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Biomedical subjects

Richard H Hunt

Publications and source records attributed to Richard H Hunt.

36 records · Page 2Linked to original sources
PubMed2004

Helicobacter pylori public health implications.

Population Helicobacter pylori screening and treatment has the potential to dramatically reduce global gastric cancer mortality. There is overwhelming evidence that the infection is a major cause of distal gastric adenocarcinoma. There is also randomized controlled trial evidence that H. pylori eradication reverses or ameliorates histological changes in the gastric mucosa that are important in carcinogenesis. Preliminary randomized controlled trial data suggest that screening and treatment may reduce the risk of gastric cancer although the number of cancer cases was small. Population H. pylori screening and treatment will also reduce mortality from peptic ulcer complications and reduce the burden of dyspepsia in the community. The reduction in health service dyspepsia costs means that this could be the first programme to pay for itself. From a scientific perspective, we still have insufficient evidence to conclude the benefits of population H. pylori screening are greater than the possible harms and we need more randomized controlled trial data. From a public health perspective however, sometimes screening programmes are developed with imperfect information. The medical community should be consistent and if we are instituting other population screening programmes without randomized controlled trial evidence then H. pylori testing and treatment should also be considered.

Helicobacter Infections↗
PubMed2003

Has education about Helicobacter pylori infection been effective? Worldwide survey of primary care physicians.

BACKGROUND: Confusion exists among physicians about the management of Helicobacter pylori (H. pylori) infection. We aimed to survey primary care physicians' (PCP) knowledge and management of H. pylori-related diseases. METHODS: Four-hundred and seventy randomly selected PCP from 29 countries were surveyed. RESULTS: The pathological role of H. pylori was of less concern in South Africa than the rest of the world (63% compared to 93%). The causal relationship between H. pylori and gastric and duodenal ulcers and gastric cancer was accepted by 81%, 85%, and 61% of respondents, respectively. Endoscopy was used by 62% of respondents to diagnose the infection. Histology was used by 61% of European participants for diagnosis compared to 3% in North American and 0% in South Africa. Proton-pump inhibitor (PPI)-based triple therapies were prescribed by 89% of respondents. Physicians in Oceania (35%) and South Africa (45%) were less concerned about bacterial resistance than respondents elsewhere. Sixty-three percent of respondents considered H. pylori relevant to dyspepsia management and 66% treated new dyspepsia empirically, compared to 18% who chose endoscopic diagnosis and 13% who used a H. pylori test and treat strategy. For persistent or recurrent infection, 56% of South African physicians treated with another regimen compared to 33% of PCP from elsewhere. Ninety-one percent of European participants agreed that current information on H. pylori management is helpful and 68% of PCP from other regions considered the information to be adequate. CONCLUSIONS: Current guidelines on the management of H. pylori infection have been useful for PCP worldwide. Contrasting answers to some questions may reflect differences in health care systems, epidemiology and approaches to the management of H. pylori infection between countries.

Anti-Bacterial Agents↗
PubMed2003

Meta-analysis of the relationship between cagA seropositivity and gastric cancer.

BACKGROUND & AIMS: Reports in the literature regarding the relationship of infection with cagA -positive strains of Helicobacter pylori to gastric cancer over and above H. pylori infection alone are conflicting. The aim of this study was to estimate the magnitude of the risk for gastric cancer associated with cagA seropositivity and to identify any sources of heterogeneity between studies. METHODS: A meta-analysis of case-control studies with age- and sex-matched controls, which provided raw data on the infection rates with H. pylori and cagA strains of H. pylori as detected by serology or polymerase chain reaction DNA, was performed. RESULTS: A comprehensive literature search identified 16 qualified studies with 2284 cases and 2770 controls. H. pylori and cagA seropositivity significantly increased the risk for gastric cancer by 2.28- and 2.87-fold, respectively. Among H. pylori -infected populations, infection with cagA -positive strains further increased the risk for gastric cancer by 1.64-fold (95% confidence interval [CI], 1.21-2.24) overall and by 2.01-fold (95% CI, 1.21-3.32) for noncardiac gastric cancer. Gastric cancer at the cardia is not associated with H. pylori infection or cagA -positive strains of H. pylori. Patient age and site of gastric cancer contributed to the heterogeneity between studies. CONCLUSIONS: Infection with cagA -positive strains of H. pylori increases the risk for gastric cancer over the risk associated with H. pylori infection alone. Searching for cagA status over H. pylori infection may confer additional benefit in identifying populations at greater risk for gastric cancer.

Adult↗
PubMed2003

The gastrointestinal safety of the COX-2 selective inhibitor etoricoxib assessed by both endoscopy and analysis of upper gastrointestinal events.

OBJECTIVES: Etoricoxib is a selective cyclooxygenase inhibitor that in clinical studies has improved the signs and symptoms of osteoarthritis and rheumatoid arthritis and reduced the potential for GI injury. The incidence of endoscopically detected ulcers and of clinically important upper GI events (perforations, ulcers, and bleeding episodes) was compared in patients taking etoricoxib or nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: Upper GI endoscopy was performed at intervals over 12 wk in 680 patients taking etoricoxib 120 mg once daily, ibuprofen 800 mg three times daily, or placebo in a randomized, parallel-group, double-blind study. Survival analysis was used to analyze time-to-event data for the incidence of gastric or duodenal ulcers (> or =3 mm and > or =5 mm), and the log rank test was used to compare the cumulative incidence between treatment groups. A combined analysis of upper GI events in all 10 Phase II/III clinical trials of etoricoxib (60, 90, or 120 mg) versus nonselective NSAIDs (naproxen, ibuprofen, or diclofenac) for osteoarthritis, rheumatoid arthritis, and chronic low back pain was conducted. Investigators reported potential events for adjudication by an external, blinded committee, using prespecified criteria to confirm events. All events that occurred during active treatment periods (maximum 792 days) or within 14 days of stopping treatment were included in the analysis. Time to first event was evaluated using survival analysis; the Kaplan-Meier method was used to determine the cumulative incidence, and relative risk was estimated with the Cox proportional hazards model. RESULTS: In the endoscopy study, the cumulative incidence of ulcers >/=3 mm at 12 wk in the ibuprofen group (17%) was significantly higher than in the etoricoxib group (8.1%, p < 0.001); similar results were seen for ulcers >/=5 mm. In the placebo group, the rate of ulcers >/=3 mm was 1.86%. Of 3142 patients treated with once-daily etoricoxib and 1828 patients treated with a nonselective NSAID (ibuprofen, naproxen, or diclofenac), 82 patients with investigator-reported upper GI events (71 confirmed) were eligible for the combined analysis. For etoricoxib versus NSAIDs, the rate per 100 patient-yr for confirmed events was 1.16 versus 3.05 (relative risk = 0.44, 95% CI = 0.27-0.72, p < 0.001), whereas that for investigator-reported events was 1.35 versus 3.42 (relative risk = 0.47, 95% CI = 0.30-0.74, p = 0.001). Results were driven primarily by studies with naproxen as the comparator. CONCLUSIONS: The incidence of endoscopically detected ulcers was significantly lower with etoricoxib 120 mg than with ibuprofen 2400 mg. Treatment with etoricoxib reduced the incidence of investigator-reported and confirmed adverse upper GI events by approximately 50% compared with treatment with nonselective NSAIDs.

Aged↗
PubMed2003

The evolving epidemiology of Helicobacter pylori infection and gastric cancer.

The relationship between Helicobacter pylori infection and the risk of gastric cancer has been well established in the last decade. Four meta-analyses have found that the infection increases the risk of noncardia gastric cancer by 2- to 6-fold compared with noninfected control populations. However, the role of cagA strains of H pylori in relation to gastric cancer has not been evaluated systematically. We undertook a meta-analysis of epidemiological studies examining the relationship between infection with cagA-positive strains of H pylori and the risk of gastric cancer, and found that patients who are seropositive for cagA strains of H pylori are at an increased risk for developing noncardia gastric cancer compared with those with H pylori infection alone. Therefore, searching for cagA-positive strains of H pylori may help identify populations at a greater risk for developing gastric cancer.

Animals↗
PubMed2003

Motion--Cyclo-oxygenase-2 selective nonsteroidal anti-inflammatory drugs are as safe as placebo for the stomach: arguments for the motion.

Traditional nonsteroidal anti-inflammatory drugs (NSAIDs) are known to cause gastritis, gastric and duodenal ulcers, and gastrointestinal (GI) blood loss, as well as alterations in small bowel permeability. Patients at a high risk for these complications include those who are older than 60 years of age, those with a previous history of complicated peptic disease and bleeding, and those who take high dose or multiple NSAIDs, including low dose aspirin, corticosteroids or anticoagulants. The introduction of selective inhibitors of cyclo-oxygenase-2 (COX-2) has provided effective treatment of inflammatory arthritis and musculoskeletal pain, with dramatic reductions in the risk of GI adverse events. The two most widely prescribed coxibs are celecoxib and rofecoxib, and others are being developed. Endoscopic studies have revealed that coxibs are only half as likely to induce upper GI ulceration than are traditional NSAIDs, and are as safe as placebo. Furthermore, the newer drugs do not cause excessive blood loss from the GI tract and do not affect small bowel permeability. The Vioxx Gastrointestinal Outcomes Research Study (VIGOR) revealed that the incidence of myocardial infarction was significantly lower with naproxen than rofecoxib, although this study was not designed to look at this endpoint. Coxibs are an important addition to the pharmacotherapy of inflammatory disease.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Assessment of the safety of selective cyclo-oxygenase-2 inhibitors: where are we in 2003?

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs worldwide despite their well-documented adverse gastrointestinal (GI) effects. The risk of developing a severe GI event varies from patient to patient and NSAID to NSAID. Selective cyclo-oxygenase-2 inhibitors (coxibs) have been designed to have similar efficacy but less GI toxicity than traditional NSAIDs, and have been shown to have an improved GI tolerability and less adverse events across a range of different GI safety assessments. In clinical trials, particularly VIGOR and CLASS, rofecoxib and celecoxib, respectively, significantly reduce the risk of ulcers and ulcer complications than nonselective NSAID comparators with ulcer rates comparable to placebo. The real benefit of a coxib comes from the sparing of the thromboxane and hence preservation of normal platelet function. Thus, there is less risk of bleeding with selective inhibition of COX-2, which is the most common and serious complication of non-selective NSAIDs. Moreover, bleeding can occur anywhere in the GI tract. Although some concern has been raised about the cardiovascular safety of coxibs, when used in recommended doses, there is no convincing evidence that patients treated with a coxib have an increased risk of cardiovascular thrombotic events. Different approaches have been advocated to minimize NSAID-related GI toxicity. Choice of less harmful NSAIDs such as coxib has been one of the strategies promoted in guidelines. The introduction of coxibs with a higher benefit-risk ratio has dramatically changed the therapeutic scenario for anti-inflammatory treatment in the clinical practice.

Journal Article↗
PubMed2003

A survey of the Anopheles funestus (Diptera: Culicidae) group of mosquitoes from 10 sites in Kenya with special emphasis on population genetic structure based on chromosomal inversion karyotypes.

We sampled Anopheles funestus Giles mosquitoes from 10 sites in Kenya to determine (1) the different members of this group present at these sites and (2) the population genetic structure of these species based on chromosomal inversion karyotypes with particular reference to the role of the Eastern arm of the Great Rift Valley and geographical distance as barriers to gene flow. Four members of this species group, namely An. funestus s.s., An. parensis, An. leesoni, and An. rivulorum, were found. An. funestus was found almost exclusively inside human dwellings while An. rivulorum was found almost exclusively outdoors. An. parensis was found both indoors and outdoors in comparable proportions. Earlier attempts to collect this group of mosquitoes from two of the sites yielded no mosquitoes, suggesting that numbers of mosquitoes change during the year, sometime reaching zero or very near zero. Significant levels of differentiation were observed among some An. funestus s.s. populations studied. Results suggest that the Rift Valley acts as a barrier to gene flow for An. funestus, but that levels of differentiation are not associated with the geographical distance between populations. The results are discussed in the light of the fact that inversions may have some adaptive significance to differences in environmental conditions.

Animals↗
PubMed2003

Anopheles parensis: the main member of the Anopheles funestus species group found resting inside human dwellings in Mwea area of central Kenya toward the end of the rainy season.

A total of 460 Anopheles funestus s.l. was collected inside human dwellings in Mwea, central Kenya. Of the 414 specimens that were positively identified, 1 was Anopheles leesoni and the others were Anopheles parensis. None of the 373 specimens tested were positive for Plasmodium falciparum or Plasmodium malariae sporozoites by enzyme-linked immunosorbent assay (ELISA). Of the 139 ELISA blood-meal-positive specimens, 82.01% and 1.44% had fed on cattle and humans, respectively. These results are discussed in the context of implications for malaria control through vector-control strategies.

Animals↗
PubMed2002

Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis.

BACKGROUND: The relation between H pylori infection and use of non-steroidal anti-inflammatory drugs (NSAIDs) in the pathogenesis of peptic-ulcer disease is controversial. We undertook a meta-analysis to address this issue. METHODS: By computer and manually we sought observational studies on the prevalence of peptic-ulcer disease in adult NSAID takers or the prevalence of H pylori infection and NSAID use in patients with peptic-ulcer bleeding. Summary odds ratios were calculated from the raw data. Tests for homogeneity were done. FINDINGS: Of 463 citations identified, 25 studies met inclusion criteria. In 16 studies of 1625 NSAID takers, uncomplicated peptic-ulcer disease was significantly more common in patients positive than in those negative for H pylori (341/817 [41.7%] vs 209/808 [25.9%]; odds ratio 2.12 [95% CI 1.68-2.67]). In five controlled studies, peptic-ulcer disease was significantly more common in NSAID takers (138/385 [35.8%]) than in controls (23/276 [8.3%]), irrespective of H pylori infection. Compared with H pylori negative individuals not taking NSAIDs, the risk of ulcer in H pylori infected NSAID takers was 61.1 (9.98-373). H pylori infection increased the risk of peptic-ulcer disease in NSAID takers 3.53-fold in addition to the risk associated with NSAID use (odds ratio 19.4). Similarly, in the presence of risk of peptic-ulcer disease associated with H pylori infection (18.1), use of NSAIDs increased the risk of peptic-ulcer disease 3.55-fold. H pylori infection and NSAID use increased the risk of ulcer bleeding 1.79-fold and 4.85-fold, respectively. However, the risk of ulcer bleeding increased to 6.13 when both factors were present. INTERPRETATION: Both H pylori infection and NSAID use independently and significantly increase the risk of peptic ulcer and ulcer bleeding. There is synergism for the development of peptic ulcer and ulcer bleeding between H pylori infection and NSAID use. Peptic-ulcer disease is rare in H pylori negative non-NSAID takers.

Adult↗
PubMed2002

Minimizing postcolonoscopy abdominal pain by using CO(2) insufflation: a prospective, randomized, double blind, controlled trial evaluating a new commercially available CO(2) delivery system.

BACKGROUND: Abdominal pain after colonoscopy is a common, distressing symptom resulting from bowel distension by insufflated gas. CO(2), unlike air, is rapidly cleared from the colon by passive absorption. A commercially available CO(2) delivery system has only recently become available. The effects of CO(2) and air insufflation on residual bowel gas and postprocedure pain were compared. METHODS: One hundred patients were randomized to undergo colonoscopy with insufflation of air (n = 51) or CO(2) (n = 49) by means of a regulator; 97 patients completed the study. Patients with active GI bleeding, inflammatory bowel disease, or previous colectomy were excluded. Pain scores (ordinal scale: 0 = none, to 5 = extreme) were recorded immediately after colonoscopy and at 1, 6, and 24 hours. Residual colonic gas was evaluated on abdominal radiographs at 1 hour. RESULTS: Residual colonic gas and postprocedural pain at 1 and 6 hours were significantly less in the CO(2) group. 71% of patients insufflated with room air had colonic distension in excess of 6 cm versus 4% for those in the CO(2) group. 94% of patients insufflated with CO(2) had minimal colonic gas versus 2% in whom air was used (p < 0.0001). Of patients insufflated with air, 45% and 31% had pain at, respectively, 1 hour and 6 hours, versus 7% and 9%, respectively, for those insufflated with CO(2) (respectively, p < 0.0001 and p < O.02). No complications resulted from use of the CO(2) delivery system. CONCLUSIONS: Insufflation of CO(2) rather than air significantly reduces abdominal pain and bowel distension after colonoscopy. CO(2) may be insufflated safely and effectively with the new CO(2) delivery system.

Abdominal Pain↗
PubMed2002

Evolving concepts in functional gastrointestinal disorders: promising directions for novel pharmaceutical treatments.

In recent years there has been an increasing appreciation of the complexity of functional gastrointestinal disorders. These represent a spectrum of conditions which may affect any part of the gastrointestinal tract in which there appears to be dysregulation of visceral function and afferent sensation and a strong association with emotional factors and stress. There is a clear psychological dimension, with up to 60% of irritable bowel syndrome (IBS) patients reported to have psychological co-morbidities and altered pain perception is also common in comparison with control populations. The role of the enteric nervous system, the sensory pathways and the brain as well as the influence of the latter on sympathetic and parasympathetic outflow have likewise attracted increasing interest and have led to exciting new methods to study their complex interactions. The concept of low-grade inflammation, such as might occur after infection, acting as a trigger for neuromuscular dysfunction has also led to the broad integrative hypotheses that help to explain the biopsychosocial dimensions seen in functional gastrointestinal disease. The multi-component model places a major emphasis on neurogastroenterology and enteric and neuro-immune interactions where new approaches to pharmacotherapy lie. Drugs may affect motility, visceral sensation and other aspects of gut function such as secretion or absorption. More particularly, however, has been the search for and attempts to influence important mediators of these primary gut functions. Such targets include serotonin and selected 5-HT receptors, which are involved in gut motility, visceral sensation and other aspects of gut function, CCK receptors which are involved in the mediation of pain in the gut and nociception in the CNS, opioid receptors involved in pain in the brain, spinal cord and periphery, muscarinic M3-receptors, substance P and neurokinin A and B receptors which are involved in motor adaptation and pain transmission in association with inflammation, gabba receptors involved in nociception and cannabinoid receptors which are involved in the control of acetyl choline release in the gut. With a better understanding of the structures and pathways involved in visceral perception and hyperalgesia, in the CNS, spinal cord and the gut and new pharmacological tools we will be better able to elucidate the neuropharmacology of visceral perception and its relationship to gut dysfunction. It is likely that there will be multiple therapeutic options based on the spectrum of abnormalities capable of causing the spectrum of symptoms of functional gastrointestinal disorders in any individual patient.

Autonomic Nervous System↗
PubMed2002

Evolving concepts in the pathophysiology of functional gastrointestinal disorder.

Functional gastrointestinal disorder (FGID) is common and may affect any part of the digestive tract from the esophagus to the rectum. Functional dyspepsia and the irritable bowel syndrome (IBS) are the most commonly recognized and until recently were considered distinct entities. In recent years, however, new observations and studies of the afferent nervous system have extended our concepts of both IBS and dyspepsia and suggest that these conditions may have common triggers and expression from similar pathophysiological processes.

Animals↗
PubMed2002

Risks and benefits of Helicobacter pylori eradication: current status.

In patients with diseases known to be associated with Helicobacter pylori infection, such as peptic ulcer, treatment of the underlying infection is the standard of care. However, in most major consensus management guidelines, including those published in Canada, widespread testing for H pylori infection is not recommended. This practice is not encouraged because of insufficient evidence of cost-benefit in gastric cancer prevention, the potential for increases in antibiotic resistance and the controversial hypothesis of potential negative effects of eradication in certain clinical entities. For example, there is insufficient evidence to recommend against eradicating H pylori discovered in a patient with symptoms of gastroesophageal reflux disease. The management guidelines designed specifically in Canada should, therefore, continue to be applied, with H pylori diagnosed and treated in appropriately selected patients.

Gastrointestinal Diseases↗
PubMed2002

Recommendations for the appropriate use of anti-inflammatory drugs in the era of the coxibs: defining the role of gastroprotective agents.

Treatment with anti-inflammatory drugs and the analgesic efficacy of conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are compromised by a two- to fourfold increased risk of gastrointestinal complications. This increased risk has resulted in an increasing use of the new selective cyclooxygenase-2 inhibitors or coxibs, which, in clinical trials and outcomes studies, reduced gastrointestinal adverse events by 50% to 65% compared with conventional NSAIDs. However, the coxibs are not available to all patients who need them, and NSAIDs are still widely used. Moreover, treatment with a coxib cannot heal pre-existing gastrointestinal lesions, and cotherapy with an anti-secretory drug or mucosal protective agent may be required. This paper addresses the management of patients with risk factors for gastrointestinal complications who are taking NSAIDs and makes recommendations for the appropriate use of 'gastroprotective' agents (GPAs) in patients who need to take an NSAID or a coxib. When economically possible, a coxib alone is preferable to a conventional NSAID plus a GPA to minimize exposure to potential gastrointestinal damage and avoid unnecessary dual therapy. Patients at high risk require a GPA in addition to a coxib.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Etiology of dyspepsia: implications for empirical therapy.

Dyspepsia describes a symptom complex thought to arise in the upper gastrointestinal tract and includes, in addition to epigastric pain or discomfort, symptoms such as heartburn, acid regurgitation, excessive burping or belching, a feeling of slow digestion, early satiety, nausea and bloating. Based on the evidence that heartburn cannot be reliably distinguished from other dyspeptic symptoms, the Rome definition appears to be too narrow and restrictive. It is particularly ill suited to the management of uninvestigated dyspepsia at the level of primary care. In patients presenting with uninvestigated dyspepsia, a symptom benefit is associated with a 'test and treat' approach for Helicobacter pylori infection. A substantial proportion of those who do not benefit prove to have esophagitis on endoscopy. In those with functional dyspepsia, the benefits of H pylori eradication, if any, appear to be modest. Hence, a 'symptom and treat' acid-suppression trial with proton pump inhibitors, and a 'test and treat' strategy for H pylori are two acceptable empirical therapies for patients with univestigated dyspepsia.

Age Factors↗
PubMed2002

14 day endoscopy study comparing risedronate and alendronate in postmenopausal women stratified by Helicobacter pylori status.

OBJECTIVE: Bisphosphonates are effective treatment for osteoporosis but have been associated with gastrointestinal (GI) mucosal injury. This study compared the incidence of gastric ulcers after treatment with risedronate, a pyridinyl bisphosphonate, or alendronate, a primary amino bisphosphonate, in healthy postmenopausal women stratified by Helicobacter pylori status. METHODS: Subjects were randomized to receive risedronate 5 mg (n = 318) or alendronate 10 mg (n = 317) daily for 14 days. Endoscopy and evaluator-blind assessments of the esophageal, gastric, and duodenal mucosa were performed at baseline and on Days 8 and 15. RESULTS: Overall, gastric ulcers > or = 3 mm were observed in 18 (6.0%) of 300 evaluable subjects in the risedronate group and 36 (12.1%) of 297 in the alendronate group during treatment (p = 0.013). On Day 8, the incidences of gastric ulcers in the risedronate and alendronate groups were 3.6% and 6.6%, respectively (p = 0.133), and on Day 15, they were 3.3% and 8.7% (p = 0.008). The incidence of gastric ulcers was not affected by H. pylori status. Mean gastric endoscopy scores at Days 8 and 15 were significantly lower in the risedronate group than in the alendronate group (p < 0.001). Mean esophageal and duodenal endoscopy scores were similar in the 2 groups at Days 8 and 15. When the treatment groups were combined, gastric endoscopy scores were significantly higher among H. pylori negative than H. pylori positive subjects at Days 8 and 15 (p < 0.05). Upper GI adverse events were reported by 18 (5.7%) subjects in the risedronate group (19 events) and 28 (8.8%) subjects in the alendronate group (32 events). Symptoms did not predict the presence of mucosal damage. CONCLUSION: Risedronate was associated with a significantly lower incidence of gastric ulcers than alendronate. H. pylori infection did not increase the incidence of bisphosphonate related gastric ulcers. The findings from this 14 day study in healthy volunteers support the hypothesis that bisphosphonates may differ from one another in their potential to produce upper GI mucosal damage.

Aged↗