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.

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.

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.

Evidence of cis-trans isomerization of 9-cis-beta-carotene during absorption in humans.

Absorption and metabolism of [13C]9-cis-beta-carotene ([13C]9c beta C) was studied in three subjects after a single oral dose. Subjects given 1.0 mg [13C]beta-carotene (mean: 99.4% 9-cis-beta-carotene, 0.6% all-trans-beta-carotene; dose A) had substantial concentrations of [13C]all-trans-beta-carotene ([13C]tr beta C) and [13C]all-trans retinol ([13C]retinol) but very low concentrations of [13C]cis-beta-carotene ([13C]cis beta C) in saponified plasma 5 h after dosing, as determined by HPLC and isotope-ratio mass spectrometry. There was no evidence of appreciable absorption of [13C]9-cis retinol. To determine the proportion of [13C]tr beta C and [13C]retinol derived from [13C]9c beta C, a second set of studies in the same subjects was performed with the same isomeric composition except with 13C labeling only in all-trans-beta-carotene (dose B). The results indicated that > 95% of plasma [13C]tr beta C and [13C]retinol observed after dose A was derived from [13C]9c beta C. The concentrations of [13C]tr beta C observed, in excess of that derived from the trace amounts of [13C]tr beta C in the dose, indicated that a significant proportion of the [13C]9c beta C dose was isomerized to [13C]tr beta C before entering the bloodstream. Although precise quantitative estimates of the extent of isomerization of 9-cis-beta-carotene could not be made, it is apparent that cis-trans isomerization of 9-cis-beta-carotene to all-trans-beta-carotene contributed to the near absence of postprandial plasma 9-cis-beta-carotene after its oral administration in humans. The observation of different ratios of beta-carotene to retinol between the two dosing protocols suggests that isomerization did not occur exclusively before uptake by the intestinal mucosa. These results indicate that isomerization of ingested 9-cis-beta-carotene before its secretion into the bloodstream limits the potential supply of 9-cis retinoids to tissues, and increases the vitamin A value of 9-cis-beta-carotene.

Relation of coronary calcium score by electron beam computed tomography to arteriographic findings in asymptomatic and symptomatic adults.

Coronary arteriography was performed on 18 asymptomatic, apparently healthy adults with elevated coronary calcium scores. To extend the range of observation to subjects with low calcium scores, arteriograms from 18 patients with exertional dyspnea and/or valvular heart disease and low calcium scores were also analyzed; these 18 patients were considered asymptomatic from the point of view of coronary artery disease (CAD). For the comparison of symptomatic and asymptomatic persons, 3 age and sex-matched symptomatic patients were also selected for each of the original 18 asymptomatic subjects. Arteriograms were analyzed by computer-assisted quantitative coronary arteriography at a remote site without knowledge of the calcium score or any other patient characteristics. In the 18 asymptomatic subjects with elevated calcium scores, the mean calcium score was 573 +/- 504 (Agatston method) and the mean worst stenosis was 45% +/- 16%. For all 36 patients without symptoms of CAD, worst stenosis was closely correlated with the square root of the calcium score (r = 0.85, p <0.0001). Patients with symptomatic coronary disease and calcium scores < 1,000 had stenoses more severe than asymptomatic persons with similar calcium scores. Most asymptomatic adults with elevated calcium scores have nontrivial, nonobstructive CAD or preclinical obstructive CAD, and the relation between coronary calcium score and severity of stenosis is highly significant. These data indicate that electron beam tomography can be used to estimate the severity of CAD in asymptomatic persons.

The transmission of Helicobacter pylori. A critical review of the evidence.

This paper critically reviews the reported data regarding the transmission of Helicobacter pylori. The mode of transmission remains poorly understood; no single transmission pathway has been clearly identified. Laboratory studies have experienced difficulty in isolating this organism from material other than gastric tissue. The problematic detection of this bacterium has presented obstacles to pinpointing portals of entry and exit and to implicating or ruling out environmental reservoirs. It is shown additionally that knowledge of H. pylori transmission is limited due to lack of solid epidemiological evidence from population-based analyses that adequately consider confounding. Reported observations in general support a person-to-person mode of transmission that occurs most frequently early in life; H. pylori is consistently linked to conditions associated with residential crowding in childhood. Laboratory studies have yielded evidence in favour of both faecal-oral and oral-oral pathways. However, a role for either waterborne or zoonotic transmission has not been ruled out. The failure of investigations to single out a mode of transmission for H. pylori signals the possibility of multiple transmission pathways.

Screening for cervical cancer in emergency centers and sexually transmitted disease clinics.

Low-income women are at increased risk of developing cervical cancer compared with middle- and upper-income women. How can poor women be reached for screening and early diagnosis of cervical cancer and its precursor stages? One answer to this question is based on the observation that a high percentage of the unscreened population has received some form of medical care within the previous 5 years. Emergency centers and sexually transmitted disease (STD) clinics often provide such care to patients who lack a regular source of health care. Thus, they represent potential resources for cervical cancer screening. However, in a survey of 19 hospitals whose patient populations include a high proportion of low-income patients, only five reported a protocol for cervical cancer screening in their emergency centers. Similarly, all 11 STD clinics included in this survey reported that fewer than 5% of their female patients had a Papanicolaou smear taken even though virtually all of them received a pelvic examination. Based on these findings, it appears that health care administrators and policymakers could intensify their cancer prevention programs by mobilizing these resources for cancer control.

High-precision gas chromatography-combustion isotope ratio mass spectrometry at low signal levels.

Precision and accuracy of gas chromatography-combustion isotope ratio mass spectrometry are investigated for sample levels down to about 5 pmol C in fatty acid methyl ester mixtures spanning 1000-fold in concentration. Precision and accuracy of isotope ratios diverge rapidly for conventional summation methods, and become unusable below 30 pmol material on column. At lower levels, mean isotope ratios were statistically different from reference values indicating bias as well as poor precision. In contrast, curve fitting, using the exponentially modified Gaussian line shape, gives improved precision for most peaks and useful results down to 3 pmol. The curve-fitting algorithm was also less sensitive to signal integration time than the summation method. These data indicate that curve fitting may be the method of choice for integration of noisy data when high-precision isotope ratios are desired.

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.

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.

Radiologic findings in anorectal gonorrhea.

Gonorrhea is the most prevalent communicable disease in the United States and the incidence of anorectal involvement is high. Anorectal gonorrhea may be clinically elusive making the radiologic findings crucial in suggesting the diagnosis. Edematous rectal mucosa with limited distensibility and small ulcerations are the prominent radiologic findings.

Hardware modifications to an isotope ratio mass spectrometer continuous-flow interface yielding improved signal, resolution, and maintenance.

A home-built combustion interface was constructed to improve signal, resolution, and maintenance of a continuous-flow gas isotope ratio system. Chromatographic peak shapes were preserved by minimizing changes in tubing diameter and dead volumes. A single piece of fused silica capillary was used to connect the gas chromatograph (GC) to the isotope ratio mass spectrometer (IRMS), thus eliminating extraneous combustion furnace and water trap fittings. Analysis of a standard mixture of hydrocarbons yielded a 2-fold increase in signal over a slightly modified conventional system. Column efficiency, expressed as trennzahl (TZ), improved significantly (Student's t-test 95% CI) by an average factor of 1.4 for replicates analyzed under similar conditions. The design is robust, requires less maintenance, and reduces leaks because the number of connections is minimized. Benefits of this system are transferable to virtually all commercially available continuous-flow systems.

High sensitivity tracer detection using high-precision gas chromatography-combustion isotope ratio mass spectrometry and highly enriched [U-13C]-labeled precursors.

The use of highly enriched, uniformly labeled fatty acid ([U-13C]) with analysis by high-precision gas chromatography-combustion isotope ratio mass spectrometry (GCC-IRMS) has been evaluated as a metabolic tracer technique. 13C/12C ratios are routinely determined to precisions (SD) of less than 0.00001 (delta PDB less than 1/1000) for greater than 10 ng of fatty acid, and less than 0.001 (delta PDB less than 100/1000) for samples of 30 pg of fatty acid, the latter corresponding to a 100-fmol sample. Baseline fatty acid 13C/12C in human plasma fractions is shown to fluctuate not more than 0.000 04 (delta PDB 4/1000) over 10 h. 13C/12C enrichments greater than 0.001 (delta PDB 100/1000) are obtained in a fatty acid plasma fraction subsequent to a 10-mg dose of 42% 13C-labeled stearic acid to a 78-kg adult. Biokinetics are discerned over an 13C/12C enrichment range of less than 0.0002 (approximately 13/1000 in delta PDB units) in plasma. A means for correction of isotope ratio contamination due to carbon-containing derivatives is presented. High-precision GCC-IRMS used in concert with highly enriched tracers is shown to possess advantages versus organic GC/MS for stable isotopic tracer detection and is superior to radiotracer methods in terms of dose sizes and analysis efficiency.

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.

Pathways of extrapelvic spread of disease: Anatomic-radiologic correlation.

Extrapelvic spread of disease, particularly from gastrointestinal tract perforations which may be clinically occult, may first present in the buttock, hip, thigh, and even lower leg, and the extraperitoneal space of the abdomen itself. Clinical manifestations at these remote sites may be very misleading. Anatomic and roentgenologic observations establish the preferential pathways of extrapelvic spread. These are related to the insertions and fascial investments of the iliopsoas, pyriformis, and obturator internus muscles and the ensheathed penetrations of the superior gluteal arteries. Superiorly, extension from the pelvic tissues seeks out the posterior pararenal compartment of the extraperitoneal region of the abdomen. Roentgenologic signs may first identify the presence, extent, and localization of the primary process.