UK practice in the prevention of central venous catheter-associated thrombosis in adults on home parenteral nutrition.

BACKGROUND: Maintaining central access is imperative for the delivery of home parenteral nutrition (HPN) in those with intestinal failure. Methods to reduce central venous catheter infection are well recognised; however, the prevention of line thrombosis is less well studied. METHODS: This paper reviews the current evidence and reports a survey of current practice within the UK. Using an electronic survey, respondents were asked to detail their use of anticoagulation in different patient groups and the type of anticoagulation used. RESULTS: 41 replies were received from 31 centres. Only one responder used low-dose warfarin routinely; 80% however anticoagulated those with a previous line thrombosis and 65% anticoagulated those that had any deep vein thrombosis or pulmonary embolus. The most commonly used anticoagulant was dose-adjusted warfarin aiming for an international normalised ratio of 2-3. CONCLUSIONS: The evidence from the current literature in both HPN and the wider field is that there is no clear evidence that anticoagulation is either beneficial or harmful in the prevention of line thrombosis. This survey suggested that practice is varied across the UK likely reflecting the lack of evidence within the current literature.

Use of parenteral nutrition in hospitals in the North of England.

BACKGROUND: Parenteral nutrition (PN) is a costly technology used widely to provide nutrition to patients who have an inaccessible or nonfunctioning intestine. A prospective survey was designed to collect data on PN for inpatients to study the current use of PN, its complications and outcomes in the north of England. The study objectives were to use the Northern Nutrition Network to collect data from all acute hospital inpatients prospectively receiving PN, for 3 months and to provide evidence for current PN practice, and to establish whether this is in line with recognized published clinical guidelines. METHODS: Using a paper-based collection tool information was recorded on aspects of PN including: total inpatient episodes, patient demographics, indications, duration, venous access used, complications, number returning to enteral feeding and mortality. The presence of a nutrition support team was also recorded. RESULTS: Data on 193 patient PN episodes were recorded totalling 1708 patient days. The median age of the patients was 67 years. Of these, 158 (82%) were deemed to have a clear indication for PN using the indications cited in the NICE guidelines (http://www.nice.org.uk). The median duration of PN was 7 days (range 1-93). Thirty (16%) patients developed complications due to PN, 23 (12%) had catheter infections which were most common on medical wards. Thirty-nine (20%) patients died within 28 days of PN starting; no deaths were attributable to PN. A total of 118 (61%) patients returned to full enteral feeding. Only three hospitals had nutrition support teams, which had no significant effect on outcomes. CONCLUSIONS: Parenteral nutrition practice in the north of England is generally in line with current guidelines, however, only three of 15 hospitals had nutrition support teams. Eighteen per cent of patients did not have a clearly documented indication for PN and 15% developed a complication, most often a catheter-related infection.

Influence of IL-6, COL1A1, and VDR gene polymorphisms on bone mineral density in Crohn's disease.

BACKGROUND: Osteoporosis is an important cause of morbidity in patients with Crohn's disease. The pathogenesis of reduced bone mineral density (BMD) is multifactorial. A range of genetic factors have been implicated in other populations of patients with osteoporosis. AIM: To investigate the influence of interleukin 6 (IL-6), collagen type 1alpha1 (COL1A1), and vitamin D receptor gene (VDR) single nucleotide polymorphisms (SNP) on BMD in patients with Crohn's disease. PATIENTS: A cohort of 245 well characterised patients with Crohn's disease were recruited from the inflammatory bowel disease register at the Freeman Hospital and Royal Victoria Infirmary, Newcastle upon Tyne, and the Queen Elizabeth Hospital, Gateshead, UK. METHODS: Patients were genotyped for IL-6 C-174G SNP, COL1A1 Sp1 binding site G T SNP, VDR Taq1, and Fok1 SNPs, and CARD15 R702W, G908R, and L1007fs SNPs. BMD was measured at the lumbar spine (LSP) and hip using dual energy x ray absorptiometry. RESULTS: A total of 158 female and 87 male patients, aged 24-70 years (mean 44), were recruited. There were no significant differences in the distribution of the tested SNPs when analysed for age, body mass index, pre/post-menopausal status, smoking, or steroid use. Two hundred and thirteen patients were genotyped for the IL-6 SNP. LSP and total hip BMD was significantly lower in patients with the GG genotype (48%) than the CC genotype (15%) (p = 0.041, p = 0.014). One hundred and eighty patients were genotyped for the COL1A1 SNP. There was no significant difference in BMD at LSP. Hip BMD was significantly lower in heterozygous patients compared with homozygous wild-types (p = 0.034). There were no significant differences in BMD between genotypes for the two VDR SNPs or the CARD15 genotypes examined. CONCLUSION: IL-6 and COL1A1 gene polymorphisms influence BMD in patients with Crohn's disease but the particular VDR gene polymorphisms studied do not have a major effect.

A randomized controlled trial of calcium with vitamin D, alone or in combination with intravenous pamidronate, for the treatment of low bone mineral density associated with Crohn's disease.

BACKGROUND: Osteoporosis is a common complication of Crohn's disease. AIM: To study the effect on the bone mineral density of a bisphosphonate (pamidronate) given intravenously, in combination with oral calcium and vitamin D supplements, compared with oral calcium and vitamin D supplements alone. METHODS: Seventy-four patients with Crohn's disease and low bone mineral density at the lumbar spine and/or hip were randomized to receive either a daily dose of 500 mg of calcium with 400 IU of vitamin D alone or in combination with four three-monthly infusions of 30 mg of intravenous pamidronate over the course of 12 months. The main outcome measure was the change in bone mineral density at the lumbar spine and hip, measured by dual X-ray absorptiometry, at baseline and 12 months. RESULTS: Both groups gained bone mineral density at the lumbar spine and hip after 12 months. There were significant (P < 0.05) changes in the pamidronate group, with gains of + 2.6%[95% confidence interval (CI), 1.4-3.0] at the spine and + 1.6% (95% CI, 0.6-2.5) at the hip, compared with gains of + 1.6% (95% CI, - 0.1-3.2) and + 0.9% (95% CI, - 0.4-2.1) at the spine and hip, respectively, in the group taking vitamin D and calcium supplements alone. CONCLUSIONS: In patients with Crohn's disease and low bone mineral density, intravenous pamidronate significantly increases the bone mineral density at the lumbar spine and hip.

Destruction of Escherichia coli O157:H7 and Salmonella enteritidis in cow manure composting.

Application of cow manure and composted manure in agricultural practice could potentially cause contamination of foodstuffs with pathogenic bacteria such as Salmonella Enteritidis and Escherichia coli O157:H7. In this study, rifampicin-resistant (RifR) E. coli O157:H7 and Salmonella Enteritidis at a level of 7 log CFU/g of raw compost feed were used to determine the effect of a bench-scale composting system on their survival. RifR E. coli O157:H7 was not detected after 72 h of composting at 45 degrees C, and RifR Salmonella Enteritidis was not detected after 48 h. The use of selective media for enrichment failed to recover in the composting samples held at 45 degrees C for 96 h. However, the pathogens showed no change in bacterial numbers when the composting system was held at room temperature. Thus, properly composted manure can be safely used in food crop production while minimizing the likelihood of microbial contamination.

Do gastric and oesophageal varices bleed at different portal pressures and is TIPS an effective treatment?

BACKGROUND: It has been suggested that gastric varices bleed at lower portosystemic pressure gradients (PSPG) than oesophageal varices and that transjugular intrahepatic portosystemic shunt (TIPS) is a particularly effective treatment in these patients. AIMS: This study was undertaken to assess the difference in PSPG measured at the time of TIPS insertion between patients bleeding from gastric and those bleeding from oesophageal varices. Rebleeding and mortality rates between the two groups were also compared. PATIENTS AND METHODS: In a five year period, 64 patients (36 males and 28 females) undergoing TIPS for acute variceal bleeding had PSPG measured at the time of TIPS insertion. 12 patients underwent TIPS for gastric variceal haemorrhage (GVH) and 52 for oesophageal variceal haemorrhage (OVH). The median age was 53 years and 40/64 patients (63%) had alcoholic liver disease. The median Child's Pugh score was 8 for GVH and 9 for OVH patients. Median follow up was 75 weeks. RESULTS: There was no significant difference in median PSPG between patients with GVH, 21 mmHg (range 15-30 mmHg) and OVH, 22 mmHg (range 12-45 mmHg). Following TIPS, PSPG was 8.5 mmHg (range 3-11 mmHg) and 9 mmHg (range 4-20 mmHg) in GVH and OVH patients respectively. Rebleeding occurred in 2/12 (16%) GVH patients and 12/52 (23%) OVH patients (p= 1.0). Mortality during follow up was 25% (4/12) in the GVH and 25% (13/52) in the OVH patients. CONCLUSION: In this study, there was no difference between the pressures at which gastric and oesophageal varices bled. Rebleeding and mortality rates were similar in the two groups. TIPS is equally effective in the treatment of both oesophageal and gastric variceal haemorrhage.

Early determinants of inflammatory bowel disease: use of two national longitudinal birth cohorts.

OBJECTIVE: To examine previously cited early risk factors for inflammatory bowel disease. DESIGN: The 1946 National Survey of Health & Development (NSHD) and the 1958 National Child Development Study (NCDS) are on-going, longitudinal birth cohort studies. A nested case-control design was used combining data from both cohorts; eight controls per case, matched for gender and social class, were selected randomly. METHODS: Data concerning maternal infection in pregnancy (NCDS only), childhood infection (measles, mumps and whooping cough), birth order, appendicectomy, breast-feeding and measures of poor housing conditions in childhood were analysed. In both cohorts, the member's hospital physician or medical records were used to confirm the diagnosis. RESULTS: Twenty-six cases of Crohn's disease and 29 cases of ulcerative colitis were identified. No significant association was found between the development of Crohn's disease or ulcerative colitis and any of the studied factors. There was a trend that those with Crohn's disease were more likely not to have been breast-fed (OR 0.4, 95% CI 0.15-1.03) and not to have had an appendicectomy (OR < 1.00). The opposite was true of those with ulcerative colitis (OR 2.76, 95% CI 0.86-9.81 and OR 2.34, 95% CI 0.69-7.46, respectively). The prevalence of inflammatory bowel disease was 5.12/1000 by the age of 43 years in NSHD and 2.02-2.54/1000 by the age of 33 years in NCDS. CONCLUSIONS: The prevalence of inflammatory bowel disease in these cohorts is among the highest recorded in Europe. Childhood factors may be different for those with Crohn's disease and ulcerative colitis. These cohorts will be increasingly valuable data sources.

Measles vaccination and inflammatory bowel disease: a national British Cohort Study.

OBJECTIVE: Measles vaccination has been suggested as a risk for inflammatory bowel disease. Atypical age of measles infection has also been associated with Crohn's disease. This study was designed to examine the relationship of measles vaccination and age of measles vaccination with later inflammatory bowel disease. METHODS: A prospective population-based national birth cohort was used, of those born in 1 wk in April 1970 in Great Britain. The data are from 7616 responding members of the 1970 British Cohort Study with complete vaccination data, who were traced at age 26 yr. A diagnosis of Crohn's disease, ulcerative colitis, and diabetes mellitus (a control disease) was obtained by survey at age 26 yr, and confirmed by physicians. Vaccination data were from survey at age 5 yr. Measles and mumps infection data were obtained from the survey at age 10 yr. Adjustment was made for sex, household crowding in childhood, and father's social class at birth. RESULTS: No statistically significant association was found between measles vaccination status at 5 yr and Crohn's disease (adjusted odds ratio [OR] 0.67, 95% confidence interval [CI] 0.27-1.63), ulcerative colitis (adjusted OR 0.57, 95% CI 0.20-1.61), or diabetes (adjusted OR 0.75, 95% CI 0.33-1.74). There was a statistically significant trend (p = 0.040) with increasing age of measles vaccination for risk of Crohn' s disease, although this was based on very few cases vaccinated after age 2 yr. CONCLUSIONS: In this cohort, monovalent measles vaccination status is not associated with inflammatory bowel disease by age 26 yr. Older age at measles vaccination needs to be examined in other studies to confirm whether it is a genuine risk for Crohn's disease.

Patients consulting with Crohn's disease in primary care in England and Wales.

OBJECTIVE: To determine annual incidence and prevalence for patients consulting their GP because of Crohn's disease in England and Wales and compare demographic details with matched controls. DESIGN: We used the fourth Morbidity Statistics in General Practice study (MSGP-4) which covered 468 042 person-years during a 12-month period in 1991-92. METHODS: All GPs reporting a patient with Crohn's disease in MSGP-4 were sent a questionnaire to confirm the diagnosis and obtain supportive details (surgical, pathological, radiological and/or endoscopic). Data concerning ethnicity, social class, smoking status, living in an urban or rural environment and employment had been collected previously. Conditional logistic regression models were used to analyse the data for cases and matched controls. RESULTS: Three hundred and fifteen patients were reported to have Crohn's disease. Replies were obtained to 251 (80%) questionnaires. The diagnosis of Crohn's disease was confirmed in 184 cases (89%) and refuted in 23 cases (11%) -- details were unavailable for 44 patients. The mean age of patients was 44 years, the female:male ratio was 1.46:1, and 108 (59%) patients had required surgery. Thirty-three of 178 (18.5%) patients were diagnosed within the study period. Hence, this study detected a prevalence for consulting Crohn's disease of 54.6-59.8/100,000 and an annual incidence of 10.1-11.1/100,000 in 1991-92. No significant differences were found between cases (n = 291) and controls (n = 1682) with regard to ethnicity, social class, smoking or living in an urban/rural environment. Patients with Crohn's disease had similar employment levels as controls, but were significantly more likely to be registered as permanently sick, odds ratio 4.01 (CI 2.21-7.29). CONCLUSIONS: This national survey, including 1% of the population, suggests there are approximately 30,600 patients consulting their GP because of Crohn's disease in England and Wales, with 5700 new cases diagnosed per year.

Anti-tuberculosis medication and the liver: dangers and recommendations in management.

In the light of three deaths due to liver failure secondary to anti-tuberculosis therapy at the Royal Free Hospital, we have reviewed the current literature, and asked--How common is liver dysfunction with anti-tuberculosis medications and how might it be prevented? Anti-tuberculosis chemotherapy is associated with abnormalities in liver function tests in 10-25% of patients. Clinical hepatitis develops in about 3%, though estimates vary, and in these patients there is likely to be significant morbidity and mortality. On the basis of reported cases of tuberculosis, 160 patients in England and Wales can be expected to develop drug-induced hepatitis due to anti-tuberculosis therapy each year. There are published guidelines from the British and American Thoracic Societies regarding the choice of drug therapy for tuberculosis. Current recommendations with regard to monitoring liver function, and what to do when these tests become abnormal, vary considerably. We suggest a protocol for using liver function tests to monitor for liver damage, and give recommendations on what action to take when these become abnormal.

Hepatocellular carcinoma arising in non-cirrhotic haemochromatosis.

Hepatocellular carcinoma arising in a patient with genetic haemachromatosis, without cirrhosis, has only been described once previously. We present a patient with a 15 year history of genetic haemachromatosis who underwent resection of a hepatocellular carcinoma in a liver with normal architecture.

Perinatal and childhood risk factors for inflammatory bowel disease: a case-control study.

OBJECTIVE: To determine whether exposure to a measles epidemic in utero or in infancy is a risk factor for the development of Crohn's disease, and to determine whether such an association can be found in individuals with subacute sclerosing panencephalitis (SSPE), a condition in which early infection with measles is known to be of aetiological importance. METHODS: A postal questionnaire was sent to 16,875 members of two national inflammatory bowel disease patient support groups. A control group was composed of friends or neighbours. Birth data were compared with the dates of measles epidemics and six possible periods of susceptibility were examined. Birth data from a national register of patients with SSPE were analysed similarly. Previously identified risk factors were also examined. RESULTS: The answers from 2522 members and 2379 controls were analysed. We found no evidence of an association between the development of Crohn's disease and exposure to a measles epidemic. The birth dates of both groups were distributed normally throughout the year. No other early risk factor for the development of inflammatory bowel disease was detected. Exposure to a measles epidemic before the age of 1 year did not emerge as a risk factor for SSPE. CONCLUSION: These data contradict reports from a recent study in central Sweden, but relatively early exposure to measles in childhood may still be a risk factor for the development of Crohn's disease.

Inherited disorders of coagulation appear to protect against inflammatory bowel disease.

BACKGROUND/AIMS: Crohn's disease and ulcerative colitis seem to be rarely associated with inherited diseases of coagulation. Histological and hematologic studies suggest that thrombotic mesenteric microvascular occlusion is involved in the pathogenesis of inflammatory bowel disease. The aim of this study was to perform a national survey to determine the prevalence of inflammatory bowel disease among patients with inherited disorders of coagulation. METHODS: Using a postal and telephone questionnaire survey sent to directors of all 129 hemophilia centers in the United Kingdom, the number of patients with inflammatory bowel disease and either hemophilia or von Willebrand's disease was determined. The expected number of cases of inflammatory bowel disease in this population was estimated using published data. RESULTS: Of 6433 patients with hemophilia and 3129 patients with von Willebrand's disease, 4 cases of Crohn's disease were reported compared with expected 11.97-16.58 cases (standardized morbidity ratio, 0.33-0.24; 95% confidence interval, 0.90-0.01; P < 0.05). Ulcerative colitis also occurred significantly less frequently than expected: 9 observed cases in comparison with expected 19.43-31.35 cases (standardized morbidity ratio, 0.46-0.29; 95% confidence interval, 0.91-0.01; P < 0.025). CONCLUSIONS: This epidemiological study provides further evidence that thrombosis and vascular occlusion may be important in the pathogenesis of inflammatory bowel disease.

Is measles vaccination a risk factor for inflammatory bowel disease?

Measles virus may persist in intestinal tissue, particularly that affected by Crohn's disease, and early exposure to measles may be a risk factor for the development of Crohn's disease. Crohn's disease and ulcerative colitis occur in the same families and may share a common aetiology. In view of the rising incidence of inflammatory bowel disease (Crohn's disease and ulcerative colitis), we examined the impact of measles vaccination upon these conditions. Prevalences of Crohn's disease, ulcerative colitis, coeliac disease, and peptic ulceration were determined in 3545 people who had received live measles vaccine in 1964 as part of a measles vaccine trial. A longitudinal birth cohort of 11,407 subjects was one unvaccinated comparison cohort, and 2541 partners of those vaccinated was another. Compared with the birth cohort, the relative risk of developing Crohn's disease in the vaccinated group was 3.01 (95% CI 1.45-6.23) and of developing ulcerative colitis was 2.53 (1.15-5.58). There was no significant difference between these two groups in coeliac disease prevalence. Increased prevalence of inflammatory bowel disease, but not coeliac disease or peptic ulceration, was found in the vaccinated cohort compared with their partners. These findings suggest that measles virus may play a part in the development not only of Crohn's disease but also of ulcerative colitis.