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Recently, social anxiety disorder (SAD) and paranoia have been demonstrated to be closely related. However, data were primarily drawn from adult community samples or patients with schizophrenia. The present study used a cross-sectional design to evaluate a sample of adolescents with SAD (n = 30, mean age 15.3 ± 0.9 years) compared with an age- and sex-matched group of healthy controls (n = 26, mean age 15.9 ± 1.6 years). The SAD group displayed more frequent and intense paranoid thoughts than the control group (t = 4.16, p < 0.001). The level of paranoid thoughts was significantly predicted by the degree of social phobia, even after adjusting for sex and other anxiety disorders, although adjusting for depression slightly reduced the extent and significance of the prediction. A lack of awareness about the association between SAD and paranoia may lead to incorrect diagnoses (e.g. misdiagnosis of psychotic disorders), or it may negatively influence the (psycho)therapeutic process and patient outcomes. [ABSTRACT FROM AUTHOR]

Abstract: In this paper we reconstruct and discuss the network of Italian firms investing abroad, exploiting information from complex network analysis. This method, detecting the key nodes of the system (both in terms of firms and countries of destination), allows us to single out the linkages among firms without ex-ante priors. Moreover, through the examination of affiliates’ economic activity, it allows us to highlight different internationalization strategies of “leaders” in different manufacturing sectors. [Copyright &y& Elsevier]

An empirical analysis of the Italian system of banks and firms is carried out using the network theory. The emerging architecture of this economic network shows peculiar behaviors: (i) Multiple lending is very widespread; (ii) Small firms are preferentially financed by small banks; (iii) Large firms are financed by many banks; (iv) the ratio between loans and deposits is much higher for large banks than for small banks, while (v) strong size heterogeneity appears among co-financing banks, and (vi) the spanning-tree is very hierarchical. [ABSTRACT FROM AUTHOR]

The relation between age at dystonia onset and sex was investigated in 264 patients with cranial-cervical dystonia and 56 patients with upper limb dystonia. In cranial-cervical dystonia, women had a significantly greater age at the onset of dystonia than men. The association was independent of duration of disease and distance of referral, but it was no longer detectable after adjustment for educational level. In upper limb dystonia, men and women did not differ for age at dystonia onset, duration of disease, education level, or distance of referral. A significant inverse association between age at the onset of dystonia and education was observed in both cranial-cervical dystonia and upper limb dystonia series. [ABSTRACT FROM AUTHOR]

In mental health care, transition refers to the pathway of a young person from a child and adolescent mental health service (CAMHS) to an adult mental health service (AMHS). In Italy, the age of transition from adolescents to adults' mental health services is at the age of 18. Difficulties in transitioning have shown to favor patients' and families' disengagement and discontinuity of care with pharmacological treatment dropouts. On the other hand, a smooth and effective transition may improve the management of the disease and increase the chances of improvement of young schizophrenic patients. This project of roundtables, including child neuropsychiatrists (CNPs) and adult psychiatrists (Psy) throughout Italy, was aimed at exploring the problems of transition in clinical practice and collecting the proposals to improve transition management. The need to fill some cultural and organizational aspects strongly emerged to improve the transition process of adolescents with schizophrenia to adults' mental health services. On the one hand, specific training programs for both Psy and CNPs on the transition process are hoped for. On the other hand, both Psy and CNPs have expressed a need for shared official protocols, direct handover between the services including a period of shared management, and building of territorial multidisciplinary teams. All these aspects imply having a national mental health policy dedicated to taking charge of young people with mental health disorders, and accompanying them across the border between children and adults' mental health services. Improving transitional care can facilitate not only recovery but also prevention of mental illness for young people. Allocation of resources should aim at matching the epidemiological burden and reducing the heterogeneity between Italian regions.

Background: Critical illness polyneuropathy and myopathy (CIPNM) is a frequent neurological manifestation in patients with acute respiratory distress syndrome (ARDS) from coronavirus disease 2019 (COVID-19) infection. CIPNM diagnosis is usually limited to clinical evaluation. We compared patients with ARDS from COVID-19 and other aetiologies, in whom a neurophysiological evaluation for the detection of CIPNM was performed. The aim was to determine if there were any differences between these two groups in frequency of CINPM and outcome at discharge from the intensive care unit (ICU)., Materials and Methods: This was a single-centre retrospective study performed on mechanically ventilated patients consecutively admitted (January 2016-June 2020) to the ICU of Careggi Hospital, Florence, Italy, with ARDS of different aetiologies. Neurophysiological evaluation was performed on patients with stable ventilation parameters, but marked widespread hyposthenia (Medical Research Council score <48). Creatine phosphokinase (CPK), lactic dehydrogenase (LDH) and mean morning glycaemic values were collected., Results: From a total of 148 patients, 23 with COVID-19 infection and 21 with ARDS due to other aetiologies, underwent electroneurography/electromyography (ENG/EMG) recording. Incidence of CIPNM was similar in the two groups, 65% (15 of 23) in COVID-19 patients and 71% (15 of 21) in patients affected by ARDS of other aetiologies. At ICU discharge, subjects with CIPNM more frequently required ventilatory support, regardless the aetiology of ARDS., Conclusion: ENG/EMG represents a useful tool in the identification of the neuromuscular causes underlying ventilator wean failure and patient stratification. A high incidence of CIPNM, with a similar percentage, has been observed in ARDS patients of all aetiologies., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The standard approach for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME). After nCRT 20% of patients achieve a clinical complete response (pCR) and could be treated with a non-operative management (NOM)., Methods: The panel of the Italian Association of Medical Oncology (AIOM) Guidelines on rectal cancer applied the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach addressing the following question: Should NOM vs. TME be used for patients with rectal cancer with clinical complete response after nCRT? Five outcomes were identified: disease-free survival (DFS), mortality, local recurrence, colostomy rate, and functional outcomes., Results: Nine studies were included in the analysis. A higher risk of disease recurrence was observed in the NOM group compared to the TME group (RR = 1.69, 95% CI 1.08, 2.64) on the other hand, we observed a slightly positive but not significant effect on mortality of NOM (RR = 0.82, 95% CI 0.46, 1.45). Patients in the NOM group were more likely to experience local recurrence (RR = 5.37, 95% CI 2.56, 11.27) and patients in the TME group were more likely to have a permanent colostomy (RR = 0.15, 95% CI 0.08, 0.29). Only one study evaluated functional outcomes. The overall certainty of evidence was rated as very low., Conclusions: NOM was found to correlate with a higher risk of local recurrence which did not translate in worse OS and a lower colostomy rate. Due to the paucity of evidences, no recommendations are possible. NOM remains an experimental treatment; thus, patients managed with NOM should be enrolled in clinical trials with a dedicated follow-up schedule.

On 21 February 2020, a resident of the municipality of Vo', a small town near Padua (Italy), died of pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection 1 . This was the first coronavirus disease 19 (COVID-19)-related death detected in Italy since the detection of SARS-CoV-2 in the Chinese city of Wuhan, Hubei province 2 . In response, the regional authorities imposed the lockdown of the whole municipality for 14 days 3 . Here we collected information on the demography, clinical presentation, hospitalization, contact network and the presence of SARS-CoV-2 infection in nasopharyngeal swabs for 85.9% and 71.5% of the population of Vo' at two consecutive time points. From the first survey, which was conducted around the time the town lockdown started, we found a prevalence of infection of 2.6% (95% confidence interval (CI): 2.1-3.3%). From the second survey, which was conducted at the end of the lockdown, we found a prevalence of 1.2% (95% CI: 0.8-1.8%). Notably, 42.5% (95% CI: 31.5-54.6%) of the confirmed SARS-CoV-2 infections detected across the two surveys were asymptomatic (that is, did not have symptoms at the time of swab testing and did not develop symptoms afterwards). The mean serial interval was 7.2 days (95% CI: 5.9-9.6). We found no statistically significant difference in the viral load of symptomatic versus asymptomatic infections (P = 0.62 and 0.74 for E and RdRp genes, respectively, exact Wilcoxon-Mann-Whitney test). This study sheds light on the frequency of asymptomatic SARS-CoV-2 infection, their infectivity (as measured by the viral load) and provides insights into its transmission dynamics and the efficacy of the implemented control measures.

Background: Peritoneal carcinomatosis (PC) is a common manifestation of many gastrointestinal (GI) malignancies and is an advanced stage that is often associated with disseminated disease. Considerable progress has been made to achieve safe elimination of macroscopic disease using cytoreductive surgery (CRS) and more recently in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of microscopic disease or disease with minimal volume. The aim of this study was to assess the effects of such procedures on the quality of life (QoL), the long-term benefit and the functional status of the treated patients., Patients and Methods: Data from patients who underwent CRS-HIPEC for peritoneal metastasis (PM) at our center from November 2016 to November 2018 were analyzed retrospectively. The drugs administered were mitomycin and cisplatin. Quality of life (QoL) was assessed using the Euroquol-5D-5L and National Comprehensive Cancer Network Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index v2 questionnaires before CRS-HIPEC, and 1, 3 and 6 months after were administered., Results: In our series, the survival efficacy of CRS plus HIPEC was confirmed in the treatment of primary and secondary peritoneal pathologies, particularly in ovarian cancer, although larger studies are needed to investigate its role in the pathology of gastric, colonic and rectal cancer. The QoL data were promising, with essentially stable values between the preoperative and the 1-month follow-up, but with incremental benefits from the second to the third month., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Universal prevention approaches have significantly reduced children's conduct problems and aggressive behavior in the school setting, but it has not been clear whether the effects generalize into children's behavior in home and community settings in later elementary school years. The present study examined this issue using a classroom-randomized design, with 1030 students in 70 fourth and fifth grade Italian classes. The intervention model is the Coping Power Universal and the classroom teachers delivered it. Coping Power Universal produced a significant reduction in both parents' and teachers' rated conduct problems, relative to control classes, indicating that universal prevention can produce significant reductions in children's conduct problems that generalize into the home and community settings. The intervention also increased children's prosocial behaviors in school and home settings. The Coping Power Universal is a short intervention model that is believed to be a useful strategy for children's behavioral problems in the broad population., (Copyright © 2019 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.)

Objectives: We compared the clinical, laboratory, and radiological features of different subgroups of acute transverse myelitis (ATM) diagnosed according to the criteria established by the Transverse Myelitis Consortium Working Group (TMCWG) as well as of non-inflammatory acute transverse myelopathies (NIATM) to identify possible short- and long-term prognostic factors., Methods: A multicenter and retrospective study comprising 110 patients with ATM and 15 NIATM admitted to five Italian neurological units between January 2010 and December 2014 was carried out., Results: A significantly higher frequency of isolated sensory disturbances at onset in ATM than in NIATM patients (chi-square = 14. 7; P = 0.005) and a significantly higher frequency of motor symptoms in NIATM than ATM (chi-square = 12.4; P = 0.014) was found. ATM patients with high disability at discharge had more motor-sensory symptoms without (OR = 3.87; P = 0.04) and with sphincter dysfunction at onset (OR = 7.4; P = 0.0009) compared to those with low disability. Higher age (OR = 1.08; P = 0.001) and motor-sensory-sphincter involvement at onset (OR = 9.52; P = 0.002) were significantly associated with a high disability score at discharge and after a median 1-year follow-up., Conclusions: The diagnosis of ATM may prevail respect to that of NIATM when a sensory symptomatology at onset occurs. In ATM, patients older and with motor-sensory involvement with or without sphincter impairment at admission could experience a major risk of poor prognosis both at discharge and at longer time requiring a timely and more appropriate treatment.

Importance: Based on a small retrospective study, rechallenge with cetuximab-based therapy for patients with KRAS wild-type metastatic colorectal cancer (mCRC) who were previously treated with the same anti-epidermal growth factor receptor-based regimen might be efficacious. Recent data suggest the role of liquid biopsy as a tool to track molecular events in circulating tumor DNA (ctDNA)., Objective: To prospectively assess the activity of cetuximab plus irinotecan as third-line treatment for patients with RAS and BRAF wild-type mCRC who were initially sensitive to and then resistant to first-line irinotecan- and cetuximab-based therapy., Design, Setting, and Participants: Multicenter phase 2 single-arm trial conducted from January 7, 2015, to June 19, 2017. Liquid biopsies for analysis of ctDNA were collected at baseline. Main eligibility criteria included RAS and BRAF wild-type status on tissue samples; prior first-line irinotecan- and cetuximab-based regimen with at least partial response, progression-free survival of at least 6 months with first-line therapy, and progression within 4 weeks after last dose of cetuximab; and prior second-line oxaliplatin- and bevacizumab-based treatment., Interventions: Biweekly cetuximab, 500 mg/m2, plus irinotecan, 180 mg/m2., Main Outcomes and Measures: Overall response rate according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included progression-free survival and overall survival and, as an exploratory analysis, RAS mutations in ctDNA., Results: Twenty-eight patients (9 women and 19 men; median age, 69 years [range, 45-79 years]) were enrolled. Six partial responses (4 confirmed) and 9 disease stabilizations were reported (response rate, 21%; 95% CI, 10%-40%; disease control rate, 54%; 95% CI, 36%-70%). Primary end point was met because lower limit of 95% CI of response rate was higher than 5%. RAS mutations were found in ctDNA collected at rechallenge baseline in 12 of 25 evaluable patients (48%). No RAS mutations were detected in samples from patients who achieved confirmed partial response. Patients with RAS wild-type ctDNA had significantly longer progression-free survival than those with RAS mutated ctDNA (median progression-free survival, 4.0 vs 1.9 months; hazard ratio, 0.44; 95% CI, 0.18-0.98; P = .03)., Conclusions and Relevance: This is the first prospective demonstration that a rechallenge strategy with cetuximab and irinotecan may be active in patients with RAS and BRAF wild-type mCRC with acquired resistance to first-line irinotecan- and cetuximab-based therapy. The evaluation of RAS mutational status on ctDNA might be helpful in selecting candidate patients., Trial Registration: ClinicalTrials.gov Identifier: NCT02296203.

Objectives: We report a multicenter experience of urgent late open conversion (LOC), with the goal of identifying the mode of presentation, technical aspects, and outcomes of this cohort of patients., Methods: A retrospective analysis of endovascular aneurysm repair (EVAR) requiring LOC (>30 days after implantation) from 1996 to 2016 in six vascular centers was performed. Patients with aneurysm rupture or other conditions requiring urgent surgery (<24 hours) were included. Patient demographics, time interval between EVAR and LOC, endograft characteristics, previous attempts at endovascular correction, indications, operative technique, 30-day mortality and morbidity, and long-term survival were analyzed., Results: There were 42 patients (88.1% men; mean age, 75.8 ± 9.0 years) included. Among the 42 explanted grafts, 33 were bifurcated, 1 tube, 6 aortouni-iliac, and 2 side-branch devices. Suprarenal fixation was present in 78.6%. Twelve patients (28.6%) underwent endovascular reintervention before LOC. Indications for urgent LOC were aneurysm rupture in 24 of the 42 cases (57.1%), endograft infection in 11 (26.2%), endoleak associated with aneurysm growth and pain in 6 (14.3%), and recurrent endograft thrombosis in 2 (4.8%). The proximal aortic cross-clamping site was infrarenal in 38.1% of cases, suprarenal in 19.1%, and supraceliac in 42.9%. Complete removal of the endograft was performed in 32 patients (76.2%) and partial removal in 10 (proximal preservation in 7 of 10). Reconstructions were performed with Dacron grafts in 33 of the 42 cases, cryopreserved arterial allografts in 5, and endograft removal associated with prosthetic axillobifemoral bypass in 4. The 30-day mortality was 23.8%; hemorrhagic shock was an independent risk factor of early mortality (odds ratio, 10.5; 95% confidence interval, 1.5-73.7; P = .018). During a mean follow-up of 23.9 ± 36.0 months, two late aneurysm-related deaths occurred. The estimated 1- and 5-year survival rates were 62.1% and 46.1%, respectively., Conclusions: Urgent LOC after EVAR are associated with high postoperative mortality rates and poor long-term survival. Further studies are necessary to define the timing and the best treatment option for failing EVAR., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: TAS-102 is indicated for patients with metastatic colorectal cancer (mCRC) previously treated with, or not considered candidates for, available therapies. Given the complete inefficacy in half of patients, the lack of predictive factors, the palliative setting, and the financial and clinical toxicity, optimizing the cost-benefit ratio is crucial. The "ColonLife" nomogram allows an estimate of the 12-week life expectancy of patients with refractory mCRC., Materials and Methods: We collected data from patients treated at eight Italian centers in the compassionate use program. Baseline characteristics of patients who were or were not progression free at 6 months were compared. The discriminative ability of the ColonLife nomogram was assessed. Among patients who received both TAS-102 and regorafenib, clinical outcomes of the two sequences were compared., Results: This study included 341 patients. Six (2%) and 93 (27%) patients achieved response and disease stabilization, respectively. The median progression-free survival (PFS) was 2.4 months with an estimated 6-month PFS rate of 19%; the median overall survival (OS) was 6.2 months. An Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, normal lactate dehydrogenase (LDH), and a time from the diagnosis of metastatic disease of >18 months were independently associated with higher chances of a patient being progression free at 6 months. The discriminative ability of ColonLife was confirmed. Among 121 patients who received both regorafenib and TAS-102, no differences in first or second PFS or OS were reported between the two sequences., Conclusion: One out of five patients achieves clinical benefit with TAS-102. ECOG PS, LDH, and time from diagnosis of metastatic disease may help to identify these patients. Excluding patients with very short life expectancy appears a reasonable approach., Implications for Practice: Improving the cost-efficacy ratio of TAS-102 in metastatic colorectal cancer is needed to spare useless toxicities in a definitely palliative setting. Eastern Cooperative Oncology Group performance status, lactate dehydrogenase levels, and time from the diagnosis of metastatic disease may help to identify patients more likely to achieve benefit. Properly designed prognostic tools (i.e., the "ColonLife" nomogram) may enable excluding from further treatments patients with very limited life expectancy., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2018.)

In recent years, West Nile virus (WNV) lineage 2 has been spreading and causing disease outbreaks in humans and animals in Europe. In order to characterize viral diversity, we performed full-length genome sequencing of WNV lineage 2 from human samples collected during outbreaks in Italy and Greece in 2013 and 2014. Phylogenetic analysis showed that these WNV lineage 2 genomes belonged to a monophyletic clade derived from a single introduction into Europe of the prototype Hungarian strain. Correlation of phylogenetic data with geospatial information showed geographical clustering of WNV genome sequences both in Italy and in Greece, indicating that the virus had evolved and diverged during its dispersal in Europe, leading to the emergence of novel genotypes, as it adapted to local ecological niches. These genotypes carried divergent conserved amino acid substitutions, which might have been relevant for viral adaptation, as suggested by selection pressure analysis and in silico and experimental modelling of sequence changes. In conclusion, the results of this study provide further information on WNV lineage 2 transmission dynamics in Europe, and emphasize the need for WNV surveillance activities to monitor viral evolution and diversity., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Early tumor shrinkage (ETS) and depth of response (DoR) predict overall survival (OS) in first-line trials of chemotherapy ± anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC). These associations and the predictive accuracy of response measurements for survival parameters were investigated in the phase III TRIBE trial of FOLFOXIRI plus bevacizumab (bev) versus FOLFIRI plus bev., Patients and Methods: A landmark approach was adopted to define the assessable population. The distribution of RECIST response rate, ETS and DoR was compared in the two arms. Associations between response measurements and progression-free survival (PFS), post-progression survival (PPS) and OS were tested by univariate and multivariate Cox models. Prediction performance of each factor was estimated by C-index., Results: A significantly higher percentage of patients in the FOLFOXIRI plus bev arm achieved ETS ≥20%, when compared with the control arm (62.7% versus 51.9%, P = 0.025). Also the DoR was significantly higher in the triplet plus bev arm (43.4% versus 37.8%, P = 0.003). Both ETS and DoR were associated with PFS, PPS and OS at the univariate analyses and in the multivariate models stratified for other prognostic variables. Both ETS and DoR were able to predict survival as accurately as RECIST response., Conclusion: FOLFOXIRI plus bev improves ETS and DoR when compared with FOLFIRI plus bev. Achieving rapid and deep tumor shrinkage consistently delays tumor progression and prolongs survival in patients treated with first-line chemotherapy plus bev. ETS is a promising and valuable end point for clinical trials' design deserving further investigation., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Bone is an uncommon site of metastasis in patients with advanced hepatocellular carcinoma (HCC). Therefore, there are few studies concerning the natural history of bone metastasis in patients with HCC., Patients and Methods: Data on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 211 deceased HCC patients with evidence of bone metastasis were statistically analyzed., Results: The median age was 70 years; 172 patients were male (81.5%). The median overall survival was 19 months. The median time to the onset of bone metastasis was 13 months (22.2% at HCC diagnosis); 64.9% patients had multiple bone metastases. Spine was the most common site of bone metastasis (59.7%). Most of these lesions were osteolytic (82.4%); 88.5% of them were treated with zoledronic acid. At multivariate analysis, only the Child Score was significantly correlated with a shorter time to diagnosis of bone metastases (p = 0.001, HR = 1.819). The median survival from bone metastasis was 7 months. At multivariate analysis, HCC etiology (p = 0.005), ECOG performance status (p = 0.002) and treatment with bisphosphonate (p = 0.024) were associated with shorter survival after bone disease occurrence. The site of bone metastasis but not the number of bone lesions was associated with the survival from first skeletal related event (SRE) (p = 0.021) and OS (p = 0.001)., Conclusions: This study provides a significant improvement in the understanding the natural history of skeletal disease in HCC patients. An early and appropriate management of these patients is dramatically needed in order to avoid subsequent worsening of their quality of life.

A human outbreak of West Nile virus (WNV) infection caused by WNV lineage 2 is ongoing in northern Italy. Analysis of six WNV genome sequences obtained from clinical specimens demonstrated similarities with strains circulating in central Europe and Greece and the presence of unique amino acid changes that identify a new viral strain. In addition, WNV lineage 1 Livenza, responsible for a large outbreak in north-eastern Italy in 2012, was fully sequenced from a blood donor during this 2013 outbreak.

Objective: This study was conducted to assess the long-term effect of methylphenidate (MPH) or atomoxetine (ATX) on growth in attention-deficit/hyperactivity disorder (ADHD) drug-naïve children., Design: The study was an observational, post-marketing, fourth phase study., Methods: Data on height and weight were collected at baseline and every 6 months up to 24 months., Results: Both ATX and MPH lead to decreased height gain (assessed by means of z-scores); the effect was significantly higher for ATX than for MPH. At any time, height z-score decrease in the ATX group was higher than the corresponding decrease observed in the MPH group, but the difference was significantly relevant only during the first year of treatment. An increment of average weight was observed both in patients treated with MPH and in those treated with ATX. However, using Tanner's percentile, a subset of patients showed a degree of growth lower than expected. This negative effect was significantly higher for ATX than for MPH., Conclusions: We conclude that ADHD drugs show a negative effect on linear growth in children in middle term. Such effect appears more evident for ATX than for MPH.

Objective: The purpose of this study was to assess the cardiovascular effects of drugs used for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents treated in community care centers in Italy., Methods: This study was an open, prospective, observational study of youth with ADHD treated with atomoxetine (ATX) and methylphenidate (MPH). Measurements of blood pressure and heart rate, and electrocardiogram (ECG) assessment were performed at baseline and at regular intervals up to 24 months., Results: By June 2010, 1758 youth were enrolled in the Italian ADHD National Registry. Statistically significant increases were observed in cardiovascular measures: in the MPH group after 6 months in heart rate (+2.01, p = 0.01); in the ATX group after 6 months in diastolic pressure (+1.60, p = 0.01) and in heart rate (+2.93, p = 0.001), and after 12 months in heart rate (+3.26, p = 0.003). Compared with the baseline, 59 patients had an alteration of ECG during the follow-up period. Although at 12 months, the probability of detecting an abnormal ECG was higher in the MPH group than in the ATX group, only 2 out of 30 cases at 6 months with altered ECG were considered to have experienced serious adverse events. One case was treated with ATX and one with MPH, and arrhythmia was the detected abnormality., Conclusions: Treatment with MPH and ATX in youth appears to have a small but significant impact on the cardiovascular system. The long-term impact of these medications is unknown. Several clinically meaningless ECG alterations were observed mostly in MPH-treated youth. We therefore suggest evaluating cardiovascular risks at baseline.

Objective: Two main patterns of comorbidity have been described in bipolar disorder in children and adolescents: the first including preexisting attention-deficit/hyperactivity disorder (ADHD) and related disruptive behavior disorders and the second including anxiety disorders, namely, the association of co-occurring multiple anxiety disorders, usually predating the onset of bipolarity. This study was aimed at exploring whether ADHD and multiple anxiety disorders may exhibit different pathways to specific bipolar phenotypes., Method: We compared 49 youths (7 to 18 years) with bipolar disorder + ADHD without anxiety, 76 youths with bipolar disorder + multiple anxiety disorders without ADHD, and 52 youths with bipolar disorder without ADHD or multiple anxiety disorders who were referred to a third-level hospital and diagnosed according to DSM-IV-TR in the period 2005-2011. Subjects were evaluated for current and lifetime Axis I psychiatric disorders by using a structured clinical interview (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime Version) and followed up for at least 6 months., Results: Compared to both patients with bipolar disorder + multiple anxiety disorders and patients with bipolar disorder without ADHD and multiple anxiety disorders, patients with bipolar disorder + ADHD without anxiety were more frequently male, were younger, had an earlier onset of bipolar disorder, had a prevalent chronic course and irritable mood, were more likely to present with a bipolar disorder not otherwise specified diagnosis, had a greater clinical severity and functional impairment, had a manic/mixed index episode, had a higher risk of conduct disorder, and were more resistant to treatments, according to the CGI-Improvement scores (P < .0001). Patients with bipolar disorder + multiple anxiety disorders were similar to those with bipolar disorder without ADHD or multiple anxiety disorders, except for a higher rate of diagnosis of bipolar II disorder, more use of antidepressants, and less use of atypical antipsychotics., Conclusions: The presence of comorbid ADHD versus anxiety disorders is indicative of fundamental differences in the phenomenology of bipolar disorder in youth. While ADHD prior to bipolar disorder is associated with a specific bipolar phenotype, bipolar patients with multiple anxiety disorders are similar to "typical" bipolar patients., (© Copyright 2012 Physicians Postgraduate Press, Inc.)

Different moderators/mediators of risk are involved in developmental dyslexia (DD), but data are inconsistent. We explored the prevalence of season of birth and its association with gender and age of school entry in an Italian sample of dyslexic children compared to an Italian normal control group. The clinical sample included 498 children (345 boys, mean age 10.3 ± 2.1 years) with DD, the control sample 1,276 children (658 boys, mean age 10.8 ± 2.2 years) from four elementary schools from the same urban area, and with the same socio-economic status level. A prevalence of birth in autumn was found among children with DD compared to controls (34% versus 24%, p < 0.0001). Children with DD were more frequently males (p < 0.0001) and had a lower mean age of school entry (p < 0.0001). Regarding the distribution of ages, 11.4% of children with DD, but none of the subjects in the control group, started school before 5.7 years. Therefore, greater risk of DD was related to age of school entry (OR = 2.72), gender (OR = 2.16), and season of birth (OR = 1.21). Significant interactions between boys with DD born in autumn, and correct school of entry (OR = 2.56) were joint predictors of higher risk of DD. The association between birth in autumn and DD may be explained by the earlier age of school entry, which may be a critical element in the youngest children with DD or at risk to DD. Whether Italian school policy is oriented to anticipate the school entry, a closer detection of early learning disorders and associated risk factors (familial load, specific language disorders, and attention deficit hyperactivity disorder) should be warranted.

Objective: The primary aim of this study was to assess the efficacy of atomoxetine in improving ADHD and ODD symptoms in paediatric patients with ADHD and comorbid oppositional defiant disorder (ODD), non-responders to previous psychological intervention with parent support., Methods: This was a multicentre, randomised, placebo-controlled trial conducted in patients aged 6-15 years, with ADHD and ODD diagnosed according to the DSM-IV criteria by a structured clinical interview (K-SADS-PL). Only subjects who are non-responders to a 6-week standardized parent training were randomised to atomoxetine (up to 1.2 mg/kg/day) or placebo (in a 3:1 ratio) for the following 8-week double blind phase., Results: Only 2 of the 156 patients enrolled for the parent support phase (92.9% of males; mean age: 9.9 years), improved after the parent training program; 139 patients were randomised for entering in the study and 137 were eligible for efficacy analysis. At the end of the randomised double blind phase, the mean changes in the Swanson, Nolan and Pelham Rating Scale-Revised (SNAP-IV) ADHD subscale were -8.1+/-9.2 and -2.0+/-4.7, respectively in the atomoxetine and in the placebo group (p<0.001 between groups); changes in the ODD subscale were -2.7+/-4.1 and -0.3+/-2.6, respectively in the two groups (p=0.001 between groups). The CGI-ADHD-S score decreased in the atomoxetine group (median change at endpoint: -1.0) compared to no changes in the placebo group (p<0.001 between groups). Statistically significant differences between groups, in favour of atomoxetine, were found in the CHIP-CE scores for risk avoidance domain, emotional comfort and individual risk avoidance subdomains. An improvement in all the subscales of Conners Parents (CPRS-R:S) and Teacher (CTRS-R:S) subscales was observed with atomoxetine, except in the cognitive problems subscale in the CTRS-R:S. Only 3 patients treated with atomoxetine discontinued the study due to adverse events. No clinically significant changes of body weight, height and vital signs were observed in both groups., Conclusions: Treatment with atomoxetine of children and adolescents with ADHD and ODD, who did not initially respond to parental support, was associated with improvements in symptoms of ADHD and ODD, and general health status. Atomoxetine was well tolerated.

Aims and Background: We evaluated the activity in terms of time to progression (TTP) of mitomycin C and capecitabine in patients with advanced colorectal cancer who progressed after 2 lines of chemotherapy., Methods: Patients with advanced colorectal cancer undergoing third-line chemotherapy after failure of 5-FU with CPT-11 or oxaliplatin-based chemotherapy regimens were treated with capecitabine and mitomycin C., Results: Sixty-one patients were enrolled in this study. The median age was 55 years (range, 26-78 years) and the male:female ratio 21:40. We observed partial remissions in 5 patients (8%), stable disease in 25 patients (40%) and progression of disease in 31 patients (52%). Median TTP was 3 months and median survival was 6 months. Global toxicity was mild and entirely acceptable. Grade 3-4 hematological toxicity occurred in 12 patients and grade 3-4 nonhematological toxicity in 5 patients., Conclusions: The combination of capecitabine and mitomycin C could represent an effective and manageable treatment option for colorectal cancer patients failing previous chemotherapy regimens.

Objective: To determine the prevalence of teacher-rated ADHD symptoms in Italian first-graders., Method: 1891 first-graders aged 6.6-7.4 years were evaluated using a 34-item DSM-IV-referenced ADHD teacher rating questionnaire which included all the 18 DSM-IV ADHD diagnostic criteria, some Oppositional-Defiant Disorder (ODD), Conduct Disorder (CD), depression and anxiety symptoms, and questions about the child's social and scholastic impairment., Results: Criteria for ADHD were met in 7.1% (n=135) of the subjects (10.4% males and 3.8% females), 3.5% with the Inattentive subtype, 2.3% with the Hyperactive/Impulsive subtype and 1.3% with a Combined subtype. Internalizing (depression and/or anxiety) symptoms were reported in 25.9% of the subjects with ADHD symptoms, 17% showed externalizing symptoms (ODD or CD), and 12.6% showed both. Comorbid symptoms were 10 times more frequent than in subjects without ADHD symptoms. Inattentive subtype and scholastic impairment were more frequent in females, Hyperactive/Impulsive subtype and social impairment were more frequent in males., Conclusions: Even though the real prevalence of ADHD in first graders is presumably lower than that found in the present study, this screening procedure might allow detecting those children who could benefit from referral for more comprehensive assessments.

Objective: The aim of this study was to explore whether comorbid attention-deficit/hyperactivity disorder (ADHD) affects the clinical expression and outcome of obsessive-compulsive disorder (OCD) in a clinical sample., Method: A consecutive series of 94 children and adolescents (mean age, 13.6 +/- 2.8 years) with current diagnosis of OCD were included in the study. Twenty-four (25.5%) patients were diagnosed as having a comorbid ADHD. Subjects with OCD plus ADHD were compared with subjects with OCD but without ADHD., Results: Comorbid ADHD with OCD was significantly associated with a higher rate of males, an earlier onset of OCD, a greater psychosocial impairment, and a heavier comorbidity, namely, with bipolar disorder, tic disorder, and oppositional defiant disorder/conduct disorder. Phenomenology of obsessions and compulsions and outcome were not affected by ADHD comorbidity., Conclusions: A screening for ADHD should be performed in patients with OCD, as these patients and their parents are frequently not aware that the impairment may be partly due to a comorbid ADHD.

Objective: There are insufficient data on generalized anxiety disorder in children and adolescents. Symptoms and comorbidity of generalized anxiety disorder are described as a function of age, gender, and comorbidity in a consecutive series of referred children and adolescents., Method: One hundred fifty-seven outpatients (97 males and 60 females, 50 children and 107 adolescents, age range 7-18 years, mean age 13.4 +/- 2.7 years) were diagnosed as having generalized anxiety disorder, using historical information and a structured clinical interview (Diagnostic Interview for Children and Adolescents-Revised) according to the DSM-IV., Results: Feelings of tension, apprehensive expectations, negative self-image, need for reassurance, irritability, and physical complaints were reported in more than 75% of the participants. Differences in symptomatology according to age and gender were nonsignificant. Depressive disorder was the most frequent comorbidity, being present in 56% of the patients. Comorbid anxiety disorders were present in about 75% of the patients, and 21% showed externalizing disorders. Subjects with comorbid depression had less anxiety comorbidity, subjects with comorbid separation anxiety disorder had higher rates of panic disorder, and subjects with comorbid externalizing disorders had higher rates of bipolar disorder., Conclusions: Referred children and adolescents with generalized anxiety disorder are heavily symptomatic and have frequent comorbidity. A more precise definition of the clinical picture may help early diagnosis and prevention of superimposed mental disorders.

We describe a consecutive clinical sample of children and adolescents with bipolar disorder (BD), in order to define the pattern of comorbid externalizing disorders and to explore the possible influence of such a comorbidity on their cross-sectional and longitudinal clinical characteristics. The sample consisted of 59 bipolar patients: 35 males and 24 females, with a mean age 14.6 +/- 3 years (range, 7 to 18 years), diagnosed as either type I or II according to DSM-IV. All patients were screened for psychiatric disorders using historical information and a clinical interview, the Diagnostic Interview for Children and Adolescents-Revised (DICA-R). Severity and subsequent outcome of the symptomatology were recorded with the Clinical Global Impression (CGI), Severity and Improvement Scales, at the baseline and thereafter monthly for a period up to 48 months. BD disorder type I was present in 37 (62.7%) of the patients; 14 (23.7%) were affected by attention deficit-hyperactivity disorder (ADHD) and 10 (16.9%) by conduct disorder (CD). Comorbid ADHD was associated with an earlier onset of BD, while CD was highly associated with BD type I. Anxiety disorders appeared more represented in patients without CD. At the end of the observation, a lower clinical improvement was recorded in patients with CD. In our children and adolescents with BD, comorbidity with externalizing disorders such as ADHD and CD is common. The clinical implications of comorbid ADHD and CD are rather different. ADHD can be viewed as a precursor of a child-onset subtype of BD, while CD might represent a prodromal or a concomitant behavioral complication that identifies a more malignant and refractory form of BD.

Objective: To study the distribution of prior scoliosis among patients with primary adult-onset cervical dystonia (CD) and matched control subjects., Methods: Case and control subjects were selected among consecutive outpatients attending four Italian centers. Control outpatients were matched for age (+/-5 years), sex, and referral center. Information on prior scoliosis, other spine diseases, and family history of dystonia was obtained by a standardized questionnaire and supported by medical records. Conditional logistic regression models were used to adjust simultaneously for age, disease duration, and education level and to determine the independent association of exposure variables with the outcome., Results: Prior scoliosis developing in middle or late childhood or at around the puberty occurred more frequently among 72 case patients than among 144 neurologic control subjects. No subject reported conditions considered to be responsible for secondary scoliosis. The association of scoliosis and CD was not confounded by age, duration of disease, education level, other spine diseases, or family history of dystonia (adjusted odds ratio [OR] 6.8; 95% CI 1.5 to 29.5; p = 0.011). The OR of family history of dystonia (18.7; 95% CI 2.4 to 147.5; p = 0.005) fell to 11.7 (95% CI 1.3 to 103; p = 0.03) after controlling for scoliosis., Conclusions: Prior scoliosis may increase the risk of developing CD. The observed decrease in the magnitude of the association between family history of dystonia and CD after controlling for scoliosis suggests a link between the two conditions.

This study reports on self-reported depressive symptoms, assessed with the Children's Depression Inventory (CDI), in a school sample of 685 Italian students. The participants were 254 males and 431 females, the age range of the subjects was 8 to 17 years (mean age 13.0 +/- 2.8 years). The CDI mean score was 10.49 +/- 2.76. According to our data, about 10% of the subjects scored higher than the clinical threshold of 20. More than 1/3 of the students reported thoughts of death, but only 2.2% had explicit suicidal ideation. Girls scored higher than boys, and young adolescents (11-13 years) scored lower than pre-pubertal children and older adolescents, and showed fewer thoughts of death. Factorial analysis yielded seven factors, a general factor with no predominant theme, two factors related to academic self-image and body image, and four related to anhedonia-withdrawal, hypocondria-asthenia, irritability-opposition, and loss of appetite.

We studied the relationships between blepharospasm (BSP) and menopause/menarche in female patients with primary BSP (n = 83) and age-matched healthy (n = 83) and disease controls (n = 83). BSP patients and matched controls had comparable age at menopause, and there was no correlation between age at menopause and age at BSP onset. Thus, menopause probably exerts no significant influence on the age-dependent development of BSP. BSP cases tended to have a later menarche than either group of controls. The association was independent of age, disease duration and education level. Because the higher the age at menarche, the higher the age at BSP onset, later menarche was unlikely to be a risk factor for BSP. Rather, the two conditions may share pathophysiologic mechanisms, for example minor abnormality of neurotransmitter systems controlling both the motor system and the maturation of the hypothalamic-pituitary-gonadal axis responsible for the onset of puberty., (Copyright 2002 S. Karger AG, Basel)

Anxiety disorders are common in patients with depressive disorders. This preliminary study investigated some clinical correlates of comorbidity between dysthymic disorder (DD) and generalized anxiety disorder (GAD) in a clinically referred sample of children and adolescents. After psychiatric evaluation, including a diagnostic clinical interview (DICA-R), 51 patients (25 males and 26 females, mean age 13.1 years) with an index diagnosis of DD associated with GAD were compared with 22 patients (13 males and 9 females, mean age 12.9 years) diagnosed as having pure DD. The comparison between subjects (DD with or without GAD) regarding the number of depressive symptoms did not show a significant main effect of group. Suicidal ideation was significantly more frequent in the group with comorbid GAD. Internalizing disorders were more frequent in the group of DD with GAD, while externalizing disorders were more frequent in the group without GAD. Functional impairment, assessed with the Children's Global Assessment Scale, did not show significant differences between the two groups. Data are discussed in the light of conceptualizations about the relationship between chronic anxiety and depressive disorders., (Copyright 2002 S. Karger AG, Basel)

Aim of this study is to examine the effect of depressive comorbidity in 108 children and adolescents with Generalized Anxiety Disorder (GAD). Fifty-five patients with GAD and depression were compared with 53 patients with GAD without depression. Age, gender and socioeconomic status did not differentiate the groups. Patients with comorbid depression had significantly more anxiety symptoms than patients without depression. Clinical presentation of GAD and pattern of comorbidity was similar in the two groups. Subjects with comorbid depression showed a more severe functional impairment, assessed with C-GAS. Data are discussed in the light of conceptualizations about the relationship between anxiety and depression.

This study investigated the symptomatology and comorbidity of generalized anxiety disorder (GAD) in a clinically referred sample of Italian children and adolescents as a function of age and gender. The sample consisted of 58 subjects (19 children and 39 adolescents), 23 males and 35 females screened from consecutively referred children and adolescents. This sample was divided into two groups of younger children (19 subjects, eight males and 11 females aged 7 to 12 years; mean age, 9.6) and adolescents (39 subjects, 15 males and 24 females aged 12 to 18 years; mean age, 14.9). Feelings of tension, apprehension, the need for reassurance, irritability, negative self-image, and physical complaints were reported in more than 70% of the subjects. Differences in the symptomatic profile between males and females were not significant. Children and adolescents did not show significant differences in the number of symptoms. The need for reassurance was significantly more frequent in children, and brooding was more frequent in adolescents. Other anxiety disorders were commonly comorbid with GAD. More than half of the patients with GAD showed a concurrent depressive disorder; no differences were found for comorbidity between children and adolescents, except for higher rates of separation anxiety disorder in children.