formed the population-based case-series. Prevalence (total/live) rates and 95% confidence intervals were calculated as the number of cases per 10,000 births (live and stillbirths). Time trends in prevalence of all nonsyndromic CHDs and for three CHD severity groups (very severe, severe, and less severe) were plotted using a Poisson regression multilevel approach. RESULTS: The total prevalence of nonsyndromic CHD was 57.1 per 10,000 births (live births and stillbirths) for the 8-year period and remained stable across the three CHD severity groups while the live birth prevalence was 60.2 per 10,000 births. There was considerable variation in the reported total CHD prevalence and the direction of trends by registry. A decreasing prevalence of CHD was observed for the Norway and England/Wales registries, whereas the CHD prevalence increased for registries in Italy and Croatia. CONCLUSIONS: The total prevalence of CHD in Europe between the years 2008 and 2015 remained stable for all CHD and across the three CHD severity groups. The decreasing trend reported by previous studies has not continued. However, we found significant differences in the total and live birth prevalence by registry.

Cardiovascular events in statin recipients: impact of adherence to treatment in a 3-year record linkage study.

PURPOSE: In the general population, lack of adherence to statin therapy remains a widespread phenomenon and an important matter of concern both in terms of cost-effectiveness and risk-benefit profile. This study aimed to evaluate the occurrence of cardiovascular events in Italian statin recipients, focussing on the relationship between degree of adherence to therapy and occurrence of events in a 3-year follow-up. METHODS: Our cohort consisted of all patients from Emilia Romagna (4,027,275 inhabitants) who received statin prescriptions in January-February 2005 and who were followed for up to 36 months for cardiovascular hospital admission (i.e. coronary disease, cerebrovascular accidents, peripheral arthropathy), adherence to statin treatment (proportion of days covered: ≥ 80%) and use of other cardiovascular drugs. The relationship between adherence and cardiovascular events was analysed by multivariate logistic regression; age, sex, other cardiovascular drugs and previous events were covariates of the model. RESULTS: Patients non-adherent to a statin regimen over the 3-year period (76% of the cohort) had higher odds of events, irrespective of risk factors, by more than 40% when compared with adherent patients. Odds of events were in particular: strongly non-adherent, adjOR=1.19 (CI95% 1.15-1.23), slightly non-adherent, adjOR =1.25 (1.21-1.30), highly variable in the amount of statins received, adjOR=1.69 (1.62-1.77). CONCLUSIONS: This study shows the key role of adherence to statins in cardiovascular prevention at any level of risk. Appropriateness of statin use needs not only careful selection of patients to be treated, but also cooperation between patient and physician to ensure continued drug use whenever treatment is appropriate.

Epidemiology of congenital cerebral anomalies in Europe: a multicentre, population-based EUROCAT study.

OBJECTIVES: To describe the epidemiology and geographical differences in prevalence of congenital cerebral anomalies in Europe. DESIGN AND SETTING: Congenital cerebral anomalies (International Classification of Diseases, 10th Revision code Q04) recorded in 29 population-based EUROCAT registries conducting surveillance of 1.7 million births per annum (29% of all European births). PARTICIPANTS: All birth outcomes (live births, fetal deaths from 20 weeks gestation and terminations of pregnancy after prenatal diagnosis of a fetal anomaly (TOPFA)) from 2005 to 2014. MAIN OUTCOME MEASURES: Prevalence, proportion of associated non-cerebral anomalies, prenatal detection rate. RESULTS: 4927 cases with congenital cerebral anomalies were identified; a prevalence (adjusted for under-reporting) of 9.8 (95% CI: 8.5 to 11.2) per 10 000 births. There was a sixfold difference in prevalence across the registries. Registries with higher proportions of prenatal diagnoses had higher prevalence. Overall, 55% of all cases were liveborn, 3% were fetal deaths and 41% resulted in TOPFA. Forty-eight per cent of all cases were an isolated cerebral anomaly, 25% had associated non-cerebral anomalies and 27% were chromosomal or part of a syndrome (genetic or teratogenic). The prevalence excluding genetic or chromosomal conditions increased by 2.4% per annum (95% CI: 1.3% to 3.5%), with the increases occurring only for congenital malformations of the corpus callosum (3.0% per annum) and 'other reduction deformities of the brain' (2.8% per annum). CONCLUSIONS: Only half of the cases were isolated cerebral anomalies. Improved prenatal and postnatal diagnosis may account for the increase in prevalence of congenital cerebral anomalies from 2005 to 2014. However, major differences in prevalence remain between regions.

Use of fresh-frozen plasma in 2012 at the Fondazione Ca' Granda Hospital of Milan: assessment of appropriateness using record linkage techniques applied to data routinely recorded in various hospital information systems.

BACKGROUND: The Quality Unit of a research and teaching hospital in Milan assessed the increased clinical use of fresh-frozen plasma in patients treated during 2012 in order to evaluate the appropriateness of this use. MATERIALS AND METHODS: For each patient in the study, a pathology profile was generated by means of record linkage techniques involving data collected through different information systems. Patients' information was combined using the patient identifier key generating pathology profiles exported to an Excel file. The profiles were reviewed by two haematologists who identified 101 potentially inappropriate treatments for which the medical records had to be reviewed manually. RESULTS: In 2012, 490 patients were transfused and for 473 cases the automatic record linkage provided a complete profile. The information relating to the remaining patients did not match, mainly because the patients underwent outpatient procedures for which clinical information is not automatically recorded. In the overall audit only 13 treatments were judged inappropriate. DISCUSSION: Our study supports the view that record linkage techniques applied to data routinely recorded in different hospital information systems could be potentially extended to support clinical audits, enabling the generation of automated patient profiles that can be easily evaluated, relegating manual checks on medical records to doubtful cases only. Moreover, the method applied in this study allows the analysis of a full set of cases instead of sample surveys, increasing the robustness of the audit results.

A sustainable solution for the activities of the European network for surveillance of congenital anomalies: EUROCAT as part of the EU Platform on Rare Diseases Registration.

The European Commission through its Directorates-General Joint Research Centre (DG JRC) and Health and Food Safety (DG SANTE) is developing the European Platform on Rare Diseases Registration (EU RD Platform) with the objective to set European-level standards for data collection and data sharing. In the field of rare diseases the EU RD Platform will be a source of information on available rare disease patient data with large transnational European coverage. One main function of the EU RD Platform is to enable interoperability for the >600 existing RD registries in Europe. The second function is to offer a sustainable solution for two large European surveillance networks: European Surveillance of Congenital Anomalies (EUROCAT) and Surveillance of Cerebral Palsy in Europe (SCPE). EUROCAT is European network of population-based registries for the epidemiological surveillance of congenital anomalies. It covers about one third of the European birth population. The Central Database contains about 800,000 cases with congenital anomalies among livebirths, stillbirths and terminations of pregnancy, reported using the same standardised classification and coding. These high quality data enables epidemiological surveillance of congenital anomalies, which includes estimating prevalence, prenatal diagnosis and perinatal mortality rates and the detection of teratogenic exposures among others. The network also develops recommendations for primary prevention in the Rare Diseases National Plans for medicinal drugs, food/nutrition, lifestyle, health services, and environmental pollution. The network has received the European Commission's support since its inception. In order to offer a sustainable solution for the continuation of EUROCAT activities, it was agreed that EUROCAT would become part of the EU RD Platform. In 2015, the European level-coordination activities and the Central Database were transferred to the DG JRC, where the JRC-EUROCAT Central Registry is now located. This paper describes the functioning of EUROCAT in the new setting, and gives an overview of the activities and the organisation of the JRC-EUROCAT Central Registry.

Beckwith Wiedemann syndrome: A population-based study on prevalence, prenatal diagnosis, associated anomalies and survival in Europe.

Beckwith Wiedemann syndrome is a complex developmental disorder characterized by somatic overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycemia, and predisposition to embryonal tumors. We present epidemiological and clinical aspects of patients with Beckwith Wiedemann syndrome diagnosed prenatally or in the early years of life, using data from EUROCAT (European Surveillance of Congenital Anomalies) registries. The study population consisted of 371 cases identified between January 1990 and December 2015 in 34 registries from 16 European countries. There were 15 (4.0%) terminations of pregnancy after prenatal detection of severe anomaly/anomalies, 10 fetal deaths (2.7%), and 346 (93.3%) live-births. Twelve (3.6%) of the 330 live-births with available information on survival died in the first week of life, of those eleven (91.6%) were preterm. First-year survival rate was 90.9%. Prematurity was present in 40.6% of males and 33.9% of females. Macrosomia was found in 49.2% and 43.3% of preterm males and females, respectively. Of term newborns, 41.1% of males and 24% of females were macrosomic. Out of 353 cases with known time of diagnosis, 39.9% were suspected prenatally, 36.3% at birth, 7.6% were diagnosed in the first week of life, and 16.2% in the first year of life. The mean gestational age at prenatal diagnosis by obstetric ultrasound was 19.8 ±â€¯6.2 (11-39) gestational weeks. The mean prenatal diagnosis of cases where parents opted for termination of pregnancy was 15.3 ±â€¯2.4 (11-22) gestational weeks, and the mean gestational age at termination was 19.3 ±â€¯4.1 (13-26) gestational weeks. The prenatal detection rate was 64.1% (141/220) with no significant change over time. There were 12.7% of familial cases. The study confirmed the association of assisted reproductive technologies with Beckwith Wiedemann syndrome, as 7.2% (13/181) of patients were conceived by one of the methods of assisted reproductive technologies, which was three times higher compared to the general population of the countries included in the study. Twin pregnancies of undetermined zygosity were recorded in 5.7% (21/365) cases, and were on average three to four times more common than in European countries that participated in the study. The estimated mean prevalence of classical Beckwith Wiedemann syndrome in Europe was 3.8 per 100,000 births or 1:26,000 births.

Prevalence of valproate syndrome in Europe from 2005 to 2014: A registry based multi-centre study.

Women with epilepsy need to continue to take anticonvulsants during their pregnancies to prevent seizures from occurring. Since the 1980's, it has been known that the use of valproate (an anticonvulsant) in the first trimester of pregnancy is associated with an increased risk of spina bifida. Recent studies have also demonstrated increased risks of other congenital anomalies as well as a risk of cognitive impairment. Doctors in the EU are now advised not to prescribe valproate in pregnant women, in women who can become pregnant or in girls unless other treatments are ineffective or not tolerated. This study aimed to determine if there has been a reduction in the numbers of babies born with valproate syndrome in Europe from 2005 to 2014. Data from 15 European congenital anomaly registries, who are members of EUROCAT (A European network of population-based registries for the epidemiologic surveillance of congenital anomalies), identified 28 cases of valproate syndrome in 2.74 million births from 2005 to 2014. The prevalence of valproate syndrome in Europe significantly decreased from 0.22 per 10,000 births in 2005/6 to 0.03 per 10,000 births in 2013/14. One registry, Ile de la Reunion, had the majority of cases (17). After excluding these cases there still remained a decreasing trend even though it no longer reached statistical significance due to the small number of cases. This study emphasises the continued need for European collaboration in analysing rare exposures and rare anomalies.

Epidemiology of septo-optic dysplasia with focus on prevalence and maternal age - A EUROCAT study.

Septo-optic nerve dysplasia is a rare congenital anomaly with optic nerve hypoplasia, pituitary hormone deficiencies and midline developmental defects of the brain. The clinical findings are visual impairment, hypopituitarism and developmental delays. The aim of this study was to report prevalence, associated anomalies, maternal age and other epidemiological factors from a large European population based network of congenital anomaly registries (EUROCAT). Data from 29 full member registries for the years 2005-2014 were included, covering 6.4 million births. There were 99 cases with a diagnosis of septo-optic dysplasia. The prevalence of septo-optic dysplasia in Europe was calculated to lie between 1.9 and 2.5 per 100,000 births after adjusting for potential under-reporting in some registries. The prevalence was highest in babies of mothers aged 20-24 years of age and was significantly higher in UK registries compared with other EUROCAT registries (P = 0.021 in the multilevel model) and the additional risk for younger mothers was significantly greater in the UK compared to the rest of Europe (P = 0.027). The majority of septo-optic dysplasia cases were classified as an isolated cerebral anomaly (N = 76, 77%). Forty percent of diagnoses occurred in fetuses with a prenatal diagnosis. The anomaly may not be visible at birth, which is reflected in that 57% of the postnatal diagnoses occurred over 1 month after birth. This is the first population based study to describe the prevalence of septo-optic dysplasia in Europe. Septo-optic dysplasia shares epidemiological patterns with gastroschisis and this strengthens the hypothesis of vascular disruption being an aetiological factor for septo-optic dysplasia.

Three-year analysis of repeated laboratory tests for the markers total cholesterol, ferritin, vitamin D, vitamin B12 , and folate, in a large research and teaching hospital in Italy.

RATIONALE, AIMS AND OBJECTIVES: The increasing number of diagnostic tests requests all over the world is a problem that can partially be explained by inappropriate testing. Impact on the total costs of health systems becomes relevant when tests are performed in a large amount. In this paper, retesting of total cholesterol, ferritin, vitamin B12 , vitamin D, and folate is assessed. METHODS: The Quality Unit of Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano (Fondazione) decided to perform a first assessment of the appropriate use of the laboratory tests cholesterol, ferritin, vitamin B12 , vitamin D, and folate focusing on the retesting interval for the same patient in the time period January 1, 2012, to December 31, 2014, in every care setting. The minimum retesting intervals were chosen following the ACB recommendations. The Fondazione is a research and teaching hospital with 3 emergency units (adult, pediatric, and obstetric), kidney, liver, lung, cornea, and bone marrow transplant centers and a medical school. Record linkage of laboratory records selected for the time interval January 1, 2012, to December 31, 2014, was applied using tax code. For each marker, the distribution of retesting intervals was evaluated for every year and the total period. With the same record linkage variable, requests on inpatients were identified from hospital discharge records. A cost analysis of inappropriate retesting was performed for every test. RESULTS: We examined 466 035 requests for 113 019 patients. Proportions of tests judged potentially inappropriate varied between 8.1% for 1,25-dihydroxy vitamin D and 37.1% for total cholesterol. The rates of inappropriate tests from year to year never showed significant decrease, and the maximum increase corresponded to an odds ratio of 1.85 (95% CI, 1.36-2.51) for 1,25-dihydroxy vitamin D from 2012 to 2013. Calculated loss of money was approximately €500 000 in the 3 years. CONCLUSIONS: Inappropriate requests represent a waste of time and money resources. Our analysis highlighted economically unacceptable rates of inappropriate retesting, with no evidence of decreasing trend. Actions to raise awareness in clinicians or automated electronic solutions are necessary to limit unnecessary test repetitions.

Widen NomoGram for multinomial logistic regression: an application to staging liver fibrosis in chronic hepatitis C patients.

The interpretation of regression models results can often benefit from the generation of nomograms, 'user friendly' graphical devices especially useful for assisting the decision-making processes. However, in the case of multinomial regression models, whenever categorical responses with more than two classes are involved, nomograms cannot be drawn in the conventional way. Such a difficulty in managing and interpreting the outcome could often result in a limitation of the use of multinomial regression in decision-making support. In the present paper, we illustrate the derivation of a non-conventional nomogram for multinomial regression models, intended to overcome this issue. Although it may appear less straightforward at first sight, the proposed methodology allows an easy interpretation of the results of multinomial regression models and makes them more accessible for clinicians and general practitioners too. Development of prediction model based on multinomial logistic regression and of the pertinent graphical tool is illustrated by means of an example involving the prediction of the extent of liver fibrosis in hepatitis C patients by routinely available markers.

Feasibility study for the introduction of a new treatment method for benign thyroid nodules in a teaching and research hospital.

RATIONALE, AIMS AND OBJECTIVES: Numerous scientific publications have confirmed that percutaneous laser thermal ablation (LTA) represents a possible therapeutic option in selected patients with benign thyroid nodules. A study was carried out to evaluate the feasibility of adopting the LTA technique to treat benign thyroid nodules in a teaching and research hospital in northern Italy. METHODS: A cost analysis from a company's perspective determined the impact of adoption of the new technique on the overall Hospital budget, considering currently available equipment, infrastructure and personnel, equipment costs and treatment tariffs. RESULTS: The cost analysis shows that, strictly from an economic point of view, any provision of the LTA technique will result as a loss on the Hospital's balance sheet. However, it does not estimate the extent of the impact on the overall budget because it did not evaluate the savings that such a technique would make with respect to alternative therapeutic treatments. Therefore, the Hospital policy management decided to extend the current agreement with a private authorized health care structure that already carries out LTA. Also, although difficult to express in economic terms, this new technique would undoubtedly raise the profile and enhance the reputation of the Hospital. CONCLUSIONS: Using the new technique in these patients could cut costs for the entire regional health care system, widen the experience of the Hospital's endocrinology team and offer the potential for the procedure also to be provided by operators on a freelance basis within the Hospital.

The Italian institutional accreditation model for Haemophilia Centres.

BACKGROUND: In Italy, basic health needs of patients with inherited bleeding disorders are met by a network of 50 haemophilia centres belonging to the Italian Association of Haemophilia Centres. Further emerging needs, due to the increased life expectancy of this patient group, require a multi-professional clinical management of the disease and provide a challenge to the organisation of centres.In order to achieve harmonised quality standards of haemophilia care across Italian Regions, an institutional accreditation model for haemophilia centres has been developed. MATERIAL AND METHODS: To develop an accreditation scheme for haemophilia centres, a panel of experts representing medical and patient bodies, the Ministry of Health and Regional Health Authorities has been appointed by the National Blood Centre. Following a public consultation, a technical proposal in the form of recommendations for Regional Health Authorities has been formally submitted to the Ministry of Health and has formed the basis for a proposal of Agreement between the Government and the Regions. RESULTS: The institutional accreditation model for Haemophilia Centres was approved as an Agreement between the Government and the Regions in March 2013. It identified 23 organisational requirements for haemophilia centres covering different areas and activities. DISCUSSION: The Italian institutional accreditation model aims to achieve harmonised quality standards across Regions and to implement continuous improvement efforts, certified by regional inspection systems. The identified requirements are considered as necessary and appropriate in order to provide haemophilia services as "basic healthcare levels" under the umbrella of the National Health Service. This model provides Regions with a flexible institutional accreditation scheme that can be potentially extended to other rare diseases.