Applying the Participatory Slow Design Approach to a mHealth Application for Family Caregivers in Pediatric Ear, Nose, and Throat Surgery.

Pediatric ear, nose, and throat (ENT) surgery is very common, and its outcomes may improve with family education. In this regard, mobile health (mHealth) applications (apps), which are on the rise due to digital transformation, can be beneficial in healthcare. This study outlines the user-centered design and development of a mHealth app (version 5.15.0) to support family caregivers during the perioperative process of pediatric ENT surgery. Conducted over two years in an Italian maternal and child health hospital (January 2020-May 2022), the study employed a participatory design method based on the Information System Research (ISR) framework and guided by the principles of Slow Medicine. Utilizing the Relevance, Rigor, and Design cycles of the ISR framework, the mHealth app's content, functionalities, and technical features were defined and developed. A committee of fifteen experts guided the process with input from 25 family caregivers and 24 healthcare providers enrolled in the study. The mHealth app content was structured around five crucial educational moments characterizing the ENT perioperative period, providing evidence-based information on surgical procedures, strategies for preparing children for hospitalization and surgery, pain management, and post-discharge care. The mHealth app featured a function that sends customized notifications to guide caregivers at specific perioperative stages. The development of mHealth apps by implementing a rigorous, participatory, and Slow design process can foster accessible and family-centered information and care in the field of maternal and child health and beyond.

Short Oral Antibiotic Therapy for Pediatric Febrile Urinary Tract Infections: A Randomized Trial.

BACKGROUND AND OBJECTIVES: Febrile urinary tract infection (fUTI) in well-appearing children is conventionally treated with a standard 10-day course of oral antibiotic. The objective of this study is to determine the noninferiority (5% threshold) of a 5-day amoxicillin-clavulanate course compared with a 10-day regimen to treat fUTIs. METHODS: This is a multicenter, investigator-initiated, parallel-group, randomized, controlled trial. We randomly assigned children aged 3 months to 5 years with a noncomplicated fUTI to receive amoxicillin-clavulanate 50 + 7.12 mg/kg/day orally in 3 divided doses for 5 or 10 days. The primary end point was the recurrence of a urinary tract infection within 30 days after the completion of therapy. Secondary end points were the difference in prevalence of clinical recovery, adverse drug-related events, and resistance to amoxicillin-clavulanic acid and/or to other antibiotics when a recurrent infection occurred. RESULTS: From May 2020 through September 2022, 175 children were assessed for eligibility and 142 underwent randomization. The recurrence rate within 30 days of the end of therapy was 2.8% (2/72) in the short group and 14.3% (10/70) in the standard group. The difference between the 2 groups was -11.51% (95% confidence interval, -20.54 to -2.47). The recurrence rate of fUTI within 30 days from the end of therapy was 1.4% (1/72) in the short group and 5.7% (4/70) in the standard group (95% confidence interval, -10.4 to 1.75). CONCLUSIONS: This study demonstrates that a 5-day course is noninferior to a 10-day course of oral amoxicillin-clavulanate.

Study protocol for a randomised controlled trial to determine the effectiveness of a mHealth application as a family supportive tool in paediatric otolaryngology perioperative process (TONAPP).

BACKGROUND: Otorhinolaryngology (ORL) surgery is common in children, but hospitalisation, surgery, and home care after discharge are stressful experiences for young patients and their family caregivers. Findings from literature highlight a lack of time in hospitals to support ORL surgery children and their caregivers through the perioperative process, along with the risks of caregivers' autonomous web or social media resources investigation. Therefore, this study aims to evaluate the effectiveness of a mobile health application with content to support ORL patients and their caregivers in the perioperative period to reduce caregiver anxiety and child distress compared to standard care. METHODS: An open-label, two-arm randomised control trial design is being adopted. The intervention consists of a mobile health application with content to support ORL patients and their caregivers during the perioperative period. One hundred eighty participants will be enrolled and randomly assigned to the experimental group using the mHealth application or the control group. The control group receives standard information and education about the ORL perioperative period from healthcare providers orally or through brochures. The primary outcome is the difference between the intervention and control groups in preoperative caregiver state anxiety. Secondary outcome measures include children's distress before surgery and family preparation for hospitalisation. DISCUSSION: The results of this study will be critical to the implementation of a new and safe model for the management of care and education in paediatrics. This model can achieve positive organisational and health outcomes by supporting continuity of care and empowering citizens to have informed participation and satisfaction in paediatric health promotion and management. TRIAL REGISTRATION: Trial identifier: NCT05460689 registry name: ClinicalTrials.gov. Date of registration: July 15, 2022. Last update posted: February 23, 2023.

Differences in birth weight between immigrants' and natives' children in Europe and Australia: a LifeCycle comparative observational cohort study.

OBJECTIVE: Research on adults has identified an immigrant health advantage, known as the 'immigrant health paradox', by which migrants exhibit better health outcomes than natives. Is this health advantage transferred from parents to children in the form of higher birth weight relative to children of natives? SETTING: Western Europe and Australia. PARTICIPANTS: We use data from nine birth cohorts participating in the LifeCycle Project, including five studies with large samples of immigrants' children: Etude Longitudinale Française depuis l'Enfance-France (N=12 494), the Raine Study-Australia (N=2283), Born in Bradford-UK (N=4132), Amsterdam Born Children and their Development study-Netherlands (N=4030) and the Generation R study-Netherlands (N=4877). We include male and female babies born to immigrant and native parents. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome is birth weight measured in grams. Different specifications were tested: birth weight as a continuous variable including all births (DV1), the same variable but excluding babies born with over 4500 g (DV2), low birth weight as a 0-1 binary variable (1=birth weight below 2500 g) (DV3). Results using these three measures were similar, only results using DV1 are presented. Parental migration status is measured in four categories: both parents natives, both born abroad, only mother born abroad and only father born abroad. RESULTS: Two patterns in children's birth weight by parental migration status emerged: higher birth weight among children of immigrants in France (+12 g, p<0.10) and Australia (+40 g, p<0.10) and lower birth weight among children of immigrants in the UK (-82 g, p<0.05) and the Netherlands (-80 g and -73 g, p<0.001) compared with natives' children. Smoking during pregnancy emerged as a mechanism explaining some of the birth weight gaps between children of immigrants and natives. CONCLUSION: The immigrant health advantage is not universally transferred to children in the form of higher birth weight in all host countries. Further research should investigate whether this cross-national variation is due to differences in immigrant communities, social and healthcare contexts across host countries.

Final adult height in childhood-onset inflammatory bowel disease.

BACKGROUND: Long-term growth may be compromised in patients with inflammatory bowel disease (IBD). The aims of the study were to evaluate the final height in a cohort of patients with pediatric-onset IBD with respect to genetic target and to determine factors influencing long-term growth. METHODS: This is a monocentric retrospective cohort study. All patients with diagnosed prepubertal onset IBD were enrolled. Patients were classified into two groups on the basis of the achievement of target height at time of the last follow-up. Clinical parameters were also recorded. RESULTS: Eighty-tow patients were identified: 42 with Crohn's disease (CD) and 40 with ulcerative colitis (UC). The mean age at diagnosis was 11.0 (SD 4.0) years. Eighty-nine percent of patients achieved final target height. Mean difference between final and target height was -1.2 cm (SD: 5,4). No statistical significance was detected between CD and UC patients final height (P=0.16). Growth failure at the diagnosis and disease severity were the only factors associated with final height achievement failure (P=0.001 and P=0.01 respectively). CONCLUSIONS: Most part of CD and UC patients achieve the target final height. Disease severity and low height at diagnosis seem to be the two best predictive factors for low final height.

CARE 1000: randomized controlled trial for the evaluation of the effectiveness of a mHealth app for supporting the first 1000 days of life.

BACKGROUND: Recent developments in eHealth and mobile health (mHealth), as well as the introduction of information and communication technology innovations in clinical practice, such as telemedicine, telemonitoring, and remote examinations, are already changing the current scenario and will continue to generate innovations in the coming decades. The widespread use of mobile devices, with an estimated nearly 30 billion devices and more than 325,000 apps worldwide, will provide various opportunities for people to take control of their own health. Already in 2017, most of the apps available were focused on pregnancy support, more than any other medical field. There have been some reported experiences with social media and mHealth that could benefit the promotion of maternal physical and mental health during pregnancy. However, many apps targeting the first 1000 days of a child's life do not consider the continuity between the prenatal and postnatal periods and their joint impact on maternal and child health. The aim of this study is to evaluate the effectiveness of this mHealth app to support women during the first 1000 days (from conception to 24 months of age) and to improve health prevention behaviours such as immunizations during pregnancy, weight gain during pregnancy, abstinence from smoking and alcohol consumption, and adherence to the routine childhood immunization schedule. In addition, the study aims to understand the level of appreciation of this mHealth app as a tool to overcome information and communication gaps between patients and institutions. METHODS: Conduction of a randomized controlled trial. DISCUSSION: Our results will be relevant for improving this mHealth app to promote health and prevention and to support the first 1000 days of life for both mother and child. Our results will be relevant to the future expansion of such an mHealth app to promote positive health-related outcomes in patients and co-user satisfaction and to support the organization of health services. TRIAL REGISTRATION: ClinicalTrials.gov NCT05500339.

Spread of Respiratory Pathogens During the COVID-19 Pandemic Among Children in the Northeast of Italy.

The social distancing measures adopted during the coronavirus disease 2019 (COVID-19) pandemic led to a profound change in the behavioral habits of the population. This study analyzes the impact of restriction measures on the shaping of the epidemiology of common winter respiratory pathogens in the pediatric population of northeast of Italy. From August 2020 to March 2021, a total of 1,227 nasopharyngeal swabs from symptomatic pediatric patients were tested for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A and B, adenovirus, other coronaviruses, parainfluenza virus 1-4, enterovirus, bocavirus, metapneumovirus, respiratory syncytial virus, rhinovirus, Bordetella pertussis, Bordetella parapertussis, and Mycoplasma pneumoniae. To relate virus positivity with the clinic characteristics of the subjects enrolled, multinomial logistic models were estimated. SARS-CoV-2 was detected in 5.2% of the children; fever resulted as risk factor for infection [relative risk ratio (RRR) = 2.88, p = 0.034]. Rhinovirus was detected in the 40.7% of the subjects, with cough and rhinitis as risk factors (respectively, RRR = 1.79, p = 0.001 and RRR = 1.53, p = 0.018). Other coronaviruses were found in 10.8% of children and were associated to pharyngodynia (RRR = 4.94, p < 0.001). Adenovirus, observed in 11.6% of subjects, showed to have fever as risk factor (RRR = 6.44, p < 0.001). Bocavirus was detected in 3.2% of children. In conclusion, our results showed that social isolation measures had an impact on the circulation of RSV and influenza, although children under the age of 2 were most affected by the other respiratory infections. Therefore, this study highlights the need for continuing surveillance for a delayed spread of RSV and other respiratory pathogens.

Burden of non-communicable diseases among adolescents aged 10-24 years in the EU, 1990-2019: a systematic analysis of the Global Burden of Diseases Study 2019.

BACKGROUND: Disability and mortality burden of non-communicable diseases (NCDs) have risen worldwide; however, the NCD burden among adolescents remains poorly described in the EU. METHODS: Estimates were retrieved from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Causes of NCDs were analysed at three different levels of the GBD 2019 hierarchy, for which mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) were extracted. Estimates, with the 95% uncertainty intervals (UI), were retrieved for EU Member States from 1990 to 2019, three age subgroups (10-14 years, 15-19 years, and 20-24 years), and by sex. Spearman's correlation was conducted between DALY rates for NCDs and the Socio-demographic Index (SDI) of each EU Member State. FINDINGS: In 2019, NCDs accounted for 86·4% (95% uncertainty interval 83·5-88·8) of all YLDs and 38·8% (37·4-39·8) of total deaths in adolescents aged 10-24 years. For NCDs in this age group, neoplasms were the leading causes of both mortality (4·01 [95% uncertainty interval 3·62-4·25] per 100 000 population) and YLLs (281·78 [254·25-298·92] per 100 000 population), whereas mental disorders were the leading cause for YLDs (2039·36 [1432·56-2773·47] per 100 000 population) and DALYs (2040·59 [1433·96-2774·62] per 100 000 population) in all EU Member States, and in all studied age groups. In 2019, among adolescents aged 10-24 years, males had a higher mortality rate per 100 000 population due to NCDs than females (11·66 [11·04-12·28] vs 7·89 [7·53-8·23]), whereas females presented a higher DALY rate per 100 000 population due to NCDs (8003·25 [5812·78-10 701·59] vs 6083·91 [4576·63-7857·92]). From 1990 to 2019, mortality rate due to NCDs in adolescents aged 10-24 years substantially decreased (-40·41% [-43·00 to -37·61), and also the YLL rate considerably decreased (-40·56% [-43·16 to -37·74]), except for mental disorders (which increased by 32·18% [1·67 to 66·49]), whereas the YLD rate increased slightly (1·44% [0·09 to 2·79]). Positive correlations were observed between DALY rates and SDIs for substance use disorders (rs=0·58, p=0·0012) and skin and subcutaneous diseases (rs=0·45, p=0·017), whereas negative correlations were found between DALY rates and SDIs for cardiovascular diseases (rs=-0·46, p=0·015), neoplasms (rs=-0·57, p=0·0015), and sense organ diseases (rs=-0·61, p=0·0005). INTERPRETATION: NCD-related mortality has substantially declined among adolescents in the EU between 1990 and 2019, but the rising trend of YLL attributed to mental disorders and their YLD burden are concerning. Differences by sex, age group, and across EU Member States highlight the importance of preventive interventions and scaling up adolescent-responsive health-care systems, which should prioritise specific needs by sex, age, and location. FUNDING: Bill & Melinda Gates Foundation.

Incidence, prevalence and disability associated with neurological disorders in Italy between 1990 and 2019: an analysis based on the Global Burden of Disease Study 2019.

BACKGROUND: Neurological conditions are highly prevalent and disabling, in particular in the elderly. The Italian population has witnessed sharp ageing and we can thus expect a rising trend in the incidence, prevalence and disability of these conditions. METHODS: We relied on the Global Burden of Disease 2019 study to extract Italian data on incidence, prevalence and years lived with a disability (YLDs) referred to a broad set of neurological disorders including, brain and nervous system cancers, stroke, encephalitis, meningitis, tetanus, traumatic brain injury, and spinal cord injury. We assessed changes between 1990 and 2019 in counts and age-standardized rates. RESULTS: The most prevalent conditions were tension-type headache, migraine, and dementias, whereas the most disabling were migraine, dementias and traumatic brain injury. YLDs associated with neurological conditions increased by 22.5%, but decreased by 2.3% in age-standardized rates. The overall increase in prevalence and YLDs counts was stronger for non-communicable diseases with onset in old age compared to young to adult-age onset ones. The same trends were in the opposite direction when age-standardized rates were taken into account. CONCLUSIONS: The increase in YLDs associated with neurological conditions is mostly due to population ageing and growth: nevertheless, lived disability and, as a consequence, impact on health systems has increased. Actions are needed to improve outcome and mitigate disability associated with neurological conditions, spanning among diagnosis, treatment, care pathways and workplace interventions.

Essential Infantile Esotropia: A Course of Treatment From Our Experience.

Background: Essential infantile esotropia (EIE) is the most common type of childhood esotropia. Although its classical approach is surgical, less invasive techniques have been proposed as an adjunct or alternative to traditional surgery. Among them, chemodenervation with botulinum toxin (BT) has been investigated, showing variable and sometimes conflicting results. Objectives: To compare the outcomes of bilateral BT injection and traditional surgery in a pediatric population with EIE in order to optimize and standardize the therapeutic approach. Other purposes are to evaluate whether early intervention may prevent the onset of vertical ocular deviation (which is part of the clinical picture of EIE) and/or influence the development of fine stereopsis, and also to assess changes in refractive status over time among the enrolled population. Methods: A retrospective consecutive cohort study was conducted in 86 children aged 0-48 months who underwent correction of EIE. The primary intervention in naïve subjects was either bilateral BT injection (36 subjects, "BT group") or strabismus surgery (50 subjects, "surgery group"). Results: Overall, BT chemodenervation (one or two injections) was effective in 13 (36.1%) subjects. With regard to residual deviation angle, the outcomes at least 5 years after the last intervention were overlapping in children receiving initial treatment with either injection or surgery; however, the success rate of primary intervention in the surgery group was higher, and the average number of interventions necessary to achieve orthotropia was smaller. Both early treatment with chemodenervation and surgery at a later age were not found to prevent the onset of vertical ocular deviation, whereas, surprisingly, the percentage of subjects developing fine stereopsis was higher in the surgery group. Finally, with regard to the change in refractive status over time, most of the subjects increased their initial hyperopia, whereas 10% became myopic. Conclusions: Our data suggest that a single bilateral BT injection by age 2 years should be considered as the first-line treatment of EIE without vertical component; whereas, traditional surgery should be considered as the first-line treatment for all other cases and in subjects unresponsive to primary single BT injection.

Effects of Intraoperative Auditory Stimulation on Pain and Agitation on Awakening After Pediatric Adenotonsillectomy: A Randomized Clinical Trial.

Importance: Severe pain on awakening (POA) and emergence delirium (ED) are common following pediatric adenotonsillectomy. Effective preventive interventions are lacking. Objective: To determine the effects of intraoperative auditory stimulation on reduction of POA and ED after pediatric adenotonsillectomy. Design, Setting, and Participants: Single-center, double-blinded, 4-armed, randomized clinical trial of children undergoing adenotonsillectomy from March 2018 to May 2019 at a tertiary care pediatric referral center. Interventions: Children were randomized to 1 of the following groups: auditory stimulation with music, auditory stimulation with noise, ambient noise insulation with masking earplugs, and a control group receiving no intervention. Ear inserts were placed in the operating room once general anesthesia was administered. Stimulation parameters were based on the preoperative audiological evaluation and the appropriate fitting of the transduction system, including ambient noise level monitoring. Main Outcomes and Measures: The primary outcome was POA levels measured on 10-point scales according to age-appropriate validated tools. The secondary outcome was ED levels assessed according to the Pediatric Anesthesia Emergence Delirium 20-point scale. Results: A total of 104 consecutive healthy children (median [interquartile range] age at surgery, 5.0 [3.8-6.4] years) were included in the analysis. Music had a large effect size on POA (0.63; 98% CI, 0.43-0.84) and a medium effect size on ED (0.47; 98% CI, 0.21-0.75), while noise had a medium effect size on POA (0.47; 98% CI, 0.22-0.73) and a large effect size on ED (0.63; 98% CI, 0.44-0.85) compared with controls. The earplugs group showed a small effect size on POA and ED. Considering a clinically meaningful threshold of greater than 4 for POA and 10 or greater for ED at dichotomized analysis, a large effect size was achieved by music (1.39; odds ratio [OR], 0.08; 98% CI, 0.02-0.29; and 0.84; OR, 0.22; 98% CI, 0.06-0.75, respectively) and noise (0.97; OR, 0.17; 98% CI, 0.05-0.6; and 1.48; OR, 0.07; 98% CI, 0.02-0.26, respectively), while earplugs resulted in a small effect size. Conclusions and Relevance: In this randomized clinical trial, children undergoing adenotonsillectomy who received intraoperative auditory stimulation demonstrated a clinically meaningful decrease in POA and ED in the immediate postoperative period. Further research is needed to assess whether intraoperative auditory stimulation may decrease POA and ED in children undergoing other types of surgical procedures. Trial Registration: ClinicalTrials.gov Identifier: NCT04112979.

Minimally-Invasive Surgical Approach to Congenital Dacryostenosis: Proposal for a New Protocol.

Background: Congenital dacryostenosis is one of the most common ophthalmological disorders in infants, with a high spontaneous resolution rate. In patients unresponsive to conservative treatment, the first-line approach is lacrimal drainage system probing, thought there is no clear consensus on optimal timing of surgery. The optimal treatment of patients unresponsive to primary probing is also controversial. Objectives: The aim of this study is to assess the optimal timing of probing in children with congenital dacryostenosis. Other purposes are to evaluate the efficacy of repeated probing and dacryointubation in patients unresponsive to the initial surgery without evident lacrimal outflow dysgenesis, and to determine the epidemiology of these maldevelopments. Methods: A retrospective consecutive cohort study was conducted in 625 eyes of 457 patients aged 7-48 months who underwent surgery for dacryostenosis. Patients were divided into 4 cohorts according to the timing of surgery. Data were analyzed using Fisher's test. Results: The success rate of primary probing was high, without significant differences between cohorts. One-third of recurrences were related to maldevelopments, the other two-thirds were treated with a second probing or dacryointubation, with high success rates, that did not significantly differ between the procedures. All cases unresponsive to the second surgery were resolved with dacryointubation. Conclusions: Probing is highly effective and its outcome is not affected by timing of surgery. Nevertheless, we advocate for early intervention, in order to identify possible maldevelopments, which require more invasive management. In patients unresponsive to primary probing, without evident maldevelopments, repeated probing should still be considered as the first-line approach, since it's less invasive but similarly effective to dacryointubation.

Safety and family satisfaction of a home-delivered chemotherapy program for children with cancer.

BACKGROUND: Home chemotherapy programs for children with cancer are safe and feasible, and their impact on the quality of life has been reported in different countries. A home chemotherapy program was implemented between 2011 and 2019 in an Italian region. This pilot study investigates its safety and feasibility, along with parental satisfaction. METHODS: Patients between 0 and 18 years diagnosed with malignancy were included. Deceased patients and patients whose families moved abroad or interrupted contact with the service were excluded. Adverse events comprised immediate deterioration of the patient's condition, equipment failure, errors in drug storage, dose or patient identification and personnel safety issues. Parental satisfaction was explored through an email survey of 32 Likert-type and short open questions. RESULTS: Thirty-five patients received 419 doses of intravenous chemotherapy at home (cytarabine, vincristine, vinblastine). No adverse events were reported. Twenty-three families out of 25 eligible completed the survey. Most reported being "very satisfied" with the possibility of maintaining a work/domestic routine and reducing time and financial burden of hospital access. Most were "very satisfied" with the opportunity for their child of being less troubled by the treatment. Besides, most reported being "very satisfied" with the chance for healthy siblings of maintaining their routine and coping with their brother/sister's disease. Most perceived the program as safe. All families recommended extending the program to all children in the region. CONCLUSIONS: This first Italian study supports home chemotherapy as safe and effective, positively influencing the quality of life for children and their families.

National burden of cancer in Italy, 1990-2017: a systematic analysis for the global burden of disease study 2017.

We monitored the burden of cancer in Italy and its trends over the last three decades, providing estimates of cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs), for cancer overall and 30 cancer sites using data from the Global Burden of Disease study 2017. An overview of mortality trends between 1990 and 2017 was also provided. In 2017, there were 254,336 new cancer cases in men and 214,994 in women, corresponding to an age-standardized incidence rate (ASIR) of 438 and 330/100,000, respectively. Between 1990 and 2017, incident cancer cases, and, to a lesser extent, ASIRs significantly increased overall and for almost all cancer sites, but ASIRs significantly declined for lung and other tobacco-related neoplasms. In 2017, there were 101,659 cancer deaths in men (age-standardized death rate, ASDR, 158.5/100,000) and 78,918 in women (ASDR 93.9/100,000). Cancer deaths significantly increased between 1990 and 2017 (+ 18%), but ASDR significantly decreased (- 28%). Deaths significantly increased for many cancer sites, but decreased for stomach, esophageal, laryngeal, Hodgkin lymphoma, and testicular cancer. ASDRs significantly decreased for most neoplasms, with the main exceptions of cancer of the pancreas and uterus, and multiple myeloma. In 2017, cancer caused 3,204,000 DALYs. Between 1990 and 2017, DALYs and age-standardized DALY rates significantly declined (-3.4% and -33%, respectively). Age-standardized mortality rates in Italy showed favorable patterns over the last few decades. However, the absolute number of cancer cases and, to a lower extent, of cancer deaths increased likely due to the progressive ageing of the population, this calling for a continuous effort in cancer prevention, early diagnosis, and treatment.

Strabismus surgery in Angelman syndrome: More than ocular alignment.

PURPOSE: To report and evaluate strabismus surgery in children with Angelman syndrome, in order to optimize and standardize surgical approach. Other purposes are to understand the possible relation between ocular findings and motor ability, and between improvement in ocular alignment and changes in motor skills in this population. DESIGN: Observational cross-sectional study. METHODS: Medical records of pediatric patients with Angelman syndrome, who underwent strabismus surgery, were investigated. Collected data included: genotype, gender, age at the time of surgery, refractive error, pre-operative strabismus, surgical procedure, surgical outcome, gross and fine motor development assessment pre- and post-operatively. RESULTS: Seventeen subjects, aged 3-15 years, were investigated. Fourteen patients were exotropic, three esotropic. Most patients presented astigmatism. Considering the exaggerated response to standard amounts of surgery and the risk of consecutive strabismus on long term follow-up reported by previous studies in children with developmental delay, a reduction of the amount of strabismus surgery was applied. Post-operatively, all patients presented with a significative reduction of the baseline deviation angle, with all esotropic patients and 7 exotropic patients (59%) achieving orthotropia. The surgical outcomes were variable according to the type and the amount of baseline strabismus, but no case presented with exaggerated surgical response. At baseline, patients showed important delays in all motor abilities, and, post-operatively, presented a significant improvement in walking and fine motor tasks. Pre- and post-operative motor abilities were negatively correlated to astigmatism, anisometropia, and amount of deviation. CONCLUSIONS: According to our data, the standard nomograms for strabismus surgery may be successfully applied in subjects with Angelman syndrome and exotropia. Our data suggest that the reduction of the deviation angle improves motor skills in strabismic pediatric patients with Angelman syndrome.

Children exposure to inorganic and organic arsenic metabolites: A cohort study in Northeast Italy.

The aim of this study was to provide urinary levels of total arsenic (TAs) and As species as arsenobetaine (AsB), arsenocholine (AsC), inorganic As (i.e., [As(III)+As(V)]), methylarsonic acid (MMA) and dimethylarsinic acid (DMA) in 7 year-old-children (n = 200) enrolled in the Northern Adriatic Cohort II (NACII), a prospective cohort in a coastal area of Northeast Italy. TAs was determined by sector field-inductively coupled plasma mass spectrometry (SF-ICP-MS) and AsB, AsC, As(III), As(V), MMA and DMA by ion chromatography coupled to ICP-MS (IC-ICP-MS). The geometric mean (GM) for TAs was 12.9 µg/L and for [iAs + MMA + DMA] was 4.26 µg/L. The species AsB (GM of 5.09 µg/L) and DMA (GM of 3.20 µg/L) had the greatest percentage contribution to TAs levels; a greater percentage contribution from AsB is seen at TAs >10 µg/L and from DMA at TAs <10 µg/L. Urinary [iAs + MMA] levels were positively associated with [iAs + MMA + DMA] and DMA with AsB levels. Fish, shellfish and crustaceans consumption increased the AsB and TAs levels, while rice intake, mothers' education level and selenium (Se) concentration influenced the DMA concentration. Children have a high capacity to metabolize and detoxify the iAs because of the higher secondary methylation index (ratio DMA/MMA) with respect to primary methylation index (ratio MMA/iAs). In addition, the median level of [iAs + MMA + DMA] in the whole population of children was lower than the Biomonitoring Equivalent (BE) value for non-cancer endpoints. Also the Margin of Safety (MOS) value based on the population median was greater than 1, thus the exposure to the toxicologically relevant As species was not likely to be of concern.

Urinary metabolites of organophosphate and pyrethroid pesticides in children from an Italian cohort (PHIME, Trieste).

Urinary metabolites of organophosphate (OP) and pyrethroid (PYR) pesticides from seven years old children of a birth cohort study (n=199; PHIME cohort of Trieste, Italy) have been measured. Six OP and two PYR metabolites have been investigated, 2-diethylamino-6-methylpyrimidin-4-ol (DEAMPY, pirimiphos metabolite) was the one found at higher concentrations, median 3.4 ng/mL specific gravity adjusted (SG adjusted), followed by 4-nitrophenol (PNP, median 1.4 ng/mL SG adjusted) and 3,5,6-trichloro-2-pyridinol (TCPY, median 0.36 ng/mL SG adjusted), parathion and chlorpyriphos metabolites, respectively. TCPY concentrations were low in comparison to other distributions of OP metabolites in children from other studies. Accordingly, the PHIME cohort showed a distinct OP metabolite distribution with high concentrations of pirimiphos and parathion. Another specific characteristic of this cohort was the high concentration of 3-phenoxybenzoic acid (3-BPA, median 0.36 ng/mL SG adjusted), a general metabolite of PYR pesticides. Evaluation of anthropometric and socio-demographic characteristics of children and families only showed a positive association between family educational level and urinary concentrations of DEAMPY metabolite (p<0.05), which could reflect distinct dietary habits depending on the educational level. Estimated daily intakes were evaluated, all studied metabolites were found within safe levels.

Multicenter randomized, double-blind controlled trial to evaluate the efficacy of laser therapy for the treatment of severe oral mucositis induced by chemotherapy in children: laMPO RCT.

OBJECTIVES: To demonstrate the efficacy of laser photobiomodulation (PBM) compared to that of placebo on severe oral mucositis (OM) in pediatric oncology patients. The primary objective was the reduction of OM grade (World Health Organization [WHO] scale) 7 days after starting PBM. Secondary objectives were reduction of pain, analgesic consumption, and incidence of side effects. METHODS: One hundred and one children with WHO grade > 2 chemotherapy-induced OM were enrolled in eight Italian hospitals. Patients were randomized to either PBM or sham treatment for four consecutive days (days +1 to +4). On days +4, +7, and +11, OM grade, pain (following a 0-10 numeric pain rating scale, NRS) and need for analgesics were evaluated by an operator blinded to treatment. RESULTS: Fifty-one patients were allocated to the PBM group, and 50 were allocated to the sham group. In total, 93.7% of PBM patients and 72% of sham patients had OM grade < 3 WHO on day +7 (P = 0.01). A significant reduction of pain was registered on day +7 in the PBM versus sham group (NRS 1 [0-3] vs. 2.5 [1-5], P < 0.006). Reduced use of analgesics was reported in the PBM group, although it was not statistically significant. No significant adverse events attributable to treatment were recorded. CONCLUSIONS: PBM is a safe, feasible, and effective treatment for children affected by chemotherapy-induced OM, as it accelerates mucosal recovery and reduces pain.

Antibiotic Prophylaxis for Urinary Tract Infection-Related Renal Scarring: A Systematic Review.

CONTEXT: Acute pyelonephritis may result in renal scarring. Recent prospective studies have shown a small benefit of antibiotic prophylaxis in preventing symptomatic and febrile urinary tract infections (UTIs), while being underpowered to detect any influence in prevention of renal damage. OBJECTIVES: Review of the literature and a meta-analysis to evaluate the effect of antibiotic prophylaxis on UTI-related renal scarring. DATA SOURCES: Medline, Embase, and Cochrane Controlled Trials Register electronic databases were searched for studies published in any language and bibliographies of identified prospective randomized controlled trials (RCTs) performed and published between 1946 and August 2016. STUDY SELECTION: Subjects 18 years of age or younger with symptomatic or febrile UTIs, enrolled in prospective RCTs of antibiotic prophylaxis where 99mTc dimercaptosuccinic acid scans were performed at entry into the study and at late follow-up to detect new scar formation. DATA EXTRACTION: The literature search, study characteristics, inclusion and exclusion criteria, and risk of bias assessment were independently evaluated by 2 authors. RESULTS: Seven RCTs (1427 subjects) were included in the meta-analysis. Our results show no influence of antibiotic prophylaxis in preventing renal scarring (pooled risk ratio, 0.83; 95% confidence interval, 0.55-1.26) as did a subanalysis restricted to those subjects with vesicoureteral reflux (pooled risk ratio, 0.79; 95% confidence interval, 0.51-1.24). LIMITATIONS: Limitations include the small number of studies, short duration of follow-up, and insufficient children with high-grade dilating reflux and/or renal dysplasia enrolled in the studies. CONCLUSIONS: Antibiotic prophylaxis is not indicated for the prevention of renal scarring after a first or second symptomatic or febrile UTI in otherwise healthy children.

Incidence and Estimated Prevalence of Endometriosis and Adenomyosis in Northeast Italy: A Data Linkage Study.

Despite being quite frequent and having serious implications in terms of symptomatology and fertility, data on incidence and prevalence of endometriosis and adenomyosis following gold standard definitions are dramatically lacking. The average time from onset of symptoms to diagnosis in industrialized countries still ranges from five to ten years. Using the regional centralized data linkage system, we calculated incidence and prevalence of endometriosis and adenomyosis in the female population of Friuli Venezia Giulia region, Italy, for the years 2011-2013. Cases were defined as new diagnoses from hospital discharge records, following procedures allowing direct visualization for endometriosis and hysterectomy for adenomyosis, with or without histological confirmation. Diagnoses were considered "new" after verifying women had not been diagnosed in the previous ten years. Incidence of endometriosis and adenomyosis in women aged 15-50 years is 0.14%. Prevalence, estimated from incidence, is 2.00%. Adenomyosis, representing 28% of all diagnoses, becomes increasingly prevalent after the age of 50 years. Our results shows how the study of both endometriosis and adenomyosis should not be limited to women of premenopausal age. Further efforts are needed to sensitize women and health professional, and to find new data linkage possibilities to identify undiagnosed cases.