Real-time polymerase chain reaction correlates well with clinical diagnosis of Clostridium difficile infection.

AIM: To determine the clinical utility of a rapid molecular assay for Clostridium difficile infection (CDI) in an acute hospital setting. METHODS: From March to September 2011, stool specimens from inpatients in two acute hospitals with suspected CDI were tested prospectively by routine cell culture cytotoxin neutralization assay (CCNA), real-time polymerase chain reaction (PCR) using the GeneXpert (Cepheid Inc., Sunnyvale, CA, USA), and a dual testing algorithm [glutamate dehydrogenase (GDH)/toxin enzyme immuno-assay, Premier, Launch Diagnostics, Longfield, UK]. All patients with positive PCR, CCNA or discrepant results were reviewed by a multi-disciplinary team (treating clinician, gastroenterologist, microbiologist and infection control nurse). RESULTS: C. difficile detection rates were 11.7% (PCR), 6% (CCNA) and 13.8% (GDH). Out of 1034 stool specimens included in the study, 974 (94.1%) had concordant CCNA and PCR results. Eighty-nine percent (886/985) had concordant CCNA, PCR and GDH results, and 94.4% (930/985) had concordant GDH and PCR results. Using clinical diagnosis as the reference, PCR had sensitivity of 99.1%, specificity of 98.9%, positive predictive value (PPV) of 91.9% and negative predictive value (NPV) of 99.9%. CCNA on a single sample had sensitivity of 51%, specificity of 99.4%, PPV of 91.9% and NPV of 94.3%. GDH had sensitivity of 83.8%, specificity of 94.5%, PPV of 64.7% and NPV of 97.9%. Almost twice as many patients were positive by PCR compared with CCNA (121 vs 62); 54/59 of those with discrepant results were clinically confirmed as CDI. CONCLUSION: Rapid diagnosis of CDI using PCR was timely, accurate and correlated well with clinical diagnosis.

A Randomised, Cross-Over, Placebo-Controlled Study of Aloe vera in Patients with Irritable Bowel Syndrome: Effects on Patient Quality of Life.

Background. Irritable bowel syndrome (IBS) is a chronic, difficult to treat condition. The efficacy of Aloe vera in treating IBS symptoms is not yet proven. The purpose of this study was to determine if Aloe vera is effective in improving quality of life. Methods. A multicentre, randomised, double-blind, cross-over placebo controlled study design. Patients were randomised to Aloe vera, wash-out, placebo or placebo, washout, Aloe vera. Each preparation (60 mL) was taken orally twice a day. Patient quality of life was measured using the Gastrointestinal Symptoms Rating Score, Irritable Bowel Syndrome Quality of Life, EuroQol and the Short-Form-12 at baseline and treatment periods 1 and 2. Results. A total of 110 patients were randomised, but only 47 completed all questionnaires and both study arms. Statistical analysis showed no difference between the placebo and Aloe vera treatment in quality of life. Discussion. This study was unable to show that Aloe vera was superior to placebo in improving quality of life. Drop outs and other confounding factors may have impacted on the power of the study to detect a clinically important difference. Conclusion. This study failed to find Aloe vera superior to placebo in improving quality of life proven Irritable Bowel Syndrome patients.

Prospective study of liver dysfunction in pregnancy in Southwest Wales.

BACKGROUND: Liver dysfunction in pregnancy has serious consequences. Its frequency and characteristics have not been systematically documented in Britain. We have prospectively determined incidence, causes, and outcome of liver dysfunction in pregnancy in an obstetric unit in Southwest Wales, UK. METHODS: A central laboratory identified all abnormal liver tests (bilirubin >25 micro mol/l, aspartate transaminase >40 U/l, or gamma glutamyl transpeptidase >35 U/l) from patients in antenatal clinics and wards of an obstetric unit serving a population of 250 000. Patients with abnormal liver tests were assessed and followed throughout and after pregnancy [corrected]. Medical advice was provided to obstetric teams. FINDINGS: There were 4377 deliveries during the 15 month study. A total of 142 patients had abnormal liver tests. There were 206 contributing diagnoses, the great majority being pregnancy specific. Among the most important were pre-eclampsia (68), HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome (30), obstetric cholestasis (23), hyperemesis gravidarum (11), acute fatty liver of pregnancy (five), and hepatic infarct (one). Sepsis, postoperative factors, and placental pathology (51) were not uncommonly responsible but incidental or pre-existing hepatobiliary disease was infrequent (17). Sixty five patients were delivered early by induction or caesarean section because of liver dysfunction. Despite substantial liver related morbidity, there were no maternal deaths and only two intrauterine deaths. CONCLUSIONS: Liver dysfunction was seen in 3% of deliveries during a 15 month prospective study and was usually directly related to pregnancy with spontaneous recovery in the puerperium. Incidence of the most serious conditions, acute fatty liver of pregnancy and HELLP syndrome, was much greater than previously reported. Profound effects on maternal and infant health were observed but close medical and obstetric collaboration ensured low mortality.

Enteric-release glyceryl trinitrate in active Crohn's disease: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Mucosal ischaemia may contribute to the pathogenesis of Crohn's disease. Microvascular abnormalities have been found in colonic resection specimens, and mucosal levels of constitutive nitric oxide synthase are reduced. AIM: To assess the efficacy of a novel, enteric-release formulation of the nitric oxide donor, glyceryl trinitrate, aimed at increasing the mucosal circulation and relaxing smooth muscle in the affected bowel. METHODS: The trial was randomized, double-blind and placebo-controlled. Baseline disease activity was assessed by a structured symptom diary, with blood tests and a quality of life assessment. Patients with a Crohn's disease activity index of > or = 150 and < 450 were randomized to receive 12 weeks of either glyceryl trinitrate (initially 6 mg twice daily, increasing to 9 mg twice daily after 6 weeks) or an identical placebo. Assessments were repeated at 6 and 12 weeks. RESULTS: Seventy patients (22 male) entered the study; 34 were given glyceryl trinitrate and 36 placebo. At 12 weeks, there were no differences between the treatment groups in terms of Crohn's disease activity index, pain, stool frequency, inflammatory markers or quality of life scores. CONCLUSIONS: Enteric-release glyceryl trinitrate did not benefit patients with mild to moderately active Crohn's disease. Whilst ischaemia may contribute to the pathogenesis of Crohn's disease, our results fail to provide supportive evidence for this hypothesis.

Scoring systems and risk assessment for upper gastrointestinal bleeding.

Mortality associated with acute upper gastrointestinal bleeding remains high despite advances in diagnosis and therapy. This was emphasized by the findings of the seminal English National Audit of acute gastrointestinal haemorrhage undertaken by Rockall and associates in the mid-1990s. The apparent lack of progress is largely due to less selective reporting in an ageing population with greater co-morbidity. Thus some deaths will be unavoidable even with exemplary treatment. Managing high risk patients in a dedicated area with close cooperation between medical and surgical gastroenterologists has been shown to improve outcome. The challenge is to select those patients who have most to gain from such a scarce and expensive resource so that their treatment can be optimized. Various risk factors have been identified to help achieve this end. Rockall's national audit data suggest that avoidable deaths remain a problem in most district general hospitals. A simple numerical score was derived from these audit data (Rockall score) to predict rebleeding and mortality. The score is based on five variables: age, shock, co-morbidity, endoscopic diagnosis and stigmata of recent haemorrhage. It has the advantage that pre-endoscopic assessment can be made by inexperienced medical or nursing staff. The system was validated internally in a second audit by Rockall and co-workers, and subsequent external validation has come from New Zealand and the Netherlands. The score is less reliable at predicting rebleeding than death and so is, as yet, an imperfect instrument. The scoring system has also proven valuable in selecting low risk patients for early discharge (resulting in health care economies) and for comparing outcome data from different hospitals or populations. Endoscopic treatment has recently been shown to reduce rebleeding rates and perhaps mortality. These advances in therapy are becoming more widely adopted and may influence the predictive ability of the Rockall score. The study from Edinburgh, in this issue, although small and with wide confidence intervals, supports the ability of the Rockall score to identify high risk cases amongst those given endoscopic treatment. It also suggests that an adjustment of the score may be required in these circumstances to prevent overcalling the risk of rebleeding and death.