The diagnosis and treatment of Helicobacter pylori infection in Arctic regions with a high prevalence of infection: Expert Commentary.

Helicobacter pylori infection is a major cause of peptic ulcer and is also associated with chronic gastritis, mucosa-associated lymphoid tissue (MALT) lymphoma, and adenocarcinoma of the stomach. Guidelines have been developed in the United States and Europe (areas with low prevalence) for the diagnosis and management of this infection, including the recommendation to 'test and treat' those with dyspepsia. A group of international experts performed a targeted literature review and formulated an expert opinion for evidenced-based benefits and harms for screening and treatment of H. pylori in high-prevalence countries. They concluded that in Arctic countries where H. pylori prevalence exceeds 60%, treatment of persons with H. pylori infection should be limited only to instances where there is strong evidence of direct benefit in reduction of morbidity and mortality, associated peptic ulcer disease and MALT lymphoma and that the test-and-treat strategy may not be beneficial for those with dyspepsia.

Global patterns of cardia and non-cardia gastric cancer incidence in 2012.

OBJECTIVE: Globally, gastric cancer incidence shows remarkable international variation and demonstrates distinct characteristics by the two major topographical subsites, cardia (CGC) and non-cardia (NCGC). Because global incidence estimates by subsite are lacking, we aimed to describe the worldwide incidence patterns of CGC and NCGC separately. DESIGN: Using Cancer Incidence in Five Continents Volume X (CI5X), we ascertained the proportions of CGC and NCGC by country, sex and age group (<65 and ≥65 years). These derived proportions were applied to GLOBOCAN 2012 data to estimate country-specific age-standardised CGC and NCGC incidence rates (ASR). Regional proportions were used to estimate rates for countries not included in CI5X. RESULTS: According to our estimates, in 2012, there were 260,000 cases of CGC (ASR 3.3 per 100,000) and 691,000 cases of NCGC (ASR 8.8) worldwide. The highest regional rates of both gastric cancer subsites were in Eastern/Southeastern Asia (in men, ASRs: 8.7 and 21.7 for CGC and NCGC, respectively). In most countries NCGC occurred more frequently than CGC with an average ratio of 2:1; however, in some populations where NCGC incidence rates were lower than the global average, CGC rates were similar or higher than NCGC rates. Men had higher rates than women for both subsites but particularly for CGC (male-to-female ratio 3:1). CONCLUSIONS: This study has, for the first time, quantified global incidence patterns of CGC and NCGC providing new insights into the global burden of these cancers. Country-specific estimates are provided; however, these should be interpreted with caution. This work will support future investigations across populations.

The incidence rate of colectomy for medically refractory ulcerative colitis has declined in parallel with increasing anti-TNF use: a time-trend study.

BACKGROUND: Medical therapy is standard treatment for ulcerative colitis with colectomy reserved for medically refractory disease or malignancy. The introductions of ciclosporin in 1994 and anti-TNF therapy in 2005 have extended medical management options. AIM: To determine whether the colectomy incidence rate for medically refractory ulcerative colitis has changed since the introduction of anti-TNF therapy. METHODS: Adult patients with a diagnosis of ulcerative colitis and who subsequently underwent an urgent or elective colectomy for medically refractory disease in Edmonton, Canada between 1 January 1998 and 31 December 2011 were identified. Log-linear regression was used to estimate the annual percent change in the total colectomy incidence rate (urgent and elective combined) and the urgent and elective incidence rates individually, before and after 2005, the year infliximab was approved for use in ulcerative colitis. Temporal trends of drug utilisation in this study population were also described. RESULTS: During 1998-2011, 481 patients with ulcerative colitis underwent a colectomy for medically refractory disease. There was negligible change in the total colectomy incidence rate from 1998 to 2005, with an annual percent change of 4.4% (95% confidence interval (CI): -1.12% to 10.16%). From 2005-2011, following the approval and increasing use of anti-TNF therapy, the total colectomy incidence rate decreased by 16.1% (95% CI: -21.32% to -10.54%) every year to 0.9 per 100 ulcerative colitis patients in 2011. CONCLUSION: The total incidence rate of colectomy for medically refractory ulcerative colitis has declined substantially since 2005, paralleling the increased use of anti-TNF therapy in this patient population.

Helicobacter pylori infection in Canadian and related Arctic Aboriginal populations.

In 2006, the Canadian Helicobacter Study Group identified Aboriginal communities among Canadian population groups most at risk of Helicobacter pylori-associated disease. The objective of this systematic review was to summarize what is known about the H pylori-associated disease burden in Canadian and related Arctic Aboriginal populations to identify gaps in knowledge. Six health literature databases were systematically searched to identify reports on H pylori prevalence in Canadian population groups, or any topic related to H pylori in Canadian Aboriginals, Alaska Natives or Aboriginals of other Arctic regions. Identified reports were organized by subtopic and summarized in narrative form. Key data from studies of H pylori prevalence in defined populations were summarized in tabular form. A few Arctic Aboriginal communities were represented in the literature: two Canadian Inuit; one Canadian First Nation; two Greenland Inuit; one Russian Chutkotka Native; and several Alaska Native studies. These studies uniformly showed elevated H pylori prevalence; a few studies also showed elevated occurrence of H pylori-related diseases and high rates of treatment failure. Based on the evidence, it would be warranted for clinicians to relax the criteria for investigating H pylori and related diseases in patients from Arctic Aboriginal communities, and to pursue post-therapy confirmation of eradication. Additional community-based research is needed to develop public health policies for reducing H pylori-associated health risks in such communities.

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.

The role of epidemiology in understanding the health effects of Helicobacter pylori.

Helicobacter pylori infects one-half or more of the world population and causes chronic gastritis, peptic ulcer, and probably gastric cancer as well. The public-health impact of this infection is far from trivial. Chronic gastritis and peptic ulcer disease are common across populations. Gastric cancer rates have declined during this century, but this cancer remains second among causes of cancer deaths worldwide. Much has been learned about biological and clinical aspects of H. pylori, but key epidemiologic questions have not been answered. How infection results in diverse diseases, the precise modes of transmission, and a comprehensive solution to H. pylori as a public-health problem remain elusive. In this paper, we highlight methodologic challenges and outline an agenda for future research. Challenges include improving validation of detection methods and considering the limitations of these methods when interpreting epidemiologic data. The role of cofactors in H. pylori-induced diseases requires extensive exploration. Many intriguing areas of H. pylori research require the skills of epidemiologists. The discovery of an infectious etiology of common chronic diseases presents a promising opportunity for improving public health.

Effect of meal size and test duration on gastric emptying and gastric myoelectrical activity as determined with simultaneous [13C]octanoate breath test and electrogastrography in normal subjects using a muffin meal.

Our purpose was to determine the effect of meal size on gastric emptying (GE) as measured by octanoate breath test (OBT), to determine the effect of the duration of breath collections on assessment of GE by OBT, and to determine the effect of meal size on gastric myoelectrical activity as measured by electrogastrography (EGG). Fourteen normal subjects underwent two modified [13C]OBTs using muffin meals of 250 or 350 kcal mixed with 100 mg [13C]sodium octanoate. T(1/2) for GE was determined for both the entire postprandial 6-hr breath collection and a truncated initial 4-hr data set. EGG was recorded for 30 min prior to the muffin meal and 4 hr postprandially. Using the 6-hr breath collection data, the T(1/2) was 177 +/- 7 (mean +/- SEM) for the 350-kcal meal compared to 153 +/- 7 min (P < 0.01) for the 250-kcal meal. Using the 4-hr data, the T(1/2) for the 350-kcal meal was 244 +/- 32 min compared to 165 +/- 12 min (P < 0.05) for the 250-kcal meal. The ratio of postprandial to fasting EGG power of the dominant frequency for the 350-kcal meal (1.9 +/- 0.4) was higher than that for the 250-kcal meal (1.3 +/- 0.6). T(1/2) for the 350-kcal meal using 4- and 6-hr data was significantly correlated with the 4-hr power ratio (r = 0.68 and 0.67; P < 0.05, respectively), but poorly correlated for the 250-kcal meal. In conclusions, GE and EGG are affected by meal size. Using the muffin-based [13C]OBT, T(1/2) for the 350-kcal meal was significantly longer than for a 250-kcal meal. Longer T(1/2) values were obtained with shorter breath sampling durations. The postprandial to fasting power ratio for the 350-kcal meal was greater than that for the 250-kcal meal.

Transmission of Helicobacter pylori among siblings.

BACKGROUND: Helicobacter pylori infection causes chronic digestive diseases with a major public-health impact, yet the design of prevention measures is hampered by limited knowledge of transmission pathways. We studied the effect of family composition on H. pylori prevalence among rural Colombian children aged 2-9 years. METHODS: 684 children were screened for H. pylori with the 13C-urea breath test. For each child, birth order, birth spacing, number of 2-9-year-old siblings, and number of H-pylori-positive 2-9-year-old siblings was recorded. Odds ratios were estimated by logistic regression, controlling for hygiene-related exposures, socioeconomic indicators, and the number of children in the household. FINDINGS: The odds of infection increased with the number of 2-9-year-old siblings in the household (odds ratios 1.4, 2.3, 2.6, and 4.3 for one, two, three, and four to five siblings, respectively). Compared with first-born children, odds ratios for children born second and third to ninth were 1.8 (95% CI 1.0-3.3) and 2.2 (1.0-4.3), respectively. Compared with children born 10 or more years after the next older household member, those born within 4 years were 4.1 times (CI 2.0-8.6) more likely to be infected; the age gap to the next younger household member displayed a weaker effect. The number of H-pylori-positive 2-9-year-old siblings had a particularly strong effect gradient (1.5, 3.2, 5.6, and 7.1, for one, two, three, and four positive siblings, respectively). INTERPRETATION: Among rural Andean children younger than 10 years, H. pylori infection seems to be transmitted most readily among siblings who are close in age, and most frequently from older siblings to younger ones.

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.

Lessons learned from the PMI case study: the community perspective.

PIP: This summary report presents the lessons learned during the two-part qualitative case study on the efficacy of the Prevention Marketing Initiative (PMI) in its implementation of an HIV prevention program. About 179 community participants were included in the PMI program, which discussed topics ranging from organizing initial planning committees to financially sustaining federal demonstration programs. One of the successes observed was the development of rapport with schools and churches; however, during the course of its implementation, the program realized the necessity of 1) approaching the program as an ongoing process; 2) going beyond studying the target population through formative research; 3) changing the role of a community coalition as the project matures; 4) reexamining the composition of coalition in the light of the target audience; 5) advocating the project as a community resource that promotes collaboration; 6) attending the needs of coalition members; and 7) using the media in the campaign. Likewise, several lessons were also learned in the areas of youth involvement, intervention development, program implementation, and maintenance of PMI activities.^ieng

Compliance with childhood immunizations in Kern County, California.

A rapid survey was conducted to describe the immunization status of the 0- to 2-year-old population in selected communities of Kern County, California, and identify reasons for noncompliance with immunization recommendations. Households were selected by two-stage cluster sampling. Among 860 children, 38% had received immunizations on schedule, while 44% had not received the recommended doses for their age. Compliance with the immunization schedule worsened dramatically after the first year of life. Among 2 year olds, the proportion that had the recommended number of vaccine doses was 81% for MMR, 82% for polio, 65% for DTP, and 47% for Hib. Parents' main reasons for noncompliance included child's illness, procrastination, and limited access to information and services. The low levels of compliance reflect lack of active follow-up in preventive health care across socioeconomic levels. The results show the importance of aiming immunization messages at parents and physicians of 12- to 18-month-old children. The rapid survey approach offers public health agencies an efficient means of assessing community health problems and targeting programs according to need.

Age distribution of Helicobacter pylori seroprevalence among young children in a United States/Mexico border community: evidence for transitory infection.

Helicobacter pylori infection has been linked to a spectrum of gastroduodenal diseases of broad public health impact, yet the natural history of this frequently asymptomatic infection remains poorly understood. Evidence suggests that initial acquisition occurs primarily during childhood and may persist throughout life. The seroprevalence of H. pylori antibodies was examined in 365 primary schoolchildren aged 4-7 years in a low-income United States/Mexico border community from January to May 1996. Overall, 21% of the 365 children tested positive, with a significant monotonic decrease in seroprevalence by 1-year age intervals (36% in children aged 4 years, 24% in those aged 5 years, 20% in those aged 6 years, and 14% in those aged 7 years). The odds ratio for each 1-year age increase was 0.76 (95% confidence interval: 0.6, 1.0) after adjustment for relevant covariates. Given that H. pylori antibodies diminish after infection clears, this trend suggests that transient infection may be common in young children. In contrast, hepatitis A virus seroprevalence increased with age. There was a moderate association (odds ratio = 1.47, 95% confidence interval: 0.8, 2.9) of H. pylori with hepatitis A virus seroprevalence that weakened after adjustment for age and socioeconomic status (odds ratio = 1.26, 95% confidence interval: 0.6, 2.5). Follow-up studies are needed to clarify the natural history of Helicobacter pylori infection and identify predictors of initial acquisition, persistence, and recurrence.

Hepatitis B vaccination in high-risk infants: 10-year follow-up.

The long-term efficacy of hepatitis B vaccination among high-risk infants was determined in 805 vaccine responders, immunized at birth in Taiwan during 1981-1984 and followed to age 10 years, via life table survival and Cox multivariate analyses. At 10 years, cumulative persistence of antibody to hepatitis B surface antigen (anti-HBs) was 85%, and cumulative incidence of hepatitis B virus (HBV) infection was 15%. Three children became carriers. Twelve-month anti-HBs titer was the strongest predictor of efficacy. The higher the initial titer, the lower the risk of anti-HBs loss (relative risk [RR], 0.26 for titer of 100-999 mIU/mL; RR, 0.08 for titer >1000 mIU/mL; P<.001) and HBV infection (RR, 0.55 and 0.27; P<.05). Maternal hepatitis B e antigen positivity but not hepatitis B immunoglobulin dose or gender predicted greater antibody persistence to age 10 years. Because the level of antibody persistence remained high and few became carriers, booster revaccination within 10 years seems unnecessary.

Recycling of carbon into lipids synthesized de novo is a quantitatively important pathway of alpha-[U-13C]linolenate utilization in the developing rat brain.

Docosahexaenoate is important for normal neural development. It can be derived from alpha-linolenate, but carbon from alpha-linolenate is also recycled into de novo lipid synthesis. The objective of this study was to quantify the amount of alpha-linolenate used to produce docosahexaenoate versus lipids synthesized de novo that accumulate in the brain of the developing rat. A physiological dose of carbon-13-labeled alpha-linolenate was injected into the stomachs of mother-reared 6-day-old rat pups. Total lipids of brain, liver, and gut were extracted from rats killed 3 h to 30 days after dosing. Carbon-13 enrichment was determined by isotope ratio mass spectrometry. Carbon-13-enriched alpha-linolenate was not detected in the brain at any time point, and its levels in liver and gut exceeded detection limits at most time points, so tracer mass was quantified mainly for three end products--docosahexaenoate, palmitate, and cholesterol. Carbon-13-enriched cholesterol, palmitate, docosalphahexaenoate, and water-soluble metabolites were detected in brain, liver, and gut Enrichment (in micrograms of carbon-13 per organ) in brain cholesterol exceeded that in brain docosahexaenoate by four- to 16-fold over the duration of the study. Enrichment in brain palmitate exceeded that in brain docosahexaenoate by three- to 30-fold over the first 8 days of the study. These results indicate that carbon from alpha-linolenate is not exclusively conserved for synthesis of longer n-3 polyunsaturates but is a readily accessible carbon source for de novo lipogenesis during early brain development in the suckling rat. Owing to a high rate of beta-oxidation and carbon recycling, dependence on alpha-linolenate as the sole source of docosahexaenoate may incur a potential risk of providing insufficient docosahexaenoate for the developing brain.

Comparison of electron beam computed tomography scanning and conventional risk factor assessment for the prediction of angiographic coronary artery disease.

OBJECTIVE: To determine whether electron beam computed tomography (CT) adds to conventional risk factor assessment in the prediction of angiographic coronary artery disease. BACKGROUND: Electron beam CT scanning can be used to predict the severity of coronary atherosclerosis, but whether it does so independently of conventional risk factors is unclear. METHODS: Electron beam CT scans were performed and conventional risk factors were measured in 290 men and women undergoing coronary arteriography for clinical indications. The association of the electron beam CT-derived coronary artery calcium score and conventional risk factors with the presence and severity of angiographically defined coronary atherosclerosis was analyzed by logistic regression and receiver-operator characteristics analysis. RESULTS: Age, the ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol and the coronary calcium score were significantly and independently associated with the presence of any coronary disease and obstructive coronary disease. In association with any coronary disease, odds ratios for age, the ratio of total cholesterol to HDL cholesterol and calcium score, highest quartile vs. lowest quartile, were 6.01 (95% confidence interval 2.87 to 12.56), 3.14 (1.56 to 6.31) and 94.08 (21.06 to 420.12), respectively. For obstructive coronary disease, highest quartile vs. lowest quartile, the respective odds ratios for age, the ratio of total cholesterol to HDL and calcium score were 3.86 (1.86 to 8.00), 4.11 (1.98 to 8.52) and 34.12 (12.67 to 91.86). Male gender was also significantly associated with any coronary disease (odds ratio 2.19, p=0.04) and obstructive coronary disease (odds ratio 2.07, p=0.04). Cigarette smoking was significantly associated with any coronary disease (odds ratio=2.74, p=0.004), and diabetes was significantly associated with obstructive disease (odds ratio 3.16, p=0.01). After adjustment for the coronary calcium score and other risk factors, it was determined that triglycerides, family history and hypertension were not significantly associated with any disease state. A coronary calcium score >80 (Agatston method) was associated with an increased likelihood of any coronary disease regardless of the number of risk factors, and a coronary calcium score > or = 170 was associated with an increased likelihood of obstructive coronary disease regardless of the number of risk factors (p < 0.001). CONCLUSIONS: Electron beam CT scanning offers improved discrimination over conventional risk factors in the identification of persons with any angiographic coronary disease or angiographic obstructive coronary disease.

How do clinicians practicing in the U.S. manage Helicobacter pylori-related gastrointestinal diseases? A comparison of primary care and specialist physicians.

OBJECTIVES: We sought to examine the extent to which physicians recognize H. pylori as a causal agent in peptic ulcer disease or as a potential cofactor in other gastrointestinal diseases, and to observe how this knowledge has influenced diagnostic and therapeutic practices. METHODS: We used a national mail survey in the U.S. between February and May of 1996, querying 5994 U.S. physicians (family/general practitioners [FPs], internists [IMs], and gastroenterologists) selected at random from three different membership databases of professional associations. RESULTS: The response rate was 52%. More than 95% of physicians who treat symptoms empirically would prescribe acid suppressant therapy rather than anti-H. pylori therapy. Between 43% and 66% of physicians, varying in frequency by medical specialty, would treat the infection in H. pylori-positive patients with nonulcer dyspepsia. In confirmed peptic ulcer disease, between 88% and 100% of physicians would treat the H. pylori infection, depending on the physician group and whether or not the presentation of an ulcer was recurrent. Although 103 distinct anti-H. pylori regimens were reported, 89% of the gastroenterologists and 70% of the primary care physicians (PCPs) used combinations of antimicrobials with reported cure rates of at least 80%. CONCLUSIONS: General knowledge regarding H. pylori-associated diseases was widespread among primary care physicians and gastroenterologists. However, anti-H. pylori therapies judged ineffective were reported as the first choice regimen by 5% of gastroenterologists and 18% of primary care physicians. Gastroenterologists appear to implement the latest scientific developments in the field rapidly whereas PCPs manifest a delayed response, due to either insufficient knowledge or to other factors influencing their approach to treatment.

How do practicing clinicians manage Helicobacter pylori-related gastrointestinal diseases in Germany? A survey of gastroenterologists and family practitioners.

BACKGROUND: Since the bacterium H. pylori was identified in 1982, overwhelming evidence has implicated it as the causal factor in the occurrence and relapse of peptic ulcer disease. The major objective of this study was to examine the extent to which physicians recognize H. pylori as a causal agent in peptic ulcer disease or as potential cofactor in other gastrointestinal diseases, and the extent to which this knowledge has influenced diagnostic and therapeutic practices. MATERIALS AND METHODS: Using a national mail survey in Germany in September 1995, 1197 family practitioners and 1197 gastroenterologists were selected for the study. RESULTS: Of the surveyed physicians, 756 (32%) responded. Family practitioners treated almost 50% of their patients with initial presentation of suspected ulcer disease without ordering further diagnostic tests. More than 25% of the family practitioners and 14% of the gastroenterologists reported that they do not treat diagnosed H. pylori infection in the first presentation of duodenal ulcer. At the time we conducted the study, 22% of responding family practitioners and 5% of responding gastroenterologists treated the first presentation of H. pylori-positive ulcer disease with regimens determined to be ineffective according to the available literature. CONCLUSIONS: Gastroenterologists preferred to treat H. pylori infection when the associated disease was one for which a causal relationship had been more clearly established, while family practitioners showed less discrimination. In order to provide optimal therapy aimed at minimizing the course and consequences of H. pylori-related diseases, researchers in the field must ensure continuous dissemination of current knowledge.