Acute toxic exposures in children: analysis of a three year registry managed by a Pediatric poison control Center in Italy.

INTRODUCTION: Acute pediatric poisoning is an emerging health and social problem. The aim of this study is to describe the characteristics of a large pediatric cohort exposed to xenobiotics, through the analysis of a Pediatric Poison Control Center (PPCc) registry. METHODS: This study, conducted in the Pediatric Hospital Bambino Gesù of Rome, a reference National Pediatric Hospital, collected data of children whose parents or caregivers contacted the PPCc by phone (group "P"), or who presented to the Emergency Department (group "ED"), during the three-year period 2014-2016. Data were prospectively and systematically collected in a pre-set electronic registry. Comparisons among age groups were performed and multivariable logistic regression models used to investigate associations with outcomes (hospital referral for "P", and hospital admission for "ED"group). RESULTS: We collected data of 1611 children on group P and 1075 on group ED. Both groups were exposed to both pharmaceutical and non-pharmaceutical agents. Pharmaceutical agent exposure increased with age and the most common route of exposure was oral. Only 10% among P group were symptomatic children, with gastrointestinal symptoms. Among the ED patients, 30% were symptomatic children mostly with gastrointestinal (55.4%) and neurologic symptoms (23.8%). Intentional exposure (abuse substance and suicide attempt), which involved 7.7% of patients, was associated with older age and Hospital admission. CONCLUSIONS: Our study describes the characteristics of xenobiotics exposures in different paediatric age groups, highlighting the impact of both pharmacological and intentional exposure. Furthermore, our study shows the utility of a specific PPCc, either through Phone support or by direct access to ED. PPCc phone counselling could avoid unnecessary access to the ED, a relevant achievement, particularly in the time of a pandemic.

Use of Self-Matching to Control for Stable Patient Characteristics While Addressing Time-Varying Confounding on Treatment Effect: A Case Study of Older Intensive Care Patients.

Exposure-crossover design offers a non-experimental option to control for stable baseline confounding through self-matching while examining causal effect of an exposure on an acute outcome. This study extends this approach to longitudinal data with repeated measures of exposure and outcome using data from a cohort of 340 older medical patients in an intensive care unit (ICU). The analytic sample included 92 patients who received ≥1 dose of haloperidol, an antipsychotic medication often used for patients with delirium. Exposure-crossover design was implemented by sampling the 3-day time segments prior (Induction) and posterior (Subsequent) to each treatment episode of receiving haloperidol. In the full cohort, there was a trend of increasing delirium severity scores (Mean±SD: 4.4±1.7) over the course of the ICU stay. After exposure-crossover sampling, the delirium severity score decreased from the Induction (4.9) to the Subsequent (4.1) intervals, with the treatment episode falling in-between (4.5). Based on a GEE Poisson model accounting for self-matching and within-subject correlation, the unadjusted mean delirium severity scores was -0.55 (95% CI: -1.10, -0.01) points lower for the Subsequent than the Induction intervals. The association diminished by 32% (-0.38, 95%CI: -0.99, 0.24) after adjusting only for ICU confounding, while being slightly increased by 7% (-0.60, 95%CI: -1.15, -0.04) when adjusting only for baseline characteristics. These results suggest that longitudinal exposure-crossover design is feasible and capable of partially removing stable baseline confounding through self-matching. Loss of power due to eliminating treatment-irrelevant person-time and uncertainty around allocating person-time to comparison intervals remain methodological challenges.

An Empirical Method of Detecting Time-Dependent Confounding: An Observational Study of Next Day Delirium in a Medical ICU.

Longitudinal research on older persons in the medical intensive care unit (MICU) is often complicated by the time-dependent confounding of concurrently administered interventions such as medications and intubation. Such temporal confounding can bias the respective longitudinal associations between concurrently administered treatments and a longitudinal outcome such as delirium. Although marginal structural models address time-dependent confounding, their application is non-trivial and preferably justified by empirical evidence. Using data from a longitudinal study of older persons in the MICU, we constructed a plausibility score from 0 - 10 where higher values indicate higher plausibility of time-dependent confounding of the association between a time-varying explanatory variable and an outcome. Based on longitudinal plots, measures of correlation, and longitudinal regression, the plausibility scores were compared to the differences in estimates obtained with non-weighted and marginal structural models of next day delirium. The plausibility scores of the three possible pairings of daily doses of fentanyl, haloperidol, and intubation indicated the following: low plausibility for haloperidol and intubation, moderate plausibility for fentanyl and haloperidol, and high plausibility for fentanyl and intubation. Comparing multivariable models of next day delirium with and without adjustment for time-dependent confounding, only intubation's association changed substantively. In our observational study of older persons in the MICU, the plausibility scores were generally reflective of the observed differences between coefficients estimated from non-weighted and marginal structural models.

Comparing clinical outcomes in HIV-infected and uninfected older men hospitalized with community-acquired pneumonia.

OBJECTIVES: Outcomes of community-acquired pneumonia (CAP) among HIV-infected older adults are unclear. METHODS: Associations between HIV infection and three CAP outcomes (30-day mortality, readmission within 30 days post-discharge, and hospital length of stay [LOS]) were examined in the Veterans Aging Cohort Study (VACS) of male Veterans, age ≥ 50 years, hospitalized for CAP from 10/1/2002 through 08/31/2010. Associations between the VACS Index and CAP outcomes were assessed in multivariable models. RESULTS: Among 117 557 Veterans (36 922 HIV-infected and 80 635 uninfected), 1203 met our eligibility criteria. The 30-day mortality rate was 5.3%, the mean LOS was 7.3 days, and 13.2% were readmitted within 30 days of discharge. In unadjusted analyses, there were no significant differences between HIV-infected and uninfected participants regarding the three CAP outcomes (P > 0.2). A higher VACS Index was associated with increased 30-day mortality, readmission, and LOS in both HIV-infected and uninfected groups. Generic organ system components of the VACS Index were associated with adverse CAP outcomes; HIV-specific components were not. Among HIV-infected participants, those not on antiretroviral therapy (ART) had a higher 30-day mortality (HR 2.94 [95% CI 1.51, 5.72]; P = 0.002) and a longer LOS (slope 2.69 days [95% CI 0.65, 4.73]; P = 0.008), after accounting for VACS Index. Readmission was not associated with ART use (OR 1.12 [95% CI 0.62, 2.00] P = 0.714). CONCLUSION: Among HIV-infected and uninfected older adults hospitalized for CAP, organ system components of the VACS Index were associated with adverse CAP outcomes. Among HIV-infected individuals, ART was associated with decreased 30-day mortality and LOS.

Antitoxin use and pediatric intensive care for viper bites in Rome, Italy.

In Italy viper bites represent an uncommon event, though envenomation can cause severe complications, more in children than adults, because of dose/body size ratio. We present a case series within a selected population: 10 Italian cases (from Rome surroundings) of viperbites requiring PICU admission, over a 5-year interval. Five children showed a systemic involvement, whereas the remaining patients showed a damage. All were managed and closely monitored in an ICU setting. Relevant clinical findings and therapeutic approach, ICU course and complications have been recorded. Age range was 3-15 years with mean age of 6,9 (SD±4,58) years; 2 patients needed respiratory support beyond oxygen supplementation. Most patients underwent fluid loading, while hemodynamic support was given to4/10. Median PICU stay was 60 hours (IQR=24.0-75.5). No mortality was reported. Indications and precautions for administration of antivenom in the last years have been reviewed: early treatment seems to reduce mortality/morbidity, though representing a threat for children. Current recommendations for the treatment of viper envenomation have been described, based on a literature's review and the application of these knowledges to clinical reality of our PICUs. Therefore, paediatric patients with systemic or rapidly evolving symptoms should be monitored carefully for the development of bite-related complications in an ICU setting mostly in younger children.

Exposure assessment of mycotoxins in cow's milk in Argentina.

A stochastic simulation model was developed to carry out the first quantitative risk exposure assessment of the mycotoxin level in cow's milk produced in Argentina. The prevalence and concentration of aflatoxin M1 (AFM1), deoxynivalenol (DON) and zearalenone (ZEA) were modeled at various stages through milk processes complying with Argentinean practices. Concentration of AFM1 (0.059ppb), DON (0.338ppb) and ZEA (0.125ppb) in dairy milk were estimated. The proportion of feed samples that exceeded the maximum level accepted by European regulations for AFB1, DON and ZEA were estimated at 25.07%, 0.0% and 8.9%, respectively. The percentage of milk samples that exceeded the maximum level accepted for AFB1 by the MERCOSUR (0.5ppb) and the European Union regulations (0.05ppb) were 0.81 and 32.65, respectively. The probability distribution of AFM1 concentration in milk was affected by the carry-over rate equations applied in the model. Mycotoxin levels in corn silage and concentrated feeds were the factors most correlated with mycotoxin concentrations in milk. Therefore, agricultural practices, crop management and feed production require prompt attention regarding mycotoxin issues.

Preoperative risk factors for postoperative delirium (POD) after urological surgery in the elderly.

The aim of this observational study was to investigate the occurrence of postoperative delirium (POD) in elderly patients undergoing urological surgery and to identify those factors associated with delirium. Ninety consecutive patients (81 males and 9 females; average age of 74.3 ± 0.40 years), undergoing urological surgery in University-Hospital Urological Clinic were selected. Personal, medical, cognitive and functional data, biochemical parameters, preoperative medications, conduct of surgery and anesthesia and details of hemodynamic control were collected as predictors of delirium. After surgery, the subjects were divided on the basis of delirium onset within a week observation period. Delirium was diagnosed by the Confusion Assessment Method. Delirium started the first post-operative day (2F; 6 M) and lasted 3.0 ± 0.8 days. Subjects with POD were significantly older, had a previous history of delirium, were more impaired in the instrumental activities of daily living and had poorer clock drawing test (CDT) score. Interestingly, a significantly greater number of hypotensive events were recorded during anesthesia. Age, cognitive and functional status, previous history of delirium and hypotensive episodes intrasurgery are the best predictor of POD in this setting. Our findings have implications in preventing delirium in elderly by an early and targeted evaluation.

Elevated serum ALT in children presenting to the emergency unit: Relationship with NAFLD.

BACKGROUND: Non-alcoholic fatty liver disease, ranging from hepatic steatosis to necro-inflammation with or without fibrosis (non-alcoholic steatohepatitis), is a growing clinical liver disorder in children. AIM: The goals of this study were to characterize liver disorders associated with elevated aminotransferases and establish the non-alcoholic fatty liver disease/non-alcoholic steatohepatitis prevalence in hypertransaminasemic children admitted to the emergency room. METHODS: The medical records of 3280 children (2-17 years of age) admitted to the emergency room of Bambino Gesù Children's Hospital of Rome, and presenting with hypertransaminasemia were analysed retrospectively. RESULTS: Elevation of serum alanine aminotransferases was present in 897 patients. Of these, 520 (58%) spontaneously normalized alanine aminotransferases, and 179/897 (20%) maintained persistently elevated alanine aminotransferases levels. Twenty-one patients were excluded because of medication or alcohol use. In the remaining 157 patients with elevated alanine aminotransferases, obesity was found in 87 (55%), viral infections in 52 (33%) and genetic diseases in 14 (9%). Obesity-related alanine aminotransferases elevation was associated with a histological diagnosis of non-alcoholic fatty liver disease in 85% of patients. In particular, steatosis was histologically confirmed in 74 patients; 43/74 (58%) had steatohepatitis, and 12/74 (16%) had fibrosis. CONCLUSIONS: Twenty percent of children with elevated aminotransferases on routine testing may hide non-alcoholic fatty liver disease/non-alcoholic steatohepatitis. A careful diagnostic workup of persistent hypertransaminasemia in all obese subjects is warranted in the paediatric setting.

Role of regional mechanical dyssynchrony as a determinant of functional mitral regurgitation in patients with left ventricular systolic dysfunction.

OBJECTIVE: To assess regional mechanical dyssynchrony as a determinant of the degree of functional mitral regurgitation (FMR). SETTING: Tertiary cardiology clinic. PATIENTS: 74 consecutive patients with left ventricular (LV) dysfunction (ejection fraction < 40%, mean 32.2 (SD 7.3)%) were evaluated. METHODS: Effective regurgitant orifice (ERO) area, indices of mitral deformation (systolic valvular tenting, mitral annular contraction) and of global LV function and remodelling (ejection fraction, end systolic volume, sphericity index) and local remodelling (papillary-fibrosa distance, regional wall motion score index), and tissue Doppler-derived dyssynchrony index (DI) (regional DI, defined as the standard deviation of time to peak myocardial systolic contraction of eight LV segments supporting the papillary muscles attachment) were measured. RESULTS: All the assessed variables correlated significantly with ERO. By multivariate analysis, systolic valvular tenting was the strongest independent predictor of ERO (R(2) = 0.77, p = 0.0001), with a minor influence of papillary-fibrosa distance (R(2) = 0.77, p = 0.01) and regional DI (R(2) = 0.77, p = 0.03). Local LV remodelling (regional wall motion score index: R(2) = 0.58, p = 0.001; papillary-fibrosa distance: R(2) = 0.58, p = 0.002) and global remodelling indices (sphericity index: R(2) = 0.58, p = 0.003) were the main determinants of systolic valvular tenting, whereas regional DI did not enter into the model. Regional DI was an independent predictor of ERO (R(2) = 0.56, p = 0.005) in patients with non-ischaemic LV dysfunction but not in patients with ischaemic LV dysfunction when these groups were analysed separately. CONCLUSIONS: The degree of FMR is associated mainly with mitral deformation indices. The regional dyssynchrony also has an independent association with ERO but with a minor influence; however, it is not a determinant of FMR in patients with ischaemic LV dysfunction.

Histological and microscopy FT-IR imaging study on the proliferative activity and angiogenesis in head and neck tumours.

Micro Fourier transform infrared spectroscopy enables one to study small samples because of the high quality spectra that can be obtained. Biochemical and morphological changes between control and pathological tissues of head and neck tumours have been monitored drawing three-dimensional chemical maps of the main vibrational modes in the regions of interest. Comparison between spectral and histological data shows a satisfactory degree of accordance. Among all, proliferating and regressive states of the tumours can be identified.

[Ultrasonography of normal vermiform appendix]. / Ecografia dell'appendice vermiforme normale.

The aim of this study was the detection and visualisation of the normal vermiform appendix and its characteristics by ultrasonography in adults with no clinical suggestion of acute or chronic abdominal disease. A prospective study was performed in 200 subjects. The graded-compression ultrasonography technique was used to explore the lower right quadrant of the abdomen and the pelvis. The examination was performed using a 4 MHz sector array and 7.5 MHz linear array transducer. In a few cases, a 10 MHz linear array transducer was used. The appendix was visualized in 54% of patients. In all cases where the appendix was visualized it was found to be either on the ileo-psoas muscle or directly beneath the abdominal wall. The ileo-caecal valve was visualized in 78% of cases. The transverse diameter was found to be no greater than 6.5 mm except in three cases that had a diameters ranging from 7 to 9 mm. Diameter variability along the length of the same appendix was demonstrated in 5% of subjects. Wall thickness was no greater than 2.5 mm. Our experience suggests that graded-compression ultrasonography is a valuable procedure for detecting the vermiform appendix more frequently than has been previously reported. The patients physical constitution and the anatomical location of the vermiform appendix were found to be important factors affecting the ability to visualize the vermiform appendix. The ability to visualise the normal vermiform appendix ultrasonographically supports the clinical diagnosis and excludes acute appendicitis.

A sample scanning system with nanometric accuracy for quantitative SPM measurements.

A sample scanning device operating in a working volume of 30 x 30 x 18 microm with interferometer and capacitance-based controls of displacements, is described. The xy-stage uses plane mirror linear interferometers and fast phase-meters for control of displacements of precise ball-bearing stages driven by piezo flexure actuators. The stage operates with a full range bandwidth of 200 Hz, and an estimated accuracy (k = 2) of 3 nm + 1 x 10(-3) L, where L is the lateral displacement. A novel z-stage based on a kinematic coupling between two plates, the upper one being moved by three bimorph plates and the distance being measured by three capacitive sensor, is described. The tilt of the z-stage is kept within fractions of a microrad, leading to a full range estimated accuracy of 2 nm + 2 x 10(-3) h, where h is the vertical displacement. The control bandwidth is of about 1 kHz, thus allowing fast and accurate step-height measurements. In order to test the device used in a scanning probe microscope, micrometric patterned surfaces made using high resolution e-beam lithography and precise metal deposition on silicon are imaged. Results of pitch measurements are discussed and compared with those obtained using optical diffractometry.

Effects on platelet function of combination etoposide and carboplatin chemotherapy in pediatric oncology patients.

The effects of a therapeutic course of the combination of carboplatin and etoposide on platelet function have been evaluated in 10 pediatric patients with brain tumors. Platelet count, in vitro aggregation tests, P-selectin expression and agonist-induced ATP release were evaluated before, and 7 and 15 days after one cycle of chemotherapy. The analysis of the results demonstrated the presence of an in vitro platelet aggregation defect in response to collagen and arachidonic acid in all patients 7 days after therapy. A concomitant decrease of collagen- and arachidonic acid-induced ATP release was also observed. Both platelet aggregation and ATP release returned to baseline values 15 days after chemotherapy administration. Conversely, in vitro platelet aggregation and secretion induced by ADP and epinephrine were unaltered by carboplatin and etoposide administration. Furthermore, P-selectin expression was negative at baseline and did not change after chemotherapy. These results support the hypothesis that combination etoposide and carboplatin chemotherapy in pediatric patients is responsible for possible disturbances in biochemical pathways required for platelet secretion and aggregation.