Children with medical complexity and paediatric palliative care: a retrospective cross-sectional survey of prevalence and needs.

BACKGROUND: Children with medical complexity (CMC) have been defined (Cohen et al., Pediatrics 127: 529-538, 2011.) as an emerging population potentially eligible for PPC. The current study investigated the prevalence of children with medical complexities eligible for a local palliative care network, including a paediatric hospice. METHODS: A retrospective cross-sectional survey has been conducted using children clinical charts from 14 local health authorities of our region (Emilia Romagna, Italy). RESULTS: The total number of children with life-limiting conditions was 601, with a mean age of 7.4 ± 4.8 years, a prevalence of 8.4/10.000 residents < 19 years of age and a heterogeneous presentation among the provinces in the region. Neurological diseases affect 51% of patients, followed by congenital diseases (21%) and pathologies originating in the perinatal period (6%), while only 4% of the patients had a cancer diagnosis. Patients are dependent from many devices and supports: 32% had a gastrostomy, 22% a respiratory support and 15% of patients had both of them. CONCLUSIONS: Observed regional prevalence of complex needs is lower than that published from other European countries. More research is needed to raise awareness of palliative care for children with medical complexities in order to address specific needs.

Italian pediatric nutrition survey.

INTRODUCTION: the prevalence of malnutrition in children and its impact on clinical outcomes is underrecognized by clinicians in Italy as well as worldwide. A novel definition of pediatric malnutrition has been recently proposed by a working group of the Academy of Nutrition and Dietetics and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.), based on the correlation between illness and the use of zscores of anthropometric measurements. AIM: to investigate the prevalence of malnutrition and related nutritional support among hospitalized children in Italy, in a nationwide survey performed in a single day (16/4/2015). METHODS: an open access website (http://nday.biomedia.net) was used to collected data from 73 hospitals and 101 wards in 14 Italian regions (1994 patients). Anonymous information was collected on hospitals' characteristics, patient's anthropometry, admission diagnosis, presence of chronic diseases and use of nutritional support: oral nutritional supplements (ONS), enteral nutrition (EN) or parenteral nutrition (PN). Z-scores of anthropometric measurements, calculated with Epi Info 7.1.5, defined nutritional status: wasting was identified by BMI or Weight-for-Length z-score (<-1 mild, <-2 moderate, <-3 severe), stunting by Height-for-Age Z-score <-2. WHO 2006 and CDC 2000 growth charts were used respectively for children younger and older than 2 years old. RESULTS: 1790 complete records were obtained for hospitalized patients aged 0-20 years, with median age 6.16 (0.1-20 years and 53.3% males). 52.9% were aged 0-6 years and 58.8% of children suffered from chronic diseases. Wasting was detected in 28.7% of the total sample with higher occurrence observed in age ranges 0-6 and 14-20 years, while 17.3% of patients showed stunting; surprisingly almost 27% of them were aged 0-2. A ranking of the admission diagnosis with the highest rate of malnutrition was complied. The prevalence of wasting was significantly (p < 0.005) higher amongst children with chronic diseases (34.1% vs. 27.1%); stunting prevalence tripled in patients with chronic disease (24.5% vs. 8.3%). Only 23.5% of malnourished children (17%, 25.6% and 36.7%, respectively mild, moderate and severe malnutrition) received nutritional support: 11.7% received oral nutrition supplements (ONS, modular or complete), 11.5% enteral nutrition (EN, 6.4% via nasogastric tube, 5.1% via gastrostomy) and 6.8 % received parenteral nutrition (PN); in some patients a combination of two. Nutritional support is more commonly used among stunting patients, 39.5% of children under treatment. CONCLUSION: Malnutrition of any grade was observed in nearly 1/3 and stunting in 17% of the reported hospitalized children, and it is likely to be underrecognized as the nutritional support reached only a small part of the malnourished children.

Massive hemobilia and papillomatosis of the gallbladder in metachromatic leukodystrophy: a life-threatening condition.

Polyposis of the gallbladder is rare during childhood. This condition can be associated with three other conditions: metachromatic leukodystrophy, Peutz-Jeghers' syndrome, and pancreaticobiliary maljunction. We report the case of a child with hemobilia in metachromatic leukodystrophy, which rendered cholecystectomy necessary. Macroscopically, the gallbladder measured 4.6 cm in length and showed an opaque serous surface and focal brown petechiae. Moreover, a yellow polypoid lesion of 2 cm in diameter and a diffuse thickening of the fundus wall were observed. Many reports describe the importance of the association of gallbladder papillomatosis with metachromatic leukodystrophy, but only three cases presented with massive intestinal bleeding, such as our young patient had. It is thus imperative that this life-threatening condition should be well known.

Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus (MPPH): report of a new case.

Megalencephaly (MEG), or enlargement of the brain, can either represent a familial variant with normal cerebral structure, or a rare brain malformation associated with developmental delay and neurological problems. MEG has been split into two subtypes: anatomical and metabolic. The latter features a build-up inside the cells owing to metabolic causes. Anatomical MEG has been detected in many different conditions, including many overgrowth syndromes. In 2004 Mirzaa et al. reported five non-consanguineous patients with a new MCA/MR syndrome characterized by severe congenital MEG with polymicrogyria (PMG), postaxial polydactyly (POLY) and hydrocephalus (HYD). The authors argued that these findings identified a new and distinct malformation syndrome, which they named MPPH. We report on a new case of MPPH, the first to be described after the original series (Mirzaa et al., 2004).

Parental perceptions of feeding practices in five European countries: an exploratory study.

OBJECTIVE: To gain an insight into parental perceptions of infant feeding practices in five European countries. DESIGN: An exploratory investigation using focus group discussions. Various aspects addressed included social and cultural setting for the consumption of food, infant feeding practice and behaviour, consumer health awareness and sources of information, and attitudes towards a healthy infant diet. SETTING: Focus group participants were recruited from centres in five countries, Germany, Italy, Scotland, Spain and Sweden, with three focus groups being conducted in each centre. SUBJECTS: A total of 108 parents with infants up to the age of 12 months participated in focus group discussions across these centres. METHODS: Focus groups were conducted with participants from centres in five countries. RESULTS: The majority of parents in this study chose to initiate breastfeeding and prepare infant food at home. Parents did not strictly adhere to infant feeding guidelines when introducing complementary foods into their infant's diets. There were cross-cultural differences in sources of information on infant feeding practice with the paediatrician in Germany, Italy and Spain. The health visitor in Scotland and the child welfare clinics in Sweden were the most popular sources. CONCLUSIONS: A number of cultural differences and similarities in attitudes towards infant feeding practice were revealed. This makes European wide approaches to promoting healthy infant feeding difficult as different infant feeding practices are influenced not only by parental perceptions but also by advice from health professionals and feeding guidelines. Further data need to be available on parents' attitudes and beliefs towards infant feeding practice to investigate further the rationale for differing beliefs and attitudes towards infant feeding practice. SPONSORSHIP: EU Fifth Framework QLRT 2002 02606.

Changes of gut microbiota and immune markers during the complementary feeding period in healthy breast-fed infants.

INTRODUCTION: Little is known about changes in intestinal microbiota during the important period of complementary feeding (weaning). This descriptive study investigated changes of selected gut microbiota and markers of gut permeability and the immune system in breast fed infants during the complementary feeding period. METHODS: 22 healthy, exclusively breast fed infants (from birth to 4 months) with no antibiotic intake during the month prior to the study, were followed from 4 to 9 months of age. Faecal and saliva samples were collected at the start of the study (V0) and at monthly intervals (V1-V5) for measurement of selective gut microbiota (bifidobacteria, lactobacilli, vancomycin-insensitive lactobacilli, enterobacteria, enterococci, Clostridium perfringens) using semi-selective media. Immune markers (alpha-1-antitrypsin, eosinophil cationic protein (ECP), secretory IgA and TNF-alpha were measured in saliva and secretory IgA and TNF-alpha in faecal samples. RESULTS: High stool bifidobacteria counts at the start of the study (7.99 1 1.95 log10 CFU/g faeces) remained stable throughout the 5 months of complementary feeding while counts of enterobacteria and enterococci increased with age (P < 0.05 and P = 0.02 respectively). Vancomycin-insensitive lactobacilli increased significantly during weaning for V0 to V3 (P < 0.01), and then decreased slightly (V4). Faecal Clostridium perfringens remained below the detection limit during the study and parameters measured in saliva did not change. Faecal ECP decreased significantly from 1.011.4 (V0) to 0.510.9 mg/mg protein (V5) P = 0.03. CONCLUSION: Age and/or diet modifications during complementary feeding had no impact on faecal bifidobacteria counts but increased those of enterobacteria and enterococci. Transient increases in faecal lactobacilli and vancomycin-insensitive lactobacilli counts were observed. The reduction in faecal ECP may indicate a decrease in gut permeability (reinforcement of gut mucosa integrity) during the weaning period with age [corrected]

Antitransglutaminase enzyme-linked immune-adsorbed assay in coeliac disease diagnosis: evaluation of a diagnostic algorithm.

BACKGROUND: Tissue transglutaminase is the major autoantigen recognized in the sera of coeliac patients. An enzyme-linked immune-adsorbed assay based on tissue transglutaminase was recently used to measure serum tissue transglutaminase immunoglobulins A for coeliac disease diagnosis. OBJECTIVES: To determine the sensitivity, the specificity, the positive and negative predictive values of an immunoenzymatic assay based on guinea pig tissue transglutaminase, to compare antititransglutaminase immunoenzymatic assay to the antiendomysium immunofluorescent assay, and to define a cost-effective sequence to execute serum antibody determination in coeliac patients. METHODS: We assessed for coeliac disease antibodies 91 pediatric patients with symptoms suggestive of coeliac disease, and 23 patients with coeliac disease on a gluten-free diet as controls. RESULTS: Antitransglutaminase immunoglobulins A showed 93.1% sensitivity, 93.6% specificity, 87.1% positive and 96.7% negative predictive values. Antitransglutaminase immunoglobulins A were significantly higher in antiendomysium positive subjects. Correlation between antitransglutaminase immunoglobulins A and antigliadin immunoglobulins A was not significant. DISCUSSION: Our results show that antitransglutaminase immunoenzymatic assay represents a cost-effective strategy for patients' serological evaluation and it could substitute EMA determination, which could be considered a second level evaluation.

[Sedation in pediatric digestive endoscopy]. / Sedazione in endoscopia digestiva pediatrica.

Sedation for children doing diagnostic or operative pediatric gastrointestinal endoscopy (PE) procedures is performed differently over the world and no consensus is yet agreed on the best paediatric endoscopy sedation (PES). Some centres do not use any sedation, especially in infants, most centre use some form of sedation: conscious sedation, deep sedation and general anaesthesia. We review sedation drugs and describe our centre protocol on 188 consecutive PE: oral premedication with flunitrazepam (0.05 mg/kg/dose) at least 30 min before procedure, petidine (1 mg/kg) followed by increasing boluses of midazolam (0.05 mg/kg up to a maximal 0.2 mg/kg or 5 mg) were given i.v. to obtain a conscious sedation. All PE could be performed and ended safely, PES resulted satisfactory in approximately 65% of patient having conscious sedation. SaO2 < 90% was observed in 2% of cases, one child had a respiratory depression after PE that resolved with flumanezil. Endoscopy and sedation was always performed by the PE team in the immediate vicinity of anaesthesiologists at work. PE can be safely performed with conscious sedation. Basic and advanced resuscitation skills are needed for the PE team who wish to perform both endoscopic and sedation procedures.

Helicobacter pylori eradication can induce platelet recovery in idiopathic thrombocytopenic purpura.

Recent reports have suggested an association between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP). The prevalence of H pylori infection and the effect of its eradication in a series of 30 ITP patients were investigated. H pylori infection has been documented in 13 patients (43.33%) by 13C urea breath test and confirmed by histologic examination. Bacterium eradication with antibiotics, obtained in 12 of 13 infected patients (92.3%), led to a complete response in 4 (33.33%) and to a partial response (platelets 90 x 10(9)/L-120 x 10(9)/L) in 2 (16.66%). The response was maintained for a median of 8.33 months, but 1 patient relapsed 7 months after eradication. Search for H pylori infection seems appropriate in ITP patients at diagnosis. Bacterium eradication provides a new good option for a nonimmunosuppressive treatment in some ITP patients.

Liver disease does not affect lipolysis as measured with the 13C-mixed triacylglycerol breath test in children with cystic fibrosis.

BACKGROUND: Liver disease associated with cystic fibrosis may not only limit the solubilisation and absorption of the products of fat digestion, but also may depress the activity of pancreatic lipase. The purpose of this study was to measure the effect of liver disease on triacylglycerol lipolysis using the 13C-mixed triacylglycerol breath test. METHODS: Forty children with cystic fibrosis took 13C-mixed triacylglycerol with a standard breakfast and the child's normal pancreatic enzyme replacement therapy. Breath samples were collected before and every 30 minutes after ingestion for 6 hours. The cumulative percentage dose of 13C recovered at 6 hours was calculated from sequential measurements of 13C enrichment of breath CO2, measured by isotope ratio mass spectrometry. Liver abnormalities and portal hypertension were defined by ultrasound scan and clinical examination. RESULTS: Twenty-four children had liver abnormalities, including 5 with portal hypertension. No difference was found between cumulative percentage dose of 13C recovered at 6 hours in 16 children with no liver abnormality (mean, 21.4%+/-11.1%), 19 children with liver abnormalities (22.2%+/-10.0%) and 5 children with portal hypertension (20.9%+/-7.1%). CONCLUSION: Intestinal lipolysis is not reduced in cystic fibrosis liver disease when measured using the 13C mixed triacylglycerol breath test. These findings affirm the test's use as an indirect measure of fat digestion that is not affected by inadequate intraluminal bile salts or liver disease.

Is the 13C-acetate breath test a valid procedure to analyse gastric emptying in children?

BACKGROUND/PURPOSE: Scintigraphy is regarded as the "gold standard" procedure in measuring gastric emptying (GE) rates. 13C-acetate breath test (ABT), which already has been validated in adults, is a noninvasive and nonradioactive alternative method. The aim of the current study was to validate ABT against technetium Tc 99m scintigraphy in children affected by delayed GE. METHODS: Sixty children were recruited and divided into 2 groups: group A, 30 healthy controls; group B, 30 patients with gastroesophageal reflux, and scintigraphy-documented DGE (15 neurologically impaired). After an overnight fast, all of them underwent ABT using 25 to 150 mg 13C-acetate. Breath samples were obtained at baseline and then every 10 minutes for 2 hours. The 13CO2 to 12CO2 ratio in breath samples was analysed by isotope ratio mass spectrometry. Data are expressed as follows: time of peak 13C exhalation (tP13CO2b) and half emptying time in ABT (t(1/2b)), and scintigraphy half emptying time (t(1/2s)). RESULTS: In controls tP13CO2b was 37 +/- 13 minutes and t(1/2b) 74 +/- 12 minutes. In patients tP13CO2b and t(1/2b) were, respectively, 65 +/- 26 minutes and 104 +/- 18 minutes t(1/2s) was 91 +/- 21 minutes. In group B tP13CO2b and t(1/2b) were delayed significantly compared with controls, respectively, P < .03 and P < .01. In group B significant correlation between t(1/2s) and t(1/2b) was noted (r1 = 0.97). A close correlation was also observed between t(1/2s) and tP13CO2b (r2 = 0.95). CONCLUSION: The 13C ABT is an easy, reliable, and less expensive procedure for measuring GE, and its results closely correlate with those of scintigraphy in a paediatric population.

13C and H2 breath tests to study extent and site of starch digestion in children with cystic fibrosis.

BACKGROUND: Starch is an important source of energy for children with cystic fibrosis, but little is known about their capacity to digest it. METHODS: A 13C breath test was used to measure starch digestion and oxidation in 16 children with cystic fibrosis (median [range] age, 7.9 [4-15] years; 7 girls, 9 boys) and 5 normal healthy control subjects (median age, 8.3 [7-13] years; 3 girls, 2 boys). A test meal of 13C flour and lactulose was consumed and breath samples were obtained half-hourly thereafter for 6 hours to measure 13C enrichment by isotope ratio mass spectrometry and H2 by electrochemistry. The test was repeated on 10 children with cystic fibrosis when they were taking pancreatic supplements. RESULTS: The median (range) cumulative percentage 13C dose recovery (cPDR), was 35% (18-52%) in control subjects, 18% (9-33%) in children with cystic fibrosis without enzymes, and 29% (22-51%) in those with pancreatic supplements. cPDR differed significantly between healthy control subjects and children with cystic fibrosis without enzymes (p = 0.01) and between children with cystic fibrosis with and without enzymes (p < 0.0001), but there was no difference between control subjects and children with cystic fibrosis taking enzymes (p = 0.5). Eight children with cystic fibrosis had a cPDR within control range, and in six there was a second peak in 13CO2 enrichment coincident with an increase in H2. CONCLUSIONS: Starch digestion and oxidation are diminished in children with cystic fibrosis, but pancreatic enzymes restored them to near normal levels. A second peak in 13CO2 enrichment, suggestive of colonic starch fermentation was absent in healthy children, but present in some children with cystic fibrosis and abolished by pancreatic enzymes.

Prevalence of Helicobacter pylori infection detected by serology and 13C-urea breath test in HIV-1 perinatally infected children.

BACKGROUND: Conflicting results have been reported in adults with human immunodeficiency virus (HIV-1) who were investigated for Helicobacter pylori infection. Most studies indicate a lower prevalence than is found in the general population. The purposes of this study were to evaluate H. pylori prevalence by noninvasive methods in a population of children perinatally infected with HIV-1 and to correlate H. pylori prevalence with HIV-1-related clinical and immunologic status. METHODS: H. pylori infection was studied in 45 children perinatally infected with HIV-1 by performing serologic testing of anti-H. pylori immunoglobulin G antibodies and the 13C-urea breath test. RESULTS: Eight children with HIV-1 (17.7%) were positive by serology, and nine (20%) were positive by 13C-urea breath test. No significant differences related to age, previous antibiotic treatment, immunoglobulin administration, antiretroviral treatment, abdominal pain, CD4+ cell count, number of HIV-1 RNA copies, and frequency of severe immunodepression were noted between children with positive 13C-urea breath test results and those with negative results. Children with positive results were significantly more likely to have severe clinical manifestations. CONCLUSIONS: The results show, by both serology and 13C-urea breath test, a prevalence of H. pylori infection comparable with the prevalence in the normal population of the same age. H. pylori prevalence has probably been underestimated in patients with HIV. Results of serologic and histologic analyses for H. pylori require cautious interpretation, especially in severely immunodeficient patients.

Importance of measuring CO2-production rate when using 13C-breath tests to measure fat digestion.

Stable isotope breath tests offer a safe, repeatable non-invasive method of measuring fat digestion. They involve the ingestion of a substrate labelled with 13C followed by serial measurements of the 13C:12C ratio in expired CO2, from which the percentage of the 13C dose recovered (PDR) can be calculated. However PDR depends on the CO2-production rate. Our aim was to compare results obtained using directly measured CO2-production rates with those calculated from two predicted values. Twelve normal healthy children and twenty-four children with cystic fibrosis (CF) (without or with the normal dose of enzyme supplementation) were studied with 1,3-distearyl, 2[carboxyl-13C] octanoyl glycerol. The volume of CO2 produced (litres/min) was measured at rest for 30 min approximately 3 h after substrate ingestion, and the results were converted to mmol/min. For each subject the expected BMR was calculated from the equation of Schofield (1985), based on sex, age, weight and height, and from these values, CO2-production rate was derived. Surface area was calculated and an estimated value of 5 mmol/m2 per min (Shreeve et al. 1970) was used. Using these three CO2-production rates, three different PDR were calculated and compared. In healthy children there was a close concordance between measured and predicted CO2-production rates, but children with CF had a mean measured CO2-production rate 39% higher than normal children. This use of normal data for predicted CO2-production rates in children with CF underestimates cumulative PDR. If direct measurements of CO2-production rate are not available or impossible to perform the VCO2 obtained from the BMR calculated using the equations of Schofield (1985) or Shreeve et al. (1970) can be used in normal children. However, if accurate results for PDR are to be obtained, CO2-production rates should be measured when performing breath tests in conditions where energy expenditure and/or CO2-production rate are not expected to be normal.

13Carbon mixed triglyceride breath test and pancreatic enzyme supplementation in cystic fibrosis.

Children with cystic fibrosis have variable degrees of exocrine pancreatic insufficiency which, if untreated, is the main cause of fat malabsorption. The impact of pancreatic enzyme supplementation on fat digestion was measured in 41 children with cystic fibrosis, 11 healthy controls, and five children with mucosal diseases by a non-invasive test of intraluminal lipolysis using 13carbon (13C) labelled mixed triglyceride (1,3-distearyl, 2[13C] octanoyl glycerol). The children with cystic fibrosis without pancreatic supplements had a median (range) 13C cumulative percentage dose recovered over six hours (cPDR) of 3.1% (0-31.7), the controls 31.0% (21.8-41.1), and the subjects with mucosal disease 27.8% (19.7-32.5). In 23 subjects with cystic fibrosis the usual dose of pancreatic enzyme supplements increased the cPDR to a median of 23.9% (0-45.6), and twice the usual dose of enteric coated microspheres increased the cPDR to 31.1% (11.1-47.8). There was no significant difference between the median cPDR of normal controls and children with mucosal disease, but there was a highly significant difference between these groups and children with untreated cystic fibrosis. Thirteen children with cystic fibrosis had no 13C recovery in their breath without enzymes and 10 showed marked increases with regular enzymes. In eight children doubling the dose of enzymes caused no or minimal improvement. The mixed triglyceride breath test offers a simple, non-invasive way of assessing the need for pancreatic enzyme supplementation in children with cystic fibrosis and could be used to optimise treatment.

[Beta-cell secretion in patients with thalassemia major]. / Secrezione beta-cellulare nei pazienti con thalassemia major.

Diabetes mellitus is one of the main endocrinological disease complicating the course of thalassemia major. This study aimed evaluate beta-cell secretion in 24 patients with thalassemia major attending the hematological Day Hospital at the Pediatric Clinic in Modena where transfusion therapy is performed in all thalassemic patients so as to maintain minimum hemoglobin levels above 10.5 g/dl, together with intensive ferrochelating therapy (desferrioxamine 50-60 mg/kg/die s.c. 6 days a week). A C peptide challenge with glucagon was performed in three patients already receiving insulin therapy for diabetes mellitus; this unexpectedly revealed a slight residual beta-cell secretion. An intravenous glucose tolerance test (IVGTT) was performed in the remaining 21 non-diabetic patients, with widely varying findings regarding insulin secretion: from below 50 microUl/ml in 5 patients to above 200 microUl/ml in 5 patients, and between 50 and 150 microUl/ml in the remaining 11 patients. This study therefore confirmed that insulin secretion frequently alters in thalassemic patients. Moreover, insulin secretion is not correlated to ferritinemia or influenced by familiar diabetes or patient age.