Aliment Pharmacol Ther 2011; 34: 125–145
Summary
Background Cross‐sectional imaging techniques, including ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI), are ...increasingly used for evaluation of Crohn’s disease (CD).
Aim To perform an assessment of the diagnostic accuracy of cross‐sectional imaging techniques for diagnosis of CD, evaluation of disease extension and activity and diagnosis of complications, and to provide recommendations for their optimal use.
Methods Relevant publications were identified by literature search and selected based on predefined quality parameters, including a prospective design, sample size and reference standard. A total of 68 publications were chosen.
Results Ultrasonography is an accurate technique for diagnosis of suspected CD and for evaluation of disease activity (sensitivity 0.84, specificity 0.92), is widely available and non‐invasive, but its accuracy is lower for disease proximal to the terminal ileum. MRI has a high diagnostic accuracy for the diagnosis of suspected CD and for evaluation of disease extension and activity (sensitivity 0.93, specificity 0.90), and is less dependent on the examiner and disease location compared with US. CT has a similar accuracy to MRI for assessment of disease extension and activity. The three techniques have a high accuracy for identification of fistulas, abscesses and stenosis (sensitivities and specificities >0.80), although US has false positive results for abscesses. As a result of the lack of radiation, US or MRI should be preferred over CT, particularly in young patients.
Conclusions Cross‐sectional imaging techniques have a high accuracy for evaluation of suspected and established CD, reliably measure disease severity and complications; they may offer the possibility to monitor disease progression.
Aliment Pharmacol Ther 2012; 35: 209–221
Summary
Background Even with the current most effective treatment regimens, a relevant proportion of patients will fail to eradicate Helicobacter pylori ...infection.
Aim To evaluate the role of rifabutin in the treatment of H. pylori infection.
Methods Bibliographical searches were performed in MEDLINE. Data on the efficacy of rifabutin‐containing regimens on H. pylori eradication were combined and meta‐analysed using the generic inverse variance method.
Results Rifabutin shows good in vitro activity against H. pylori. Mean H. pylori rifabutin resistance rate (calculated from 11 studies including 2982 patients) was 1.3% (95% confidence interval = 0.9–1.7%). When only studies including patients naïve to H. pylori eradication treatment were considered, this figure was even lower (0.6%). On the other hand, higher values of rifabutin resistance were calculated (1.59%) when only post‐treatment patients were considered. Overall, mean H. pylori eradication rate (intention‐to‐treat analysis) with rifabutin‐containing regimens (1008 patients) was 73% (67–79%). Respective cure rates for second‐line (223 patients), third‐line (342 patients) and fourth/fifth‐line (95 patients) rifabutin therapies were 79% (67–92%), 66% (55–77%) and 70% (60–79%) respectively. For treating H. pylori infection, almost all studies have administered rifabutin 300 mg/day; this dose seems to be more effective than 150 mg/day. The ideal length of treatment remains unclear, but 10‐ to 12‐day regimens are generally recommended. The mean rate of adverse effects was 22% (19–25%). Myelotoxicity is the most significant, although this complication was rare. Until now, all patients have recovered of leucopenia uneventfully in a few days, and there have been no reports of infection or other adverse outcomes related to it.
Conclusion Rifabutin‐containing rescue therapy constitutes an encouraging strategy after multiple (usually three) previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole, tetracycline and levofloxacin.
Aliment Pharmacol Ther 2011; 34: 604–617
Summary
Background Traditional standard triple therapy for Helicobacter pylori infection (PPI‐clarithromycin‐amoxicillin) can easily be converted to ...non‐bismuth quadruple (concomitant) therapy by the addition of a nitroimidazole twice daily.
Aim To critically review evidence on the role of non‐bismuth quadruple therapy (PPI‐clarithromycin‐amoxicillin‐nitroimidazole) in the treatment of H. pylori infection.
Methods Bibliographical searches were performed in MEDLINE and relevant congresses.
Results The first randomised comparison of the non‐bismuth quadruple therapy and the sequential (PPI‐amoxicillin 5 days plus PPI‐clarithromycin‐nitroimidazole 5 days) regimens recently concluded that both were similar in terms of efficacy and safety and that the sequential administration protocol may be unnecessarily complex. Several randomised controlled trials (and one meta‐analysis) have demonstrated that non‐bismuth quadruple therapy is more effective than and is equally well tolerated as standard triple therapy. A meta‐analysis of 15 studies (1723 patients) revealed a mean H. pylori cure rate (intention‐to‐treat) of 90% for non‐bismuth quadruple therapy. A tendency towards better results with longer treatments (7–10 days vs. 3–5 days) has been observed, so it seems reasonable to recommend the length of treatment by achieving maximal cure rates (10 days). Clarithromycin resistance may reduce the efficacy of non‐bismuth quadruple therapy, although the decrease in eradication rates seems to be far lower than in standard triple therapy. Experience with the non‐bismuth quadruple therapy in patients with metronidazole‐resistant strains is still very limited.
Conclusions Non‐bismuth quadruple (concomitant) therapy appears to be an effective, safe, and well‐tolerated alternative to triple therapy and is less complex than sequential therapy. Therefore, this regimen appears well suited for use in settings where the efficacy of triple therapy is unacceptably low.
Summary
Background
Elderly patients represent an increasing proportion of the inflammatory bowel disease (IBD) population.
Aim
To critically review available data regarding the care of elderly IBD ...patients.
Methods
Bibliographic searches (MEDLINE) up to June 2013.
Results
Approximately 10–15% of cases of IBD are diagnosed in patients aged >60 years, and 10–30% of the IBD population are aged >60 years. In the elderly, IBD is easily confused with other more common diseases, mainly diverticular disease and ischaemic colitis. The clinical features of IBD in older patients are generally similar to those in younger patients. Crohn's disease (CD) in elderly patients is characterised by its predominantly colonic localisation and uncomplicated course. Proctitis and left‐sided ulcerative colitis are more common in patients aged >60 years. Infections are associated with age and account for significant mortality in IBD patients. The treatment of IBD in the elderly is generally similar. However, the therapeutic approach in the elderly should be ‘start low‐go slow’. The benefit of thiopurines in older CD patients remains debatable. Although the indications for anti‐tumour necrosis factors in the elderly are generally similar to those for younger patients, lower response and higher adverse events have been reported in the elderly. Surgery in elderly patients does not generally differ. Ileal pouch‐anal anastomosis can be successful, provided the patient retains good anal sphincter function.
Conclusions
Management of the older IBD patient differs from that of younger patients; therefore, conventional practice algorithms may have to be modified to account for advanced age.
Summary
Background
Patients with ulcerative colitis (UC) have an increased risk of developing colorectal cancer (CRC); however, the magnitude of this effect is open to debate.
Aim
To assess the risk ...of CRC in UC patients by systematic review and meta‐analysis.
Methods
A systematic literature search was performed up to November 2013. We selected studies describing the incidence and prevalence of CRC in patients with UC. Articles were assessed for quality using the Newcastle‐Ottawa Scale. Cumulative incidence and incidence rates of CRC were combined and analysed using the generic inverse variance method. Sub‐analyses were performed to identify factors associated with an increased risk of developing CRC.
Results
A total of 81 studies (181 923 patients) met the inclusion criteria. The incidence rate of CRC in patients with UC was 1.58 per 1000 patient‐years (py) 95% confidence interval (CI), 1.39–1.76. Results were heterogeneous (I2 = 81–89%). The incidence rate was 4.02/1000 py (95%CI = 2.74–5.31) in studies that only included patients with extensive colitis, and 1.24/1000 py (95%CI = 1.01–1.47) in population‐based studies. The incidence rate was 0.91/1000 py (95%CI = 0.61–1.2) in the first decade of disease, 4.07/1000 py (95%CI = 2.58–5.56) in the second, and 4.55/1000 py (95%CI = 2.64–6.46) in the third. The incidence rate decreased from 4.29/1000 py in the studies published in the 1950s to 1.21/1000 py in studies published in the last decade.
Conclusions
The risk of patients with ulcerative colitis developing colorectal cancer has decreased steadily over the last six decades, but the extent and duration of the disease increase this risk.
Summary
Background
The decreasing efficacy of H. pylori eradication treatments over time makes the search for better regimens and adjuvant medications a priority.
Aim
To conduct a meta‐analysis of ...studies comparing rabeprazole or esomeprazole with other proton pump inhibitors (PPI) or with each other in H. pylori eradication treatment.
Methods
Selection of Studies: Randomised clinical trials comparing esomeprazole or rabeprazole with first‐generation PPIs (omeprazole‐lansoprazole‐pantoprazole) or with each other.
Results
The meta‐analysis (35 studies, 5998 patients) showed higher eradication rates for esomeprazole than for first‐generation PPIs: 82.3% vs. 77.6%; OR = 1.32(1.01–1.73); NNT = 21. Rabeprazole also showed better results than first‐generation PPIs: 80.5% vs. 76.2%; OR = 1.21(1.02–1.42); NNT = 23. PPI dosage sub‐analysis: only esomeprazole 40 mg b.d. improved results 83.5% esomeprazole vs. 72.4% first generation; OR = 2.27(1.07–4.82); NNT = 9. Whereas rabeprazole 10 and 20 mg b.d. maintained results, esomeprazole 20 mg b.d. obtained lower efficacy. Esomeprazole vs. rabeprazole sub‐analysis (five studies): no significant differences were found: 78.7% vs. 76.7%; OR = 0.90(0.70–1.17). CYP2C19 sub‐analysis: Genotype did not significantly affect eradication either in first OR = 1.76(0.99–3.12) or new generation OR = 1.19(0.73–1.95) PPIs. However, sub‐analysis considering only extensive metaboliser patients showed higher eradication with new‐generation PPIs OR = 1.37(1.02–1.84).
Conclusions
Esomeprazole and rabeprazole show better overall H. pylori eradication rates than first‐generation PPIs. This clinical benefit is more pronounced in esomeprazole 40 mg b.d. regimens. In CYP2C19 extensive metabolisers, new‐generation PPIs are more effective than first‐generation PPIs for H. pylori eradication. However, a general recommendation of using new‐generation PPIs in all scenarios remains unclear.
Summary
Background
A quadruple therapy has been generally recommended as rescue regimen for Helicobacter pylori eradication failures.
Aims
To systematically review the efficacy and tolerance of ...levofloxacin‐based rescue regimens, and to conduct a meta‐analysis of studies comparing these regimens with quadruple therapy for H. pylori eradication failures.
Methods
Selection of studies – levofloxacin‐based rescue regimens. For the meta‐analysis, randomized‐controlled trials comparing levofloxacin‐based and quadruple regimens. Search strategy – electronic and manual. Assessment of study quality – independently by two reviewers. Data synthesis –‘intention‐to‐treat’ eradication rate.
Results
Mean eradication rate with levofloxacin‐based regimens was 80%. Ten‐day regimens were more effective than 7‐day combinations (81% vs. 73%; P < 0.01). The meta‐analysis showed better results with levofloxacin than with the quadruple combination (81% vs. 70%; OR = 1.80; 95% CI = 0.94–3.46). This difference reached statistical significance and heterogeneity markedly decreased when a single outlier study was excluded or when only high‐quality studies were considered. Meta‐analysis showed less adverse effects with levofloxacin than with quadruple regimen, both overall (19% vs. 44%; OR = 0.27; 95% CI = 0.16–0.46) and regarding severe adverse effects (0.8% vs. 8.4%; OR = 0.20; 95% CI =0.06–0.67).
Conclusions
After H. pylori eradication failure, levofloxacin‐based rescue regimen is more effective and better tolerated than the generally recommended quadruple therapy. A 10‐day combination of levofloxacin–amoxicillin–proton pump inhibitor constitutes an encouraging second‐line alternative.
Aliment Pharmacol Ther 2011; 34: 1255–1268
Summary
Background A decrease in the Helicobacter pylori eradication rate after standard triple therapy has been suggested in recent years.
Aim To assess ...the efficacy of standard triple therapy in the eradication of H. pylori through an epidemiological analysis of all published Spanish trials. A secondary aim was to review the prevalence of clarithromycin resistance in Spain.
Methods Articles on H. pylori eradication in Spain published in peer‐reviewed journals were identified through MEDLINE searches. Studies that included a triple therapy consisting of any proton pump inhibitor with clarithromycin (500 mg b.d.) and amoxicillin (1 g b.d.) for up to 14 days were selected. Spanish studies evaluating the prevalence of clarithromycin resistance were also reviewed. Meta‐analysis was performed using the generic inverse variance method.
Results The pooled eradication rates by year from Spanish studies evaluating the efficacy of the standard triple regimen revealed a relatively constant rate over the years. Overall, the analysis of the 32 studies (4727 patients) showed a mean H. pylori cure rate of 80% (95% CI = 77–82%) by intention‐to‐treat and 83% (81–86%) by per‐protocol. When only peptic ulcer disease or 7‐day regimens were considered, results were similar. Based on 13 studies (3293 patients), mean clarithromycin resistance rate was 8% (5–10%).
Conclusion Although a decrease in the H. pylori eradication rate after triple therapy has been suggested in recent years, cure rates with this regimen did not change in Spain between 1997 and 2008. However, this by no means indicates that the efficacy of standard triple therapy in Spain is acceptable, as it has been calculated to be around only 80%. Therefore, it is evident that new strategies to improve first‐line treatment are urgently needed.
Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori ...were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.
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