Psychological impact of multigene cancer panel testing in patients with a clinical suspicion of hereditary cancer across Spain.

OBJECTIVE: Patients' psychological reactions to multigene cancer panel testing might differ compared with the single-gene testing reactions because of the complexity and uncertainty associated with the different possible results. Understanding patients' preferences and psychological impact of multigene panel testing is important to adapt the genetic counselling model. METHODS: One hundred eighty-seven unrelated patients with clinical suspicion of hereditary cancer undergoing a 25-gene panel test completed questionnaires after pretest genetic counselling and at 1 week, 3 months, and 12 months after results to elicit their preferences regarding results disclosure and to measure their cancer worry and testing-specific distress and uncertainty. RESULTS: A pathogenic variant was identified in 38 patients (34 high penetrance and 4 moderate penetrance variants), and 54 patients had at least one variant of uncertain significance. Overall, cancer panel testing was not associated with an increase in cancer worry after results disclosure (P value = .87). Twelve months after results, carriers of a moderate penetrance variant had higher distress and uncertainty scores compared with carriers of high penetrance variants. Cancer worry prior to genetic testing predicted genetic testing specific distress after results, especially at long term (P value <.001). Most of the patients reported the wish to know all genetic results. CONCLUSIONS: Our results suggest that patients can psychologically cope with cancer panel testing, but distress and uncertainty observed in carriers of moderate penetrance cancer variants in this cohort warrant further research.

The TRIM proteins in cancer: from expression to emerging regulatory mechanisms.

New clinical evidence suggests that dysregulation of the ubiquitin-mediated destruction of tumor suppressors or oncogene products is probably engaged in the etiology of leukemia and carcinoma. The superfamily of tripartite motif (TRIM)-containing protein family is among the biggest recognized single protein RING finger E3 ubiquitin ligases that are considered vital carcinogenesis regulators, which is not shocking since TRIM proteins are engaged in various biological processes, including cell growth, development, and differentiation; hence, TRIM proteins' alterations may influence apoptosis, cell proliferation, and transcriptional regulation. In this review article, the various mechanisms through which TRIM proteins exert their role in the most prevalent malignancies including lung, prostate, colorectal, liver, breast, brain cancer, and leukemia are summarized.

Systematic review: Rabeprazole-based therapies in Helicobacter pylori eradication.

AIM: To perform a systematic review of the efficacy of rabeprazole-based therapies in Helicobacter pylori eradication, and to conduct a meta-analysis comparing the efficacy of rabeprazole and other proton pump inhibitors when co-prescribed with antibiotics. METHODS: Studies evaluating rabeprazole plus antibiotics were considered. Only randomized trials comparing rabeprazole and other proton pump inhibitors with antibiotics, and differing only in the proton pump inhibitor, were included in the meta-analysis. Electronic and manual bibliographic searches were conducted. The percentage (weighted mean) of successful eradication was calculated. Meta-analysis was performed by combining the odds ratios (OR) of the individual studies. RESULTS: The eradication rates were as follows: 14-day rabeprazole-amoxicillin, 73%; rabeprazole-amoxicillin-clarithromycin for 3, 5, 7 and 10 days, 44%, 72%, 78% and 75%, respectively; low-dose rabeprazole (20 mg/day), amoxicillin and clarithromycin for 7 days, 81%; high-dose rabeprazole (40 mg/day), amoxicillin and clarithromycin for 7 days, 75%; 7-day rabeprazole-clarithromycin-nitroimidazole, 85%. Twelve comparative studies were included in the meta-analysis. The eradication rate with rabeprazole plus antibiotics was 79%; it was 77% with other proton pump inhibitors (OR = 1.15; 95% confidence interval, 0.93-1.42). Sub-analysis comparing rabeprazole at low doses (10 mg b.d.) with other proton pump inhibitors at standard doses (omeprazole 20 mg b.d. or lansoprazole 30 mg b.d.) showed no differences. CONCLUSIONS: Rabeprazole achieves similar H. pylori eradication rates to omeprazole and lansoprazole when co-prescribed with antibiotics. Low doses of rabeprazole (10 mg b.d.), when administered with two antibiotics, may be sufficient to eradicate H. pylori infection.

Meta-analysis: Helicobacter pylori eradication therapy vs. antisecretory non-eradication therapy for the prevention of recurrent bleeding from peptic ulcer.

AIM: To perform a meta-analysis comparing the efficacy of Helicobacter pylori eradication therapy vs. antisecretory non-eradication therapy for the prevention of recurrent bleeding from peptic ulcer. METHODS: A search was made of the Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL and several congresses for controlled clinical trials comparing the efficacy of H. pylori eradication therapy vs. antisecretory non-eradication therapy for the prevention of peptic ulcer re-bleeding. Studies with all patients taking non-steroidal anti-inflammatory drugs were excluded. Extraction and quality assessment of the studies were performed by two reviewers. RESULTS: In the first meta-analysis, the mean percentage of re-bleeding in the H. pylori eradication therapy group was 4.5%, compared with 23.7% in the non-eradication therapy group without long-term antisecretory therapy [odds ratio, 0.18; 95% confidence interval (CI), 0.09-0.37; 'number needed to treat' (NNT), 5; 95% CI, 4-8]. In the second meta-analysis, the re-bleeding rate in the H. pylori eradication therapy group was 1.6%, compared with 5.6% in the non-eradication therapy group with maintenance antisecretory therapy (odds ratio, 0.25; 95% CI, 0.08-0.76; NNT, 20; 95% CI, 12-100). When only patients with successful H. pylori eradication were included, the re-bleeding rate was 1%. CONCLUSIONS: The treatment of H. pylori infection is more effective than antisecretory non-eradication therapy (with or without long-term maintenance antisecretory treatment) in the prevention of recurrent bleeding from peptic ulcer. Consequently, all patients with peptic ulcer bleeding should be tested for H. pylori, and eradication therapy should be prescribed to infected patients.

Meta-analysis: proton pump inhibitors vs. H2-receptor antagonists--their efficacy with antibiotics in Helicobacter pylori eradication.

BACKGROUND: It is unknown whether proton pump inhibitors are superior to H2-receptor antagonists in Helicobacter pylori eradication regimens. AIM: To perform a meta-analysis comparing the efficacy of both antisecretors when co-prescribed with antibiotics. METHODS: Randomized clinical trials comparing proton pump inhibitors vs. H2-receptor antagonists with the same antibiotics were selected. Data sources included PubMed, the Cochrane Controlled Trials Register and abstracts from congresses up to January 2002. A meta-analysis was performed by combining the odds ratios. RESULTS: Twenty studies fulfilled the inclusion criteria. In the intention-to-treat analysis, the mean eradication rates with proton pump inhibitors and H2-receptor antagonists plus antibiotics were 74% [95% confidence interval (CI), 71-76%] and 69% (95% CI, 66-71%), respectively. The odds ratio for this comparison was 1.31 (95% CI, 1.09-1.58). The number needed to treat with proton pump inhibitors to achieve eradication success, compared with H2-receptor antagonists, was 25. When studies prescribing very high doses of H2-receptor antagonists (two of the outliers) were excluded, the odds ratio (for proton pump inhibitors vs. H2-receptor antagonists) increased to 1.37, the number needed to treat decreased to 20 and the heterogeneity between the studies decreased. CONCLUSIONS: Overall, proton pump inhibitors are more effective than H2-receptor antagonists when prescribed at usual doses with antibiotics to eradicate H. pylori infection.

H. pylori eradication therapy vs. antisecretory non-eradication therapy (with or without long-term maintenance antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer.

BACKGROUND: Peptic ulcer is the main cause for upper gastrointestinal haemorrhage, and Helicobacter pylori infection is the main etiologic factor for peptic ulcer disease. Maintenance antisecretory therapy has been the standard long-term treatment for patients with bleeding ulcers to prevent recurrent bleeding. On the other hand, the precise efficacy of H. pylori eradication for the prevention of rebleeding from peptic ulcer is unknown. OBJECTIVES: To compare the efficacy of H. pylori eradication therapy vs. antisecretory non-eradication therapy (with or without long-term maintenance antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (the Cochrane Library issue 4, 2003), MEDLINE (January 1966 to January 2004), EMBASE (January 1988 to January 2004), CINAHL (January 1982 to January 2004), and reference lists of articles. We also conducted a manual search from several congresses. SELECTION CRITERIA: Controlled clinical trials comparing the efficacy of H. pylori eradication therapy vs. antisecretory non-eradication therapy (with or without long-term maintenance antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer. DATA COLLECTION AND ANALYSIS: Extraction and quality assessment of studies were done by two reviewers. Study authors were contacted for additional information. MAIN RESULTS: Seven studies with a total of 578 patients were included in the first meta-analysis: mean percentage of rebleeding in H. pylori eradication therapy group was 2.9%, and in the non-eradication therapy group without subsequent long-term maintenance antisecretory therapy it was 20% (OR 0.17, 95% CI 0.10 to 0.32; there was no statistical evidence of heterogeneity; NNT was 7, 95% CI 5 to 11). Three studies with a total of 470 patients were included in the second meta-analysis: mean percentage of rebleeding in H. pylori eradication therapy group was 1.6%, and in non-eradication therapy group with long-term maintenance antisecretory therapy it was 5.6% (OR 0.25, 95% CI 0.08 to 0.76; heterogeneity was not demonstrated; NNT was 20, 95% CI 12 to 100). SUBANALYSIS: Excluding patients taking non-steroidal anti-inflammatory drugs (NSAIDs) at the time of recurrent bleeding resulted in a rebleeding rate of 2.7% (first meta-analysis) or 0.78% (second meta-analysis) in the group receiving H. pylori eradication therapy. When only patients with H. pylori eradication success were included, rebleeding rate was 1.1% in H. pylori eradication therapy group, and NNT decreased from 7 to 6. In some cases, recurrence of H. pylori infection seemed to be responsible for recurrence of bleeding. REVIEWERS' CONCLUSIONS: Treatment of H. pylori infection is more effective than antisecretory non-eradicating therapy (with or without long-term maintenance antisecretory therapy) in preventing recurrent bleeding from peptic ulcer. Consequently, all patients with peptic ulcer bleeding should be tested for H. pylori infection, and eradication therapy should be prescribed to H. pylori-positive patients.

H. pylori eradication therapy vs. antisecretory non-eradication therapy (with or without long-term maintenance antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer.

BACKGROUND: Peptic ulcer is the main cause for upper gastrointestinal haemorrhage, and Helicobacter pylori infection is the main etiologic factor for peptic ulcer disease. Maintenance antisecretory therapy has been the standard long-term treatment for patients with bleeding ulcers to prevent recurrent bleeding. On the other hand, the precise efficacy of H. pylori eradication for the prevention of rebleeding from peptic ulcer is unknown. OBJECTIVES: To compare the efficacy of H. pylori eradication therapy vs. antisecretory non-eradication therapy (with or without long-term maintenance antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (the Cochrane Library issue 1, 2003), MEDLINE (January 1966 to March 2003), EMBASE (January 1988 to March 2003), CINAHL (January 1982 to March 2003), and reference lists of articles. We also conducted a manual search from several congresses. SELECTION CRITERIA: Controlled clinical trials comparing the efficacy of H. pylori eradication therapy vs. antisecretory non-eradication therapy (with or without long-term maintenance antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer. DATA COLLECTION AND ANALYSIS: Extraction and quality assessment of studies were done by two reviewers. Study authors were contacted for additional information. MAIN RESULTS: Six studies with a total of 355 patients were included in the first meta-analysis: mean percentage of rebleeding in H. pylori eradication therapy group was 4.5%, and in the non-eradication therapy group without subsequent long-term maintenance antisecretory therapy it was 23.7% (OR 0.18, 95% CI 0.09 to 0.37; there was no statistical evidence of heterogeneity; NNT was 5, 95% CI 4 to 8). Three studies with a total of 470 patients were included in the second meta-analysis: mean percentage of rebleeding in H. pylori eradication therapy group was 1.6%, and in non-eradication therapy group with long-term maintenance antisecretory therapy it was 5.6% (OR 0.25, 95% CI 0.08 to 0.76; heterogeneity was not demonstrated; NNT was 20, 95% CI 12 to 100). Subanalysis. Excluding patients taking non-steroidal anti-inflammatory drugs (NSAIDs) at the time of recurrent bleeding resulted in a rebleeding rate of 4% (first meta-analysis) or 0.78% (second meta-analysis) in the group receiving H. pylori eradication therapy. When only patients with H. pylori eradication success were included, rebleeding rate was 1% in H. pylori eradication therapy group, and NNT decreased from 5 to 4. In some cases, recurrence of H. pylori infection seemed to be responsible for recurrence of bleeding. REVIEWER'S CONCLUSIONS: Treatment of H. pylori infection is more effective than antisecretory non-eradicating therapy (with or without long-term maintenance antisecretory therapy) in preventing recurrent bleeding from peptic ulcer. Consequently, all patients with peptic ulcer bleeding should be tested for H. pylori infection, and eradication therapy should be prescribed to H. pylori-positive patients.

Oral ofloxacin versus parenteral imipenem-cilastatin in the treatment of osteomyelitis.

We conducted a prospective, randomized, open-label trial, comparing oral ofloxacin with intravenous imipenem-cilastatin for the treatment of chronic osteomyelitis in order to evaluate the efficacy and tolerance. Hospitalized patients with diagnosis of chronic osteomyelitis and isolation of susceptible organisms to ofloxacin and imipenem/cilastatin were eligible for enrollment. Ofloxacin was administered orally (400 mg every 12 hours), and imipenem-cilastatin was given intravenously (500 mg every 6 hours). Organisms were considered susceptible to ofloxacin when the minimal inhibitory concentration (MIC) was <2 micrograms/ml, and to imipenem-cilastatin when the MIC was <4 micrograms/ml. Thirty-two patients were enrolled, 16 in each group. In the intent to treat analysis 11 (69%) patients in the ofloxacin group and eight (50%) in the imipenem-cilastatin group were cured (p = 0.473; 95% confidence interval of the difference from -14.7% to 52.2%). In the per protocol analysis 10 (91%) patients in the ofloxacin group and seven (70%) in the imipenem/cilastatin group were cured (p = 0.311; 95% confidence interval of the difference from -12.2% to 54%). Our trial suggests that oral ofloxacin is as effective as parenteral therapy with betalactam antibiotics in the treatment of osteomyelitis, which could allow a reduction of the period of hospitalization and economic costs.

Helicobacter pylori and bleeding duodenal ulcer: prevalence of the infection and role of non-steroidal anti-inflammatory drugs.

BACKGROUND: Several authors have reported low prevalence of Helicobacter pylori infection in patients with upper gastrointestinal bleeding (UGIB). Our aim was to study the prevalence of H. pylori in bleeding duodenal ulcer (DU), with both invasive and non-invasive methods, and to assess the role of non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: Ninety-two patients with bleeding DU were prospectively studied. The use of NSAIDs was evaluated by specific questionnaire. As a control group, 428 patients undergoing outpatient evaluation for the investigation of dyspepsia and found to have a DU at endoscopy were included. At endoscopy, two antral biopsies were obtained (H&E stain). A 13C-urea breath test was carried out in all patients. Breath test was repeated in patients treated with omeprazole during the hospitalization if H. pylori was not detected with the first test. RESULTS: Gastric biopsies could be obtained in 39 patients with UGIB. Three patients with UGIB treated with omeprazole and being H. pylori-negative with the first breath test were finally considered infected with the second test. Overall, 92.4% (95% CI, 85%-96%) of the patients with UGIB were infected (89.7% with histology and 92.4% with breath test (P = 0.15)). Concordance kappa value for both diagnostic tests was 0.64. NSAID intake was more frequent in patients with UGIB (34%) than in those without UGIB (5.6%) (P < 0.001), while H. pylori infection was less frequent in patients with UGIB (92.4% (85%-96%)) than in those without UGIB (99.1% (98%-100%); P < 0.001). Even in patients with UGIB, NSAID intake was the only risk factor in 5% of cases. The proportion of cases without H. pylori infection and without NSAID intake was very low in both bleeding and non-bleeding ulcers (2% and 0.5%, respectively; P = 0.146). H. pylori prevalence in bleeding ulcers was of 84% (67%-93%) in patients with NSAID intake, and 96.7% (89%-99%) when patients taking NSAIDs were excluded. In the multivariate analysis, NSAID intake (odds ratio, 9.8 (5.2-18.4)) correlated with UGIB; however, neither H. pylori status nor the interaction between H. pylori infection and NSAID intake correlated with UGIB. In the multivariate analysis in the subgroup of patients with UGIB, NSAID use was the only variable which correlated with H. pylori prevalence (odds ratio, 0.18 (0.03-0.97)). CONCLUSIONS: The most important factor associated with H. pylori-negative bleeding DU is NSAID use, and if this factor is excluded prevalence of infection is almost 100% (97%), similar to that found in patients with non-bleeding DU (and without NSAID intake). Bleeding DU patients with neither H. pylori infection nor NSAID use are extremely rare (only 2%), which suggests that the pathogenesis of bleeding DU is similar to that of non-complicated DU disease.