Management of coeliac disease patients after the confirmation of diagnosis in Central Europe.

BACKGROUND: Recently published paediatric guidelines for diagnosing coeliac disease do not include recommendations on the follow-up of coeliac disease patients. GOAL: The aim of this study was to assess the management practices and experience of coeliac disease patients with their follow-up appointments in Central Europe. STUDY: Gastroenterologists and coeliac disease patients in five Central European countries were asked to complete the web-based questionnaire focusing on coeliac disease management practices. RESULTS: Answers from 147 gastroenterologists and 2041 coeliac disease patients were available for the analysis. More than half of the gastroenterologists (58.5%) schedule the first follow-up visit within 3 months after the diagnosis. At follow-up, tissue transglutaminase antibodies are checked in almost all patients (95.9%). Approximately two-thirds (60.7%) of gastroenterologists refer all of their patients to the dietitian at diagnosis. Similarly, 42.8% of coeliac disease patients reported that they had not been appointed to a dietitian. Almost one-third of coeliac disease patients (30.8%) reported that they had no follow-up appointments with gastroenterologist at all. CONCLUSIONS: Follow-up of coeliac disease patients is suboptimal in Central Europe. Many patients are not followed regularly. A lot of patients are not referred to a dietitian. The recommendations on the optimal follow-up of coeliac disease patients are needed in order to improve patient care.

The Knowledge About Celiac Disease Among Healthcare Professionals and Patients in Central Europe.

OBJECTIVES: Celiac disease (CD) remains undiagnosed for a long time in many adult and pediatric patients. We assessed the knowledge about CD among healthcare professionals (HCPs) and CD patients in Central Europe (CE). METHODS: HCPs and CD patients from 5 CE countries were asked to complete the web-based questionnaire about CD. The questions were divided into subsections on epidemiology, clinical presentation, diagnostics, treatment, and follow-up. Achieved scores of different specialists managing patients with CD were compared and regional differences in patients' knowledge were analyzed. RESULTS: Questionnaire was completed by 1381 HCPs and 2262 CD patients or their caregivers from Croatia, Hungary, Germany, Italy, and Slovenia. Mean score achieved by HCPs was 50.9%, and by CD patients 56.4%. Pediatric gastroenterologists scored the highest (69.4%; P < 0.001). There were significant differences in knowledge of patients from different CE regions with German participants scoring the highest (58.3%). Members of CD societies scored higher compared with nonmembers (mean score 58% vs 53.2%; P < 0.001) and patients diagnosed less than 5 years ago scored higher compared with those diagnosed more than 10 years ago (mean score 57.3% vs 54.6%; P < 0.001). CONCLUSIONS: The knowledge about CD among HCPs and CD patients is not satisfactory. Further awareness-raising and learning activities are needed to improve HCPs' knowledge and to minimize the number of unrecognized patients and unnecessary diagnostic delays. Patients should be better informed about their disease to reach higher compliance with the gluten-free diet.

Clinical Presentation in Children With Coeliac Disease in Central Europe.

OBJECTIVES: During the past decades, there has been a shift in the clinical presentation of coeliac disease (CD) to nonclassical, oligosymptomatic, and asymptomatic forms. We assessed clinical presentation of CD in children and adolescents in Central Europe. METHODS: Paediatric gastroenterologists in 5 countries retrospectively reported data of their patients diagnosed with CD. Clinical presentation was analyzed and the differences among very young (<3 years) and older children and adolescents were studied. RESULTS: Data from 653 children and adolescents (median age 7 years 2 months; 63.9% girls) from Croatia, Germany, Hungary, Italy, and Slovenia were available for the analysis. One fifth (N = 134) of all children were asymptomatic. In symptomatic children, the most common leading symptom was abdominal pain (33.3%), followed by growth retardation (13.7%) and diarrhoea (13.3%). The majority of symptomatic children (47.6%; N = 247) were polysymptomatic. Abdominal pain was the most common symptom in polysymptomatic (66.4%) as well as in monosymptomatic children (29.7%). Comparing clinical presentation of CD in very young children (younger than 3 years) with older children (3 years or older), we found that symptoms and signs of malabsorption were significantly more common in younger (P < 0.001), whereas abdominal pain and asymptomatic presentation were more common in older children and adolescents (both P < 0.001). CONCLUSION: In children with CD, abdominal pain has become the most common symptom. However, in younger children, symptoms of malabsorption are still seen frequently. This raises a question about the underlying mechanism of observed change in clinical presentation in favour of nonclassical presentation and asymptomatic disease at certain age.

Incidence and Geographical Variability of Pediatric Inflammatory Bowel Disease in Croatia: Data From the Croatian National Registry for Children With Inflammatory Bowel Disease.

The aim of this study was to determine the annual incidence and geographic distribution of pediatric inflammatory bowel disease (IBD) in Croatia. This is a prospective, cohort, multicenter observational study based on the data obtained from the Croatian national registry for children with IBD. Children and adolescents younger than 18 years diagnosed with IBD, in time period between June 1, 2016, and May 31, 2017, were recruited. In total, 51 new cases were identified; 19 Crohn's disease, 28 ulcerative colitis, and 8 IBD-unclassified. Male preponderance of all 3 types of the disease was noticed. The median age at diagnosis was 14.8 years. The calculated annual incidence of pediatric IBD per 100 000 persons per year was 7.05 (2.63 for Crohn's disease, 3.87 for ulcerative colitis, and 0.55 for IBD-unclassified). A north to south gradient was observed with almost 2 times higher incidence in the northern region of the country.

IBD phenotype at diagnosis, and early disease-course in pediatric patients in Croatia: data from the Croatian national registry.

BACKGROUND: Pediatric inflammatory bowel disease (IBD) presents with extensive phenotype. The aim of this study was to determine the phenotype of pediatric IBD patients in Croatia at diagnosis and follow-up. METHODS: Children were prospectively recruited into Croatian IBD national registry. Data on diagnostic evaluation, therapy and 1-year follow-up were collected. RESULTS: A total of 51 newly diagnosed patients were recruited (19 Crohn's disease (CD), 28 ulcerative colitis (UC) and 4 IBD-unclassified (IBD-U)). Most common location in CD was ileocolonic disease (52.6%), and pancolitis in UC (53.6%). The recommended complete diagnostic algorithm was performed only in 29.4% of patients. First-line therapy used in CD was exclusive enteral nutrition for remission induction (84.2%) and azathioprine for maintenance (73.7%). In patients with UC, aminosalicylates were the most common drug used (89.3%). By the end of the first year 41.2% of CD and 53.9% of UC patients had one or more relapses and required treatment escalation. CONCLUSION: Our data confirm extensive intestinal involvement in pediatric IBD and relatively high relapse rate during the first year of follow-up. More effort should be invested on the national level to implement more stringent adherence to the current European guidelines. IMPACT: The key message of our article is that pediatric IBD in Croatia shows extensive intestinal involvement with high relapse rates in first year of follow-up. It is the first cohort study reporting on the phenotype of pediatric IBD in Croatia, but also investigates adherence to diagnostic and therapeutic European guidelines which is not commonly reported. The study is national based, thus having the greatest impact on Croatian health care,stressing out that more effort should be invested on the national level to implement more stringent adherence to the current European guidelines.

The Use of Biopsy and "No-Biopsy" Approach for Diagnosing Paediatric Coeliac Disease in the Central European Region.

OBJECTIVES: The current European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) guidelines introduced the option to diagnose coeliac disease (CD) in children and adolescents without upper endoscopy if the defined criteria are met. The aim of our study was to evaluate how frequently paediatric gastroenterologists in Central Europe used the "no-biopsy" approach and how often the duodenal biopsy could have been omitted. METHODS: Medical records of patients aged < 19 years diagnosed with CD in 2016 from five European countries were analysed, focusing on levels of transglutaminase antibodies (TGA) at the time of diagnosis and on whether the diagnosis was confirmed using duodenal biopsy or "no-biopsy" approach. Clinical presentation and delays until final diagnosis were analysed according to diagnostic approach. RESULTS: Data from 653 children (63.9% female, median age: 7 years, range: 7 months-18.5 years) from Croatia, Hungary, Germany, Italy, and Slovenia were analysed. One fifth (n = 134) of included children were asymptomatic at diagnosis. Of 519 symptomatic children, 107 (20.6%) were diagnosed by the "no-biopsy" approach. Out of the remaining 412 children who underwent duodenal biopsies, 214 (51.9%) had TGA ≥ 10 times upper level of normal (ULN) and would have been eligible for the "no-biopsy" approach. Signs and symptoms of malabsorption were more frequent in children diagnosed without duodenal biopsies. There were no differences in diagnostic delays with respect to the diagnostic approach. CONCLUSION: In this cohort, about 60% of symptomatic CD patients could have been diagnosed without duodenal biopsies. The aim of the "no-biopsy" approach was to make the diagnostic procedure less challenging without compromising its reliability. However, this option was applied only in 20%, in spite of fewer burdens to the family and reduced costs. The reasons for this discrepancy are unknown. Physicians should be made more aware about the reliability of CD diagnosis without biopsies when the ESPGHAN guidelines for CD diagnosis are followed.

Is There a Role of Using a Rapid Finger Prick Antibody Test in Screening for Celiac Disease in Children?

INTRODUCTION: Celiac disease (CD) is an autoimmune disease triggered by gluten in genetically predisposed individuals. Despite the increasing prevalence of CD, many patients remain undiagnosed. Standard serology tests are expensive and invasive, so several point-of-care tests (POC) for CD have been developed. We aimed to determine the prevalence of CD in first-grade pupils in Primorje-Gorski Kotar County, Croatia, using a POC test. METHODS: A Biocard celiac test that detects IgA antibodies to tissue transglutaminase in whole blood was used to screen for celiac disease in healthy first-grade children born in 2011 and 2012 who consumed gluten without restrictions. RESULTS: 1478 children were tested, and none of them were tested positive with a rapid test. In 10 children (0,6%), IgA deficiency has been suspected; only 4 of them agreed to be tested further for total IgA, anti-tTG, and anti-DGP antibodies. IgA deficiency was confirmed in 3 patients, and in all 4 children, CD has been excluded. CONCLUSION: Our results have not confirmed the usefulness of the POC test in screening the general population of first-grade schoolchildren. Further research is needed to establish the true epidemiology of CD in Primorje-Gorski Kotar County and to confirm the value of the rapid test in comparison with standard antibody CD testing.

Diagnostic Delays in Children With Coeliac Disease in the Central European Region.

OBJECTIVES: Coeliac disease (CD) is a systemic autoimmune disorder affecting about 1% of the population. Many patients remain undiagnosed or are diagnosed with substantial delay. We assessed diagnostic delays in symptomatic CD children in Central Europe (CE). METHODS: Paediatric gastroenterologists in 5 CE countries retrospectively reported data of their patients diagnosed in 2016. Age at first CD-related symptom(s), first visit to paediatric gastroenterologist and confirmed diagnosis were used to determine diagnostic delays. RESULTS: Data from 393 children (65% girls, median age 7 years, range 7 months to 18.5 years) from Croatia, Hungary, Germany, Italy, and Slovenia were analysed. Median duration from first symptom(s) to visit to paediatric gastroenterologist was 5 months (range 0-10 years; preschool 4 months, school-aged 5 months), and further duration until final diagnosis was 1 month (range 0-5 years) with significant regional differences (P < 0.001). Median diagnostic delay was 6 months (range 0-10 years; preschool 5 months, school-aged 7 months). Type of clinical presentation had little, however, significant effect on delays. Reduced body mass in delays longer than 3 years compared with delays shorter than 1 year was found (z score -0.93 vs -0.39, P < 0.05). CONCLUSIONS: Time from first symptoms to CD diagnosis in children in 5 CE countries is slightly shorter compared with few other small paediatric studies, and significantly shorter than reported for adults. Nevertheless, delays of more than 3 years in 6.6% of children are worrisome. Raising awareness about the variable symptoms and implementation of reliable diagnostic tools will further reduce diagnostic delays.

Advances in diagnosis of chronic liver diseases in pediatric patients.

BACKGROUND: Chronic liver diseases (CLD) present important clinical problem in children with various age-dependent causes. Nonalcoholic fatty liver disease (NAFLD) with its increasing prevalence is a major problem with regard to its timely recognition and the need for long-term disease monitoring. At present, a perfect non-invasive method for the evaluation of liver fibrosis is not available. METHODS: A non-systematic literature search was performed to summarize the current knowledge about transient elastography (TE) with controlled attenuation parameter (CAP) in children with CLD. Ovid MEDLINE, Ovid EMBASE, Google scholar, and The Cochrane Library databases were searched for relevant articles evaluating TE in the pediatric population. RESULTS: Normal values of liver stiffness measurements (LSM) according to the age are given, as well as the advantages and disadvantages of the method. The utility of TE in specific liver disease in pediatric population is summarized. CONCLUSIONS: TE with CAP is a valuable non-invasive method for the liver-damage assessment. Clinical interpretation of TE results should be made in parallel with the assessment of the patient's demographics, disease etiology, and essential laboratory parameters.

An Infant With Unusually High Unconjugated Hyperbilirubinemia Due to Coexistence of Hereditary Spherocytosis and Gilbert Syndrome.

Hereditary spherocytosis is the most frequent congenital hemolytic anemia and is characterized with variable degree of anemia, jaundice, and splenomegaly. In the case of severe hyperbilirubinemia out of proportion with hemolysis, other causes of hyperbilirubinemia must be considered. Gilbert syndrome (GS) is an autosomal dominant disorder characterized with intermittent hyperbilirubinemia without any other sign and symptom of liver disease as a result of reduced activity of uridine diphosphate-glucuronyl transferase 1A1. The calculated rate of coexistence of these 2 diseases is 15 to 35/million births. Here we present a 21-month-old girl with hereditary spherocytosis diagnosed at the age of 40 days with hyperbilirubinemia out of proportion of hemolysis which led to diagnosis of GS. Thereby, the diagnosis of GS should be considered in unexplained unconjugated hyperbilirubinemia in different age groups, including infants and toddlers.

Unlicensed and off-label drug use in hospitalized children in Croatia: a cross-sectional survey.

PURPOSE: The aim of this study was to determine the prevalence and pattern of unlicensed and off-label drugs prescribed to hospitalized children at the Department of Paediatrics, University Hospital Rijeka, Croatia. METHODS: A prospective cross-sectional study was performed on 1 day each month during a 12 month period and included all hospitalized children and adolescents. RESULTS: A total of 1,643 prescriptions for 198 different drugs were prescribed to 531 out of 691 (77%) hospitalized patients. Forty-six percent of the different drugs were prescribed in an unlicensed or off-label manner. Of all drug prescriptions, 25% were either unlicensed or off-label. Forty-eight percent of the patients received either an unlicensed or off-label drug. The most frequently prescribed off-label drugs were proton pump inhibitors. CONCLUSION: Unlicensed and off-label drug use is common. It is not illegal and may be clinically appropriate but is associated with a number of clinical, safety, and ethical issues. Regulatory authorities should use existing clinical evidence on the use of off-label and unlicensed drugs in decision making. Marketing authorization holders and national regulatory authorities should monitor for any safety concerns associated with unlicensed and off-label drug use and take appropriate measures as well as identify research priorities and mandate clinical studies to resolve important questions.

Chronic intussusception in children caused by Ascaris lumbricoides.

Chronic intussusception (CI) is defined as an intussusception lasting for 14 days or more. Because the clinical manifestations are non-specific, the diagnosis is usually delayed. Symptoms include intermittent abdominal pain, sometimes an abdominal mass is palpable and there is a marked weight loss. Diagnosis is based on typical features revealed by ultrasound or barium enema and CT investigations. Therapy is surgical with obligatory exclusion of possible underlying lesions. We report a case of a 3.5-year-old girl with chronic intussusception. Laboratory blood findings revealed sideropenic anemia and stools positive for Ascaris lumbricoides. Anti-parasitic therapy with mebendazole was repeatedly administered with early improvements but soon after symptoms relapsed. During surgery an ileocolic chronic intussusception extending to hepatic flexure was found. Postoperative control examinations proved complete healing. We suspected that Ascaris lumbricoides infestation was an etiologic factor for the development of chronic intussusception in the child.

Coping with changes in the Defined Daily Dose in a longitudinal drug consumption database.

OBJECTIVE: To illustrate the best approach to accurate representation of temporal evolution of drug consumption, when confronted with changes over time in the Defined Daily Dose (DDD) measurement unit. METHOD: As an example, drug consumption (2001-2005) at the University Hospital Rijeka was expressed with the corresponding DDD in each year; and with the DDD value of the last year of the observation time window. By visual appraisal, results with both methods were compared with the graph of drug consumption trends expressed in physical units (mg, IU, etc.). RESULTS: Of 20 drugs for which the DDD value has changed in the 5 year period, 5 were used in Rijeka hospital: erythropoietin parenteral, budesonide nasal spray, repaglinide oral, amoxicillin with clavulanic acid parenteral, and fentanyl transdermal. Graphs for individual drugs with the year by year method showed artificial jerks in the years proceeding the year of DDD change. Representation of total hospital consumption did not differ notably with the two methods. CONCLUSION: Drug consumption data should be calculated with the latest DDD value in the time window. The policy of the World Health Organisation to keep changes to the system of DDD to a minimum should be continued.

[Electrogastrography in diagnosis of gastric motility disorder in children]. / Vaznost elektrogastrografije u dijagnostici poremecaja motiliteta zeluca u djecjoj dobi.

Gastrointestinal (GI) motility disorders are common in children. Modern technology has enabled better understanding, monitoring and treatment of these disorders. While gastric anatomic structures are developed prenatally, myoelectric activity and motility develop after the birth. Electrogastrography (EGG) measures gastric myoelectric activity by electrodes that are positioned on the skin. The frequency of gastric waves varies between 0.5-9.0 c/min, usually between 2.0-4.0 c/min with amplitudes between 50 and 500 microV. Frequency above 4.0 c/min is called tachygastria, bellow 2.0 c/min bradygastria, and if the dominant frequency cannot be measured it is defined as gastric arrhythmia. EGG is useful for monitoring of normal gastric function, determining motoric gastric diseases in different states and for the evaluation of treatment of a disease. The method is non-invasive, cheap and safe and is easily performed. These characteristics make the method useful in pediatrics. The future of the method depends mainly on the technical improvement of measurement and data analysis which is crucial for better result interpretation.

Antimicrobial prescribing at a university hospital: justified or 'just in case': testing a new scoring system as a key quality indicator.

OBJECTIVE: To evaluate the quality of antimicrobial drug prescribing at a university hospital in the Department of Medicine, by using a new scoring system as a quality indicator. DESIGN: a prospective, longitudinal survey, during a 21-week period. The necessity of antimicrobial treatment of all in-patients at the Department of Medicine, to whom new antimicrobials were prescribed, was assessed by using a scoring system based on the presence of signs and symptoms of an infection. If the sum's total score was 3 or more, the antimicrobial treatment was deemed justifiable; if the score was less than 3, the antimicrobial treatment was regarded as questionable. SETTING: Department of Medicine (279 hospital-beds) at the University Hospital Center Rijeka, a 1200-patient-bed teaching hospital in Croatia. RESULTS: Antimicrobials were prescribed to 15% of the total patients. They were given as a treatment to 89% of the patients, and in 67% of the cases, this treatment was administered empirically. According to the scoring system, 29% of the patients did not have a justified indication for antimicrobial treatment. CONCLUSION: The proposed quality indicator (scoring system) that we used is a simple method for the quality assessment of antimicrobial use. It has indicated areas that require in-depth analysis.

Antibiotic use profile at paediatric clinics in two transitional countries.

PURPOSE: In this study, we evaluated antibiotic utilisation pattern at two paediatric clinics in different European (transitional) countries: Croatia (Rijeka) and Russia (Smolensk). METHODS: Antibiotic utilisation during the year 2000 was observed using the ATC/defined daily doses (DDD) methodology (ATC code-J01). Drug-usage data was expressed in numbers of DDD/100 bed-days and the DU90% profile. RESULTS: In Rijeka, 35 different systemic antibiotics were used and in Smolensk 22. The overall consumption of antibiotic drugs in Rijeka was more than three times higher than in Smolensk (28.96 vs 8.3 DDD/100 bed-days). The top five antibiotic drugs used in Smolensk were amoxicillin, mydecamicin, ampicilin, doxycylin, gentamicin; and in Rijeka cefuroxime axetil, ceftriaxone, azytromycin, ceftibuten and amoxicillin. CONCLUSION: Differences in antibiotic prescribing patterns are greater than expected. The pattern of antibiotic utilisation in both countries implies that regional control measures and guidelines for antibiotic use in children should be urgently established.

Utilization of antimicrobials in Rijeka (Croatia).

PURPOSE: In this study, the extent and pattern of inpatient and outpatient antimicrobial drug use was investigated in Rijeka, Croatia, and the impact of control measures was evaluated. METHODS: Consumption of antibacterials for the years 2000 and 2001 was monitored using the ATC/DDD methodology. RESULTS: During the investigation period, the antimicrobial utilization at the University Hospital Center (UHC) Rijeka has decreased by 14%. In the outpatient setting of the County of Primorje and Gorski kotar, the antimicrobial utilization was similar during both years. At the UHC Rijeka, not only the amount, but the pattern of antibacterial utilization also has changed in contrast to the outpatient setting where the pattern of antimicrobial prescribing remained the same. CONCLUSIONS: The control measures for antibiotic use that were introduced in the outpatient setting did not influence the prescribing habit of primary care physicians, while the impact of hospital antibiotic use control measures was satisfactory. Further investigation is needed to evaluate the impact of these measures on bacterial resistance patterns.