Will eradication of Helicobacter pylori improve symptoms of non-ulcer dyspepsia? This meta-analysis is potentially misleading.
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Dyspepsia↗
Biomedical subjects
D Forman
Publications and source records attributed to D Forman.
Pharmacological interventions for non-ulcer dyspepsia.
BACKGROUND: The commonest cause of upper gastrointestinal symptoms is non-ulcer dyspepsia (NUD) and yet the pathophysiology of this condition has been poorly characterised and the optimum treatment is uncertain. It is estimated that pound450 million is spent on dyspepsia drugs in the UK each year. OBJECTIVES: This review aims to determine the effectiveness of six classes of drugs (antacids, histamine H2 antagonists, proton pump inhibitors, prokinetics, mucosal protecting agents and antimuscarinics) in the improvement of either the individual or global dyspepsia symptom scores and also quality of life scores patients with non-ulcer dyspepsia. SEARCH STRATEGY: Trials were located through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and SIGLE, using appropriate subject headings and text words, searching bibliographies of retrieved articles, and through contacts with experts in the fields of dyspepsia and pharmaceutical companies. SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing drugs of any of the six groups with each other or with placebo for non-ulcer dyspepsia (NUD). DATA COLLECTION AND ANALYSIS: Data were collected on dyspeptic symptom scores either individual or global symptom assessments and also quality of life scores and adverse effects. MAIN RESULTS: A total of 11775 citations were obtained. 144 trials were retrieved and 94 trials fulfilled our eligibility criteria. However, subsequent data extraction was not possible in 37 trials. Fifty trials were excluded as they did not meet our eligibility criteria. The final 57 trials were included in the final meta-analysis. Prokinetics (12 trials with dichotomous outcomes generating 829 patients; relative risk reduction [RRR] = 50%; 95% confidence intervals [CI] = 30 to 65%) and H2RAs (8 trials generating 1,125 patients; RRR = 30%; 95% CI = 4 to 48%) were significantly more effective than placebo. Proton pump inhibitors (4 trials generating 1,248 patients; RRR = 12%; 95% CI = -1 to 24%) and Bismuth salts (6 trials generating 311 patients; RRR = 40%; 95% CI = -3 to 65%) were superior to placebo but this was of marginal statistical significance. Antacids (one trial generating 109 patients; RRR = -2%; 95% CI = -36% to 24%) and sucralfate (two trials generating 246 patients; RRR = 29%; 95% CI = -40% to 64%) were not statistically significantly superior to placebo. A funnel plot suggested that the prokinetic result could be due to publication bias. The funnel plot of H2RAs did not show any evidence of publication bias but the quality of the trials was generally poor. REVIEWER'S CONCLUSIONS: There is some evidence that anti-secretory therapy may be effective in NUD. The trials evaluating prokinetic therapy are difficult to interpret as the meta-analysis result could have been due to publication bias. Further research using prokinetics and anti-secretory therapy is required before any firm conclusions can be reached. The effect of these drugs is likely to be small and many patients will need to take them on a long-term basis so the therapies assessed need to be inexpensive and well tolerated.
Dyspepsia↗
Initial management strategies for dyspepsia.
BACKGROUND: This review considers management strategies (combinations of initial investigation and empirical treatments) for dyspeptic patients. OBJECTIVES: To determine the effectiveness, acceptability, and cost effectiveness of the following initial management strategies for patients presenting with dyspepsia (a) initial pharmacological therapy (including endoscopy for treatment failures) (b) early endoscopy (c) testing for Helicobacter pylori and endoscope only those positive (d) H.pylori eradication therapy with or without prior testing. SEARCH STRATEGY: Trials were located through electronic searches and extensive contact with trialists. SELECTION CRITERIA: All randomised controlled trials of dyspeptic patients presenting in primary care. DATA COLLECTION AND ANALYSIS: Data was collected on dyspeptic symptoms, quality of life and use of resources. MAIN RESULTS: Ten papers reporting 12 comparisons were found. Trials comparing proton pump inhibitors (PPI) with antacids (2 trials) and H2 receptor antagonists (3 trials), and of early endoscopy compared with initial acid suppression (3 trials) were pooled. PPIs were significantly more effective than both H2RA s and antacids. Relative risks (RR) and 95% CI were, for PPI: antacid 0.72 (0.64-0.80), PPI: H2RA 0.63 (0.47-0.85). Results for other drug comparisons were either absent or inconclusive. Early endoscopy was not more effective than initial prescribing (RR 0.90 (0.77-1.04), but current studies lack power. No eligible trials of H.pylori test and endoscopy or test and eradicate were found. REVIEWER'S CONCLUSIONS: PPIs are effective in the treatment of dyspepsia in these trials which may not adequately exclude patients with gastro-oesophageal reflux disease. The relative efficacy of H2RA and PPI is uncertain. Early investigation may benefit some patients with dyspepsia. The review will be updated shortly with several large trials that have recently been completed.
Anti-Bacterial Agents↗
Eradication of helicobacter pylori for non-ulcer dyspepsia.
BACKGROUND: Helicobacter pylori (H pylori) is the main cause of peptic ulcer disease. The role of H pylori in non-ulcer dyspepsia is less clear. OBJECTIVES: To determine the effect of H pylori eradication on dyspepsia symptoms and quality of life scores in patients with non-ulcer dyspepsia. SEARCH STRATEGY: Trials were identified through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and SIGLE, using appropriate subject headings and keywords, searching bibliographies of retrieved articles, and through contacts with experts in the fields of dyspepsia and with pharmaceutical companies. SELECTION CRITERIA: All parallel group randomised controlled trials (RCTs) comparing drugs to eradicate H pylori with placebo or other drugs known not to eradicate H pylori for patients with non-ulcer dyspepsia. DATA COLLECTION AND ANALYSIS: Data were collected on individual and global dyspeptic symptom scores, quality of life measures and adverse effects. Dyspepsia outcomes were dichotomised into minimal/resolved versus same/worse symptoms. MAIN RESULTS: Seven randomised controlled trials were included in the systematic review. Five trials compared proton pump inhibitor dual or triple therapy with a proton pump inhibitor + placebo antibiotics, and evaluated dyspepsia at 6-12 months in 1,385 patients. H pylori eradication was significantly superior to placebo in treating non ulcer dyspepsia (relative risk reduction = 7%; 95% CI = 1% to 12%; p=0.02) and there was no significant heterogeneity between the studies. The number needed to treat to cure one case of dyspepsia = 19 (95% CI = 11 to 132). A further two trials compared Bismuth based H pylori eradication with an alternative pharmacological agent. These trials were smaller and had a shorter follow-up but suggested H pylori eradication was more effective than either H2 receptor antagonists or sucralfate in treating non-ulcer dyspepsia. REVIEWER'S CONCLUSIONS: H pylori eradication may be an effective therapy for H pylori positive non-ulcer dyspepsia. This result is not robust and further evidence on the efficacy of H pylori eradication in non ulcer dyspepsia would be helpful. The effect is modest and economic models would help establish whether this approach is cost-effective. This review will be updated as results from other ongoing trials (Malfertheiner 2000) are made available.
Anti-Bacterial Agents↗
The glutathione precursor L-2-oxothiazolidine-4-carboxylic acid protects against liver injury due to chronic enteral ethanol exposure in the rat.
L-2-oxothiazolidine-4-carboxylic acid (OTC) is a cysteine prodrug that maintains glutathione in tissues. Here, its effect on alcohol-induced liver injury in an enteral alcohol feeding model was investigated. Male Wistar rats were given control high-fat or ethanol containing diets enterally for 4 weeks. Treated rats received 500 mg/kg/d of dietary OTC. Ethanol delivery, weight gain, and the cyclic pattern of ethanol in the urine were not different between the OTC-ethanol and ethanol groups. After 4 weeks, serum aspartate transaminase (AST), necrosis and inflammation were elevated significantly by ethanol compared with appropriate high-fat controls, effects blocked by OTC. Moreover, ethanol elevated hepatic tumor necrosis factor alpha (TNF-alpha) messenger RNA (mRNA) and the nuclear transcription factor nuclear factor kappaB (NFkappaB) 2-3 fold. NFkappaB in isolated Kupffer cells was also increased by ethanol. These effects were all blocked by OTC treatment. Additionally, superoxide production was higher in Kupffer cells isolated from ethanol-treated rats, an effect blunted by OTC. OTC also increased circulating glutathione (GSH) levels about 2-fold; however, GSH levels were not affected by ethanol or OTC in livers from the groups studied. Surprisingly, GSH was elevated by ethanol and OTC treatment in isolated Kupffer cells about 2-fold. Moreover, GSH (Ki-10 micromol/L) and cysteinyl-glycine, but not oxidized glutathione (GSSG) or OTC, blunted the LPS-induced increase in calcium in isolated Kupffer cells, possibly by activating a glycine-gated chloride channel due to their structural similarity with glycine. Collectively, it is concluded that GSH is protective, in part, by increasing circulating GSH, which blunts activation of Kupffer cells via the glycine-gated chloride channel.
Animals↗
Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours.
Testicular germ-cell tumours (TGCT) affect 1 in 500 men and are the most common cancer in males aged 15-40 in Western European populations. The incidence of TGCT has risen dramatically over the last century. Known risk factors for TGCT include a history of undescended testis (UDT), testicular dysgenesis, infertility, previously diagnosed TGCT (ref. 7) and a family history of the disease. Brothers of men with TGCT have an 8-10-fold risk of developing TGCT (refs 8,9), whereas the relative risk to fathers and sons is fourfold (ref. 9). This familial relative risk is much higher than that for most other types of cancer. We have collected samples from 134 families with two or more cases of TGCT, 87 of which are affected sibpairs. A genome-wide linkage search yielded a heterogeneity lod (hlod) score of 2.01 on chromosome Xq27 using all families compatible with X inheritance. We obtained a hlod score of 4.7 from families with at least one bilateral case, corresponding to a genome-wide significance level of P=0.034. The proportion of families with UDT linked to this locus was 73% compared with 26% of families without UDT (P=0.03). Our results provide evidence for a TGCT susceptibility gene on chromosome Xq27 that may also predispose to UDT.
Adolescent↗
Trends over time in Helicobacter pylori gastritis in Kenya.
OBJECTIVE AND DESIGN: There is increasing evidence to link infection of the gastric mucosa by Helicobacter pylori with the subsequent development of gastric cancer. This study was undertaken to document the progression of H. pylori gastritis in a rural Kenyan population with a moderate gastric cancer risk. METHOD: Biopsy follow-up study of 51 H. pylori-positive patients over an average of 5.5 years. RESULTS: In the study group, the number of individuals with moderate to severe atrophy rose from 17 (33%) to 22 (43%), an annual increase of 1.8% [95% confidence interval (CI) -0.9% to 4.4%]. There was significant progression of atrophy (P< 0.05) in those with low overall scores for graded morphological variables at initial endoscopy. Intestinal metaplasia did not progress; indeed four out of 12 patients initially diagnosed with intestinal metaplasia showed no evidence of it in their follow-up biopsies. CONCLUSIONS: H. pylori gastritis with atrophy may provide a suitable environment within the gastric mucosa for the development of gastric cancer but it is likely that other factors in this population determine further progress towards dysplasia and cancer.
Adult↗
The proportion of upper gastrointestinal symptoms in the community associated with Helicobacter pylori, lifestyle factors, and nonsteroidal anti-inflammatory drugs. Leeds HELP Study Group.
OBJECTIVE: Upper gastrointestinal disorders are common in the community, yet the determinants of these symptoms are poorly characterized. The association between upper gastrointestinal symptoms and Helicobacter pylori (H. pylori), socioeconomic status, nonsteroidal antiinflammatory drug (NSAID) use, smoking, alcohol, and coffee intake was assessed in a cross-sectional survey. METHODS: Subjects between the ages of 40-49 yr were randomly selected from the lists of 36 primary care centers. Participants attended their local primary care center and were interviewed by a researcher using a validated dyspepsia questionnaire. H. pylori status was determined by a nonfasting 13C-urea breath test. RESULTS: A total of 32,929 subjects were invited, and 8,407 (25%) attended and were eligible. Of these, 2,329 (28%) were H. pylori positive and 3,177 (38%) had dyspepsia. Also, 44% of H. pylori-infected participants reported dyspepsia compared with 36% of uninfected subjects [odds ratio = 1.39; 95% confidence interval (CI) 1.26-1.53]. H. pylori infection remained a significant risk factor for dyspepsia in a multiple logistic regression model (odds ratio = 1.21; 95% CI 1.09-1.34), suggesting that 5% of dyspepsia in the population is attributable to H. pylori. NSAIDs, low educational attainment, renting accommodation, absence of central heating, sharing a bed with siblings, and being married were also significantly associated with dyspepsia in this model. Smoking, but not drinking alcohol or coffee, was marginally associated with dyspepsia, but this finding was not robust. These factors were not associated with any dyspepsia subtype. CONCLUSIONS: H. pylori is significantly associated with dyspepsia and may be responsible for 5% of upper gastrointestinal symptoms in the community.
Adult↗
Aetiology, pathology and staging of testicular tumours
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Journal Article↗
The management of dyspepsia: a systematic review.
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Anti-Ulcer Agents↗
Meat and cancer: a relation in search of a mechanism.
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Amines↗
Gastric cancer, cytotoxin-associated gene A-positive Helicobacter pylori, and serum pepsinogens: an international study. The Eurogst Study Group.
BACKGROUND & AIMS: CagA-positive Helicobacter pylori infection has been more closely associated with gastric disease than CagA-negative infection. This study evaluated whether geographic variation in the prevalence of CagA could explain variation in gastric cancer rates. METHODS: The Eurogast study was conducted in 17 centers in 13 countries. Gastric cancer rates were calculated for each center, and serum samples from approximately 2850 subjects were assayed for immunoglobulin G antibodies to H. pylori and CagA and for pepsinogens A and C. RESULTS: The proportion of CagA-positive H. pylori infections varied across the centers, but this variation did not explain any more of the variation in gastric cancer rates than H. pylori alone. Subjects with CagA-positive infection had, however, significantly higher pepsinogen levels and a lower pepsinogen A/C ratio than subjects with CagA-negative infection; this pattern was observed consistently across the study centers. CONCLUSIONS: Variation in the seroprevalence of CagA did not explain geographic variation in gastric cancer rates any better than H. pylori alone. However, the consistent variation in pepsinogen levels with CagA status across the study centers supports the importance of the role of CagA in the development of gastric disease.
Adult↗
Risk factors for testicular germ cell tumours by histological tumour type. United Kingdom Testicular Cancer Study Group.
There are two main histological groups of testicular germ cell tumours, which may have different risk factors. Some authors have analysed potential risk factors by histological group but few consistent differences have been identified. In this paper we examine risk factors for pure seminoma and other tumours using data from the United Kingdom case control study of testicular cancer. Seven hundred and ninety-four cases were included in the study, each with a matched control; 400 cases had pure seminoma tumours, and 394 had other testicular tumours. The risk of seminoma associated with undescended testis was slightly higher than that for other tumours (odds ratio of 5.3 compared with 3.0). When split at the median age at diagnosis, this difference was greater in men aged 32 and over (odds ratio of 11.9 compared with 5.1) than in the younger men (3.0 compared with 2.5). Risks associated with testicular or groin injuries were higher in the non-seminoma group, as was the risk for a history of sexually transmitted disease. The protective effect of a late puberty was more marked for tumours of other histologies. Some differences were also detected for participation in sports. Whilst some of the differences detected may have arisen by chance, the stronger association between undescended testis and pure seminoma has been identified by a number of other studies and may reflect a genuine difference in aetiology.
Adult↗
Maternal and child constitutional factors and the frequency of melanocytic naevi in children.
This study examined the association between numbers of benign melanocytic naevi in 7-year-old children in Oxfordshire born in 1988-9 with their mother's arm naevus count, and maternal and child pigmentation factors. We believe this is the first time that the relationship between child and maternal naevus counts has been reported. A high naevus count in the child was associated with male sex (P = 0.009), freckling (P = 0.001) and propensity of the child to burn in the sun (P = 0.05). A low naevus count was observed in red-haired children (P = 0.02). The strongest association of child's naevus count was with a high maternal arm naevus count, independent of the child's pigmentation factors (trend P < 0.0001). Maternal pigmentation factors were not associated with child's naevus count independent of the child's own pigmentation factors. Maternal arm naevus counts may be a better predictor of child naevus count than the child's own pigmentation factors and children. There has not been examination, however, of the relationship between naevus counts in children and those in their parents. We therefore conducted a study of the occurrence of naevi in children aged 7-8 years in Oxfordshire, examining, in addition to sex and pigmentation factors in the child, the relationship of maternal pigmentation factors and maternal naevus counts with naevi in their offspring.
Age Factors↗
Should we go further and screen and treat?
Helicobacter pylori is probably the most common human bacterial infection in the world, and, in a minority of infected individuals, it can cause life-threatening disease. As testing procedures and treatment regimens become cheaper and more reliable, is the screening of asymptomatic populations to identify and treat infected individuals justified? Evidence on which to base an answer to this question is sparse, but there are several reasons to believe that a screen-and-treat strategy for H. pylori infection might constitute a viable public health intervention. Screening can be sensitive, H. pylori eradication regimens are increasingly effective, and both screening for and eradicating the bacterium are relatively inexpensive. There are, however, a number of concerns that can be addressed only through further research. Decisive evidence concerning all the risks and benefits of a screen-and-treat strategy will be derived only from large, long-term, randomized, controlled trials.
Helicobacter Infections↗
Association between infections with CagA-positive or -negative strains of Helicobacter pylori and risk for gastric cancer in young adults. Research Group on Prevention of Gastric Carcinoma Among Young Adults.
OBJECTIVE: We assessed the association between infection with CagA-positive and -negative Helicobacter pylori and the risk of gastric cancer in young adults. METHODS: CagA IgG antibodies were measured in sera of subjects participating in a case-control study in Japan. The study subjects were 103 gastric cancer patients <40 yr of age, 100 inpatients with benign diseases, and 101 screenees younger than age 43 yr. RESULTS: Compared with the H. pylori-negative/CagA-negative (H. pylori-/CagA-) group, both the H. pylori-positive/CagA-negative (H. pylori+/CagA-) group and the H. pylori-positive/CagA-positive (H. pylori+/CagA+) groups showed elevated odds ratios for intestinal-type, diffuse-type, early, advanced, proximal, and distal gastric cancers. All the relationships were significant except for the H. pylori+/CagA- group in relation to proximal cancer. The overall odds ratios (95% confidence intervals) for gastric cancer in the H. pylori+/CagA- and the H. pylori+/CagA+ groups were 15.0 (6.4, 35.2) and 14.6 (6.7, 31.9), respectively. Between these two groups, no significant difference was observed in risks for intestinal-type, diffuse-type, early, advanced, proximal, or distal gastric cancer. CONCLUSIONS: In those <40 yr of age, it is concluded that both CagA-positive and CagA-negative H. pylori infections are related to risks of intestinal-type, diffuse-type, early, advanced, and distal gastric cancers.
Adult↗
Automated collection of quality-of-life data: a comparison of paper and computer touch-screen questionnaires.
PURPOSE: To evaluate alternative automated methods of collecting data on quality of life (QOL) in cancer patients. After initial evaluation of a range of technologies, we compared computer touch-screen questionnaires with paper questionnaires scanned by optical reading systems in terms of patients' acceptance, data quality, and reliability. PATIENTS AND METHODS: In a randomized cross-over trial, 149 cancer patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, version 2.0 (EORTC QLQ-C30), and the Hospital Anxiety and Depression Scale (HADS) on paper and on a touch screen. In a further test-retest study, 81 patients completed the electronic version of the questionnaires twice, with a time interval of 3 hours between questionnaires. RESULTS: Fifty-two percent of the patients preferred the touch screen to paper; 24% had no preference. The quality of the data collected with the touch-screen system was good, with no missed responses. At the group level, the differences between scores obtained with the two modes of administration of the instruments were small, suggesting equivalence for most of the QOL scales, with the possible exception of the emotional, fatigue, and nausea/vomiting scales and the appetite item, where patients tended to give more positive responses on the touch screen. At the individual patient level, the agreement was good, with a kappa coefficient from 0.57 to 0.77 and percent global agreement from 61% to 97%. The electronic questionnaire had good test-retest reliability, with correlation coefficients between the two administrations from 0.78 to 0.95, kappa coefficients of agreement from 0.55 to 0.90, and percent global agreement from 56% to 100%. CONCLUSION: Computer touch-screen QOL questionnaires were well accepted by cancer patients, with good data quality and reliability.
Adult↗
A reversible cause of hypercapnic respiratory failure: lower motor neuronopathy associated with renal cell carcinoma.
We describe a unique case of a patient with a reversible paraneoplastic motor neuronopathy who presented with hypercapnic respiratory failure. The patient developed progressive respiratory and limb muscle weakness until treated with removal of a renal cell carcinoma, which was followed by a complete resolution of neuromuscular symptoms. The literature of paraneoplastic motor neuronopathies is reviewed, specifically in reference to respiratory failure.
Aged↗