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Biomedical subjects

D Forman

Publications and source records attributed to D Forman.

At least 55 records · Page 3Linked to original sources

Ten year follow up of ulcerative colitis patients with and without low grade dysplasia.

BACKGROUND AND AIMS: Low grade dysplasia (LGD) is believed to predispose to colorectal cancer (CRC), and proctocolectomy has been advocated when this is identified. Between 1978 and 1990, 160 patients with longstanding extensive ulcerative colitis (UC) were recruited for annual colonoscopic surveillance and 40 developed LGD at some stage. We report the outcome of this cohort 10 years after the original study ended. METHODS: Retrospective cohort study and histopathological review of the original diagnoses of LGD. The outcome of 158/160 (98.8%) patients was established in 2000. RESULTS: Of the 128 patients still alive and with an intact colon at the end of 1990, two were not traceable, 29 had LGD, and 97 had no dysplasia (controls). After 10 years, high grade dysplasia (HGD) or CRC developed in 3/29 LGD (10%) and in 4/97 controls (4.0%). Kaplan-Meier analysis from 1991 to death or colectomy did not show a statistically significant difference between the two groups (log rank test p=0.63). Histopathological review demonstrated the unreliability of LGD diagnosis. Agreement between pathologists was uniformly poor: kappa <0.4 for all comparisons. CONCLUSION: LGD diagnosis is not sufficiently reliable to justify prophylactic colectomy. Conservative management of established LGD cases should not be ruled out.

Adult↗

The cost-effectiveness of population Helicobacter pylori screening and treatment: a Markov model using economic data from a randomized controlled trial.

BACKGROUND: Economic models have suggested that population Helicobacter pylori screening and treatment may be a cost-effective method of reducing mortality from gastric cancer. These models are conservative as they do not consider that the programme may reduce health service peptic ulcer and other dyspepsia costs. We have evaluated the economic impact of population H. pylori screening and treatment over 2 years in a randomized controlled trial and have incorporated the results into an economic model exploring the impact of H. pylori eradication on peptic ulcer disease and gastric cancer. METHODS: Subjects between the ages of 40 and 49 years were randomly invited to attend their local primary care centre. H. pylori status was evaluated by (13)C-urea breath test and infected individuals were randomized to receive omeprazole, 20 mg b.d., clarithromycin, 250 mg b.d., and tinidazole, 500 mg b.d., for 7 days or identical placebos. Economic data on health service costs for dyspepsia were obtained from a primary care note review for the 2 years following randomization. These data were incorporated into a Markov model comparing population H. pylori screening and treatment with no intervention. RESULTS: A total of 2329 of 8407 subjects were H. pylori positive: 1161 were randomized to receive eradication therapy and 1163 to receive placebo. The cost difference favoured the intervention group 2 years after randomization, but this did not reach statistical significance (11.42 ponds sterling per subject cost saving; 95% confidence interval, 30.04 ponds sterling to -7.19 pounds sterling; P=0.23). Analysis by gender suggested a statistically significant dyspepsia cost saving in men (27.17 ponds sterling per subject; 95% confidence interval, 50.01 pounds sterling to 4.32 pounds sterling; P=0.02), with no benefit in women (-4.46 per subject; 95% confidence interval, -33.85 pounds sterling to 24.93 pounds sterling). Modelling of these data suggested that population H. pylori screening and treatment for 1,000,000 45-year-olds would save over 6,000,000 pounds sterling and 1300 years of life. The programme would cost 14, 200 pounds sterling per life year saved if the health service dyspepsia cost savings were the lower limit of the 95% confidence intervals and H. pylori eradication had only a 10% efficacy in reducing mortality from distal gastric cancer and peptic ulcer disease. CONCLUSIONS: Modelling suggests that population H. pylori screening and treatment are likely to be cost-effective and could be the first cost-neutral screening programme. This provides a further mandate for clinical trials to evaluate the efficacy of population H. pylori screening and treatment in preventing mortality from gastric cancer and peptic ulcer disease.

Adult↗

Lung cancer: district active treatment rates affect survival.

STUDY OBJECTIVE: This study investigates variation in management and treatment of lung cancer patients and determines the impact of any variation in treatment on survival. DESIGN: A retrospective study of population based data held by the Northern & Yorkshire Cancer Registry and Information Service (NYCRIS), comparing active treatment rates for lung cancer with survival by districts. SETTING The then 17 districts in Yorkshire and South Humber, England. PATIENTS: 22 654 patients registered with lung cancer between 1986 and 1994 and followed up until end of 1996. RESULTS: The overall rates of active treatment (surgery, radiotherapy, and chemotherapy) varied between districts from 37% to 56%. One year survival (with 95% CI) was significantly better in the districts with highest rates of active treatment 23% (22% to 24%) compared with 19% (17% to 20%) for those with lowest treatment rates. Non-small cell lung cancer patients (55%) in the districts with highest active treatment rates had an age adjusted relative risk of death during the follow up period, relative to risk of death in the districts with the lower treatment rates of 0.88 (0.83 to 0.92). Clinically diagnosed patients (34%) had an age adjusted RR of 0.92 (0.86 to 0.96). RR in small cell cancer (11%) was not significant. CONCLUSION: This study has shown wide variations in the rates of active treatment for lung cancer patients within districts across one large region of England. Active treatment was strongly associated with improved survival, especially in non-small cell lung cancer.

Adult↗

A minimum estimate for the incidence of gastric cancer in Eastern Kenya.

We documented available information concerning incident cases of gastric cancer in part of Kenya's Eastern Province between 1991 and 1993. By reviewing the records of all major health facilities in the area, 200 cases of gastric carcinoma were found giving an annual average crude incidence rate of 7.01 per 100 000 males and 3.7 for females (world age-standardised rates, 14.3 for males and 7.1 for females). There is likely to be underascertainment of cases especially among those aged over 65 years. Previous incidence estimates for the same area of Kenya were reviewed and a 10-fold increase in the recorded indirectly standardised incidence rate between the periods 1965-70 and 1991-93 was noted but this may be due to improved diagnostic facilities. The recent rates in this part of Kenya are comparable to Eastern European rates and similar to those recorded in other highland regions of Africa.

Adult↗

Cancer survival.

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Humans↗

Psychological interventions for non-ulcer dyspepsia.

BACKGROUND: Studies have also shown that NUD patients have higher scores of anxiety, depression, neurotism, chronic tension, hostility, hypochondriasis, and tendency to be more pessimistic when compared with the community controls. OBJECTIVES: This review aims to determine the effectiveness of psychological interventions including psychotherapy, psychodrama, cognitive behavioral therapy, relaxation therapy, guided imagery or hypnosis in the improvement of either individual or global dyspepsia symptom scores and also quality of life scores patients with non-ulcer dyspepsia (NUD). SEARCH STRATEGY: Trials were located through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and PsycLIT, using appropriate subject headings and text words and searching bibliographies of retrieved articles. SELECTION CRITERIA: All randomised controlled trials (RCTs) or quasi-randomised studies assessing the effectiveness of psychological interventions (including psychotherapy, psychodrama, cognitive behavioural therapy, relaxation therapy, guided imagery or hypnosis) for non-ulcer dyspepsia (NUD). DATA COLLECTION AND ANALYSIS: Data were collected on individual, global dyspepsia symptom scores, as well as measures of quality of life (QoL) scores and adverse effects. MAIN RESULTS: The three trials identified showed that there was improvement in the dyspepsia symptom scores at the end of treatment and one trial showed improvement in the psychological parameters. However, meta-analysis was not possible as these trials used different psychological interventions and two of the trials only reported mean change in symptoms and did not give standard deviations of this change. REVIEWER'S CONCLUSIONS: Psychological intervention in the form of psychodynamic psychotherapy and cognitive behavioral therapy may be useful in the treatment of NUD. However, we need more trials to assess dyspepsia symptom scores and also psychological intervention in order to give us a clearer picture of the role of psychological intervention in NUD.

Cognitive Behavioral Therapy↗

Cancer survival increases in Europe, but international differences remain wide.

The EUROCARE project analysed cancer survival data from 45 population-based cancer registries in 17 European countries, revealing wide international differences in cancer survival. We calculated 5-year relative survival for 1836287 patients diagnosed with one of 13 cancers during the period 1978-1989. The data, from 20 cancer registries in 13 countries, were grouped into four regions: Finland, Sweden, Iceland (Northern Europe); Denmark, England and Scotland (UK and Denmark); France, The Netherlands, Germany, Italy and Switzerland (Western Europe); Estonia and Poland (Eastern Europe), and broken down into four periods (1978-1980, 1981-1983, 1984-1986, 1987-1989). For each cancer, mean European and regional survival was estimated as the weighted mean of 5-year relative survival in each country. Survival increased with time for all tumours, particularly for cancers of testis (12% increase, i.e. from 79.9 to 91.9%), breast, large bowel, skin melanoma (approximately 9-10%), and lymphomas (approximately 7%). For most solid tumours, survival was highest in Northern Europe and lowest in Eastern Europe, and also low in the UK and Denmark. Regional variation was less marked for the lymphomas. Survival improved more in Western than Northern Europe, and the differences between these regions fell for bowel cancer (from 8.0% for those diagnosed in 1978-1980 to 2% for those diagnosed in 1987-1989), breast cancer (from 7.4% to 3.9%), skin melanoma (from 13.4% to 11.0%) and Hodgkin's disease (from 7.2 to 0.6%). For potentially curable malignancies such as Hodgkin's disease, large bowel, breast and testicular cancers, there were substantial increases in survival, suggesting an earlier diagnosis and more effective treatment. The persisting regional differences suggest there are corresponding differences in the availability of diagnostic and therapeutic facilities, and in the effectiveness of healthcare systems.

Adolescent↗

Monitoring the changing pattern of esophago-gastric cancer: data from a UK regional cancer registry.

OBJECTIVES: The aim of this study was to evaluate the reliability and adequacy of the existing system of cancer registration in the United Kingdom to monitor past and future trends in esophago-gastric cancer incidence. METHODS: The Northern and Yorkshire UK Cancer Registry was interrogated for all cases of esophageal and gastric cancer occurring between 1984 and 1993. Data concerning year of registration, subsite, histology, sex, and ages were recorded and analyzed. RESULTS: A total of 22,300 cases were identified from an estimated population of 6.7 million. The overall age- and sex-standardized incidence of gastric cancer fell over the 10-year period from 12.8 to 10.5 per 100,000 (p < 0.001) while esophageal cancer increased from 4.6 to 5.4 cases per 100,000 (p = 0.006). Adenocarcinoma of the gastric cardia increased in proportion from 29.1% to 52.2% (p < 0.0001), 70.4% of esophageal and 71% of gastric cancer registrations were recorded without details of subsite. For 25% of esophageal cancers and 36% of gastric cancers there was no histological information. CONCLUSIONS: While the trend toward an increasing incidence of adenocarcinoma at the esophago-gastric junction reported in earlier studies appears to be confirmed, the high incidence of imprecise subsite reporting of cancer registry data illustrated in this study should make us look critically at the findings of other cancer registry data. Recognition of cancer of the esophago-gastric junction as distinct from other gastric and esophageal subsites may improve accuracy of recording and allow cancer registry data to more accurately monitor the changes in esophagogastric cancer incidence in subsequent analyses.

Adenocarcinoma↗

Levels of malondialdehyde-deoxyguanosine in the gastric mucosa: relationship with lipid peroxidation, ascorbic acid, and Helicobacter pylori.

Helicobacter pylori infection is associated with elevated gastric mucosal concentrations of the lipid peroxidation product malondialdehyde and reduced gastric juice vitamin C concentrations. Malondialdehyde can react with DNA bases to form the mutagenic adduct malondialdehyde-deoxyguanosine (M(1)-dG). We aimed to determine gastric mucosal levels of M(1)-dG in relation to H. pylori infection and malondialdehyde and vitamin C concentrations. Patients (n = 124) attending for endoscopy were studied. Levels of antral mucosal M(1)-dG were determined using a sensitive immunoslot-blot technique; antral mucosal malondialdehyde was determined by thiobarbituric acid extraction, and gastric juice and antral mucosal ascorbic acid and total vitamin C were determined by high-performance liquid chromatography. Sixty-four H. pylori-positive patients received eradication therapy, and endoscopy was repeated at 6 and 12 months. Levels of M(1)-dG did not differ between subjects with H. pylori gastritis (n = 85) and those with normal mucosa without H. pylori infection (n = 39; 56.6 versus 60.1 adducts/10(8) bases) and were unaffected by age or smoking habits. Malondialdehyde levels were higher (123.7 versus 82.5 pmol/g; P < 0.001), gastric juice ascorbic acid was lower (5.7 versus 15.0 micromol/ml; P < 0.001), and antral mucosal ascorbic acid was unchanged (48.0 versus 42.7 micromol/g) in H. pylori gastritis compared with normal mucosa. Multiple regression analysis revealed that M(1)-dG increased significantly with increasing levels of malondialdehyde, antral ascorbic acid, and total antral vitamin C. M(1)-dG levels were unchanged 6 months (63.3 versus 87.0 adducts/10(8) bases; P = 0.24; n = 38) and 12 months (66.7 versus 77.5 adducts/10(8) bases; P = 0.8; n = 13) after successful eradication of H. pylori. M(1)-dG thus is detectable in gastric mucosa, but is not affected directly by H. pylori.

Adult↗

Systematic review and economic evaluation of Helicobacter pylori eradication treatment for non-ulcer dyspepsia. Dyspepsia Review Group.

OBJECTIVES: To evaluate efficacy and cost effectiveness of Helicobacter pylori eradication treatment in patients with non-ulcer dyspepsia infected with H pylori. DESIGN: Systematic review of randomised controlled trials comparing H pylori eradication with placebo or another drug treatment. Results were incorporated into a Markov model comparing health service costs and benefits of H pylori eradication with antacid treatment over one year. DATA SOURCES: Six electronic databases were searched for randomised controlled trials from January 1966 to May 2000. Experts in the field, pharmaceutical companies, and journals were contacted for information on any unpublished trials. Trial reports were reviewed according to predefined eligibility and quality criteria. MAIN OUTCOME MEASURES: Relative risk reduction for remaining dyspeptic symptoms (the same or worse) at 3-12 months. Cost per dyspepsia-free month estimated from Markov model based on estimated relative risk reduction. RESULTS: Twelve trials were included in the systematic review, nine of which evaluated dyspepsia at 3-12 months in 2541 patients. H pylori eradication treatment was significantly superior to placebo in treating non-ulcer dyspepsia (relative risk reduction 9% (95% confidence interval 4% to 14%)), one case of dyspepsia being cured for every 15 people treated. H pylori eradication cost pound56 per dyspepsia-free month during first year after treatment. CONCLUSION: H pylori eradication may be cost effective treatment for non-ulcer dyspepsia in infected patients but further evidence is needed on decision makers' willingness to pay for relief of dyspepsia.

Antacids↗

Prospective study of cyclin D1 overexpression in Barrett's esophagus: association with increased risk of adenocarcinoma.

BACKGROUND: Esophageal adenocarcinoma commonly arises from a precancerous condition, Barrett's esophagus, in which the normal squamous epithelium is replaced by a columnar cell-lined epithelium. Genetic alterations occurring in this process could serve as biomarkers for the risk of malignant progression, improve surveillance, and contribute to early diagnosis. We examined two potential biomarkers, cyclin D1 and p53, in a prospective cohort of Barrett's esophagus patients. METHODS: A total of 307 patients were enrolled in an endoscopic surveillance cohort, and esophageal biopsy specimens were collected at each endoscopy. Incident cases of adenocarcinoma were matched to control patients within the cohort by duration of follow-up, age, sex, and length of columnar cell-lined epithelium at recruitment. Biopsy specimens were analyzed for cyclin D1 and p53 protein levels by immunohistochemistry. Statistical tests were two-sided. RESULTS: A total of 12 cases of adenocarcinoma occurred within the follow-up period, and tumor biopsy specimens from 11 cases stained positive for cyclin D1. Biopsy specimens from eight of these patients taken at recruitment also stained positive for cyclin D1. A case-control analysis of biopsy specimens obtained at recruitment revealed a statistically significantly increased risk of progression to adenocarcinoma in Barrett's esophagus patients whose biopsy specimens were cyclin D1 positive (odds ratio [OR] = 6. 85; 95% confidence interval [CI] = 1.57-29.91; P =.0106) but not in patients whose biopsy specimens were p53 positive (OR = 2.99; 95% CI = 0.57-15.76; P =.197). CONCLUSIONS: Cyclin D1-positive staining could be a useful biomarker in identifying Barrett's esophagus patients at high risk of esophageal adenocarcinoma. Given the complexity of genetic alterations in the natural history of this cancer, additional biomarkers will be required to increase the sensitivity and specificity of molecular diagnosis.

Adenocarcinoma↗