Lilian S. Murray

Symptomatic Benefit from Eradicating Helicobacter pylori Infection in Patients with Nonulcer Dyspepsia

BACKGROUND The eradication of Helicobacter pylori infection is beneficial in patients with gastric or duodenal ulcers. The value of eradicating the infection in patients with dyspepsia and no evidence of ulcer disease is not known. METHODS We performed a randomized, placebo-controlled trial comparing the efficacy of treatment for two weeks with 20 mg of omeprazole orally twice daily, 500 mg of amoxicillin three times daily (with 500 mg of tetracycline three times daily substituted for amoxicillin in patients allergic to penicillin), and 400 mg of metronidazole three times daily (160 patients) with that of omeprazole alone (158 patients) for resolving symptoms of dyspepsia in patients with H. pylori infection but no evidence of ulcer disease on upper gastrointestinal endoscopy. Symptoms were assessed with the Glasgow Dyspepsia Severity Score, with resolution of symptoms defined as a score of 0 or 1 in the preceding six months (maximal score, 20). One year later the patients were assessed to determine the frequency of the resolution of symptoms. RESULTS One month after the completion of treatment, 132 of 150 patients (88 percent) in the group assigned to received omeprazole and antibiotics had a negative test for H. pylori, as compared with 7 of 152 (5 percent) in the group assigned to receive omeprazole alone. One year later, dyspepsia had resolved in 33 of 154 patients (21 percent) in the group given omeprazole and antibiotics, as compared with 11 of 154 (7 percent) in the group given omeprazole alone (95 percent confidence interval for the difference, 7 to 22 percent; P<0.001). Among the patients in the group given omeprazole and antibiotics, the symptoms resolved in 26 of the 98 patients (27 percent) who had had symptoms for five years or less, as compared with 7 of the 56 patients (12 percent) who had had symptoms for more than five years (P=0.03). CONCLUSIONS In patients with H. pylori infection and nonulcer, or functional, dyspepsia, treatment with omeprazole and antibiotics to eradicate the infection is more likely to resolve symptoms than treatment with omeprazole alone.

Increased prevalence of precancerous changes in relatives of gastric cancer patients: critical role of H. pylori

BACKGROUND & AIMS Helicobacter pylori is believed to predispose to gastric cancer by inducing gastric atrophy and hypochlorhydria. First-degree relatives of patients with gastric cancer have an increased risk of developing gastric cancer. The aim of this study was to determine the prevalence of atrophy and hypochlorhydria and their association with H. pylori infection in first-degree relatives of patients with gastric cancer. METHODS H. pylori status, gastric secretory function, and gastric histology were studied in 100 first-degree relatives of patients with noncardia gastric cancer and compared with those of controls with no family history of this cancer. RESULTS Compared with healthy controls, relatives of patients with gastric cancer had a higher prevalence of hypochlorhydria (27% vs. 3%) but a similar prevalence of H. pylori infection (63% vs. 64%). Relatives of cancer patients also had a higher prevalence of atrophy (34%) than patients with nonulcer dyspepsia (5%) matched for H. pylori prevalence. Among the relatives of cancer patients, the prevalence of atrophy and hypochlorhydria was increased only in those with evidence of H. pylori infection, was greater in relatives of patients with familial cancer than in relatives of sporadic cancer index patients, and increased with age. Eradication of H. pylori infection produced resolution of the gastric inflammation in each subject and resolution of hypochlorhydria and atrophy in 50% of the subjects. CONCLUSIONS Relatives of patients with gastric cancer have an increased prevalence of precancerous gastric abnormalities, but this increase is confined to those with H. pylori infection. Consequently, prophylactic eradication of the infection should be offered to such subjects.

Analysis of factors predictive of mortality in alcoholic hepatitis and derivation and validation of the Glasgow alcoholic hepatitis score

Introduction: Alcoholic hepatitis is associated with a high short term mortality. We aimed to identify those factors associated with mortality and define a simple score which would predict outcome in our population. Methods: We identified 241 patients with alcoholic hepatitis. Clinical and laboratory data were recorded on the day of admission (day 1) and on days 6–9. Stepwise logistic regression was used to identify variables related to outcome at 28 days and 84 days after admission. These variables were included in the Glasgow alcoholic hepatitis score (GAHS) and its ability to predict outcome assessed. The GAHS was validated in a separate dataset of 195 patients. Results: The GAHS was derived from five variables independently associated with outcome: age (p = 0.001) and, from day 1 results, serum bilirubin (p<0.001), blood urea (p = 0.019) and, from day 6–9 results, serum bilirubin (p<0.001), prothrombin time (p = 0.002), and peripheral blood white blood cell count (p = 0.001). The GAHS on day 1 had an overall accuracy of 81% when predicting 28 day outcome. In contrast, the modified discriminant function had an overall accuracy of 49%. Similar results were found using information at 6–9 days and when predicting 84 day outcome. The accuracy of the GAHS was confirmed by the validation study of 195 patients The GAHS was equally accurate irrespective of the use of the international normalised ratio or prothrombin time ratio, or if the diagnosis of alcoholic hepatitis was biopsy proven or on the basis of clinical assessment. Conclusions: Using variables associated with mortality we have derived and validated an accurate scoring system to assess outcome in alcoholic hepatitis. This score was able to identify patients at greatest risk of death throughout their admission.

Spreading depolarisations and outcome after traumatic brain injury: a prospective observational study

BACKGROUND Pathological waves of spreading mass neuronal depolarisation arise repeatedly in injured, but potentially salvageable, grey matter in 50-60% of patients after traumatic brain injury (TBI). We aimed to ascertain whether spreading depolarisations are independently associated with unfavourable neurological outcome. METHODS We did a prospective, observational, multicentre study at seven neurological centres. We enrolled 109 adults who needed neurosurgery for acute TBI. Spreading depolarisations were monitored by electrocorticography during intensive care and were classified as cortical spreading depression (CSD) if they took place in spontaneously active cortex or as isoelectric spreading depolarisation (ISD) if they took place in isoelectric cortex. Investigators who treated patients and assessed outcome were masked to electrocorticographic results. Scores on the extended Glasgow outcome scale at 6 months were fitted to a multivariate model by ordinal regression. Prognostic score (based on variables at admission, as validated by the IMPACT studies) and spreading depolarisation category (none, CSD only, or at least one ISD) were assessed as outcome predictors. FINDINGS Six individuals were excluded because of poor-quality electrocorticography. A total of 1328 spreading depolarisations arose in 58 (56%) patients. In 38 participants, all spreading depolarisations were classified as CSD; 20 patients had at least one ISD. By multivariate analysis, both prognostic score (p=0·0009) and spreading depolarisation category (p=0·0008) were significant predictors of neurological outcome. CSD and ISD were associated with an increased risk of unfavourable outcome (common odds ratios 1·56 [95% CI 0·72-3·37] and 7·58 [2·64-21·8], respectively). Addition of depolarisation category to the regression model increased the proportion of variance in outcome that could be attributed to predictors from 9% to 22%, compared with the prognostic score alone. INTERPRETATION Spreading depolarisations were associated with unfavourable outcome, after controlling for conventional prognostic variables. The possibility that spreading depolarisations have adverse effects on the traumatically injured brain, and therefore might be a target in the treatment of TBI, deserves further research. FUNDING US Army CDMRP PH/TBI research programme.

Randomised trial of endoscopy with testing for Helicobacter pylori compared with non-invasive H pylori testing alone in the management of dyspepsia

Abstract Objective: To compare the efficacy of non-invasive testing for Helicobacter pylori with that of endoscopy (plus H pylori testing) in the management of patients referred for endoscopic investigation of upper gastrointestinal symptoms. Design: Randomised controlled trial with follow up at 12 months. Setting: Hospital gastroenterology unit. Participants: 708 patients aged under 55 referred for endoscopic investigation of dyspepsia, randomised to non-invasive breath test for H pylori or endoscopy plus H pylori testing. Main outcome measure: Glasgow dyspepsia severity score at one year. Use of medical resources, patient oriented outcomes, and safety were also assessed. Results: In 586 patients followed up at 12 months the mean change in dyspepsia score was 4.8 in the non-invasive H pylori test group and 4.6 in the endoscopy group (95% confidence interval for difference −0.7 to 0.5, P=0.69). Only 8.2% of patients followed up who were randomised to breath test alone were referred for subsequent endoscopy. The use of non-endoscopic resources was similar in the two groups. Reassurance value, concern about missed pathology, overall patient satisfaction, and quality of life were similar in the two groups. The patients found the non-invasive breath test procedure less uncomfortable and distressing than endoscopy with or without sedation. No potentially serious pathology requiring treatment other than eradication of H pylori was missed. Conclusion: In this patient group, non-invasive testing for H pylori is as effective and safe as endoscopy and less uncomfortable and distressing for the patient. Non-invasive H pylori testing should be the preferred mode of investigation. What is already known on this topic Endoscopy is a commonly used investigation for upper gastrointestinal symptoms, but its effectiveness has been questioned Non-invasive testing for Helicobacter pylori has been shown to predict endoscopic diagnosis in patients with dyspepsia What this study adds In patients less than 55 years of age with uncomplicated dyspepsia, non-invasive testing for H pylori is as effective and as safe as endoscopy Non-invasive H pylori testing is as reassuring to the patient as endoscopy and is less uncomfortable and distressing

Neuropathology in vegetative and severely disabled patients after head injury

Objective: To discover if the neuropathology differs in head-injured patients who were in a vegetative state (VS) or were severely disabled at time of death. Methods: Review of 35 VS cases and 30 severely disabled cases treated in this institute in the acute stage, surviving at least a month; all brains were fixed for 3 weeks before full neuropathologic examination. Results: The severely disabled cases were older, had a higher incidence of skull fracture and of evacuated intracranial hematoma, and they had more cortical contusions. Diffuse axonal injury (DAI) was less common in the severely disabled cases, particularly its most severe grade. Structural damage in the thalamus was much less common in severely disabled cases. Half of the severely disabled patients had neither grade 2 or 3 DAI nor thalamic damage and 10 of these 15 cases did not have ischemic brain damage either. These combinations did not occur in a single VS case. However, some severely disabled cases had similar lesions to VS cases, and this included some patients who were in a minimally conscious state as well as some who were out of bed and mobile. Conclusions: Half the severely disabled cases had only focal brain damage, a feature not found in any VS cases. In the severely disabled patients with lesions similar to those of VS cases it is likely that a greater quantitative amount of damage occurred in the VS cases.

Randomised comparison of uterine artery embolisation (UAE) with surgical treatment in patients with symptomatic uterine fibroids (REST trial): 5-year results.

Please cite this paper as: Moss J, Cooper K, Khaund A, Murray L, Murray G, Wu O, Craig L, Lumsden M. Randomised comparison of uterine artery embolisation (UAE) with surgical treatment in patients with symptomatic uterine fibroids (REST trial): 5‐year results. BJOG 2011;118:936–944.

The Helicobacter pylori breath test: a surrogate marker for peptic ulcer disease in dyspeptic patients.

BACKGROUND: There is interest in noninvasive H pylori testing as a means of predicting diagnosis and determining management in dyspeptic patients. AIMS: To assess the value of the 14C urea breath test as a predictor of peptic ulcer disease in patients presenting with dyspepsia. PATIENTS AND METHODS: 327 consecutive patients referred for investigation of dyspepsia had a 14C urea breath test performed before endoscopy. Patients were not included if they had previously confirmed ulcer disease, previous gastric surgery, or were taking non-steroidal anti-inflammatory drugs. RESULTS: Of the 182 patients with a positive 14C urea breath test, duodenal and/or gastric ulcers were present in 45% and erosive duodenitis in a further 2%. Oesophagitis was present in 12% of the breath test positive patients with two thirds of the oesophagitis patients having co-existent ulcer disease. The prevalence of ulcer disease in the H pylori positive dyspeptic patients was independently related to smoking and previous investigation status. If previously uninvestigated, the prevalence of ulcers was 67% in smokers and 46% in non-smokers. If previous upper gastrointestinal investigations were negative, the prevalence of ulcers was 53% in smokers and 28% in non-smokers. Of the 136 patients with a negative breath test, only 5% had peptic ulcers. The most frequent endoscopic finding in these H pylori negative subjects was oesophagitis, being present in 17%. CONCLUSIONS: This study demonstrates that a positive H pylori test is a powerful predictor of the presence of underlying ulcer disease in dyspeptic patients, especially if smokers, and that a negative H pylori test is a powerful predictor of the absence of ulcer disease. It also indicates that a negative upper gastrointestinal investigation does not preclude subsequent presentation with ulcer disease.

Correlates of objectively measured physical activity and sedentary behaviour in English children

BACKGROUND Evidence on the correlates of objectively measured physical activity and sedentary behaviour in childhood is limited. This study aimed to identify correlates of physical activity and sedentary behaviour among 7-year-old children in England. METHODS Physical activity was measured using Actigraph accelerometry in 480 participants as part of the Gateshead Millennium Study during 2006-07. Twenty-two potential correlates across five domains (demographic and biological; psychological, cognitive and emotional; behavioural; social and cultural; physical environmental) were tested for associations with total volume of habitual physical activity, moderate-vigorous intensity physical activity (MVPA) and sedentary behaviour. Multiple linear regression analysis was used. RESULTS Seven correlates, including four that are potentially modifiable, were significantly associated with total physical activity, MVPA and sedentary behaviour in final models: gender, child weight status, maternal age, child interest in active play, active commuting to school, parenting practice and season. Four of these variables were significantly associated with all three constructs in final models. The final models explained 18, 18 and 24% of variance in total volume of physical activity, MVPA and sedentary behaviour, respectively. CONCLUSION A number of potentially modifiable factors are associated with increased physical activity and/or reduced sedentary behaviour in English children. These could be valuable targets of future interventions.

Development of a Traumatic Intracranial Hematoma after a “Minor” Head Injury

We have analyzed features of patients who had what appeared initially to be a minor head injury but who developed an acute traumatic intracranial hematoma. Over a 10-year period, 183 patients who were able to open their eyes spontaneously, were oriented to person, place, and time, and who obeyed commands when they were first seen at a hospital subsequently underwent operation for an acute intracranial hematoma. The hematoma was extradural in 54% of these patients. A history of altered consciousness or symptoms of headache and vomiting were present in 61% of the patients; 33% had a focal neurological deficit, and 43% had either focal deficit or signs of a basal skull fracture. A skull fracture was shown radiologically in 60% of patients, including 52% of those not clinically suspected of having an intracranial lesion. Six months after injury, 77% of the patients had made a moderate or good recovery. The possibility that a patient who has recently sustained a head injury might develop an acute intracranial hematoma can never be completely discounted, even when there are no abnormal clinical signs, and a skull x-ray retains a useful place in the investigation of selected patients with a minor head injury.