@article {10826, title = {Off-label drugs use in pediatric palliative care.}, journal = {Ital J Pediatr}, volume = {44}, year = {2018}, month = {2018 Nov 29}, pages = {144}, abstract = {

BACKGROUND: Paediatric palliative care (PPC) aim to ensure the control of symptoms and the best possible quality of life for patients whose underlying disease, characterized by an unstoppable evolution and negative prognosis, no longer responds to specific treatments. The scientific evidence in this context are very deficient and, in order to obtain welfare objectives consistent with the situation, in the overwhelming majority of cases the prescription of drugs is off-label for indication of use and/or for age and/or for way of administration and/or formulation. The Agenzia Italiana del Farmaco - AIFA and the Italian Society of Palliative Care (Societ{\`a} Italiana di Cure Palliative - SICP), under a dedicated working group, wrote a document that collects the scientific evidence available to support the off-label use of medicines more frequently used in PPC. The goal is to certify the consolidated off-label use of these drugs and propose their use under the Law 648/96, in the absence of data from its pivotal clinical trials. Aim of the commentary is to report the conditions for this important work and to present the 10 drugs, usually used off-label in PPC and in pain therapy, now included in Law 648/96.

CONCLUSION: This work is deemed essential to resolve, at least in part, the lack of availability of medicines researched and approved.

}, issn = {1824-7288}, doi = {10.1186/s13052-018-0584-8}, author = {De Zen, Lucia and Marchetti, Federico and Barbi, Egidio and Benini, Franca} } @article {10549, title = {ADA2 deficiency (DADA2) as an unrecognised cause of early onset polyarteritis nodosa and stroke: a multicentre national study.}, journal = {Ann Rheum Dis}, volume = {76}, year = {2017}, month = {2017 Oct}, pages = {1648-1656}, abstract = {

OBJECTIVES: To analyse the prevalence of mutations in patients diagnosed with early onset livedo reticularis and/or haemorrhagic/ischaemic strokes in the context of inflammation or polyarteritis nodosa (PAN). Forty-eight patients from 43 families were included in the study.

METHODS: Direct sequencing of was performed by Sanger analysis. Adenosine deaminase 2 (ADA2) enzymatic activity was analysed in monocyte isolated from patients and healthy controls incubated with adenosine and with or without an ADA1 inhibitor.

RESULTS: Biallelic homozygous or compound heterozygous mutations were detected in 15/48 patients. A heterozygous disease-associated mutation (p.G47V) was observed in two affected brothers. The mean age of onset of the genetically positive patients was 24 months (6 months to 7 years). Ten patients displayed one or more cerebral strokes during their disease course. Low immunoglobulin levels were detected in six patients. Thalidomide and anti-TNF (tumour necrosis factor) blockers were the most effective drugs. Patients without mutations had a later age at disease onset, a lower prevalence of neurological and skin manifestations; one of these patients displayed all the clinical features of adenosine deaminase 2deficiency (DADA2) and a defective enzymatic activity suggesting the presence of a missed mutation or a synthesis defect.

CONCLUSIONS: DADA2 accounts for paediatric patients diagnosed with PAN-like disease and strokes and might explain an unrecognised condition in patients followed by adult rheumatologist. Timely diagnosis and treatment with anti-TNF agents are crucial for the prevention of severe complications of the disease. Functional assay to measure ADA2 activity should complement genetic testing in patients with non-confirming genotypes.

}, keywords = {Adenosine Deaminase, Adolescent, Age of Onset, Case-Control Studies, Child, Child, Preschool, DNA Mutational Analysis, Female, Heterozygote, Homozygote, Humans, Immunoglobulins, Immunosuppressive Agents, Infant, Intercellular Signaling Peptides and Proteins, Italy, Livedo Reticularis, Male, Pedigree, Polyarteritis Nodosa, Stroke, Thalidomide, Tumor Necrosis Factor-alpha, Young Adult}, issn = {1468-2060}, doi = {10.1136/annrheumdis-2016-210802}, author = {Caorsi, Roberta and Penco, Federica and Grossi, Alice and Insalaco, Antonella and Omenetti, Alessia and Alessio, Maria and Conti, Giovanni and Marchetti, Federico and Picco, Paolo and Tommasini, Alberto and Martino, Silvana and Malattia, Clara and Gallizi, Romina and Podda, Rosa Anna and Salis, Annalisa and Falcini, Fernanda and Schena, Francesca and Garbarino, Francesca and Morreale, Alessia and Pardeo, Manuela and Ventrici, Claudia and Passarelli, Chiara and Zhou, Qing and Severino, Mariasavina and Gandolfo, Carlo and Damonte, Gianluca and Martini, Alberto and Ravelli, Angelo and Aksentijevich, Ivona and Ceccherini, Isabella and Gattorno, Marco} } @article {1879, title = {Burden of disease caused by otitis media: systematic review and global estimates.}, journal = {PLoS One}, volume = {7}, year = {2012}, month = {2012}, pages = {e36226}, abstract = {

BACKGROUND: Otitis media (OM) is a leading cause of health care visits and drugs prescription. Its complications and sequelae are important causes of preventable hearing loss, particularly in developing countries. Within the Global Burden of Diseases, Injuries, and Risk Factors Study, for the year 2005 we estimated the incidence of acute OM, chronic suppurative OM, and related hearing loss and mortality for all ages and the 21 WHO regional areas.

METHODS: We identified risk factors, complications and sequelae of OM. We carried out an extensive literature review (Medline, Embase, Lilacs and Wholis) which lead to the selection of 114 papers comprising relevant data. Data were available from 15 of the 21 WHO regions. To estimate incidence and prevalence for all countries we adopted a two stage approach based on risk factors formulas and regression modelling.

RESULTS: Acute OM incidence rate is 10.85\% i.e. 709 million cases each year with 51\% of these occurring in under-fives. Chronic suppurative OM incidence rate is 4.76 {\textperthousand} i.e. 31 million cases, with 22.6\% of cases occurring annually in under-fives. OM-related hearing impairment has a prevalence of 30.82 per ten-thousand. Each year 21 thousand people die due to complications of OM.

CONCLUSIONS: Our study is the first attempt to systematically review the available information and provide global estimates for OM and related conditions. The overall burden deriving from AOM, CSOM and their sequelae is considerable, particularly in the first five years of life and in the poorest countries. The findings call for incorporating OM-focused action within preventive and case management strategies, with emphasis on the more affected.

}, keywords = {Cost of Illness, Hearing Loss, Humans, Internationality, Otitis Media}, issn = {1932-6203}, doi = {10.1371/journal.pone.0036226}, author = {Monasta, Lorenzo and Ronfani, Luca and Marchetti, Federico and Montico, Marcella and Vecchi Brumatti, Liza and Bavcar, Alessandro and Grasso, Domenico and Barbiero, Chiara and Tamburlini, Giorgio} } @article {1902, title = {Management of cryptorchidism: a survey of clinical practice in Italy.}, journal = {BMC Pediatr}, volume = {12}, year = {2012}, month = {2012}, pages = {4}, abstract = {

BACKGROUND: An evidence-based Consensus on the treatment of undescended testis (UT) was recently published, recommending to perform orchidopexy between 6 and 12 months of age, or upon diagnosis and to avoid the use of hormones. In Italy, current practices on UT management are little known. Our aim was to describe the current management of UT in a cohort of Italian children in comparison with the Consensus guidelines. As management of retractile testis (RT) differs, RT cases were described separately.

METHODS: Ours is a retrospective, multicenter descriptive study. An online questionnaire was filled in by 140 Italian Family Paediatricians (FP) from Associazione Culturale Pediatri (ACP), a national professional association of FP. The questionnaire requested information on all children with cryptorchidism born between 1/01/2004 and 1/01/2006. Data on 169 children were obtained. Analyses were descriptive.

RESULTS: Overall 24\% of children were diagnosed with RT, 76\% with UT. Among the latter, cryptorchidism resolved spontaneously in 10\% of cases at a mean age of 21.6 months. Overall 70\% of UT cases underwent orchidopexy at a mean age of 22.8 months (SD 10.8, range 1.2-56.4), 13\% of whom before 1 year. The intervention was performed by a paediatric surgeon in 90\% of cases, with a success rate of 91\%. Orchidopexy was the first line treatment in 82\% of cases, while preceded by hormonal treatment in the remaining 18\%. Hormonal treatment was used as first line therapy in 23\% of UT cases with a reported success rate of 25\%. Overall, 13 children did not undergo any intervention (mean age at last follow up 39.6 months). We analyzed the data from the 5 Italian Regions with the largest number of children enrolled and found a statistically significant regional difference in the use of hormonal therapy, and in the use of and age at orchidopexy.

CONCLUSIONS: Our study showed an important delay in orchidopexy. A quarter of children with cryptorchidism was treated with hormonal therapy. In line with the Consensus guidelines, surgery was carried out by a paediatric surgeon in the majority of cases, with a high success rate.

}, keywords = {Child, Preschool, Chorionic Gonadotropin, Cryptorchidism, Gonadotropin-Releasing Hormone, Guideline Adherence, Humans, Infant, Italy, Male, Middle Aged, Orchiopexy, Pediatrics, Physician{\textquoteright}s Practice Patterns, Practice Guidelines as Topic, Questionnaires, Retrospective Studies, Treatment Outcome}, issn = {1471-2431}, doi = {10.1186/1471-2431-12-4}, author = {Marchetti, Federico and Bua, Jenny and Tornese, Gianluca and Piras, Gianni and Toffol, Giacomo and Ronfani, Luca} } @article {1940, title = {Recurrent fever and fitful abdominal pain in a child.}, journal = {Gastroenterology}, volume = {143}, year = {2012}, month = {2012 Aug}, pages = {e11-2}, keywords = {Abdominal Pain, Child, Female, Fever, Giant Lymph Node Hyperplasia, Humans, Recurrence}, issn = {1528-0012}, doi = {10.1053/j.gastro.2012.01.050}, author = {Zanchi, Chiara and Paloni, Giulia and Marchetti, Federico} } @article {1818, title = {Should cardiac involvement be included in the criteria for diagnosis of Churg Strauss syndrome?}, journal = {J Pediatr}, volume = {160}, year = {2012}, month = {2012 Apr}, pages = {707}, keywords = {Adolescent, Churg-Strauss Syndrome, Heart Diseases, Humans, Male}, issn = {1097-6833}, doi = {10.1016/j.jpeds.2011.09.057}, author = {Amaddeo, Alessandro and Ventura, Alessandro and Marchetti, Federico and Benettoni, Alessandra and Londero, Margherita} } @article {1787, title = {Vertebral defects in patients with Peters plus syndrome and mutations in B3GALTL.}, journal = {Ophthalmic Genet}, volume = {32}, year = {2011}, month = {2011 Nov}, pages = {256-8}, keywords = {Abnormalities, Multiple, Alternative Splicing, Child, Preschool, Cleft Lip, Consanguinity, Cornea, Female, Galactosyltransferases, Glucosyltransferases, Growth Disorders, Humans, Limb Deformities, Congenital, Point Mutation, Spine}, issn = {1744-5094}, doi = {10.3109/13816810.2011.587082}, author = {Faletra, Flavio and Athanasakis, Emmanouil and Minen, Federico and Fornasier, Federico and Marchetti, Federico and Gasparini, Paolo} } @article {1629, title = {Hepatic glycogenosis in an adolescent with diabetes.}, journal = {J Pediatr}, volume = {157}, year = {2010}, month = {2010 Dec}, pages = {1042}, keywords = {Adolescent, Diabetes Mellitus, Type 1, Female, Glycogen Storage Disease, Humans, Liver Diseases}, issn = {1097-6833}, doi = {10.1016/j.jpeds.2010.06.018}, author = {Bua, Jenny and Marchetti, Federico and Faleschini, Elena and Ventura, Alessandro and Bussani, Rossana} }