[Diagnosis and treatment of Helicobacter pylori infection in pediatrics: recommendation for 2014 clinical practice]. / Diagnosi e terapia dell'infezione da Helicobacter pylori in pediatria: raccomandazioni per la pratica clinica del 2014.

Helicobacter pylori (H. pylori) infection is a large worldwide infection usually acquired during childhood, whose prevalence in pediatric population varies, with lower incidence rates in developed countries compared to developing countries (up to 10-15% and 70%, respectively). Diagnosis can be performed both with endoscopic-based methods and noninvasive diagnostic tests, such as urea breath test and fecal antigen. Current guidelines recommend endoscopic evaluation of the young patients, in order to determine the underlying cause of abdominal pain. Even in case of suspected functional pain, patient should not be investigated for infection, unless upper endoscopy is performed to rule out organic causes. Nowadays, in pediatric population, applications of noninvasive tests are limited to verifying eradication after therapy and to investigating the presence of infection in asymptomatic patients with first-degree relatives affected by gastric cancer. Since correlation between abdominal pain and H. pylori gastritis, in absence of peptic ulcer disease is still debated, "test and treat" strategy is not recommended in children. As for adults, treatment regimens are based on the combination of proton-pump inhibitor and two or more antibiotics, for 7-14 days, depending on resistance rates of geographic areas.

Evaluation of cardiovascular risk factors, events, and costs across four BMI categories.

OBJECTIVE: The purpose of this study was to analyze the 1-year cost of cardiovascular (CV) events by body mass index (BMI) subgroups from a US employer health plan perspective. DESIGN AND METHODS: Patients aged 20-64 years from the GE Centricity Electronic Medical Record, National Health and Nutrition Examination Survey, and MarketScan databases were used to determine prevalence of risk factors (RFs) and CV events and 1-year costs. Risk factors included hypertension (HTN), diabetes, and hyperlipidemia (HLD) and CV events included myocardial infarction, angina, heart failure, and stroke. CV event costs were determined from claims by ICD-9 code in patients with overweight/obesity. RESULTS: Of 220,136 patients identified in GE, BMI was 25-26.9 in 19.4%, 27-29.9 in 30.4%, 30-34.9 in 27.9%, and ≥35 in 22.3%. Patients with diabetes, HTN, and HLD increased with BMI from 1.8% (25-26.9) to 11.4% (≥35) in males and 1.1% to 6.8% in females. Prevalence of CV events increased from 0.1% with no RFs up to 10.2% with multiple RFs. The average 1-year cost per patient increased from $1122 to $2383 as BMI increased. CONCLUSIONS: Patients with higher BMI values had an increased prevalence of RFs and CV events, which lead to higher average 1-year costs.

Interleukin-10 and transforming growth factor-beta1 in cord blood: relationship with paternal allergy and cesarean section.

AIM: To measure Interleukin-10 (IL-10) and transforming growth factor-beta1 (TGF-beta1) in cord blood and assess their relationship with parental allergy and perinatal characteristics. METHODS: In a neonatal care unit 212 consecutive full-term and appropriate for gestational age newborns were recruited. IL-10 and TGF-beta1 levels were determined in cord blood by high sensitivity ELISA. Perinatal characteristics, mode of delivery and presence of allergy in parents were recorded. RESULTS: Out of 212 newborns, 136 were of non-allergic parents and 76 (35.8%) of one or both allergic parents. In newborns of allergic fathers median IL-10 levels tended to be lower (0.67 vs. 1.06 pg/mL, p = 0.07) and TGF-beta1 levels were significantly lower (40.9 vs. 45.3 ng/mL, p = 0.008) than in newborns of non-allergic parents. Multiple general regression analysis showed that presence of paternal allergy (beta=-0.19, p = 0.003) to be born by cesarean section (beta=-0.21, p = 0.03) and younger gestational age (beta= 0.14, p = 0.04) independently contributed to decrease TGF-beta1 levels (multiple R = 0.38, p < 0.0001). CONCLUSION: Paternal allergy and cesarean section are associated to decreased TGF-beta1, which might be the mediator of the increased risk of atopy development. Cord blood IL-10 and TGF-beta1 levels of our newborn series could be used as reference values for further studies on these relationships.

Inflammatory bowel disease in children and adolescents in Italy: data from the pediatric national IBD register (1996-2003).

BACKGROUND: The purpose was to assess in Italy the clinical features at diagnosis of inflammatory bowel disease (IBD) in children. METHODS: In 1996 an IBD register of disease onset was established on a national scale. RESULTS: Up to the end of 2003, 1576 cases of pediatric IBD were recorded: 810 (52%) ulcerative colitis (UC), 635 (40%) Crohn's disease (CD), and 131 (8%) indeterminate colitis (IC). In the period 1996-2003 an increase of IBD incidence from 0.89 to 1.39/10(5) inhabitants aged <18 years was observed. IBD was more frequent among children aged between 6 and 12 years (57%) but 20% of patients had onset of the disease under 6 years of age; 28 patients were <1 year of age. Overall, 11% had 1 or more family members with IBD. The mean interval between onset of symptoms and diagnosis was higher in CD (10.1 months) and IC (9 months) versus UC (5.8 months). Extended colitis was the most frequent form in UC and ileocolic involvement the most frequent in CD. Upper intestinal tract involvement was present in 11% of CD patients. IC locations were similar to those of UC. Bloody diarrhea and abdominal pain were the most frequent symptoms in UC and IC, and abdominal pain and diarrhea in CD. Extraintestinal symptoms were more frequent in CD than in UC. CONCLUSIONS: The IBD incidence in children and adolescents in Italy shows an increasing trend for all 3 pathologies. UC diagnoses exceeded CD.

[Treatment of Helicobacter pylori in children]. / Il trattamento dell'Helicobacter pylori nell'infanzia.

BACKGROUND: There are very few studies that compare therapeutic protocols against H. pylori infection in children and the few available data derive from studies that usually evaluate the remission of symptoms or the accuracy of diagnostic procedures before and after treatment. Furthermore, no randomised, controlled clinical trials using placebo have been carried out in children. METHODS: We systematically collected data from the pediatric literature on the treatment of H. pylori to assess the efficacy of various treatments. This review included all articles and letters published since 1987 and all abstracts presented at the three main international meetings from 1997 to 1999. The results of studies published in English and French journals were collected and analysed. RESULTS: We only found 30 articles and 17 abstracts containing results on the treatment of H. pylori, carried out respectively in a total of 870 and 1552 children. All the data collected seemed to indicate that single-therapy or dual therapy with an antisecretory drug combined with an antibiotic showed a low level of efficacy. Dual therapy proved effective, in the form of bismuth and one antibiotic (amoxycillin or a nitroimidazole) or two antibiotics when administered for two or more weeks. The same was true of triple therapy based on bismuth or a proton pump inhibitor associated with two antibiotics. Triple therapies were less effective in children than in adults, and although triple therapies based on bismuth were more effective when administered for at least two weeks, the triple therapies based on a proton pump inhibitor showed a comparable level of efficacy irrespective of duration. CONCLUSIONS: Dual therapies in children using two antibiotics appear to have a similar efficacy as triple therapies, and if the latter contain a proton pump inhibitor, they show a similar efficacy irrespective of duration. For this reason, it does not seem necessary to administer them for more than one week.

Usefulness of Helicobacter pylori stool antigen test to monitor response to eradication treatment in children.

BACKGROUND: The monitoring of the results of eradication treatment is a crucial step for patients with Helicobacter pylori gastritis. A non-invasive test for H. pylori antigens in stools (HpSA) was recently validated for children. AIM: To evaluate the accuracy of HpSA in monitoring eradication treatment in children. METHODS: In 60 children, H. pylori gastritis was diagnosed by endoscopy and the 13C-urea breath test. The children were treated and returned for a follow-up (13)C-urea breath test 6 weeks after the end of treatment. Children were considered cured when the (13)C-urea breath test was negative. Stool were collected at baseline, and at 2 and 6 weeks. Stool antigens were measured by HpSA. RESULTS: According to (13)C-urea breath test, 6 weeks after the end of treatment 49 children were cured and 11 were still H. pylori-positive. The sensitivity and specificity of HpSA on stools collected 2 weeks after therapy were 100%. At 6 weeks specificity was 93.9 and sensitivity 100%. Results by visual reading were concordant with the plate-reader in all but two cases at baseline. CONCLUSIONS: HpSA is accurate for monitoring treatment in children as early as 2 weeks after therapy, when information is most useful and unachievable with other tests. Results by visual reading are accurate, and this can make the test cheaper and more practical.

A systematic review of Helicobacter pylori eradication treatment schedules in children.

METHODS: We systematically reviewed all available data in the paediatric literature on treatment for Helicobacter pylori infection to determine overall efficacy of different schedules. A comprehensive search of all published articles and letters from 1987, and of abstracts presented at three main meetings on this topic between 1997 and 1999, was carried out. Results from all English and French papers, letters and abstracts were extracted and analysed. RESULTS: Only 30 full articles and 16 abstracts were found, with results on eradication of H. pylori in 870 and 1552 children, respectively. Monotherapy or dual therapy with an antisecretory drug plus one antibiotic showed a very low efficacy. Dual therapies with bismuth plus one antibiotic (either amoxycillin or a nitro- imidazole) or two antibiotics when administered for 2 or more weeks were as effective as either bismuth-based or proton pump inhibitor-based triple therapies. Triple therapies were less effective than in adults, and while bismuth-based triple therapies were more effective when given for 2 weeks than for one week, proton pump inhibitor-based triple therapies have a similar efficacy irrespective of the duration. CONCLUSION: In children dual therapies seemed as effective as triple therapies, and longer courses of proton pump inhibitor-base triple therapies are not better than shorter ones.

Validation of the 13C-urea breath test for the diagnosis of Helicobacter pylori infection in children: a multicenter study.

OBJECTIVE: The 13C-urea breath test (13C-UBT) is a safe, noninvasive, and accurate test for the detection of Helicobacter pylori (H. pylori) infection in adults. The aim of this study was to evaluate sensitivity and specificity of 13C-UBT in children using different types of test meal, doses of 13C-urea and breath sampling intervals. As yet, a validated, standardized 13C-UBT protocol for children has not been formulated. METHODS: 13C-UBT was performed in 115 children and repeated within 3 days, modifying the test meal or the dose of 13C-urea. H. pylori status was assessed by histology and rapid urease test. 13C-UBT was performed using 100 mg or 50 mg of 13C-urea and a fatty test meal (100 FA; 50 FA), 50 mg of 13C-urea, and a carbohydrate test meal (50 CA). Breath samples were collected every 10 min for 60 min. RESULTS: The 13C-UBT in children was highly sensitive and specific with all three protocols used. The best combination of sensitivity (97.92%) and specificity (97.96%) was obtained with Protocol 50 FA at 30 min with a cut-off of 3.5 per mil. CONCLUSIONS: The 13C-UBT is an accurate test for the detection of H. pylori infection also in children. Administration of 50 mg of 13C-urea, a fatty test meal, and breath sampling at 30 min appears to be the most convenient protocol.

Transmission of Helicobacter pylori infection.

Helicobacter pylori infection is one of the most common bacterial infections worldwide. It is accepted as the major cause of chronic gastritis, peptic ulcer, carcinoma of the distal part of the stomach and gastric lymphoma. However, how and when the infection is acquired remain largely unknown. Identification of mode of transmission is vital for developing preventive measures to interrupt its spread, but studies focused on this issue are difficult to implement. From epidemiological studies, it is known that there are great differences in the prevalence of infection in different populations and in ethnic groups originating from high prevalence regions. This is likely related to inferior hygienic conditions and sanitation. In developing countries, infection occurs at a much earlier age. In developed countries, the prevalence of infection is related to poor socioeconomic conditions, particularly density of living. Humans seem to be the only reservoir of H pylori, which spread from person to person by oral-oral, fecal-oral or gastro-oral routes. Most infections are acquired in childhood, possibly from parents or other children living as close contacts. Infection from the environment or from animals cannot be entirely excluded.

Linkage disequilibrium between intra-locus variants in the aminopeptidase n gene and test of their association with coeliac disease.

Coeliac disease (CD) is a multigenic and multifactorial enteropathy triggered by gluten-composing proteins. A possible involvement of the intestinal Aminopeptidase N (APN) was investigated by an association analysis. SSCP analysis detected four variants at position 281, 378, 956 and 2957 (referred to no. g178535, GenBank) that were studied in 193 Italian CD families. The haplotypic combinations were determined from family segregation and pairwise linkage disequilibria (D' = D/Dmax) between the polymorphic sites were calculated. Significant D' values ranged between 0.78 and 0.31. Association with CD was tested by TDT (Transmission Disequilibrium Test) utilizing as markers the nucleotide substitutions and their haplotypic combinations. No statistically significant transmission distortion to the probands or to their clinically silent sibs was observed. Our data exclude an involvement in CD of the tested markers and of further undetected variation in strong linkage disequilibrium (D' approximately equal to 1) with them. The power of the test was not adequate to detect an association with an unknown polymorphism which is not in complete linkage disequilibrium with those analysed.

Clinical significance of Helicobacter pylori seropositivity and seronegativity in asymptomatic blood donors.

To determine the clinical significance of Helicobacter pylori seropositivity and seronegativity in healthy blood donors, we carried out a serological evaluation of Helicobacter pylori status and endoscopy in a healthy blood donors population. In all, 1010 donors were screened for Helicobacter pylori by IgG ELISA and assessed for pepsinogen I and gastrin levels by RIA; 298 IgG seropositive and 61 seronegative subjects underwent endoscopy with biopsies. Of 359, 165 were also tested for CagA by western blotting. Of the 298 IgG seropositives, 274 were shown to be infected on biopsy testing. Endoscopy revealed 70 peptic ulcers, 41 cases of erosive duodenitis, and two gastric cancers. In all 105 seropositive donors were tested for CagA and 69 were CagA positive [34/58 gastritis (58.6%), 24/35 duodenal ulcer (68.6%) and 11/12 gastric ulcer (91.6%)]. Histologically active/chronic gastritis was associated with CagA: 88.4% vs 50% (CagA seropositive vs seronegative). Of the 61 IgG seronegatives, 59 were negative on biopsy testing. At endoscopy three had duodenitis. Of the 60/61 IgG seronegatives tested for CagA, one had a moderate reaction. Duodenal ulcer donors showed higher pepsinogen I levels than donors without duodenal ulcers (97.7 microg/ml vs 80.9 microg/ml respectively). Screening for Helicobacter pylori and anti-CagA seropositivity and pepsinogen I can identify individuals likely to have gastroduodenal pathology even in the absence of symptoms.

Management of Helicobacter pylori infection in children.

When trying to decide which children with Helicobacter pylori infection should be treated and at what stage they should be tested, we should take into account the fact that eradication of the infection may be useful both to induce symptom remission and to prevent later complications in adulthood. However, well designed studies to identify those infected children who are at risk of developing complications or have symptoms due to the infection are still lacking. Current literature only gives information on how to treat children with H pylori infection. Treatment regimens that include two drugs are usually more effective than in adults, and produce an eradication rate of 70-80%, but they should be given for at least two weeks, shorter treatments being less effective. Antibiotic resistance can impair eradication rate and the frequency of resistant strains in children should be studied. Combinations of antibiotics with antisecretory drugs are highly effective in adults, but triple therapy with two antibiotics and an antisecretory drug has been seldom tried in children; compliance is often poor so that the eradication rate is often similar to that produced by dual therapy. Compliance strongly influences eradication, and short simple treatment regimens that produce rapid symptom remission with few side effects are needed to optimise patient compliance. After treatment, eradication must be proved. Serological tests can help, provided that pretreatment serum is available and three to six months have passed since the treatment. A 13C-ureabreath test (13C-UBT) should be performed at least six weeks after treatment, but false negative results can occur and cut-off must be adjusted.

Creating a team approach to hospital and college of pharmacy relationships: a strategy to integrate missions to enhance education and patient care.

Academic medical centers continue to bear the burden of the additional costs of professional education. Such institutions and their affiliated colleges of pharmacy are challenged to sustain the degree of professional staffing required to deliver quality education and patient care services. Historically, these relationships have not always proven to be cooperative and mutually beneficial. As managers and deans attempt to maximize the productivity of their financial and human resources, they will need to creatively structure relationships that effectively meet those diverse professional missions that sometimes seem to exist in conflict or that each seem to be successful only at the expense of the other. Pharmacists who act as both faculty, delivering experiential education, and clinical staff providing patient care, are significantly stressed in their attempts to meet the sometimes conflicting objectives of these multiple missions. The survival of precepted experiential education in pharmacy and of pharmaceutical care in academic medical center hospitals will likely depend upon a model of cooperative relationship, such as the venture described by Jorgenson, et al.

Salivary immunoglobulin G assay to diagnose Helicobacter pylori infection in children.

An in-house enzyme-linked immunosorbent assay (ELISA) for measurement of Helicobacter pylori-specific immunoglobulin G (IgG) and IgA in saliva was evaluated by comparison with histopathologic (Giemsa staining) and biochemical (urease quick test) examination of gastric biopsy specimens obtained from 112 children referred for diagnostic gastroscopy. Serum H. pylori IgG was also measured in a subgroup of 50 children by the same ELISA. Salivary H. pylori IgG levels were significantly higher in H. pylori-positive (n = 57) than in H. pylori-negative (n = 55) children (P < 0.001). The sensitivity and specificity of the salivary IgG test were 93 and 82%, respectively; the positive and negative predictive values were 84 and 92%, respectively; and the accuracy was 87.5%. Salivary H. pylori IgA did not distinguish H. pylori-positive from H. pylori-negative children. The performance of serum H. pylori IgG was slightly (3 to 6%) better than that of salivary H. pylori IgG. The salivary IgG test can be considered a useful tool for the screening of H. pylori infection in children.