Family Pediatrician and Public Health collaboration, an alliance to increase vaccination coverage: an experience with MenB vaccination in Italy.

Background: Invasive Meningococcal Disease is a severe disease mainly affecting infants and young children. Most infections are caused by serogroups A, B, C, W, X, and Y. In the last 10 years, serogroup B has been the main cause of Invasive Meningococcal Disease in Europe. Recent data resulting from an observational study conducted in Italy show a significant reduction in the number of Invasive Meningococcal Disease cases due to Neisseria meningitidis B after the introduction of vaccine 4CMenB. Thus, the Naples Team of Federation of Italian Primary Care Pediatricians and the Public Health Department started an active collaboration focused on vaccination process management (named "Progetto Via") with the aim of increasing Meningococcal B vaccination coverage. Study design: Source of data is the regional platform "GE.VA.". Every Primary care Pediatrician uses daily to record vaccination activity. This platform is integrated with data entered by operators of the District/Vaccination Center. Methods: Time: January 2019 - December 2019. The Federation of Italian Primary Care Pediatricians/Naples organized a meeting to identify six coordinators. The pediatricians could choose to counsel in their own offices and send children to the vaccination center or to counsel and vaccinate directly in their own clinics. Results: A total of 78 pediatricians took part in the project: 46 did only counseling and 32 did both counseling and vaccination in their medical clinic. Data obtained show an overall average vaccination coverage growth of about 13% in the first 4 months of the survey, and a further growth of about 11% in the following seven months, with a total growth in the entire period of 24%. The pediatricians' counseling is essential to recover non-compliant subjects, considering both the relationship of trust with the families and the visits already scheduled as an ideal moment for vaccinations' status check. Conclusions: The project highlights how an effective collaboration between family pediatricians and the Local Health Authority becomes valuable in getting closer to reach the Ministerial goal of 95%. Vaccination coverage increased significantly when family pediatricians supported the activity of vaccine centers in distress in many regional situations. The trust relationship, the hourly availability and the capillary network of family pediatricians' clinics were key elements for the success of this project and were also recognized by parents.

Colon capsule endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

PillCam colon capsule endoscopy (CCE) is an innovative noninvasive, and painless ingestible capsule technique that allows exploration of the colon without the need for sedation and gas insufflation. Although it is already available in European and other countries, the clinical indications for CCE as well as the reporting and work-up of detected findings have not yet been standardized. The aim of this evidence-based and consensus-based guideline, commissioned by the European Society of Gastrointestinal Endoscopy (ESGE) is to furnish healthcare providers with a comprehensive framework for potential implementation of this technique in a clinical setting.

Diagnostic performance of Baveno IV criteria in cirrhotic patients with upper gastrointestinal bleeding: analysis of the F7 liver-1288 study population.

BACKGROUND & AIMS: The definition of failure to control bleeding agreed upon at the Baveno IV consensus meeting, included the Adjusted Blood Requirement Index [ABRI: number of blood units/(final-initial hematocrit+0.01)]. ABRI ≥0.75 denotes failure. However, timing for hematocrit measurements was not defined. The aims of this study were: (1) to assess the Baveno IV criteria performance to classify treatment success or failure to control bleeding at 5 days, (2) to determine the appropriate timing for hematocrit. METHODS: Two hundred and forty-two cirrhotic patients with gastrointestinal bleeding were independently classified by three clinical experts according to the Baveno IV criteria, by analysis of the database of a randomized trial. ABRI was calculated by using the closest hematocrit to the 5 day time point from the first trial product administration (ABRI-1) or after the latest transfusion within the 5-day period (ABRI-2). The gold standard for success/failure for 5-day control of bleeding was the clinical judgment of the three independent observers based on all the clinical and follow-up data. RESULTS: Inter-observer agreement for the final outcome assessment was 0.82 and a final consensus was obtained in 236/242 patients. Inter-observer agreement on patient classification with Baveno IV criteria was 0.70 with ABRI-1 and 0.84 with ABRI-2. c-statistics for correct patients classification were 0.86 for ABRI-1, 0.84 for ABRI-2, and 0.88 for Baveno IV criteria without ABRI. ABRI-1 caused misclassification of 27 patients and ABRI-2 of 39. CONCLUSIONS: Baveno IV criteria are accurate to assess outcome of patients with variceal bleeding. There is a substantial observer variability linked to timing of hematocrits for ABRI calculation. With the current definition ABRI does not add to the performance of the other criteria.

European Society of Gastrointestinal Endoscopy (ESGE): recommendations (2009) on clinical use of video capsule endoscopy to investigate small-bowel, esophageal and colonic diseases.

These recommendations on video capsule endoscopy, an emerging technology with an impact on the practice of endoscopy, were developed by the European Society of Gastrointestinal Endoscopy (ESGE) Guidelines Committee. The first draft of each section was prepared by one or two members of the writing team, who were selected as experts on the content of that section on the basis of their published work. They used evidence-based methodology, performing MEDLINE and PubMed literature searches to identify relevant clinical studies. Abstracts from scientific meetings were included only if there was no published full paper on a particular topic. If there was disagreement, the first author of the Guideline made the final decision. Recommendations were graded according to the strength of the supporting evidence. The draft guideline was critically reviewed by all authors and submitted to the ESGE councillors for their critical review before approval of the final document. The ESGE Guidelines Committee acknowledges that this document is based on a critical review of the data available at the time of preparation and that further studies may be needed to clarify some aspects. Moreover, this Guideline may be revised as necessary to account for changes in technology, new data, or other aspects of clinical practice. This document should be regarded as supplying recommendations only to gastroenterologists in providing care to their patients. It is not a set of rules and should not be construed as establishing a legal standard of care, or as encouraging, advocating, requiring, or discouraging any particular treatment. These recommendations must be interpreted according to the clinician's knowledge, expertise, and clinical judgment in the management of individual patients and, if necessary, a course of action that varies from recommendations must be undertaken.

Acute variceal bleeding: pharmacological treatment and primary/secondary prophylaxis.

Variceal bleeding is one of the most severe complications of portal hypertension related to liver cirrhosis. Primary prophylaxis is considered mandatory in patients with cirrhosis and high-risk oesophageal varices, and once varices have bled, every effort should be made to arrest the haemorrhage and prevent further bleeding episodes. In acute variceal bleeding, vasoactive drugs that lower portal pressure should be started even before endoscopy, and should be maintained for up to 5 days. The choice of vasoactive drug should be made according to local resources. Terlipressin, somatostatin and octreotide can be used; vasopressin plus transdermal nitroglycerin may be used if no other drug is available. In variceal bleeding, antibiotic therapy is also mandatory. In primary and secondary prophylaxis, beta-blockers are the mainstay of therapy. In secondary prophylaxis (but not in primary prophylaxis) these drugs can be combined with organic nitrates.

Small-bowel neoplasms in patients undergoing video capsule endoscopy: a multicenter European study.

BACKGROUND AND STUDY AIM: Small-bowel tumors account for 1% - 3% of all gastrointestinal neoplasms. Recent studies with video capsule endoscopy (VCE) suggest that the frequency of these tumors may be substantially higher than previously reported. The aim of the study was to evaluate the frequency, clinical presentation, diagnostic/therapeutic work-up, and endoscopic appearance of small-bowel tumors in a large population of patients undergoing VCE. PATIENTS AND METHODS: Identification by a questionnaire of patients with VCE findings suggesting small-bowel tumors and histological confirmation of the neoplasm seen in 29 centers of 10 European Countries. RESULTS: Of 5129 patients undergoing VCE, 124 (2.4%) had small-bowel tumors (112 primary, 12 metastatic). Among these patients, indications for VCE were: obscure gastrointestinal bleeding (108 patients), abdominal pain (9), search for primary neoplasm (6), diarrhea with malabsorption (1). The main primary small-bowel tumor type was gastrointestinal stromal tumor (GIST) (32%) followed by adenocarcinoma (20%) and carcinoid (15%); 66% of secondary small-bowel tumors were melanomas. Of the tumors, 80.6% were identified solely on the basis of VCE findings. 55 patients underwent VCE as the third procedure after negative bidirectional endoscopy. The lesions were single in 89.5% of cases, and multiple in 10.5%. Retention of the capsule occurred in 9.8% of patients with small-bowel tumors. After VCE, 54/124 patients underwent 57 other examinations before treatment; in these patients enteroscopy, when performed, showed a high diagnostic yield. Treatment was surgery in 95% of cases. CONCLUSIONS: Our data suggest that VCE detects small-bowel tumors in a small proportion of patients undergoing this examination, but the early use of this tool can shorten the diagnostic work-up and influence the subsequent management of these patients.

Antibodies to tissue-type plasminogen activator (t-PA) in patients with inflammatory bowel disease: high prevalence, interactions with functional domains of t-PA and possible implications in thrombosis.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have an increased prevalence of thromboembolic events. The pathogenetic mechanisms of these events include reduced fibrinolysis, which may be caused by antibodies to tissue-type plasminogen activator (t-PA). OBJECTIVES: To evaluate anti-t-PA antibodies in patients with IBD, considering clinical, biochemical and functional characteristics. PATIENTS AND METHODS: We immunoenzymatically measured anti-t-PA antibodies in plasma from 97 consecutive IBD patients and 97 age- and sex-matched healthy controls. We also assessed the antibody interactions with different epitopes of t-PA, the antibody inhibition on t-PA activity and the correlations with clinical features and other serum antibodies. RESULTS: IBD patients had higher median anti-t-PA antibody levels (5.4 U mL(-1) vs. 4.0 U mL(-1); P < 0.0001): 18 patients were above the 95th percentile of the controls (OR 5.3; 95% CI 1.7-16.3; P < 0.003), and the six with a history of thrombosis tended to have high levels (6.9 U mL(-1)). Anti-t-PA antibody levels did not correlate with IBD type, activity, location or treatment, or with age, sex, acute-phase reactants or other antibodies. The anti-t-PA antibodies were frequently IgG1 and bound t-PA in fluid phase; they recognized the catalytic domain in 10 patients and the kringle-2 domain in six. The IgG fraction from the three patients with the highest anti-t-PA levels slightly reduced t-PA activity in vitro. CONCLUSIONS: The prevalence of anti-t-PA antibodies is high in IBD patients. By binding the catalytic or kringle-2 domains of t-PA, these antibodies could lead to hypofibrinolysis and contribute to the prothrombotic state of IBD.

Use of the Given Patency System for the screening of patients at high risk for capsule retention.

BACKGROUND: Capsule enteroscopy is a non-invasive diagnostic tool for the study of the small bowel. Due to the risk of capsule retention, capsule enteroscopy is contraindicated in patients with suspected small bowel strictures. The Given Patency Capsule is a disintegration time-controlled capsule developed to identify patients with strictures that may cause capsule enteroscopy retention. The presence of the patency capsule within the patient's body can be detected by a radio-frequency scanner. AIM OF THE STUDY: To evaluate safety and usefulness of the patency capsule in preventing capsule retention in patients at high risk. PATIENTS AND METHODS: Thirty-two patients were studied. Indications for patency capsule were: (A) Crohn's disease (18), (B) previous intestinal surgery (7), (C) previous obstruction (1), A+B (3), A+C (1), B+C (2). Patients were evaluated with the scanner at 72 h from ingestion. RESULTS: At 72 h, 24 patients had already excreted the intact capsule in the stool. Of these, two experienced abdominal pain during capsule passage. In the other eight patients, the scanner detected the presence of the patency capsule. Four of them excreted the capsule intact in the stool after 72-96 h, the remaining four never found the capsule in the stool. The 26 patients who excreted the patency capsule intact without experiencing abdominal pain were deemed eligible for the capsule enteroscopy procedure, which was performed uneventfully in the 25 who agreed to undergo the examination. CONCLUSIONS: The patency capsule is useful to identify, among patients at high risk, those who can be submitted to capsule enteroscopy without risks of capsule retention.

Carriage of CARD15 variants and smoking as risk factors for resective surgery in patients with Crohn's ileal disease.

BACKGROUND: It is controversial whether CARD15 variants are truly associated with a more severe form of Crohn's disease. The relative role of CARD15 genotype and smoking in Crohn's disease progression is also debated. AIM: To investigate the association between CARD15 variants and history of resective surgery in patients with Crohn's ileal disease, taking into account smoking as a possible confounding factor. METHODS: We originally assessed CARD15 genotype in 239 north Italian Crohn's disease patients (mean follow-up: 10.1 +/- 8.1 years). We then focused on 193 patients with proven ileal involvement, 70 of whom (36.3%) carried CARD15-mutated alleles (G908R, R702W, L1007fs). RESULTS: Carriage of CARD15 variants was positively associated with family history and ileal-only disease and negatively associated with uncomplicated behaviour at maximal follow-up (P < 0.05). Ileal resection was the only variable independently associated with CARD15 variants at multivariate analysis (OR 3.8; 95% CI 1.6-9.2; P = 0.003). Kaplan-Meier analysis showed that ileal resection was favoured both by CARD15 variant-carriage (P = 0.01) and by smoking (P = 0.05), but smoking did not affect progression to surgery in variant carriers (P = 0.31). Thirteen of 14 (93%) patients being resection-free at 15-year follow-up, had CARD15 wild-type genotype (P = 0.01), whereas only seven (50%) had never smoked (P = 1.0). CONCLUSIONS: In summary, CARD15 variant-associated Crohn's ileitis is virtually committed to stricturing and/or penetrating disease and, eventually, to resective surgery. Smoking accelerates progression to surgery in patients with wild-type CARD15 genotype, but it seems to exert no additional effect in CARD15-variant carriers.

Contribution of the cystathionine beta-synthase gene (844ins68) polymorphism to the risk of early-onset venous and arterial occlusive disease and of fasting hyperhomocysteinemia.

The frequency of the heterozygous 844ins68 mutation of the cystathionine beta-synthase (CBS) gene and of its association with the homozygous C677T transition of the methylenetetrahydrofolate reductase (MTHFR) gene, plasma fasting tHcy, folate and vitamin B12 levels were evaluated in 309 consecutive patients with objectively diagnosed early-onset venous (n = 200) or arterial thromboembolic disease (n = 109) recruited over 25 months in Milan (North Italy) and Naples (South Italy). The above gene polymorphisms were also evaluated in a population of 787 unmatched controls, 204 of whom--similar to patients for age- and sex-distribution--had fasting tHcy, vitamins and activated protein C resistance measured in their plasma. Moderate fasting hyperhomocysteinemia was detected in 15.5% of patients and in 5.9% of 204 controls (Mantel-Haenszel OR after stratification for type of occlusive disease and gender: 2.88; 1.48-5.32). The frequencies of the 677TT mutation of the MTHFR gene and of the heterozygous 844ins68 insertion of the CBS gene were not significantly different in the patient (19.4% and 6.9%) and the control population (16.5% and 7.8%), but the association of the two gene polymorphisms found in 3.9% of patients and in 1.1% of controls - was significantly associated with an increased risk of venous or arterial occlusive diseases (RR = 3.63; 1.48-8.91). The MTHFR 677TT mutation (RR: 6.92; 3.86-12.4) and its association with the 844ins68 insertion (RR: 21.9; 8.35-57.4), but not the isolated insertion (RR: 0.71), were more frequent in patients and controls with fasting hyperhomocysteinemia than in normohomocysteinemic subjects, irrespective of the type of occlusive disease (venous or arterial). When adjusted for determinants of hyperhomocysteinemia in the patient and the control populations (generalized linear model), fasting tHcy levels were significantly higher in subjects with association of the two gene abnormalities (24.2+/-3.8 micromol/L) than in subjects with the MTHFR 677TT mutation only (14.0+/-5.8 micromol/L, p = 0.004). Activated protein C resistance was significantly more prevalent in venous patients (9.9%) than in controls (3.9%, OR = 2.69; 1.08-6.88). Six of 21 venous patients with APC-resistance also had hyperhomocysteinemia (RR = 5.04; 0.68-37.6), but isolated fasting hyperhomocysteinemia retained statistical significance for the association with venous occlusive disease (RR = 2.84; 1.34-6.01). Heterozygosity for the 844ins68 mutation of the CBS gene is not per se a risk factor for premature arterial and/or venous occlusive diseases. However, when detected in combination with thermolabile MTHFR, it increases by almost 4-fold the risk of occlusive diseases (arterial and/or venous), by increasing the risk and the degree of fasting hyperhomocysteinemia.

High prevalence of hyperchomocysteinemia in patients with inflammatory bowel disease: a pathogenic link with thromboembolic complications?

BACKGROUND AND AIMS: Why patients with inflammatory bowel disease are at increased risk for thrombosis is unknown. Since they may have impaired absorption of vitamins that regulate the metabolism of homocysteine, we tested the hypothesis that they have hyperhomocysteinemia, an established risk factor for arterial and venous thrombosis. METHODS: The concentrations of total homocysteine (tHcy), folate and cobalamin were measured in blood samples from 61 consecutive patients with inflammatory bowel disease and 183 age- and sex-matched healthy controls. RESULTS: The mean (+/- S.D.) concentration of plasma tHcy was higher in patients (12.2 +/- 7.7 micromol/l) than in controls (10.5 +/- 4.6, p = 0.045). Eight patients (13%) had concentrations of tHcy higher than the 95th percentile of distribution among controls, as compared with 9 healthy controls (5%, p = 0.04). The prevalence of folate deficiency was higher in patients (15%) than in controls (5%, p = 0.02). Oral administration of folate, cobalamin and pyridoxine to 15 patients for 30 days decreased their mean tHcy levels from 20.3 +/- 9.9 to 9.5 +/- 3.4 (p <0.001). CONCLUSIONS: In patients with inflammatory bowel disease there is an increased prevalence of hyperhomocysteinemia, which can be corrected by the administration of folate, cobalamin and pyridoxine. The high prevalence of hyperhomocysteinemia may account for the thrombotic risk of IBD patients; whether or not its correction will decrease the thrombotic risk should be tested in properly designed clinical trials.

Natural history of portal hypertension in patients with cirrhosis.

All patients with cirrhosis will eventually develop portal hypertension and esophagogastric varices. Bleeding from ruptured esophagogastric varices is the most severe complication of cirrhosis and is the cause of death in about one third of patients. The rate of development and growth of esophageal varices is poorly defined but in general seem to be related to the degree of liver dysfunction. Once varices have formed, they tend to increase in size and eventually to bleed. In unselected patients, the incidence of variceal bleeding is about 20% to 30% at 2 years. Variceal size is the single most important predictor of a first variceal bleeding episode. Several prognostic indexes based on endoscopic and clinical parameters have been developed to predict the risk of bleeding; however, their degree of accuracy is unsatisfactory. Death caused by uncontrolled bleeding occurs in about 6% to 8% of patients; the 6-week mortality rate after a variceal hemorrhage is 25% to 30%. There are no good prognostic indicators of death caused by uncontrolled bleeding or death within 6 weeks. Untreated patients surviving a variceal hemorrhage have a 1- to 2-year risk of rebleeding of about 60% and a risk of death of about 40% to 50%. The risk of bleeding is greatest in the first days after a bleeding episode and slowly declines thereafter. All patients surviving a variceal hemorrhage must be treated to prevent rebleeding. Varices can also be found in the stomach of cirrhotic patients, alone or in association with esophageal varices. Gastric varices bleed less frequently but more severely than esophageal varices. Portal hypertensive gastropathy is a common feature of cirrhosis, and its prevalence parallels the severity of portal hypertension and liver dysfunction. Portal hypertensive gastropathy can progress from mild to severe and vice-versa or even disappear completely. Acute bleeding from portal hypertensive gastropathy seems to be relatively uncommon, and less severe than bleeding from varices.

Beta-blockers in the secondary prevention of gastrointestinal haemorrhage in well-compensated cirrhotics. A multicentre randomised controlled study.

To assess the efficacy of beta-blockers in the prevention of rebleeding in selected cirrhotics and to compare the tolerability, safety of, and patient compliance with, a selective and a non-selective beta-blocker, 94 patients were randomly assigned to propranolol (32), atenolol (32), or placebo (30). Randomisation was made at least 15 days after the bleeding episode. Propranolol was given orally in increasing doses until the resting pulse rate was reduced by approximately 25%. Atenolol was given at a fixed dose of 100 mg/day. Patients were followed up for a mean of 357 days. Rebleeding occurred in 14 patients in the placebo group, 10 in the atenolol group and 8 in the propranolol group. The incidence of rebleeding was significantly lower in patients receiving propranolol than in those on placebo (PR vs PL: p less than 0.01, log-rank test). Atenolol was less effective than propranolol (AT vs PL: p = 0.065, log-rank test) but bleeding-free survival was improved for patients on active drugs compared with those patients on placebo (PR vs PL: p = 0.01; AT vs PL: p = 0.05, log-rank test). Retrospective analysis revealed that, whatever the type of treatment, abstinence from alcohol was crucial in preventing rebleeding. It was concluded that beta-blocker treatment is effective in preventing rebleeding from oesophageal varices in carefully selected alcoholic cirrhotics who survive at least 2 weeks after acute variceal haemorrhage and who cease drinking.

Folate pathway gene alterations in patients with neural tube defects.

Periconceptional folate supplementation reduces the recurrence and occurrence risk of neural tube defects (NTD) by as much as 70%, yet the protective mechanism remains unknown. Inborn errors of folate and homocysteine metabolism may be involved in the aetiology of NTDs. Previous studies have demonstrated that both homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, and combined heterozygosity for the C677T and for another mutation in the same gene, the A1298C polymorphism, represent genetic risk factors for NTDs. In an attempt to identify additional folate related genes that contribute to NTD pathogenesis, we performed molecular genetic analysis of folate receptors (FRs). We identified 4 unrelated patients out of 50 with de novo insertions of pseudogene (PS)-specific mutations in exon 7 and 3'UTR of the FRalpha gene, arising by microconversion events. All of the substitutions affect the carboxy-terminal amino acid membrane tail, or the GPI anchor region of the nascent protein. Furthermore, among 150 control individuals, we also identified one infant with a gene conversion event within the FRalpha coding region. This study, though preliminary, provides the first genetic association between molecular variations of the FRalpha gene and NTDs and suggests that this gene can act as a risk factor for human NTD.

Review article: definition and diagnosis in portal hypertension--continued problems with the Baveno consensus?

The goals of the Baveno workshops were to develop consensus definitions of key events related to portal hypertension and variceal bleeding, and to produce guidelines to facilitate the conduct and reporting of clinical trials. The consensus definitions concern the diagnosis of active bleeding, failure to control bleeding, the criteria to distinguish continuing bleeding from rebleeding, and the means of assessing failure to prevent rebleeding. The guidelines concern the timing of diagnostic endoscopy, the policy for blood volume restitution, the measures to prevent infection and encephalopathy, and the treatment options for acute bleeding, as well as primary and secondary prophylaxis. The intention of the experts who developed the guidelines was that, as feedback from their practical application develops, they should be adapted to better fit the practical needs. The applicability of the Baveno definitions has been evaluated in a study where the definitions of clinically significant bleeding, failure to control bleeding, the time frame for the acute bleeding episode and the definition of rebleeding were tested. The main criticism raised in this study was that tachycardia, one of the criteria that define failure to control bleeding, was misleading in 15% of patients who had the symptom but were not bleeding.

Review article: diagnosis, monitoring and treatment of distal colitis.

The diagnostic work-up of ulcerative colitis at presentation is based on the collection of clinical, microbiological, radiological, endoscopic and histologic data. Serological markers are characterized by too low a sensitivity to be commonly utilized in clinical practice. Although endoscopic and histologic features are characterized by very high sensitivity and specificity for the diagnosis of ulcerative colitis, negative stool cultures and parasites are mandatory to exclude an infectious aetiology at presentation. The treatment of choice of an acute flare-up of distal ulcerative colitis is represented by oral or topical mesalazine, or a combination of both, whereas the use of topical or systemic steroids should be restricted to patients who prove to be refractory to first-line treatments. Preliminary data suggest that the achievement of endoscopic and histologic remission after an acute flare of the disease might be associated with a prolonged remission.

Controlled trial of oral 5-aminosalicylic acid for the prevention of early relapse in Crohn's disease.

BACKGROUND: Recent data indicate that 5-aminosalicylic acid (5-ASA) is most effective in preventing relapse of Crohn's disease in patients with a short duration of remission before enrollment. AIM: To evaluate the efficacy of oral 5-ASA treatment, started immediately after achieving steroid-induced remission, in preventing clinical relapses of Crohn's disease. METHODS: Patients with active Crohn's disease, achieving remission on steroids, were randomized to oral 5-ASA 3 g/day or placebo, while steroids were tapered over 6 weeks. The trial was terminated after interim analysis showed a slightly higher relapse rate in the 5-ASA group, and the calculated probability of seeing a statistically significant difference by completing the study was minimal. RESULTS: Final analysis included 117 patients (58 taking 5-ASA and 59 taking placebo; follow-up 9.2 +/- 6.5 months). Cumulative relapse rates at 6 and 12 months were 34% and 58% in 5-ASA patients and 31% and 52% in placebo patients, respectively (rate difference +0.095; 95% CI = -0.085 to +0.274). Subgroups analysis showed that 5-ASA was equally ineffective in patients with ileal, colonic or ileocolonic disease. CONCLUSIONS: Contrary to previous results, in our study early introduction of treatment with oral 5-ASA did not prevent relapse in Crohn's disease patients treated with steroids to induce remission.

A new mesalazine gel enema in the treatment of left-sided ulcerative colitis: a randomized controlled multicentre trial.

BACKGROUND: A new mesalazine rectal gel preparation (without propellant gas) has been recently developed to improve topical treatment in distal ulcerative colitis. AIM: To evaluate the efficacy, safety and patient tolerability of mesalazine gel enema compared with mesalazine foam enema in the treatment of patients with acute left-sided ulcerative colitis. METHODS: In a randomized multicentre investigator-blind parallel group trial, 103 patients with mild to moderate left-sided colitis or proctosigmoiditis were randomly allocated to mesalazine 2 g gel enema (n = 50 evaluable patients) and mesalazine 2 g foam enema (n = 53 evaluable patients) for 4 weeks. Clinical symptoms, endoscopic and histological findings were assessed at entry, 2 and 4 weeks. Patients' evaluation of treatment tolerability and acceptability was assessed at 2 and 4 weeks. RESULTS: After 4 weeks of treatment, clinical remission was achieved by 76% of mesalazine gel enema-treated patients and 69% of patients treated with mesalazine foam enema (P = 0.608). Endoscopic remission rates at week 4 were 51 and 52% for the mesalazine gel and foam enemas, respectively (P = 0.925). Histological remission was achieved by 30% of patients in both groups. Patients reported that the new mesalazine gel preparation was significantly better tolerated than the foam enema. Patients in the foam group had significantly more difficulty in retention (25% vs. 6%, P < 0.05), abdominal bloating (50% vs. 26%, P < 0.005) and discomfort during administration (48% vs. 26%, P < 0.05). CONCLUSION: The new mesalazine gel enema is efficacious and significantly better tolerated than the mesalazine foam enema.

Longer treatment with vasoactive drugs to prevent early variceal rebleeding in cirrhosis.

Bleeding oesophageal varices (BOV), resulting from portal hypertension, can prove fatal. Not only is it important to stop the initial bleeding, which may lead to hypovolaemic shock, but also to treat this condition in the longer term, and, consequently, the prevention of rebleeding needs to be addressed. This review highlights the current findings on the haemostatic drug, terlipressin, focusing particular attention on the potential for longer-term treatment strategies in the prevention of rebleeding. The efficacy of terlipressin in treating acute BOV, its low incidence of severe side-effects (comparable to those of somatostatin) and its favourable comparison with sclerotherapy in the prevention of early rebleeds, all indicate the potential for terlipressin administration to be extended to 5 days in the longer-term treatment of BOV. In addition, terlipressin administration, in conjunction with sclerotherapy, can significantly reduce the likelihood of rebleeding compared with sclerotherapy alone and further supports its potential use in the longer-term treatment of BOV.

Somatostatin, somatostatin analogues and other vasoactive drugs in the treatment of bleeding oesophageal varices.

Somatostatin and its analogues have been compared with a variety of other treatments for the treatment of variceal bleeding in cirrhotic patients. Meta-analyses of studies comparing somatostatin or octreotide with vasopressin or terlipressin have shown that somatostatin is somewhat superior to vasopressin and equivalent to terlipressin in controlling bleeding and has significantly fewer side effects; no difference in mortality was observed. Octreotide was somewhat better than vasopressin and terlipressin in controlling bleeding, with similar mortality. Meta-analysis of trials comparing somatostatin or octreotide with endoscopic sclerotherapy shows that both drugs are equivalent to sclerotherapy for bleeding control, early rebleeding and survival. Complications are much less frequent with drug treatment. Nine trials have compared endoscopic therapy with therapeutic regimens combining endoscopic treatment with somatostatin, octreotide or vapreotide. Meta-analysis show that the combined regimens increase the 5 days bleeding control rate of endoscopic treatments by over 20%, although there is no difference in mortality. Comparisons of somatostatin and octreotide with combined regimens of sclerotherapy + somatostatin and sclerotherapy + octreotide have shown that the combined regimens were better than drug treatments alone in controlling bleeding and preventing early rebleeding, while complications were significantly less frequent with drug therapy.