Meta-analysis: Helicobacter pylori eradication treatment efficacy in children.

BACKGROUND: Several meta-analyses assessing the efficacy of anti-Helicobacter pylori treatment in adults have been published but a comparable meta-analysis in children is lacking. AIMS: To summarize the efficacy of treatments aimed at eradicating H. pylori in children and to identify sources of variation in treatment efficacy across studies. METHODS: We searched Medline, reference lists from published study reports, and conference proceedings for anti-H. pylori treatment trials in children. Weighted meta-regression models were used to find sources of variation in efficacy. RESULTS: Eighty studies (127 treatment arms) with 4436 children were included. Overall, methodological quality of these studies was poor with small sample sizes and few randomized-controlled trials. The efficacy of therapies varied across treatment arms, treatment duration, method of post-treatment assessment and geographic location. Among the regimens tested, 2-6 weeks of nitroimidazole and amoxicillin, 1-2 weeks of clarithromycin, amoxicillin and a proton pump inhibitor, and 2 weeks of a macrolide, a nitroimidazole and a proton pump inhibitor or bismuth, amoxicillin and metronidazole were the most efficacious in developed countries. CONCLUSIONS: Before worldwide treatment recommendations are given for eradication of H. pylori, additional well-designed randomized placebo-controlled paediatric trials are needed, especially in developing countries where both drug resistance and disease burden is high.

Review article: epidemiology and management of gastro-oesophageal reflux in children.

The management of gastro-oesophageal reflux disease (GERD) continues to garner vast amounts of attention among physicians who care for adults. However, there is an increasing awareness of the fact that this disease, as well as several other lifelong digestive diseases (i.e. Crohn's disease) may actually have their origins in childhood. Paediatric gastro-oesophageal reflux (GER) is likely to share a similar pathophysiology to adult GER, and mounting evidence from published preliminary data suggests a genetic susceptibility to GERD. However, further studies will be necessary to confirm this hypothesis. In children, GER has a distinct presentation from that in adults, with the diagnostic work-up based upon the patient's age as well as their presenting signs and symptoms. Like their adult counterparts, the early detection and treatment of GER in children may result in a better long-term outcome, improved quality-of-life, and a reduction in overall healthcare burden. While the treatment of GER in infants tends to be conservative (i.e. positioning during feeding, smaller feedings), its management in older children parallels that of adults and includes lifestyle changes and pharmacological therapy. However, with persistent symptoms, acid suppression is the mainstay of GERD management in both children and adults. Several studies in children have verified that acid suppression with a proton pump inhibitor is superior to histamine-2 receptor antagonists. Among the proton pump inhibitors, both lansoprazole and omeprazole have been the subject of published adult and paediatric studies demonstrating their short and long-term safety, in addition to their efficacy in a variety of oesophageal and supra-oesophageal GERD related conditions. These two proton pump inhibitors are manufactured as capsules containing enteric-coated granules that can be emptied into soft foods or liquids without compromising their pharmacological effects or pharmacokinetic properties. Lansoprazole is also available as a strawberry-flavoured suspension that is acceptable to children and as an oral disintegrating tablet.

A comprehensive review of the natural history of Helicobacter pylori infection in children.

Across populations of children, Helicobacter pylori prevalence ranges from under 10% to over 80%. Low prevalence occurs in the U.S., Canada, and northern and western Europe; high prevalence occurs in India, Africa, Latin America, and eastern Europe. Risk factors include socioeconomic status, household crowding, ethnicity, migration from high prevalence regions, and infection status of family members. H. pylori infection is not associated with specific symptoms in children; however, it is consistently associated with antral gastritis, although its clinical significance is unclear. Duodenal ulcers associated with H. pylori are seldom seen in children under 10 years of age. H. pylori-infected children demonstrate a chronic, macrophagic, and monocytic inflammatory cell infiltrate and a lack of neutrophils, as compared with the response observed in adults. The effect of H. pylori infection on acid secretion in children remains poorly defined. The events that occur during H. pylori colonization in children should be studied more thoroughly and should include urease activity, motility, chemotaxis, adherence, and downregulation of the host response. The importance of virulence determinants described as relevant for disease during H. pylori infection has not been extensively studied in children. Highly sensitive and specific methods for the detection of H. pylori in children are needed, especially in younger pediatric populations in which colonization is in its early phases. Criteria for the use of eradication treatment in H. pylori-infected children need to be established. Multicenter pediatric studies should focus on the identification of risk factors, which can be used as prognostic indicators for the development of gastroduodenal disease later in life.

Current therapy for Helicobacter pylori infection in children and adolescents.

Helicobacter pylori infects approximately 50% of the world's population and is a definitive cause of gastroduodenal disease (ie, gastritis, duodenal and gastric ulcers) in children and adults. Four consensus conferences held around the globe have brought together clinicians, scientists, epidemiologists and health care economists to discuss the role of the gastric pathogen H pylori in human gastroduodenal disease. At each of these conferences, the overriding objective was to reach a consensus on the development of practical guidelines for the diagnosis and treatment of H pylori-infected individuals. However, it was not until the Canadian H pylori Consensus Conference, held in November 1997, that the issues of H pylori infection in children were addressed. Therapies for H pylori infection in children, presented in part at the First Canadian Pediatric H pylori Consensus Conference, held in Victoria, British Columbia, November 1998, are reviewed in this paper.

Helicobacter pylori infection in children.

A number of scientific breakthroughs since H pylori first became recognized as a human pathogen have increased our understanding of the pathogenesis of gastroduodenal disease. In particular, advances in molecular bacteriology and the complete sequencing of the H pylori genome in 1999, and soon thereafter the human genome, provide tools allowing better delineation of the pathogenesis of disease. These molecular tools for both bacteria and host should now be applied to multicenter pediatric studies that evaluate disease outcome. More recent developments indicate that a better understanding of the microbial-host interaction is critical to furthering knowledge with respect to H pylori-induced diseases. Studies are needed to evaluate either DNA-based or more traditional protein-based vaccines, to evaluate more specific antimicrobials that confer minimal resistance, and to evaluate probiotics for the management of H pylori infection. Multicenter multinational studies of H pylori infection in the pediatric population, which include specific, randomized controlled eradication trials, are essential to extend current knowledge and develop better predictors of disease outcome.

Pediatric gastritis and peptic ulcer disease.

Inflammation of the gastric and duodenal mucosa is the end result of an imbalance between mucosal defensive and aggressive factors. The degree of inflammation and imbalance between defensive and aggressive factors can then result in varying degrees of gastritis and/or mucosal ulceration. Gastritis and ulcers of the duodenum or stomach can be classified as primary or secondary. The majority of children with chronic gastritis and ulcers in the stomach or duodenum have secondary inflammation or mucosal ulceration. These secondary ulcers generally occur due to a systemic condition like head trauma or overwhelming sepsis, or as sequelae to drug ingestion (i.e. non-steroidal anti-inflammatory agents), but secondary gastroduodenal ulcers can also occur in specific disease conditions such as Zollinger-Ellison syndrome or Crohn's disease. In almost all children with primary duodenal or gastric ulcers mucosal inflammation and, less frequently, ulceration is caused by a spiral shaped, gram-negative, microaerobic rod Helicobacter pylori. Recent epidemiological evidence has linked chronic H. pylori infection with the development of gastric carcinomas.

Self-image of punk rock and nonpunk rock juvenile delinquents.

The purpose of this study was to provide some understanding of punk rockers. Although they have received media attention in the depiction of their unusual hair and clothing styles, there is limited information about their personalities. In this study a delinquent group of punk rockers was compared with a delinquent group of nonpunk rockers on self-image, a personality factor related to teenagers' mental health and adjustment. Each group consisted of 20 subjects, 15 males and 5 females, aged 14 to 17. Subjects were administered a Screening Questionnaire, the Offer Self-Image Questionnaire (OSIQ), and the California Psychological Inventory (CPI) while detained at a Southern California juvenile hall. Interest in the CPI was focused on the Socialization (So) scale. A one-way analysis of variance was conducted on each of the five OSIQ dimensions. No significant differences were found between the groups. The importance of these findings is that even though punk rockers may look and act unusual, they may actually be similar to other groups. Due to possibly invalid CPI test protocols a t test and content analysis of the CPI So scale was conducted. The t test was significant and the chi-square analyses were significant on two questions of the CPI So scale. This suggests that there may be differences between the groups in terms of family dynamics. Professionals can utilize these findings in their work with this misunderstood segment of society.

Laryngeal granuloma: a complication of prolonged endotracheal intubation.

Laryngeal granuloma is an uncommon complication arising from irritation of the laryngeal structures. We present a case where bilateral laryngeal granulomas became clinically evident 3 mo after orthognathic surgery. The patient, a 19-yr-old female, developed acute dyspnea after experiencing gradual voice loss. Excision of the lesions under endotracheal general anesthesia led to an uneventful outcome. The causes, predisposing factors, diagnostic features, and treatment of laryngeal granuloma are reviewed.

Superior orbital fissure syndrome. Secondary to infected dentigerous cyst of the maxillary sinus.

Superior orbital fissure syndrome is a rare condition that presents itself as gross and persistent edema of the periorbital tissues, proptosis, subconjunctival ecchymosis, ptosis, ophthalmoplegia, dilation of the pupil, absence of direct light reflex and presence of consensual light reflex. The corneal reflex is lost, sensation is diminished over the forehead, and it is possible that the dimensions of the superior orbital fissure are reduced. Infection, however, is not often reported as the etiology. The case presented here describes an unusual occurrence of superior orbital fissure syndrome secondary to an infected dentigerous cyst of the maxillary sinus and its management.

Joint ESPGHAN/NASPGHAN guidelines for the management of helicobacter pylori in children and adolescents (Update 2016)

BACKGROUND: Because of the changing epidemiology of Helicobacter pylori infection and low efficacy of currently recommended therapies, an update of the European Society for Paediatric Gastroenterology Hepatology and Nutrition/North American Society for Pediatric Gastroenterology, Hepatology and Nutrition recommendations for the diagnosis and management of H pylori infection in children and adolescents is required. METHODS: A systematic review of the literature (time period: 2009-2014) was performed. Representatives of both societies evaluated the quality of evidence using GRADE (Grading of Recommendation Assessment, Development, and Evaluation) to formulate recommendations, which were voted upon and finalized using a Delphi process and face-to-face meeting. RESULTS: The consensus group recommended that invasive diagnostic testing for H pylori be performed only when treatment will be offered if tests are positive. To reach the aim of a 90% eradication rate with initial therapy, antibiotics should be tailored according to susceptibility testing. Therapy should be administered for 14 days, emphasizing strict adherence. Clarithromycin-containing regimens should be restricted to children infected with susceptible strains. When antibiotic susceptibility profiles are not known, high-dose triple therapy with proton pump inhibitor, amoxicillin, and metronidazole for 14 days or bismuth-based quadruple therapy is recommended. Success of therapy should be monitored after 4 to 8 weeks by reliable noninvasive tests. CONCLUSIONS: The primary goal of clinical investigation is to identify the cause of upper gastrointestinal symptoms rather than H pylori infection. Therefore, we recommend against a test and treat strategy. Decreasing eradication rates with previously recommended treatments call for changes to first-line therapies and broader availability of culture or molecular-based testing to tailor treatment to the individual child.

Upper gastrointestinal bleeding in haemophiliacs: incidence and relation to use of non-steroidal anti-inflammatory drugs.

This multicentre study sought to estimate the incidence of upper gastrointestinal (UGI) bleeding in haemophiliacs and its relationship to use of non-steroidal anti-inflammatory drugs (NSAIDs). Cox models were used to estimate relative hazards (RH) with 95% confidence intervals (CI) for postulated risk factors. Conditional logistic regression and stored sera were used to assess UGI bleeding risk with Heliobacter pylori seropositivity in cases compared with closely matched controls. During a mean of 17.4 months (range 2-34), 2285 participants, ages 13-89 (mean 36.5) were followed for 3309 person-years (py). Forty-two experienced a UGI bleeding event (incidence 1.3 per 100 py), most from ulcer (11), gastritis (four), varices (five) and Mallory Weiss tears (eight). RH was significantly increased with traditional NSAID use for <1 month (OR: 3.66; 95% CI: 1.1-11.9), but not with coxibs use. RH was significantly and independently increased with age >46 years (3.5; 95% CI: 1.1-10.6) and hepatic decompensation (4.4; 95% CI: 1.7-11.6). Likelihood of bleeding was substantially but not significantly increased (OR: 4.6; 95% CI: 0.3-83.9) with H. pylori seropositivity. These findings suggest that coxibs are a safer alternative than traditional NSAIDs in the treatment of haemophilic arthropathy.

New approaches to Helicobacter pylori infection in children.

Helicobacter pylori infection is usually acquired during childhood, and evidence-based guidelines regarding diagnosis and treatment of infected children have been recently published. Diseases associated with H. pylori infection are gastritis, duodenal ulcers, mucosal-associated lymphoid-type (MALT) lymphoma, and gastric adenocarcinoma. The association of specific symptoms with H. pylori infection in children and adults (ie, recurrent abdominal pain and nonulcer dyspepsia) remains controversial. Additionally, the role of H. pylori in gastroesophageal reflux disease or in extra-gastrointestinal diseases (ie, coronary artery disease) lacks sufficient evidence to demonstrate causality. The diagnosis of H. pylori-associated diseases in children can reliably be made through gastroduodenal endoscopy with biopsies. Clinical trials are underway for the validation of noninvasive diagnostic tests for the H. pylori-infected child, and current guidelines recommend eradication therapy for infected children with duodenal and gastric ulcer, gastric lymphoma, and atrophic gastritis with intestinal metaplasia. The natural history of childhood H. pylori infection is poorly described. Moreover, rational approaches to the prevention and control of childhood H. pylori infection are critically needed, requiring characterization of the determinants for acquisition and persistence and the disease outcomes following eradication.

Findings from routine urinalysis and hematocrit on ambulatory oral and maxillofacial surgery patients.

A significant number of previously undetected pathologic conditions was disclosed when routine urinalysis and hematocrit determination were done on a large number of patients who came for treatment to a private oral and maxillofacial surgery office. This discovery of abnormalities could cause alteration of plans for contemplated surgery or anesthesia and is a contribution to the good health of patients seen.

The disease spectrum of Helicobacter pylori: the immunopathogenesis of gastroduodenal ulcer and gastric cancer.

Helicobacter pylori is a gram-negative bacterium that resides under microaerobic conditions in a neutral microenvironment between the mucus and the superficial epithelium of the stomach. From this site, it stimulates cytokine production by epithelial cells that recruit and activate immune and inflammatory cells in the underlying lamina propria, causing chronic, active gastritis. Although epidemiological evidence shows that infection generally occurs in children, the inflammatory changes progress throughout life. H. pylori has also been recognized as a pathogen that causes gastroduodenal ulcers and gastric cancer. These more severe manifestations of the infection usually occur later in life and in a minority of infected subjects. To intervene and protect those who might be at greatest risk of the more severe disease outcomes, it is of great interest to determine whether bacterial, host, or environmental factors can be used to predict these events. To date, several epidemiological studies have attempted to define the factors affecting the transmission of H. pylori and the expression of gastroduodenal disease caused by this infection. Many other laboratories have focused on identifying bacterial factors that explain the variable expression of clinical disease associated with this infection. An alternative hypothesis is that microorganisms that cause lifelong infections can ill afford to express virulence factors that directly cause disease, because the risk of losing the host is too great. Rather, we propose that gastroduodenal disease associated with H. pylori infection is predominantly a result of inappropriately regulated gastric immune responses to the infection. In this model, the interactions between the immune/inflammatory response, gastric physiology, and host repair mechanisms would dictate the disease outcome in response to infection.