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OBJECTIVESWe evaluated the long-term results of aortic root (AR) preservation and replacement in patients operated on for acute type A aortic dissection.METHODSOut of 302 patients discharged after repair of acute aortic dissection (1977–2019), 124 patients had an AR ≥40 mm, which was preserved in 84 (68%, group A) patients and replaced in 40 (32%, group B) patients. Group B patients were younger (mean age 57 ± 12 vs 62 ± 11 years, P = 0.07), with a mean AR of 47 vs 43 mm and ≥moderate aortic insufficiency in 65% vs 30%. Survival, causes of death and reoperations were analysed at mean follow-up of 9 ± 8 years (6 months to 40 years).RESULTSActuarial survival of discharged patients at 5, 10 and 15 years was 97% (0.89–0.99), 78% (0.67–0.90) and 75% (0.64–0.88) in group A, and 85% (0.71–0.95), 62% (0.44–0.78) and 57% (0.39–0.76) in group B (log-rank test P = 0.2). Nine patients in group A (7 patients for aortic insufficiency and dilatation of the root and 2 patients for pseudoaneurysm) and 1 patient of group B (pseudoaneurysm of the right coronary button) required proximal reoperation without deaths. At 5, 10 and 15 years, the cumulative incidence of proximal aortic reoperations was 5%, 9% and 25% in group A, and 0%, 3% and 3% in group B (P = 0.02). At multivariable analysis AR >45 mm [hazard ratio (HR) 6.8, P = 0.026] and age (HR 0.9, P = 0.016) were independently associated with proximal reoperation.CONCLUSIONSAR preservation in acute type A dissection showed acceptable long-term outcomes. Nevertheless, a more aggressive approach appears a valid option, especially in patients with AR diameter >45 mm.

Background The lack of epidemiological and clinical data is a major obstacle in health service planning for rare diseases. Patient registries are examples of real-world data that may fill the information gap. Objective We describe the Rare Disease Registry of the Friuli Venezia Giulia region of Italy and its potential for research and health planning. Methods The Rare Disease Registry data were linked with information on mortality, hospital discharges, ambulatory care, and drug prescriptions contained in administrative databases. All information is anonymous, and data linkage was based on a stochastic key univocal for each patient. Average annual costs owing to hospitalizations, outpatient care, and medications were estimated. Results Implementation of the Registry started in 2010, and 4250 participants were registered up to 2017. A total of 2696 patients were living in the region as of January 1, 2017. The overall raw prevalence of rare diseases was 22 per 10,000 inhabitants, with higher prevalence in the pediatric population. The most common disease groups were congenital malformations, chromosomal and genetic syndromes, and circulatory and nervous diseases. In 2017, 30 patients died, 648 were hospitalized, and 2355 received some type of ambulatory care. The total annual estimated cost was approximately €6.5 million, with great variability in the average patient cost across diseases. Conclusions The possibility of following the detailed real-world care experience of patients with each specific rare disease and assessing the costs related to each step in their care path represents a unique opportunity to identify inefficiencies, optimize care, and reduce waste of resources.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: 1. To assess the effectiveness, safety and appropriate dose regimen of ERT in people with MPS IV A. 2. To determine whether evidence from NRSIs (which potentially offers longer follow‐ups) can contribute to the ERT efficacy evidence‐base, and to determine the potential need for additional RCT evidence. 3. To consolidate recommendations for the design of future clinical trials.

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

Life expectancy of patients with glycogen storage disease (GSD) type I has improved considerably, opening new problems correlated with adult age. In females polycystic ovaries (PCOs) has been described as frequently associated with the disease, however successful pregnancies have been reported. Whether or not GSD I is associated with impaired reproductive function is still unclear.Data about female patients with GSD Ia and Ib, who were 16 years or older, were obtained from clinical records and interviews.A total of 32 women with GSD I (25 GSD Ia, 7 GSD Ib), median age 26 years (range 16-55), were included. 9/32 patients had delayed menarche, 17/32 had irregular cycles, 8/22 had documented polycystic ovaries. Five successful spontaneous pregnancies in four patients with GSD Ia and two in a woman with GSD Ib were reported. The latter had development and enlargement of hepatic adenomas during pregnancies.Despite the high prevalence of irregular menstruation cycles and polycystic ovaries, fertility seems not to be impaired in women with GSD I. During pregnancy monitoring for adenoma development is mandatory.

Osteopenia is described as a relevant sign of bone involvement in Gaucher disease (GD) both in pediatric and adult patients. Furthermore, abnormal bone metabolism is considered to play a role in growth and pubertal delay. To analyze the long-term effect of enzyme replacement therapy (ERT) on bone mineral density (BMD), a retrospective observational study was conducted in a cohort of 18 GD pediatric patients (13 males, 5 females; median age 9.2 years). They received biweekly infusions of 20-60 IU/kg of alglucerase/imiglucerase. Clinical, laboratory and imaging parameters were evaluated every 2 years. According to the International Society of Clinical Densitometry guidelines, a Z-score ≤ -2.0 was considered pathological. Nine patients (group P0) began ERT during infancy and nine (group P1) during puberty. At baseline, in three patients (16.6 %; 1P0, 2P1) Z-score was ≤ -2.0 (range -2.47 to -2.25). In patient P0 it normalized after 2 years, while in the 2P1 patients (splenectomized siblings) it persisted abnormal. The remaining 15 patients (83.4 %) always presented a normal value. In group P0, Z-score improved in infancy but showed a significant decrease during puberty, on the contrary it constantly improved in group P1. Furthermore, at baseline group P0 showed a higher median Z-score than group P1: 0.79 (0.38; 1.50) and -1.61 (-2.25; -1.56) respectively. The use of correct BMD standards to interpret bone loss during pediatric age suggests a limited significance of bone loss in these patients. Moreover, the persistence of residual disease activity may affect normal bone growth during puberty in GD populations.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is a well-accepted procedure for the diagnosis and biological characterization of breast carcinoma. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status have a strong prognostic and predictive value in invasive breast carcinoma (IBC). ThinPrep (TP) cytology, which uses an alcohol-based fixative, is increasingly being used for immunocytochemistry. In this study, the authors compared the immunocytochemical evaluation of hormone receptors (HR) and HER2 on TP-processed FNAC with the immunohistochemical analysis performed on the corresponding formalin-fixed paraffin-embedded (FFPE) breast tumor specimens, which are considered the gold standard. METHODS: FNACs were performed on 116 primary IBCs at the time of diagnosis and subjected to immunocytochemical evaluation of HR and HER2 using the TP method. The same markers were immunohistochemical evaluated on the corresponding FFPE tissue specimens. HER2 fluorescent in situ hybridization analysis was performed only on the equivocal immunohistochemical results. RESULTS: The HR results of the TP cytology specimens showed a very good agreement with those of the corresponding FFPE tissue samples (Cohen kappa test = 0.92; concordance rate = 98%) for estrogen receptor, and a good agreement (kappa = 0.76; concordance rate = 90.9%) for progesterone receptor. A perfect agreement (kappa = 1) was observed between TP and FFPE tissue samples in evaluating HER2 status. CONCLUSIONS: Alcohol-based fixation seems not to affect the immunocytochemical evaluation of HR and HER2. Considering the high levels of agreement between the evaluation of HR and HER2, on both cytology specimens and on the corresponding FFPE tissue samples, the authors concluded that the TP technique can be routinely used for the biological characterization of IBC. Cancer (Cancer Cytopathol) 2012;. © 2012 American Cancer Society.

Aim. To synthesise the evidence available in the literature on the effectiveness of the ultrasound bladder scanner in reducing the risk of urinary tract infection. Background. Acute urinary retention is the inability to empty the bladder notwithstanding it being full and is frequent in the postoperative period. Using the ultrasound bladder scanner for the measurement of urinary residue, nurses are able to evaluate the presence of urinary retention, monitor the volume and the excessive relaxation of the bladder and avoid unnecessary catheterisations. The association between urinary catheterisation and urinary tract infection is well documented in the literature. Design. A meta-analysis was conducted. Method. An extensive review was carried out by two researchers using multiple databases, including all articles published from 1 January 1986–8 February 2008. No restrictions were adopted with regard to language. Studies on (1) documenting hospitalised patients with a need to evaluate bladder urinary volume, (2) comparing the use of the ultrasound bladder scanner vs. the clinical judgment of the nurses in the evaluation of acute urinary retention followed by a decision regarding whether or not to apply a bladder catheter and (3) those documenting the impact on urinary tract infection associated with catheterisation were included. Results. A total of 61 articles were retrieved, of which 58 were excluded because they did not meet the inclusion criteria. The overall effectiveness of the bladder ultrasound scanner in the reduction of urinary tract infection associated with catheterisation was OR 0·27 (IC95% 0·16–0·47; p-value 0·00000294, variance 0·08, weight 12·50). Discussion. The ultrasound bladder scanner helps to define and monitor bladder urinary volume and therefore, to catheterise patients only when necessary. Although there were numerous factors affecting the clinical heterogeneity of the included studies, the reduction in risk of urinary tract infection associated with catheterisation was consistent. Conclusion. The use of the ultrasound bladder scanner for evaluating and monitoring the residue volume in immediate postoperative patients, aged 18 or above, reduces unnecessary catheterisations and therefore the risk of urinary tract infection associated with catheterisation. Relevance to clinical practice. The systematic use of the ultrasound bladder scanner in the peri-operative period could increase the appropriateness of catheterisation and reduce patient discomfort, costs and days of hospitalisation associated with urinary tract infection associated with catheterisation.

Niemann-Pick C disease (NPCD) is a rare autosomal recessive neurovisceral disorder with a heterogeneous clinical presentation. Cholestan-3β,5α,6β-triol and 7-ketocholesterol have been proposed as biomarkers for the screening of NPCD. In this work, we assessed oxysterols levels in a cohort of Italian patients affected by NPCD and analyzed the obtained results in the context of the clinical, biochemical and molecular data. In addition, a group of patients affected by Niemann-Pick B disease (NPBD) were also analyzed. NPC patients presented levels of both oxysterols way above the cut off value, except for 5 siblings presenting the variant biochemical phenotype who displayed levels of 3β,5α,6β-triol below or just above the cut-off value; 2 of them presented also normal levels of 7-KC. Both oxysterols were extremely high in a patient presenting the neonatal systemic lethal phenotype. All NPB patients showed increased oxysterols levels. In conclusion, the reported LC-MS/MS assay provides a robust non-invasive screening tool for NPCD. However, false negative results can be obtained in patients expressing the variant biochemical phenotype. These data strengthen the concept that the results should always be interpreted in the context of the patients' clinical picture and filipin staining and/or genetic studies might still be undertaken in patients with normal levels of oxysterols if symptoms are highly suggestive of NPCD. Both oxysterols are significantly elevated in NPB patients; thus a differential diagnosis should always be performed in patients presenting isolated hepatosplenomegaly, a common clinical sign of both NPCD and NPBD.

OBJECTIVES Improvement of clinical results in heart transplantation (HTx) has favoured the expansion of indication criteria towards aged population. The impact of increasing recipient age is controversial and, owing to donor shortage, the debate still remains whether HTx is justified for older patients. We analysed age as a prognostic factor at long-term after HTx and if it should be a determinant in organ allocation. METHODS Data of 364 consecutive patients who underwent cardiac transplantation between 1999 and 2014 at the University Hospital of Udine were analysed. Patients were divided into three groups according to age (Group 1: 18-40, Group 2: 41-59, Group 3: ≥ 60 years) and survival and major complications were evaluated at long-term (mean follow-up 6.7 ± 4.5 years, range 1-15.7 years). RESULTS Preoperatively, renal failure (2.9, 16.1, 39.5%, P < 0.01) and cardiovascular factors such as diabetes (1.2, 17.1, 36.4%, P < 0.01), systemic hypertension (5.9, 31.5, 40.8%, P < 0.01) and dyslipidaemia (5.9, 40.3, 42.9%, P < 0.01) were more common in older patients (Group 3), as well as ischaemic cardiopathy (0, 42.6, 49.7%, P < 0.01). Donor age was lower in younger recipients (Group 1) (33 ± 15, 39 ± 14, 45 ± 14 years, P < 0.01). Older patients showed a worse long-term survival (hazard ratio 1.7; 1.1-2.5), also after adjusting for major cardiovascular risk factors, renal failure and donor age. In fact, 15-year survival was 100% in Group 1, while at 1, 5, 10 and 15 years survival was 88, 78, 69 and 56% in Group 2, and 87, 68, 49 and 43% in Group 3, respectively. Even major long-term complications were less frequent in younger patients in terms of neoplasms (P < 0.01), rehospitalizations (P < 0.01) and a tendency to higher freedom from other complications such as cytomegalovirus infections, renal failure and dialysis. CONCLUSIONS Our results showed a significantly different outcome according to recipient age, even when adjusted for major risk factors. Notably, patients younger than 40 years showed 100% long-term survival, and apparent lower rate of complications due to immunosuppression. Since 15-year survival in patients ≤40 years is twice that of patients ≥60 years, recipient age should be taken into account in organ allocation.

Background Gaucher disease, a rare disorder, is caused by inherited deficiency of the enzyme glucocerebrosidase. It is unique among the ultra-orphan disorders in that four treatments are currently approved by various regulatory authorities for use in routine clinical practice. Hitherto, because of the relatively few people affected worldwide, many of whom started therapy during a prolonged period when there were essentially no alternatives to imiglucerase, these treatments have not been systematically evaluated in studies such as randomized controlled trials now considered necessary to generate the highest level of clinical evidence. Objectives To summarize all available randomized controlled study data on the efficacy and safety of enzyme replacement therapies and substrate reduction therapy for treating Gaucher disease. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register. Additional searches were conducted on ClinicalTrials.gov for any ongoing studies with potential interim results, and through PubMed. We also searched the reference lists of relevant articles and reviews. Date of last search: 07 August 2014. Selection criteria All randomized and quasi-randomized controlled studies (including open-label studies and cross-over studies) assessing enzyme replacement therapy or substrate reduction therapy, or both, in all types of Gaucher disease were included. Data collection and analysis Two authors independently assessed the risk of bias in the included studies, and extracted relevant data. Main results Of the 488 studies retrieved by the electronic searches, eight met the inclusion criteria and were analysed (300 participants). Response parameters were restricted to haemoglobin concentration, platelet count, spleen and liver volume and serum biomarkers (chitotriosidase and CCL18). Only one publication reported a 'low risk of bias' score in all parameters assessed, and all studies included were randomized. Four studies reported the responses to enzyme replacement therapy of previously untreated individuals with type 1 Gaucher disease. Two studies investigated maintenance enzyme replacement therapy in people with stable type 1 Gaucher disease previously treated for at least two years. One study compared substrate reduction therapy, enzyme replacement therapy and a combination thereof as maintenance therapy in people with type 1 Gaucher disease previously treated with enzyme replacement therapy. One study examined substrate reduction therapy in people with chronic neuronopathic (type 3) Gaucher disease who continued to receive enzyme replacement therapy. Treatment-naive participants had similar increases in haemoglobin when comparing those receiving imiglucerase or alglucerase at 60 units/kg, imiglucerase or velaglucerase alfa at 60 U/kg, taliglucerase alfa at 30 units/kg or 60 units/kg, and velaglucerase alfa at 45 units/g or 60 units/kg. For platelet count response in participants with intact spleens, a benefit for imiglucerase over velaglucerase alfa at 60 units/kg was observed, mean difference -79.87 (95% confidence interval -137.57 to -22.17). There were no other significant differences in platelet count response when comparing different doses of velaglucerase alfa and of taliglucerase alfa, and when comparing imiglucerase to alglucerase. Spleen and liver volume reductions were not significantly different in any enzyme replacement therapy product or dose comparison study. Although a dose effect on serum biomarkers was not seen after nine months, a significantly greater reduction with higher dose was reported after 12 months in the velaglucerase study, mean difference 16.70 (95% confidence intervaI 1.51 to 31.89). In the two enzyme replacement therapy maintenance studies comparing infusions every two weeks and every four weeks, there were no significant differences in haemoglobin concentration, platelet count, and spleen and liver volumes over a 6 to 12 month period when participants were treated with the same cumulative dose. A total of 25 serious adverse events were reported, nearly all deemed unrelated to treatment. There are, as yet, no randomized trials of substrate reduction therapy in treatment-naive patients that can be evaluated. Miglustat monotherapy appeared as effective as continued enzyme replacement therapy for maintenance of hematological, organ and biomarker responses in people with type 1 Gaucher disease previously treated with imiglucerase for at least two years. In those with neuronopathic Gaucher disease, no significant improvements in haemoglobin concentration, platelet count or organ volumes occurred when enzyme replacement therapy was augmented with miglustat. One randomized controlled study assessing substrate reduction therapy was published immediately prior to producing the final version of this review, and this, along with a further ongoing study (expected to be published in the near future), will be assessed for eligibility in a future update of the review. Authors' conclusions The results reflect the limitations of analysing evidence restricted to prospective randomized controlled trials, especially when dealing with chronic rare diseases. This analysis suggests that, during the first year of treatment, different recombinant glucocerebrosidases are bio-similar and non-inferior in safety and efficacy for surrogate biological response parameters. Enzyme replacement therapy given at 30 to 45 units/kg body weight every two to four weeks was generally as effective as the 60 unit/kg dose for the assessed clinical outcomes. The analysis emphasise the need to determine whether it is realistic to carry out multi-decade prospective clinical trials for rare diseases such as type 1 Gaucher disease. With large treatment effects on the classical manifestations of the disorder, therapeutic investigations in Gaucher disease mandate innovative trial designs and methodology to secure decisive data concerning long-term efficacy and safety – with the realization that knowledge about disease-modifying actions that are sustained are of crucial importance to people with this chronic condition.

Childhood injuries are a major public health problem in Italy. From a study conducted in 1984, injury rates were found to be higher in Trieste, in the north-east of the country, than in other Italian areas. We conducted a new study to evaluate whether injury rates and patterns have changed in Trieste. There are three emergency rooms (ER) in Trieste. We collected and analyzed information on all injured children 0–16 years of age attending these ER in 2003 (child population 0–16 years of age was 28,000). We calculated the annual injury risk overall and by age. We described characteristics of the children (age, sex) and injuries (place, cause, type, affected body part, severity). 5,928 injured children attended the ER, and the annual injury risk was 21.5%. The home was the most frequent place where injuries occurred, especially among the youngest children. The most commonly injured body parts were the limbs and, among the youngest children, the head and face. Approximately 20% of children had moderate to severe injuries (AIS>1), and less then 3% were admitted to the hospital. In comparison to the previous study, there have been no significant changes in the annual risk of childhood injury and in the injury patterns. On the contrary, we observed a dramatic reduction in the frequency of hospitalization, which is probably attributable to the recent implementation of short observation and to the improvement of diagnostic/therapeutic paths in the ER. In conclusion, childhood injuries are still a relevant public health problem in this Italian area and new efforts are needed to prevent them.

OBJECTIVES The higher risk of adverse aortic events in patients with bicuspid aortic valve (BAV) disease and ascending aorta aneurysm is known, but the management of moderate aortic root dilatation in younger patients is a controversial issue. The aim of the study was to compare survival in patients with or without root replacement. METHODS We reviewed 166 consecutive patients with BAV disease and concomitant ascending aorta aneurysm (mean ascending aorta diameter: 51.4 ± 7.2 mm) undergoing cardiac surgery from 1994 to 2010. A total of 77 patients underwent Bentall procedure (90.9% male, mean age: 55.7 ± 12.7 years, Bentall group), whereas the remaining 89 patients underwent aortic valve replacement with supracoronary ascending aorta replacement (SAAR 71.9% male, mean age: 60.5 ± 11.2 years, SAAR group, P = 0.002). The preoperative mean diameter of the root was 44.0 ± 7.2 mm in the Bentall, and 38.5 ± 4.8 mm in the SAAR group (P < 0.0001). RESULTS In-hospital mortality was 2.6% in the Bentall, and 2.3% in the SAAR groups. Overall survival was 84 and 81% in the Bentall (median follow-up: 105 months) versus 89 and 88% in the SAAR (median follow-up: 73 months) groups at 10 and 15 years (P = 0.36), respectively. The mean cardiopulmonary bypass (CPB) time was 201 ± 56 min and 174 ± 58 min (P = 0.0016), the mean cross-clamp time 156 ± 42 min and 132 ± 38 min (P = 0.0008) in the Bentall and SAAR groups, respectively. Four sudden deaths have occurred in the Bentall group and in 2 in the SAAR group. Progressive dilatation of the aortic root in the SAAR group was not significat (postoperative mean diameter: 36.3 ± 4.4 mm). Neither subgroup of patients in the SAAR with preoperative moderate dilatation of aortic root had significat aortic dilatation at the mean follow-up of 73 ± 39 months (preoperative diameter: 43.5 ± 2.3 mm versus postoperative: 39.1 ± 4.2 mm). One patient in Bentall and 1 in the SAAR groups were reoperated for tubular graft infection. CONCLUSIONS In patients with BAV disease, ascending aorta aneurysm and moderate dilatation of the root, the significat reduction of CPB and cross-clamp times, the stability of the residual root at long term and the low risk of adverse aortic events associated with SAAR compared with the Bentall procedure have led us to consider the isolated aortic valve replacement with supracoronary aorta replacement an alternative strategy to the Bentall procedure, especially in high-risk and older patients.

Background The chronic neuropathic form of Gaucher disease (GD3) is characterised by hepatosplenomegaly, anaemia, thrombocytopenia, bone alterations and central neurological involvement. Enzyme replacement therapy (ERT) has been demonstrated to be effective in non neuropathic Gaucher disease, but long term results in patients with GD3 are still limited and contrasting. A possible role of genotype in determining the response to ERT has been hypothesised. Patients and methods All patients affected by GD3, treated with ERT, and followed-up in 4 different Italian centres (Udine, Catanzaro, Sassari and Florence) were included. Data on clinical conditions, laboratory values, neurological and neuropsychological examinations, radiological and electrophysiological features were collected retrospectively from clinical records. Results Ten patients (6 females, 4 males) with four different genotypes (L444P/L444P, L444P/F231I, P159T/unknown, C.115+1G>A/N188S) were identified. They received ERT infusions from 3 to 21 years. Haematological parameters and organomegaly improved/normalised in all patients. Three patients showed severe progressive skeletal deformities. 6/10 patients were neurologically asymptomatic when they started ERT for systemic symptoms. During the follow-up, 2/6 developed an important central nervous system disease; 2/6 developed mild central symptoms; and 2/6 did not show any neurological symptom after 5, and 20 years of treatment respectively, despite the presence of epileptiform abnormalities at the electroencephalogram. Overall, neurological involvement worsened over time in 6/10 patients, 3 of whom developed progressive myoclonic encephalopathy and died. Conclusions ERT improved the systemic manifestations in patients with GD3, but was not able to counteract the progression of neurological symptoms in the long term.

To investigate the prescriptions of systemic antibiotics in a population of pregnant women in Italy, to identify socio-demographic factors associated with increased risk of being prescribed potentially unsafe medications, to compare prescriptions before and during pregnancy and to identify the prescribing General Practitioners (GPs).A retrospective study based on administrative anonymous databases included all women resident of the Friuli Venezia Giulia Region who delivered babies in 2011 (n=9196). The antibiotic prescription risk was calculated by trimester and overall, and compared with that in the year before. Multivariate logistic regression analyses assessed the role of socio-demographic factors on the risk of being prescribed medications that should not be used as first-line.6688 women (72.7%) were prescribed medicines (27363 prescriptions) during their pregnancies. Antibiotics were prescribed to 2279 women (24.8%), less commonly during pregnancy than before. Prescriptions were more frequent in the second and third trimesters. 1736 women were prescribed antibiotics other than first-line medicines (of which, seven tetracyclines and 58 quinolones, which are frankly not recommended). Those women were more frequently younger and less educated. The GPs responsible for those prescriptions were identified.In order to improve the prescription of antibiotics in pregnancy, an audit with the GPs is warranted to understand their motivations, discuss clinical cases and build consensus guidelines on which antibiotics should be preferred for use in pregnancy.

Background Chemotherapy administration is a high-risk process. Aim of this study was to evaluate the frequency, type, preventability, as well as potential and actual severity of outpatient chemotherapy prescribing errors in an Oncology Department where electronic prescribing is used. Methods Up to three electronic prescriptions per patient record were selected from the clinical records of consecutive patients who received cytotoxic chemotherapy between January 2007 and December 2008. Wrong prescriptions were classified as incomplete, incorrect or inappropriate. Error preventability was classified using a four-point scale. Severity was defined according to the Healthcare Failure Mode and Effect Analysis Severity Scale. Results Eight hundred and thirty-five prescriptions were eligible. The overall error rate was 20%. Excluding systematic errors (i.e. errors due to an initially faulty implementation of chemotherapy protocols into computerized dictionaries) from the analysis, the error rate decreased to 8%. Incomplete prescriptions were the majority. Most errors were deemed definitely preventable. According to error presumptive potential for damage, 72% were classified as minor; only 3% had the potential to produce major or catastrophic injury. Sixty-eight percent were classified as near misses; adverse drug events had no or little effect on clinical outcome. Conclusions Chemotherapy prescribing errors may arise even using electronic prescribing. Although periodic audits may be useful to detect common errors and guide corrective actions, it is crucial to get the computerized physician order entry system and set-ups correct before implementation.

Analysis of relative importance of side effects of anticancer therapy is extremely useful in the process of clinical decision making. There is evidence that patients' perception of the side effects of anticancer treatments changes over time.Aim of this study was to evaluate the cancer patients' perceptions of physical and non-physical side effects of contemporary anticancer therapy. Four hundred and sixty-four patients entered the study (153 men and 311 women). Participants were asked to rank their side effects in order of distress by using two sets of cards naming physical and non-physical effects, respectively. Influencing factors, including treatment and patient characteristics, were also analysed.Patients ranked the non-physical side effect 'Affects my family or partner' first. 'Constantly tired' and 'Loss of hair' were ranked second and third, respectively. Significant differences from previous studies on this topic emerged. In particular, 'Vomiting', a predominant concern in previous studies, almost disappeared, whereas 'Nausea' and 'Loss of hair' remained important side effects in the patients' perception. Interestingly, marital status was predominant in driving patients' perception, being associated with several side effects ('Constantly tired', 'Loss of appetite', 'Affects my work/Home duties', 'Affects my social activities', 'Infertility'). Other significant factors influencing patient's perception of side effects included age, disease characteristics and ongoing anticancer therapy.This study provided information on current status of patients' perceptions of side effects of anticancer treatment. These results could be used in pre-treatment patient education and counselling.

Glycogenosis type II, a genetic muscle-wasting disorder, results in a spectrum of clinical phenotypes. Enzyme replacement therapy is effective in the infantile form of the disease, while little is known about its effectiveness in late-onset disease, especially in juvenile patients. The purpose of this retrospective cohort study was to assess the long-term effects of enzyme replacement therapy (ERT) in juvenile glycogenosis type II (GSDII). Eight Italian juvenile GSDII patients, receiving biweekly infusions of 20 mg/kg recombinant human α-glucosidase for at least 72 months, were enrolled (median age at therapy start was 11.8 years). Six-minute walk test (6MWT) and forced vital capacity (FVC), measured in upright position, were chosen as the principal outcome measures. Global motor disability (modified Walton scale (WS)), muscle enzymes levels [creatine phosphokinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST), alanine transaminase (ALT)] and body mass index (BMI) were also analysed both at baseline (therapy start) and annually afterwards. At baseline, most patients (six out of eight) did not show muscle function impairment (WS ≤ 2). The performance at 6MWT showed a slight improvement during follow-up as well as FVC. Muscle enzymes levels showed a clear decrease after the 1st year of treatment while remained stable afterwards. An overall decrease in BMI was also observed during follow-up, although at the individual level, trends were variable. Conclusion: ERT is effective in stabilising both motor and lung functions in juvenile patients with GSDII, possibly slowing down the rate of disease progression. Randomised controlled trials are needed to understand whether early treatment allows juvenile patients to reach adulthood with a more beneficial residual muscular function than untreated patients.

Glycogen storage disease type I (GSD I) is a chronic metabolic disease that requires a lifelong strict dietetic treatment to avoid hypoglycemia and can lead to severe complications during adult age. Impaired quality of life (QoL) has been reported in affected children, but this aspect has not been previously investigated in adults.To assess QoL in adult patients with GSD I.Italian patients with GSD type Ia and Ib, who were 16 years or older, were asked to complete the SF-36 questionnaire, assessing their QoL. Data on demographic characteristics and clinical history were collected from clinical records and interviews.Thirty-eight patients (22 females, 16 males; 27 with GSD Ia, 11 with GSD Ib, median age 26.5 years) completed the SF-36 questionnaire. Overall, when compared to normal values, patients with GSD I had lower median scores in general health perception and social functioning, but better median scores for bodily pain and mental health. Patients with GSD Ib had a lower Z-score than GSD Ia patients for emotional health problems. Male patients showed better Z-scores in physical functioning, general health perception, and social functioning when compared to females. Emotional health problems Z-score was lower in nephropathic patients.QoL can be impaired in adult patients with GSD I. The results of this study show that patients with GSD type Ib, women, and those with renal complications are more likely to experience a poorer QoL.

Background. Enzyme Replacement Therapy (ERT) is the standard of care in Gaucher disease. The effects of withdrawal or reduced doses are debated, thus a retrospective cohort study was conducted to investigate clinical and laboratory differences in 34 Gaucher type 1 patients experiencing an ERT dosage reduction after the forced temporary imiglucerase shortage in 2009. Methods. Haemoglobin concentration, leukocytes and platelets counts, and chitotriosidase activity were assessed at baseline and after 6 and 12 months (t0, t6, t12), while bone pain, energy, work or school performance, concentration, memory and social life every 3 months. Results. The cohort was made up of 18 males and 16 females (medians: age 41.8 years, therapy duration 14.1 years, dosage reduction 35.5%). Haemoglobin, leukocytes and platelets remained substantially stable, while chitotriosidase activity showed an increase, especially after t6. Age, splenectomy or genotype were not associated with laboratory parameters changes, except for a significant median increase of chitotriosidase activity in non-splenectomised patients after 12 months (p = 0.01). At 3, 6, 9 and 12 months, more than 50% patients reported at least one problem in subjective well-being (56%, 65%, 70%, 58%, respectively), while bone pain occurred or worsened in 13/33, 13/32, 7/28 and 5/26 patients, respectively. No bone crises were reported. Conclusions. Drug reduction did not induce substantial modification in the laboratory values but seems to have influenced the well-being perception of some Gaucher patients. Thus, bone pain, general health and quality of life should be carefully monitored during ERT reductions.

Ectodermal dysplasia is a rare disease which affects at least two ectodermal-derived structures such as hair, nails, skin, sweat glands and teeth. Approximately 200 different conditions have been classified as an ectodermal dysplasia and X-linked hypohidrotic ectodermal dysplasia (XHED) represents the commonest form. Clinically, XHED is characterized by hypotrichosis, hypohidrosis and hypodontia. A variety of ocular manifestations have been reported in XHED, the most common being dryness of eyes due to tear deficiency and instability of the film secondary to the absence of meibomian gland function. Here we report a child with the distinctive clinical features of XHED confirmed with molecular diagnosis who presented with infantile bilateral glaucoma, in addition to the classical ocular involvement in XHED.

The aim of the present study is to evaluate the clinical and biological factors (including markers of angiogenesis) as potential predictors of prognosis and benefit from metronomic therapy in patients with advanced breast cancer (ABC). Recent data suggest antiangiogenic activity of metronomic therapy. The study population included 62 patients with pretreated ABC who received cyclophosphamide and methotrexate orally. Tumour samples were analysed by immunohistochemistry for HER2, Ki-67, thymidine phosphorylase (TP), vascular endothelial growth factor and vascular endothelial growth factor receptor. The results from immunohistochemical analysis and clinico-pathological variables were studied to test their potential association with benefit from metronomic therapy. The median overall survival, progression-free survival and survival postprogression were 7.1 (range 0.2-38.3), 2.6 (range 0.2-28.9) and 3 (range 0-34.2) months, respectively. Among the clinical variables, age, performance status and previous therapy with taxanes were significantly associated with outcomes. Among the molecular markers, TP was found to be associated with progression-free survival. Metronomic therapy is an effective choice for ABC. Young women with a more indolent disease had the greatest benefit from this treatment. TP tumour expression might aid decision making but these findings must be confirmed in larger prospective, properly designed studies.

To evaluate the accuracy of hospital discharge data as a source of Amyotrophic Lateral Sclerosis (ALS) cases for epidemiological studies or disease registries, a validation study was performed. All records of patients discharged in 2005 and 2006 with principal or secondary International Classification of Diseases, 9th rev., Clinical Modification (ICD 9 CM) diagnosis code of ALS (335.20), other anterior horn cell disease (335), spinal cord disease (336), hereditary and idiopathic peripheral neuropathy (356), inflammatory and toxic neuropathy (357), myoneural disorders (358), muscular dystrophies and myopathies (359), were selected from the electronic archive of discharge data of the University Hospital of Udine, Friuli Venezia Giulia Region, North East Italy. Corresponding clinical documentation was reviewed to ascertain the presence of El Escorial criteria, the gold standard. Sensitivity of the ICD 9 CM discharge code 335.20 was 93% (95%CI: 82–99%) and decreased to 91% (95%CI: 77–98%) when suspect ALS was excluded. Specificity was 99% (95%CI: 97–99%). The ICD 9 CM discharge code 335.20 can identify a high percentage of hospitalizations of patients truly affected by ALS and of patients with no ALS, among selected neurological diagnostic codes. To ensure complete ALS case ascertainment, prospective population-based registries or epidemiologic studies require active prospective surveillance and use of multiple sources, among them hospital discharge archives can provide accurate information.

A subgroup analysis comparing elderly (age > or =70 years; n=95) with younger (age

6080 Background: The role of IT in preventing CT prescribing errors is unclear. Comparing their frequency across different studies is unworthy, due to inconsistencies in error classification, strat...

e19623 Background: Analysis of relative importance of side effects of anticancer therapy is extremely useful in the process of clinical decision making. Previous studies have surveyed what patients...

e17527 Background: Physicians are reluctant partners in error reporting. Insufficient evidence exists on what may affect IR in a specific cultural and organizational context. The primary endpoint of our study was to offer a critical perspective on the dominant attitudes toward IR systems among health operators of Friuli-Venezia Giulia cancer network. The survey was part of a Health Department patient safety project. Methods: A preliminary PubMed and ASCO database search was performed (keywords: incident/error reporting, attitudes, barriers, blame/safety culture, cancer, oncology, chemotherapy). Two web-based questionnaires were administered to health personnel of Oncology Units (OU) with developing and existing IR systems, respectively. Data were collected in a MySQL database and managed by PhpMyAdmin. SAS 9.1 was used for the analysis of frequency distributions. Results: Target population: 14 OU; 2 University Hospitals, 1 Scientific Institute for Research, Hospitalization, and Health Care (SIRHHC) (2 OU), 10 Hospital Centers; 262 operators (83 physicians, 172 nurses, 2 pharmacists, 5 technicians). Overall response rate: 44.6%; physician/nurse 59/36%; University Hospital (n = 99)/SIRHHC (n = 55)/Hospital Center (n = 101) 73%/9%/38%. Knowledge of risk management issues: 86% (90% of untrained operators from IR-free centers). Eighty-six percent of all operators showed a favourable attitude toward voluntary IR systems. Main reasons: patient safety improvement (65%); organizational growth (38%); professional duty (20.5%). A 78.5% preference for computerized forms was recorded. On a five-point scale, IR features rating 5 in >50% of the answers were: simplicity (85%); getting a feed-back (76%); exhaustivity (66%); adoption of organization more than individual recommendations (59%). Specific training, feedback guarantee and plainness of reporting forms were suggested by 90, 64, and 51% of all operators as essential measures for system acceptance and user satisfaction. Conclusions: Logistic and organizational factors (i.e., time constraints, work overload, resource allocation to incident reporting more than investigation and learning back) should be taken in account by county health directors aiming for successful reporting systems. No significant financial relationships to disclose.