Geospatial analysis of Helicobacter pylori infection in South Australia: Should location influence eradication therapy?

BACKGROUND AND AIM: Rates of antimicrobial-resistant Helicobacter pylori infection are rising globally; however, geospatial location and its interaction with risk factors for infection have not been closely examined. METHODS: Gastric biopsy specimens were collected to detect H. pylori infection at multiple centers in Adelaide, South Australia, between 1998 and 2017. The geospatial distribution of antibiotic-resistant H. pylori in the Greater Adelaide region was plotted using choropleth maps. Moran's I was used to assess geospatial correlation, and multivariate linear regression (MLR) was used to examine associations between migration status, socioeconomic status, age, gender, and rates of H. pylori positivity and antibiotic resistance. Geographically weighted regression (GWR) was used to determine the extent to which the associations varied according to geospatial location. RESULTS: Of 20 108 biopsies across 136 postcodes within the Greater Adelaide region, 1901 (9.45%) were H. pylori positive. Of these, 797 (41.9%) displayed clarithromycin, tetracycline, metronidazole, or amoxicillin resistance. In MLR, migration status was associated with the rate of H. pylori positivity (ß = 3.85% per 10% increase in a postcode's migrant population; P < 0.001). H. pylori positivity and resistance to any antibiotic were geospatially clustered (Moran's I = 0.571 and 0.280, respectively; P < 0.001 for both). In GWR, there was significant geospatial variation in the strength of the migrant association for both H. pylori positivity and antibiotic resistance. CONCLUSION: Our study demonstrates the heterogeneous geospatial distribution of H. pylori positivity and antibiotic resistance, as well as its interaction with migrant status. Geographic location and migrant status are important factors to consider for H. pylori eradication therapy.

Increasing Helicobacter pylori clarithromycin resistance in Australia over 20 years.

BACKGROUND: Helicobacter pylori infection is responsible for considerable morbidity and mortality worldwide, and eradication rates are falling in many countries, primarily due to clarithromycin and metronidazole resistance. AIMS: There is a paucity of contemporary Australian data, which we sought to address by evaluating local rates of resistance of H. pylori to amoxicillin, clarithromycin, metronidazole and tetracycline over the past 20 years. METHODS: All gastric biopsy specimens collected at endoscopy to detect H. pylori infection at a single centre underwent routine culture and antibiotic susceptibility testing between 1998 and 2017. Specimens from 12 842 patients were cultured for H. pylori, of which 1473 positive cultures were tested for antibiotic susceptibility. RESULTS: Antibiotic resistance to clarithromycin increased by 3.7% per year (incidence rate ratio [IRR] 1.037; P = 0.014) over 20 years, with a corresponding 5.0% annual increase in minimum inhibitory concentration (MIC) (odds ratio 1.050; P < 0.001). Since 2010, average clarithromycin resistance has exceeded 20%, with >25% of isolates resistant in the past 2 years of data capture. In contrast, rates of resistance to metronidazole (35.3%), amoxicillin (0.14%) and tetracycline (0.34%) and their MIC have remained stable. Review of a representative sample (n = 120; 8%) of these patients revealed that only 5% had documented prior H. pylori eradication therapy. CONCLUSIONS: Over the past 20 years there has been a substantial rise in clarithromycin resistance, with stable metronidazole resistance and low rates of resistance to amoxicillin and tetracycline. Current first-line H. pylori eradication therapy may fail to achieve adequate eradication rates, and optimal first-line therapy in Australia should be revisited.

How did the ancient bacterium, Helicobacter pylori, cause an epidemic of chronic duodenal ulceration?

The association of Helicobacter pylori with chronic duodenal ulceration was a seminal observation in the short history of gastroenterology. However, H. pylori is now known to be an ancient bacterium, whereas there is persuasive evidence that the epidemic of duodenal ulceration began in the second half of the 19th century and continued into the second half of the 20th century. Possible explanations for the epidemic include genomic changes in the organism and environmental or other influences on the human host. While genomic changes resulted in the appearance of virulence factors, these seem likely to have appeared thousands of years ago with minimal effects on gastritis because of coexisting suppression of gastric immunity. In contrast, the emergence of duodenal ulceration is best explained by a change in the pattern of gastritis from inflammation involving the antrum and body in most individuals to a significant minority (10-20%) with antral gastritis but with relative sparing of the body of the stomach. In the latter group, the increase in serum gastrin (particularly G17) associated with antral gastritis had trophic effects on gastric parietal cells with an increase in the parietal cell mass and hypersecretion of gastric acid. Hypersecretion of acid is seen as the major risk factor for duodenal ulceration with significant contributions from environmental factors including smoking and use of nonsteroidal, anti-inflammatory drugs. Host factors favoring changes in the pattern of gastritis include delayed acquisition of infection and improved nutrition; both with enhancing effects on mucosal immunity.

Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients With Ulcerative Colitis: A Randomized Clinical Trial.

Importance: High-intensity, aerobically prepared fecal microbiota transplantation (FMT) has demonstrated efficacy in treating active ulcerative colitis (UC). FMT protocols involving anaerobic stool processing methods may enhance microbial viability and allow efficacy with a lower treatment intensity. Objective: To assess the efficacy of a short duration of FMT therapy to induce remission in UC using anaerobically prepared stool. Design, Setting, and Participants: A total of 73 adults with mild to moderately active UC were enrolled in a multicenter, randomized, double-blind clinical trial in 3 Australian tertiary referral centers between June 2013 and June 2016, with 12-month follow-up until June 2017. Interventions: Patients were randomized to receive either anaerobically prepared pooled donor FMT (n = 38) or autologous FMT (n = 35) via colonoscopy followed by 2 enemas over 7 days. Open-label therapy was offered to autologous FMT participants at 8 weeks and they were followed up for 12 months. Main Outcomes and Measures: The primary outcome was steroid-free remission of UC, defined as a total Mayo score of ≤2 with an endoscopic Mayo score of 1 or less at week 8. Total Mayo score ranges from 0 to 12 (0 = no disease and 12 = most severe disease). Steroid-free remission of UC was reassessed at 12 months. Secondary clinical outcomes included adverse events. Results: Among 73 patients who were randomized (mean age, 39 years; women, 33 [45%]), 69 (95%) completed the trial. The primary outcome was achieved in 12 of the 38 participants (32%) receiving pooled donor FMT compared with 3 of the 35 (9%) receiving autologous FMT (difference, 23% [95% CI, 4%-42%]; odds ratio, 5.0 [95% CI, 1.2-20.1]; P = .03). Five of the 12 participants (42%) who achieved the primary end point at week 8 following donor FMT maintained remission at 12 months. There were 3 serious adverse events in the donor FMT group and 2 in the autologous FMT group. Conclusions and Relevance: In this preliminary study of adults with mild to moderate UC, 1-week treatment with anaerobically prepared donor FMT compared with autologous FMT resulted in a higher likelihood of remission at 8 weeks. Further research is needed to assess longer-term maintenance of remission and safety. Trial Registration: anzctr.org.au Identifier: ACTRN12613000236796.

Cost-effective options for the prevention and management of gastrointestinal and liver disease in the Asia-Pacific region.

The Asia-Pacific region contains more than half of the world's population and is markedly heterogeneous in relation to income levels and the provision of public and private health services. For low-income countries, the major health priorities are child and maternal health. In contrast, priorities for high-income countries include vascular disease, cancer, diabetes, dementia, and mental health disorders as well as chronic inflammatory disorders such as hepatitis B and hepatitis C. Cost-effectiveness analyses are methods for assessing the gains in health relative to the costs of different health interventions. Methods for measuring health outcomes include years of life saved (or lost), quality-adjusted life years, and disability-adjusted life years. The incremental cost-effectiveness ratio measures the cost (usually in US dollars) per life year saved, quality-adjusted life year gained, or disability-adjusted life year averted of one intervention relative to another. In low-income countries, approximately 50% of infant deaths (< 5 years) are caused by gastroenteritis, the major pathogen being rotavirus infection. Rotavirus vaccines appear to be cost-effective but, thus far, have not been widely adopted. In contrast, infant vaccination for hepatitis B is promoted in most countries with a striking reduction in the prevalence of infection in vaccinated individuals. Cost-effectiveness analyses have also been applied to newer and more expensive drugs for hepatitis B and C and to government-sponsored programs for the early detection of hepatocellular, gastric, and colorectal cancer. Most of these studies reveal that newer drugs and surveillance programs for cancer are only marginally cost-effective in the setting of a high-income country.

Patient-controlled analgesia with inhaled methoxyflurane versus conventional endoscopist-provided sedation for colonoscopy: a randomized multicenter trial.

OBJECTIVE: Inhaled methoxyflurane (Penthrox, Medical Device International, Melbourne, Australia) has been used extensively in Australasia (Australia and New Zealand) to manage trauma-related pain. The aim is to evaluate the efficacy, safety, and outcome of Penthrox for colonoscopy. DESIGN: Prospective randomized study. SETTING: Three tertiary endoscopic centers. PATIENTS: Two hundred fifty-one patients were randomized to receive either Penthrox (n = 125, 70 men, 51.4 ± 1.1 years old) or intravenous midazolam and fentanyl (M&F; n = 126, 72 men, 54.9 ± 1.1 years old) during colonoscopy. MAIN OUTCOME MEASUREMENT: Discomfort (visual analogue scale [VAS] pain score), anxiety (State-Trait Anxiety Inventory Form Y [STAI-Y] anxiety score), colonoscopy performance, adverse events, and recovery time. RESULTS: Precolonoscopy VAS pain and STAI-Y scores were comparable between the 2 groups. There were no differences between groups in (1) pain VAS or STAI Y-1 anxiety scores during or immediately after colonoscopy, (2) procedural success rate (Penthrox: 121/125 vs M&F: 124/126), (3) hypotension during colonoscopy (7/125 vs 8/126), (4) tachycardia (5/125 vs 3/126), (5) cecal arrival time (8 ± 1 vs 8 ± 1 minutes), or (6) polyp detection rate (30/125 vs 43/126). Additional intravenous sedation was required in 10 patients (8%) who received Penthrox. Patients receiving Penthrox alone had no desaturation (oxygen saturation [SaO(2)] < 90%) events (0/115 vs 5/126; P = .03), awoke quicker (3 ± 0 vs 19 ± 1 minutes; P < .001) and were ready for discharge earlier (37 ± 1 vs 66 ± 2 minutes; P < .001) than those receiving intravenous M&F. LIMITATIONS: Inhaled Penthrox is not yet available in the United States and Europe. CONCLUSIONS: Patient-controlled analgesia with inhaled Penthrox is feasible and as effective as conventional sedation for colonoscopy with shorter recovery time, is not associated with respiratory depression, and does not influence the procedural success and polyp detection.

Preferences for CT colonography and colonoscopy as diagnostic tests for colorectal cancer: a discrete choice experiment.

OBJECTIVE: Computed tomography colonography (CTC) is an alternative diagnostic test to colonoscopy for colorectal cancer and polyps. The aim of this study was to determine test characteristics important to patients and to examine trade-offs in attributes that patients are willing to accept in the context of the diagnosis of colorectal cancer. METHODS: A discrete choice study was used to assess preferences of patients with clinical indications suspicious of colorectal cancer who experienced both CTC and colonoscopy as part of a diagnostic accuracy study in South Australia. Results were analyzed by using a mixed logit model and presented as odds ratios (ORs) for preferring CTC over colonoscopy. RESULTS: Colonoscopy was preferred over CTC as the need for a second procedure after CTC increased (OR of preferring CTC to colonoscopy = 0.013), as the likelihood of missing cancers or polyps increased (OR of preferring CTC to colonoscopy = 0.62), and as CTC test cost increased (OR of preferring CTC to colonoscopy = 0.65-0.80). CTC would be preferred to colonoscopy if a minimal bowel preparation was available (OR = 1.7). Some patients were prepared to trade off the diagnostic and therapeutic advantage of colonoscopy for a CTC study with a less intensive bowel preparation. Preferences also varied significantly with sociodemographic characteristics. CONCLUSIONS: Despite CTC's often being perceived as a preferred test, this may not always be the case. Informed decision making for diagnostic tests for colorectal cancer should include discussion of the benefits, downsides, and uncertainties associated with alternative tests, as patients are willing and able to make trade-offs between what they perceive as the advantages and disadvantages of these diagnostic tests.

Cells, cytokines and inflammatory bowel disease: a clinical perspective.

Ulcerative colitis and Crohn's disease are chronic inflammatory disorders of the GI tract. Although the disorders can usually be distinguished on clinical and pathological criteria, there are similarities in natural history and response to therapy. The purpose of this article is to examine the inflammatory infiltrate in both disorders and the cytokine profiles in intestinal mucosa and peripheral blood. For both disorders, the predominant cells in inflamed mucosa are neutrophils and lymphocytes positive for CD4. There are also increases in the number of B cells, macrophages, dendritic cells, plasma cells, eosinophils and perhaps mast cells. Cytokine levels and cytokine expression are also similar for both disorders, with increases in TNF-α and IFN-γ consistent with a Th1 response. As inflammation occurs in a microbial environment, one possibility is that the nature of the inflammatory response is largely independent of initiating factors. One concept that might be useful is that of initiating cells and cytokines and effector cells and cytokines. Persuasive evidence exists for a defect in phagocytic cells in Crohn's disease, perhaps with the expansion of a subset of activated macrophages. There are also possible links to natural killer cells and changes in the regulation of IL-8 and perhaps IL-22. For ulcerative colitis, the cellular events are less clear, but natural killer T cells may be important as initiating cells, and there is some evidence for upregulation of cytokines involved in Th2 responses, including IL-4 and IL-13. For both disorders, proinflammatory cytokines include TNF-α, IL-12, IL-23, and perhaps IL-17 and IFN-γ. Research challenges include the identification, activation and function of subsets of inflammatory cells, as well as new ways to terminate the inflammatory response.

Morphometric evaluation of duodenal biopsies in celiac disease.

OBJECTIVES: The Marsh classification is a semiquantitative method for the diagnosis and monitoring of changes in duodenal biopsies in celiac disease. We have explored the possibility that quantitative changes in villous area and crypt length (morphometry) may provide better information on changes in duodenal morphology, particularly after the introduction of a gluten-free diet. METHODS: We measured villous height, apical and basal villous widths, and crypt length in 57 adults with celiac disease and 83 control subjects. Villous area was calculated as a trapezoid approximation. Serial changes in villous area and crypt length were determined at regular intervals for up to 4 years after the introduction of a gluten-free diet. Morphometric changes were also correlated with Marsh grade, self-reported adherence to a gluten-free diet, and changes in celiac serology. RESULTS: The gluten-free diet resulted in a progressive increase in villous area and a progressive decrease in crypt length. Morphometric improvement reached a plateau after 6-12 months with mean villous area attaining a value approximately half that of control subjects. Morphometric data were more sensitive than Marsh grade. Improvement in morphometric indices was significantly associated with the disappearance of anti-endomysial IgA antibody but not with dietary compliance. CONCLUSIONS: Morphometry is a sensitive way to document changes in duodenal biopsies in celiac disease. In adults treated with a gluten-free diet, it is uncommon for villous area to return to values observed in control subjects, but morphometric improvement is associated with the disappearance of anti-endomysial IgA antibody.

The future of endoscopy.

Extraordinary developments have occurred in the field of endoscopy over the past 40 years. The era that began with the fiberoptic endoscope (fiberscope) has now moved to the videoscope and, more recently, to the capsule endoscope. Videoendoscopy will remain the major form of endoscopy for the next 5-10 years but, thereafter, diagnostic procedures including colonoscopy will increasingly be performed by capsule endoscopy. This change will be largely driven by patient preference rather than superior results from capsule studies. Image analysis of capsule studies will be accelerated by software that highlights abnormal areas and, by 2025, capsule studies will be 'read' by computer. For the next decade, more complex therapeutic procedures will be performed by a new group of therapeutic endoscopists using advanced videoscopes. Several new therapeutic procedures will emerge but natural orifice transluminal approaches will need to compete with advances in laparoscopic techniques. It is also likely that health administrators faced with escalating medical costs will demand that new and more expensive procedures not only facilitate patient care but result in superior health outcomes.

Colonoscopy: Art or science?

The focus on colorectal neoplasia has led to an exponential increase in the use of colonoscopy in many countries. Although colonoscopy facilitates the diagnosis and treatment of colonic disease, there are public health issues that include access, training, diagnostic accuracy, complications and additions to health-care costs. Because of this, colonoscopists have a responsibility to ensure that the procedure is appropriate, safe and of high-quality. This article addresses the issue of variation in technical skills that is known to exist within the endoscopic community, even among individuals with similar experience. While some of this variation reflects innate manual dexterity, another aspect is variation in the adoption of technical manoeuvers that facilitate various aspects of the procedure including rates for cecal intubation. Although technical manoeuvers are difficult to evaluate in controlled trials, there is persuasive data that high cecal intubation rates can be achieved by minimizing inflation and looping in the sigmoid colon and by the appropriate use of positional changes and abdominal pressure. In difficult settings, there is also benefit from the use of non-standard endoscopes and various accessories including overtubes.

Single-center study comparing computed tomography colonography with conventional colonoscopy.

AIM: To compare the results from computed tomography (CT) colonography with conventional colonoscopy in symptomatic patients referred for colonoscopy. METHODS: The study included 227 adult outpatients, mean age 60 years, with appropriate indications for colonoscopy. CT colonography and colonoscopy were performed on the same day in a metropolitan teaching hospital. Colonoscopists were initially blinded to the results of CT colonography but there was segmental unblinding during the procedure. The primary outcome measures were the sensitivity and specificity of CT colonography for the identification of polyps seen at colonoscopy (i.e. analysis by polyp). Secondary outcome measures included an analysis by patient, extracolonic findings at CT colonography, adverse events with both procedures and patient acceptance and preference. RESULTS: Twenty-five patients (11%) were excluded from the analysis because of incomplete colonoscopy or poor bowel preparation that affected either CT colonography, colonoscopy or both procedures. Polyps and masses (usually cancers) were detected at colonoscopy and CT colonography in 35% and 42% of patients, respectively. Of nine patients with a final diagnosis of cancer, eight (89%) were identified by CT colonography as masses (5) or polyps (3). For polyps analyzed according to polyp, the overall sensitivity of CT colonography was 50% (95% CI, 39%-61%) but this increased to 71% (95% CI, 52%-85%) for polyps > or = 6 mm in size. Similarly, specificity for all polyps was 48% (95% CI, 39%-58%) increasing to 67% (95% CI, 56%-76%) for polyps > or = 6 mm. Adverse events were uncommon but included one colonic perforation at colonoscopy. Patient acceptance was high for both procedures but preference favoured CT colonography. CONCLUSION: Although CT colonography was more sensitive in this study than in some previous studies, the procedure is not yet sensitive enough for widespread application in symptomatic patients.