Review article: psychosocial factors in the quality of life of patients with inflammatory bowel disease.

Information on quality of life in inflammatory bowel disease is limited. Despite the clear importance of this topic to patients, quality of life measurement is seldom undertaken in day-to-day management of patients or included in clinical trials. Although previous reviews have dealt with quality of life, the area of psychosocial functioning has not been specifically addressed. The aim of this study was to review the psychosocial factors affecting quality of life in patients with inflammatory bowel disease, using an electronic search of MEDLINE, EMBASE, CINAHL and psycINFO. Of the 751 articles identified by the search, 107 were considered relevant and included in the review. A number of psychosocial factors appear to be important, including gender, socioeconomic status, ethnicity and perceived stress. To improve the quality of life in patients with inflammatory bowel disease, clinicians' attention needs to be drawn towards this subject, with an awareness of those patient groups more vulnerable to impaired quality of life. These identified variables also represent important factors, which should be adjusted for when conducting research into quality of life in these patients.

Review article: the treatment of Helicobacter pylori infection.

The discovery of Helicobacter pylori has stimulated great interest in its role in gastritis, non-ulcer dyspepsia and peptic ulceration. Treatment regimens to eradicate this organism from gastric mucosa have also received considerable attention. Current recommendations limit the use of triple drug combinations only to specific patient groups.

Prescribing patterns for dyspepsia in primary care: a prospective study of selected general practitioners.

AIM: To define prescribing patterns for symptomatic dyspeptic patients in a cross-section of general practitioners in Leeds, United Kingdom. METHODS: Nine general practitioners from a range of practices took part in a prospective observational study of prescribing patterns for dyspepsia. All consultations with symptomatic dyspeptic patients were recorded over a 4-month period. Symptoms were recorded as ulcer-like, reflux-like, or nonspecific, and details of recent therapy, previous investigations and any prescription issued were noted. RESULTS: 257 consecutive consultations were recorded (new patients 23%, consulted before but not investigated 33%, previously investigated 44%). 93% of consultations resulted in a prescription (antacids 24%, prokinetic/motility agent 8%, H2-receptor antagonist 36%, proton pump inhibitor 24%, Helicobacter pylori eradication therapy 8%). 42.5% of new patients received an acid-suppressing drug as first-line therapy, of which only 32% had tried over-the-counter remedies. Symptom-type (ulcer-like, reflux-like or nonspecific) significantly influenced choice of empiric therapy (P < 0.001), though prescribing was still variable. Although around 60% of patients with previously negative investigations or only minor disease received acid-suppressing drugs, such patients were six times more likely to receive 'less potent' treatments (no prescription, antacid or motility agent) than those with known acid-peptic disease (odds ratio 6.23, P < 0.01). Only 30% of patients with previously documented peptic ulcer received H. pylori eradication therapy, yet patients with a wide range of other diagnoses received this form of treatment. CONCLUSIONS: Management guidelines may help to promote a more consistent and selective use of newer treatments, and promote more cost-effective patient care.

Clinical economics review: Helicobacter pylori-associated peptic ulcer disease.

The high prevalence and chronic nature of peptic ulcer disease have traditionally resulted in a major economic burden on health care systems. In 1991, for example, peptic ulcer disease was estimated to account for over one-third of all National Health Service expenditure on gastrointestinal diseases. It is now well established that elimination of Helicobacter pylori can lead to a dramatic reduction in gastroduodenal ulcer relapse, with obvious clinical benefits. This review considers the economic implications of the use of H. pylori eradication therapy in peptic ulcer disease.

Clinical economics review: gastroenterology.

In the prevailing climate of cost containment, doctors are increasingly expected to consider the economic consequences of treatment choices. Clinical (or medical) economics attempts to apply economic principles to the description and analysis of the costs of medical interventions, so as to identify how best to spend scarce health care resources. Such economic evaluations may assess the overall financial burden of a disease to society as a whole (macro-economics), or attempt to compare alternative treatment strategies for a specific clinical situation (micro-economics). In addition to expenditure on drugs and investigations (direct medical costs), economic studies may consider a variety of other costs. These include direct costs borne by patients (e.g. prescription charges, travel, food), indirect costs to society owing to lost productivity (resulting from morbidity or premature mortality) and even intangible costs which assign a monetary value to outcomes of disease such as pain, distress and anxiety. Four main types of economic analysis are in current use. Cost-minimization analysis attempts to identify the least expensive option in situations where there are a range of equally effective treatments for a given clinical condition, whereas cost-effectiveness analysis allows management strategies differing both in cost and efficacy to be compared. The cost-effectiveness of health care programmes targeting different disease states may also be compared using cost-utility analysis, in which health benefits are translated into a common utility-based unit of outcome, such as the Quality Adjusted Life Year (QALY). Cost-benefit analysis attempts to quantify health outcomes in monetary terms, so that the net result provides an assessment of value-for-money of health interventions. Gastrointestinal disorders are amongst the commonest of complaints, and considerable health care resources are consumed in treatment. Issues of cost-effectiveness are likely to assume increasing importance in gastroenterology because of the ever expanding range of drug choice, the increasing number of high cost treatments and the development of new therapeutic interventions.

Clinical economics review: medical management of inflammatory bowel disease.

Inflammatory bowel diseases, although they are uncommon and rarely fatal, typically present during the period of economically productive adult life. Patients may require extensive therapeutic intervention as a result of the chronic, relapsing nature of the diseases. Their medical management includes oral and topical 5-amino salicylic acid derivatives and corticosteroids, as well as antibiotics and immunosuppressive therapies. Assessing the cost-effectiveness of rival treatments requires valid, reliable global assessments of outcome which consider quality of life, as well as the usual clinical end-points. Macro-economic studies of the overall impact of inflammatory bowel disease on health care systems have so far been largely confined to North America, where the total annual US costs, both direct and indirect, incurred by the estimated 380 000-480 000 sufferers has been put at around US2bn. Drugs were estimated to account for only 10% of total costs, whereas surgery and hospitalization account for approximately half. Studies from Europe suggest that the proportion of patients with Crohn's disease and ulcerative colitis who are capable of full time work is 75% and 90%, respectively. However, whilst only a minority of inflammatory bowel disease patients suffer chronic ill health and their life expectancy is normal, obtaining life assurance may be problematic, suggesting a misconception that inflammatory bowel disease frequently results in a major impact on an individual's economic productivity.

Dyspepsia workload in urban general practice and implications of the British Society of Gastroenterology Dyspepsia guidelines (1996).

AIM: To define the characteristics of patients consulting with active dyspeptic symptoms in urban general practice, and to consider the implications of applying the British Society of Gastroenterology Dyspepsia management guidelines. DESIGN: Prospective observational study over a period of 12 months. SETTING: Two multipartner, two-centre general practices in the City of Leeds (UK) with a combined target population of 11 011 registered patients. SUBJECTS: A total of 340 patients consulting with active dyspeptic symptoms (52% male; mean age 53 years, range 16-89 years). RESULTS: Of the practice population, 3% consulted with dyspepsia (first-time consulter: 19%; previous consulter not yet investigated: 30%; previously investigated: 51%). Of 168 undiagnosed patients, 43% had upper abdominal pain (dysmotility-like symptoms in 42%), 35% had reflux symptoms, 22% had mixed symptoms, 12% had 'alarm' symptoms and 18% had a history of NSAID use. Patients < 45 years old with simple dyspepsia accounted for 32% of undiagnosed cases. A fifth of the workload was in dealing with undiagnosed dyspeptics over 45 years old. One per cent of the population would require endoscopy if all undiagnosed cases either > 45 years or with complicated dyspepsia were investigated. Of 172 previously investigated patients, 29% had negative tests, 25% had 'minor' findings, and 45% had evidence of acid-peptic disease. Patients with duodenal ulcer disease accounted for 12% of the total workload. CONCLUSIONS: A knowledge of the characteristics of patients consulting with dyspepsia in primary care should allow the adaptation of guidelines, to ensure advice is relevant to local case mix and compatible with local resources.

Helicobacter pylori associated chronic gastritis and peptic ulceration in patients taking non-steroidal anti-inflammatory drugs.

Helicobacter pylori is now recognized as a frequent cause of histological chronic gastritis, and this has radically changed our understanding of this common condition. In the light of these developments, the traditional view that non-steroidal anti-inflammatory drugs are one of the common 'environmental' causes of chronic gastritis has been re-examined. Gastric mucosal biopsies have been studied from 430 patients undergoing routine upper gastrointestinal endoscopy, 99 of whom had recently been taking non-steroidal anti-inflammatory drugs. No significant association was found between the use of these drugs and either the presence of chronic gastritis or the frequency of colonization with H. pylori, although there was a strong association (P less than 0.0001) between H. pylori and gastritis. Non-steroidal anti-inflammatory drugs appear, however, to modify the inflammatory process in the gastric body, leading to a lower frequency of atrophic gastritis (P less than 0.05). The majority of peptic ulcers were associated with H. pylori irrespective of non-steroidal anti-inflammatory drug use, but there was a higher frequency of H. pylori negative ulceration in the patients who had used these agents (P less than 0.04). Peptic ulceration was uncommon in the absence of either H. pylori or recent non-steroidal anti-inflammatory drug use.

Local immune response to gastric Campylobacter in non-ulcer dyspepsia.

Colonising Campylobacter pyloridis were identified histologically in gastric biopsy specimens from 89% of 83 patients with non-ulcer dyspepsia and chronic gastritis, but not in 58 dyspeptic patients with normal mucosa. The presence and population density of organisms was associated with the presence of intraepithelial neutrophils. In vivo coating of the organisms by host immunoglobulin was investigated by immunoperoxidase staining of IgA, IgG, and IgM in 54 biopsy specimens. IgA coated bacteria were seen in all cases of active gastritis, and in 60% of biopsy specimens without intraepithelial neutrophils. Coating with IgG or IgM, or both, was correlated with activity of gastritis and was rarely seen in the absence of a neutrophil infiltrate.

Interleukin 10 in Helicobacter pylori associated gastritis: immunohistochemical localisation and in vitro effects on cytokine secretion.

BACKGROUND/AIMS: Interleukin 10 (IL-10) is a counter-inflammatory peptide implicated in the downregulation of human intestinal immune responses. Enhanced secretion of IL-10 has been documented in gastric biopsy organ culture in Helicobacter pylori infection. This study aimed to define the cellular origins of IL-10 in H pylori associated gastritis, and to determine the effects of endogenous IL-10 on proinflammatory cytokine secretion in vitro. METHODS: Endoscopic biopsies were obtained from the gastric antrum at endoscopy from patients with dyspepsia. Two pairs of antral biopsies were cultured in vitro for 24 hours, one pair in the presence of neutralising anti-IL-10 monoclonal antibody, the other pair as controls. The cytokine content of culture supernatants (tumour necrosis factor alpha (TNF-alpha), IL-6, and IL-8) was determined by enzyme linked immunosorbent assay and corrected for biopsy weight. Helicobacter pylori status was established by histology and biopsy urease test, and histopathology graded by the Sydney system. In a subgroup of patients, western blotting was used to establish CagA serological status. Immunohistochemistry for IL-10 was performed on formalin fixed tissues using a combination of microwave antigen retrieval and the indirect avidin-biotin technique. Immunoreactivity was scored semiquantitatively. RESULTS: In vitro culture was performed in 41 patients: 31 with H pylori positive chronic gastritis and 10 H pylori negative. In vitro secretion of TNF-alpha, IL-6, and IL-8 for "control" biopsies was significantly higher in H pylori positive versus negative samples, with values of TNF-alpha and IL-6 correlating with the degree of active and chronic inflammation and being higher in CagA seropositive cases. No evidence for enhanced cytokine secretion was seen in biopsies cocultured in the presence of anti-IL-10 monoclonal antibody. Immunohistochemistry was performed in 29 patients, of whom 13 were H pylori positive. IL-10 immunoreactivity was observed in the surface epithelium in all H pylori positive cases and in 13 of 16 negative cases, especially in areas of surface epithelial degeneration. Lamina propria mononuclear cells (LPMNCs) were positively stained in all H pylori positive cases and in 12 of 16 negative cases, with a significantly greater proportion of positive LPMNCs in the positive group. CONCLUSIONS: This study localised IL-10 protein to the gastric epithelium and LPMNCs. In vitro proinflammatory cytokine secretion was increased in H pylori infection (especially CagA positive infection), but blocking endogenous IL-10 secretion did not significantly increase cytokine secretion. IL-10 is implicated in H pylori infection and might "damp down" local inflammation. The role of gastric IL-10 secretion in determining the clinicopathological outcome of infection merits further study.

Evaluation of a commercial ELISA for serodiagnosis of Helicobacter pylori infection.

A commercial ELISA for the detection of Helicobacter pylori IgG antibodies was evaluated using serum from 242 patients attending an endoscopy clinic. The efficacy of the ELISA was assessed in relation to the histological detection of H pylori on antral mucosal biopsy specimens. In patients under 61 years of age (n = 138) the ELISA was 97.5% sensitive and 85.5% specific for H pylori infection, with a positive predictive value of 91% and a negative predictive value of 96%. Over the whole group the sensitivity of the ELISA was 93.8% and the specificity 79.3%. The positive predictive value and negative predictive values were, respectively, 90% and 87%. These results suggest that the Bio-Rad GAP IgG H pylori ELISA is suitable for serodiagnosis of H pylori infections for most clinical purposes and thus makes H pylori serology available to routine diagnostic laboratories.

Campylobacter pyloridis and acid induced gastric metaplasia in the pathogenesis of duodenitis.

Biopsy specimens of gastric and duodenal mucosa from 290 patients were examined histologically for metaplasia and Campylobacter pyloridis. Estimates of pH on samples of fasting gastric juice from 55 of the patients were performed, and mucosal biopsy specimens from 33 patients were also cultured for C pyloridis. Active duodenitis was seen in 34 duodenal biopsy specimens. Thirty (88%) of the patients with active duodenitis had both greater than 5% gastric metaplasia in the duodenal specimen and C pyloridis associated gastritis. These two factors coexisted in only 0.43% of patients with no duodenal inflammation. When C pyloridis were seen histologically in duodenal biopsy specimens they were confined to areas of gastric metaplasia and never occurred in the absence of a polymorph infiltrate. Of the 55 patients with measurements of gastric juice pH, gastric metaplasia was present in the duodenum in 20 of 42 with a pH of less than 2.5, and in 0 of 13 with a pH of greater than 2.5. These results suggest that acid induced gastric metaplasia in the duodenum and C pyloridis associated gastritis may be synergistic in the pathogenesis of duodenitis; the metaplastic gastric epithelium allows C pyloridis to colonise the duodenal mucosa, where it produces an acute inflammatory response.

Helicobacter pylori, gastritis, and peptic ulceration in the elderly.

AIMS: To determine the histopathological types of gastritis, presence of H pylori, and of peptic ulceration in patients aged 70 and over, compared with younger adults. METHODS: Gastric antral and corpus biopsy specimens from 112 elderly patients were classified and graded histologically according to the Sydney system. Details of recent antibiotic and non-steroidal anti-inflammatory drug use were recorded. Eighty four of the patients were positive for H pylori IgG antibodies and parietal cell antibodies. The results were compared with those from a series of 124 adult patients aged under 60. RESULTS: H pylori were visible at histological examination in only 57 of 87 (65.5%) elderly patients with chronic gastritis (excluding "special forms") compared with 72 of 79 (91.1%) of the younger patients with gastritis (p < 0.0002). Severe atrophy of the corpus mucosa was significantly associated with absence of H pylori (p < 0.002), and was present in eight of 30 elderly patients with helicobacter negative gastritis. Other explanations for absence of H pylori include recent antibiotic intake, more intestinal metaplasia, and lower bacterial load in elderly patients (p < 0.05). Autoimmune gastritis and NSAID use did not seem to be relevant. Serodiagnosis showed reduced sensitivity (81%) in patients who were helicobacter positive histologically, but was positive in 14 of 23 (61%) with H pylori negative gastritis histologically, suggesting either current infection that had been missed or previous infection. Peptic ulceration was significantly associated with NSAID use, but not with H pylori in the elderly. CONCLUSIONS: The spectrum of gastritis is different in the elderly, compared with younger adults, due to a significant group with chronic gastritis who are H pylori negative on histological examination. NSAID use, but not demonstration of H pylori (at histological examination) is associated with peptic ulceration in the elderly.

Immune responses to Helicobacter pylori in children with recurrent abdominal pain.

The systemic immune response to Helicobacter pylori was examined in 69 children with recurrent abdominal pain and upper gastrointestinal symptoms. Twenty one (30%) children were histologically positive for H pylori. Eighteen of the 21 positive subjects and two H pylori negative subjects (one with normal mucosa, one with lymphocytic gastritis) were positive for H pylori IgG antibodies by enzyme linked immunosorbent assay (ELISA) (86% sensitivity, 98% specificity). In children with H pylori associated gastritis, there was a significant positive correlation (p less than 0.05) between IgG antibody titres and patient age. Intra-assay comparison of sera from histologically negative adults with those of histologically negative children showed that the cut off for positivity in the ELISA for adults was greater than that for children. Immunoblotting showed IgG positivity in 20 of the 21 patients with H pylori infection (95% sensitivity). Both ELISA and immunoblotting for IgA and IgM H pylori antibodies had poor discriminatory value for determining infection. Serological detection of H pylori IgG antibodies seems to be valuable in the assessment of children presenting with recurrent abdominal pain and other gastrointestinal symptoms, but assays must first be validated in paediatric populations.

Helicobacter pylori serology in patients with coeliac disease and dermatitis herpetiformis.

AIMS: To investigate whether Helicobacter pylori infection or autoimmune gastritis is responsible for the reported increase in gastric pathology and abnormalities of gastric function in patients with coeliac disease and dermatitis herpetiformis (DH). METHODS: Serum H pylori IgG antibodies were assayed by enzyme linked immunosorbent assay and intrinsic factor antibodies by radioimmunoassay in 99 patients with coeliac disease and 58 patients with dermatitis herpetiformis from two geographic areas. RESULTS: H pylori positivity in patients with coeliac disease and dermatitis herpetiformis increased with age, reaching 50% and 70%, respectively, in patients over 50 years. The percentage H pylori seropositivity in coeliac disease did not differ from the percentage positivity observed in 250 similarly aged blood donors from the same geographic area (Leeds). Seropositivity in patients with dermatitis herpetiformis was not significantly different from the level of positivity observed in 98 age matched patients without dermatitis herpetiformis attending the same Edinburgh dermatology clinic. Only one patient with coeliac disease had positive intrinsic factor antibodies. H pylori seropositivity in Edinburgh control subjects under 30 years of age (41.9%) was significantly higher (p less than 0.03) than in Leeds controls (18%) of corresponding age. An increasing prevalence of H pylori seropositivity with age in coeliac disease and dermatitis herpetiformis paralleled that of the control groups. CONCLUSIONS: Gastritis in coeliac disease and dermatitis herpetiformis is largely caused by H pylori infection at a level that is no different from that of the general population. Any increase in the prevalence of gastritis in these two diseases might be caused by lymphocytic gastritis rather than pernicious anaemia.

Gastric epithelium in the duodenum: its association with Helicobacter pylori and inflammation.

Duodenal biopsy specimens from 471 adults and 47 children were examined to determine the prevalence and distribution of gastric epithelium in the duodenal bulb in relation to age, gender, gastroduodenal inflammation, smoking, alcohol and consumption of nonsteroidal anti-inflammatory drugs (NSAID). Gastric metaplasia was present in the anterior wall duodenal biopsy specimen in 31%, was significantly less common in patients under 17 than in adults, and was more common in males than females. In sixty two adults who underwent multiple radial duodenal biopsy gastric metaplasia was randomly distributed around the duodenal circumference; sixty three per cent of the patients with gastric metaplasia found on multiple biopsy were detected by just the anterior biopsy. Gastric metaplasia was not obviously associated with alcohol, cigarette, or NSAID consumption. While the presence of gastric metaplasia was associated with adulthood, male sex, and low fasting gastric juice pH, its extent was associated with active duodenitis and Helicobacter-associated gastritis. On logistic regression, gastric metaplasia in the duodenum and gastric Helicobacter pylori were independent predictors of active duodenitis, but were not significantly associated with inactive duodenal inflammation. H pylori was observed in duodenal biopsy specimens from 32 patients, all with active duodenitis; bacteria were present only on foci of gastric metaplasia, and were more likely to be seen when the metaplasia was extensive. It is proposed that inflammatory injury to the duodenal mucosa by H pylori may stimulate the development of further gastric metaplasia, and that the area of duodenum susceptible to colonisation with H pylori may therefore increase progressively until mucosal integrity is compromised and ulceration supervenes.

The effect of dietary vitamin E deficiency on plasma zinc and copper concentrations.

Vitamin E and zinc have a number of functions in common, including membrane stabilisation, antioxidant function and modulation of prostaglandin metabolism. Previous studies have shown vitamin E malabsorption during zinc depletion and it appears that there is an interaction between the two nutrients. In this study we have investigated whether vitamin E deficiency affects zinc and copper concentrations in experimental animals. Male Wistar rats were maintained on a vitamin E deficient diet for either 6 or 10 months. At the end of the experimental period all animals had undetectable plasma vitamin E levels and increased red cell fragility. Plasma zinc concentrations were significantly reduced in all vitamin E deficient animals compared to control rats (p<0.002) and copper levels were reciprocally elevated (p<0.002). It appears likely that decreased zinc levels may represent redistribution of circulating zinc to tissues and cells as a secondary antioxidant, or for membrane stabilisation or prostaglandin synthesis.

The relationship between nutritional status and serum soluble interleukin-2 receptor concentrations in patients with Crohn's disease treated with elemental diet.

Serum soluble interleukin-2 receptor concentrations (sIL-2R) were measured and correlated with indices of disease activity and nutrition in 13 patients with active Crohn's disease treated with an elemental diet. The initial serum sIL-2R concentrations were raised, 1121 +/- 181 U/ml (mean +/- SEM) compared to controls, 177 +/- 22.9 U/ml (n = 18) (p < 0.001). Four weeks' treatment resulted in significant improvement in disease activity (Harvey-Bradshaw index) and 4-day faecal (111)Indium-leucocyte excretion. Serum sIL-2R concentrations did not change significantly after treatment, 789 +/- 79.8 U/ml (p > 0.05). Serum sIL-2R concentrations were inversely correlated with albumin, pre-albumin, creatinine-height index and total body potassium. Only those patients with markedly elevated sIL-2R concentrations (>800 U/ml) and severe nutritional depletion prior to treatment, showed significant reductions in sIL-2R levels with elemental dietary treatment. These results demonstrate an association between nutritional impairment and immune activation in Crohn's disease.

Precision of anthropometric measurements: the value of mid-arm circumference.

A study was carried out to examine how reproducible anthropometric measurements were within and between two observers on a group of 24 normal subjects and 20 obese individuals. A further study was performed on 28 malnourished patients with Crohn's disease undergoing a controlled trial of nutritional therapy to assess how weight change correlated with other anthropometric parameters. The measurement that was most reproducible and correlated most with weight change was mid-arm circumference. As it is the simplest measurement to perform, we recommend that it is used more often in nutritional studies.

The effect of zinc and vitamin C supplementation on the immune status of patients with Crohn's disease.

The immune status of 29 patients with Crohn's disease given oral supplements of Vitamin C, zinc or placebo for three-week periods was studied. Collectively, the patients showed T-cell hyporesponsiveness, as assessed by phytohaemagglutinin stimulation, which was significantly improved by Vitamin C. Both monocyte function, as assessed by latex phagocytosis, and pan T-Cell number were significantly reduced and were not influenced by supplementation. Humoral immunity, assessed by pokeweed mitogen-induced immunoglobulin synthesis, was normal and remained unchanged. Vitamin C supplements improved T-cell function in Crohn's disease, whereas neither Vitamin C nor zinc had a measurable effect on humoral immunity.