Assessment of small intestinal bacterial overgrowth and methane production in patients on chronic proton-pump inhibitor treatment: prevalence and role of rifaximin in its management in primary care.

BACKGROUND: Although proton pump inhibitor (PPI) drugs have considered able to induce small intestinal bacterial overgrowth (SIBO), no data are so far available from primary care (PC). We assessed the prevalence of SIBO and methane (CH4) production consequent to chronic PPI therapy using Lactulose Breath Test (LBT). Secondary aim was to explore the possible role of rifaximin in treating PPI-induced SIBO patients. METHODS: One hundred twenty-five gastroesophageal reflux disease patients, constantly treated with PPI for at least 6 months and undergoing to LBT, were retrospectively assessed. An age-matched control population (control) of 100 patients, which had not used PPI in the last 6 months, was also enrolled. In the PPI group, SIBO positive patients and CH4 producers were treated with rifaximin 1200 mg/daily for 14 days and re-checked with LBT one month after the end of treatment. The area under the curve (AUC) before and after treatment was also calculated for both SIBO positive patients and CH4 producers. RESULTS: In the PPI group, SIBO prevalence was significantly higher vs. controls (38/125 [30.4%] vs. 27/100 [27%], P<0.05). 77/125 (61.6%) PPI patients were found to be CH4 producers vs. 21/100 (21%) controls (P<0.05). Among SIBO patients in the PPI group, 34 (89.4%) were also CH4 producers vs. 17/27 (63%) controls (P<0.05). After treatment, LBT resulted negative in 15/22 SIBO patients (68.1%) (P<0.05) and in 18/34 CH4 producers (52.9%) (P<0.05). At the AUC analysis, an overall reduction of 54.2% for H2 in SIBO patients and of 47.7% for CH4 was assessed after rifaximin treatment (P<0.05). CONCLUSIONS: Our data showed that chronic use of PPI could be able to increase the prevalence of SIBO and to shift the intestinal microbial composition towards a CH4-producing flora. rifaximin could represent a useful therapeutical option for PPI-induced SIBO and for modulating CH4-producing flora.

Translational Gap between Guidelines and Clinical Medicine: The Viewpoint of Italian General Practitioners in the Management of IBS.

Irritable bowel syndrome (IBS) guidelines are generally developed by experts, with the possibility of a translational gap in clinical medicine. The aim of our study was to assess an Italian group of general practitioners (GPs) for their awareness and use of criteria for the diagnosis and management of IBS. For this purpose, a survey was carried out involving 235 GPs, divided into two groups according to their years of activity: 65 "junior general practitioners" (JGPs) (≤10 years) and 170 "senior general practitioners" (SGPs) (>10 years). JGPs were more familiar with the Rome IV Criteria and Bristol Scale than SGPs. Abdominal pain, bowel movement frequency and bloating were the symptoms most frequently used to make a diagnosis. The most probable causes of IBS were reported to be abnormal gastrointestinal motility and psychological triggers. SGPs reported more frequently than JGPs that challenging management and patient's request were motivations for a gastroenterological consultation. The practice of clinical medicine is still far from the guidelines provided by the specialists. Abdominal pain related to defecation and changes in bowel frequency are considered to be the more important symptoms for IBS diagnosis, but most GPs, both JGPs and SGPs, like to consider abdominal bloating as another useful symptom. Involving both gastroenterologists and GPs in developing shared guidelines would be highly desirable in order to improve IBS management strategies in everyday clinical practice.

Elimination of Dietary Triggers Is Successful in Treating Symptoms of Gastroesophageal Reflux Disease.

BACKGROUND: The relationship between aliments and pathophysiological abnormalities leading to gastroesophageal reflux disease (GERD) symptoms elicitation is unclear. Nevertheless, patients often report symptoms after ingestion of specific foods. AIMS: To identify in primary care setting the presence of foods able to trigger GERD symptoms, and evaluate whether a consequent specific food elimination diet may result in clinical improvement. METHODS: Diagnosis of GERD and quantification of reflux symptoms were done according to GERD-Q questionnaire (positive when > 8). During clinical data collection, patients were asked to report aliments associated with their symptoms. Also, a precompiled list of additional foods was administered to them. Then, patients were requested to eliminate the specific foods identified, and to come back for follow-up visit after 2 weeks when GERD-Q questionnaire and clinical data collection were repeated. RESULTS: One-hundred GERD (mean GERD-Q score 11.6) patients (54 females, mean age 48.7 years) were enrolled. Eighty-five patients reported at least one triggering food, mostly spicy foods (62%), chocolate (55%), pizza (55%), tomato (52%), and fried foods (52%). At follow-up visit, the diagnosis of GERD was confirmed in only 55 patients, and the mean GERD-Q score decreased to 8.9. Heartburn reporting decreased from 93 to 44% of patients, while regurgitation decreased from 72 to 28%. About half of the patients agreed to continue with only dietary recommendations. CONCLUSIONS: Most patients with GERD can identify at least one food triggering their symptoms. An approach based on abstention from identified food may be effective in the short term.

Usefulness of Pep-Test for Laryngo-Pharyngeal Reflux: A Pilot Study in Primary Care.

BACKGROUND: Gastroesophageal reflux disease is a digestive disorder characterized by nausea, regurgitation, and heartburn. Gastroesophageal reflux is the primary cause of laryngeal symptoms, especially chronic posterior laryngitis. The best diagnostic test for this disease is esophageal impedance-pH monitoring; however, it is poorly employed owing to its high cost and invasiveness. Salivary pepsin measured using a lateral flow device (Pep-test) has been suggested as an indirect marker of laryngopharyngeal reflux (LPR). The present study tested the reliability of Pep-test in diagnosing LPR in uninvestigated primary care attenders presenting with chronic laryngeal symptoms, and evaluated the raw pepsin concentration in patients with LPR. METHODS: A multicenter, non-interventional pilot study was conducted on 86 suspected patients with LPR and 59 asymptomatic subjects as controls in three Italian primary care settings. A reflux symptom index questionnaire was used to differentiate patients with LPR (score >13) from controls (score <5). Two saliva samples were collected, and comparisons between the groups were performed using two-sided statistical tests, according to variable distributions. RESULTS: There was no statistical difference in the salivary pepsin positivity between LPR patients and controls, whereas the pepsin intensity value was higher in controls than in LPR patients. CONCLUSION: A high prevalence of pepsin positivity was observed in asymptomatic controls. Pepsin measurement should not be considered as a diagnostic test for LPR in primary care patients.

Improving IBD diagnosis and monitoring by understanding preanalytical, analytical and biological fecal calprotectin variability.

BACKGROUND: The appropriate clinical use of fecal calprotectin (fCal) might be compromised by incomplete harmonization between assays and within- and between-subjects variability. Our aim was to investigate the analytical and biological variability of fCal in order to provide tools for interpreting fCal in the clinical setting. METHODS: Experiments were conducted to investigate the effects of temperature and storage time on fCal. Thirty-nine controls were enrolled to verify biological variability, and a case-control study was conducted on 134 controls and 110 IBD patients to compare the clinical effectiveness of three different fCal assays: ELISA, CLIA and turbidimetry. RESULTS: A 12% decline in fCal levels was observed within 24 h following stool collection irrespective of storage temperature. Samples were unstable following a longer storage time interval at room temperature. Within- and between-subjects fCal biological variability, at 31% and 72% respectively, resulted in a reference change value (RCV) in the region of 100%. fCal sensitivity in distinguishing between controls and IBD patients is satisfactory (68%), and the specificity high (93%) among young (<65 years), but not among older (≥65 years) subjects (ROC area: 0.584; 95% CI: 0.399-0.769). Among the young, assays have different optimal thresholds (120 µg/g for ELISA, 50 µg/g for CLIA and 100 µg/g for turbidimetry). CONCLUSIONS: We recommend a standardized preanalytical protocol for fCal, avoiding storage at room temperature for more than 24 h. Different cutoffs are recommended for different fCal assays. In monitoring, the difference between two consecutive measurements appears clinically significant when higher than 100%, the fCal biological variability-derived RCV.

Effectiveness and Safety of Pylera® in Patients Infected by Helicobacter Pylori: A Multicenter, Retrospective, Real Life Study.

BACKGROUND: Our aims were to assess the real life effectiveness and safety of the new bismuth-containing quadruple therapy in a large population of patients infected by Helicobacter pylori. METHODS: Consecutive dyspeptic H. pylori-positive patients were enrolled, both naïve for treatment and already unsuccessfully treated. Patients were treated with Pylera® 3 capsules 4 times/daily plus omeprazole 20 mg or esomeprazole 40 mg 2 times/daily for 10 days. Eradication was confirmed using a urea-breath test (at least 30 days after the end of the treatment). Efficacy and safety were assessed. RESULTS: A total of 349 patients were treated. H. pylori eradication was achieved in 316 (90.5%, 95% CIs 80.8-1.0) patients in the intention-to-treat population, and in 93.5% (95% CIs 83.5-1.0) in the per-protocol population. No difference in the eradication rate was found between naïve and previously treated patients (91.3 vs. 90.0%, p = 0.901). Adverse events occurred in 55 patients (15.8%, 95% CIs 11.9-20.1). Five patients discontinued treatment: 2 patients suffered from severe abdominal pain, one patient from headache, one patient from diarrhea, and one patient from diffuse urticarial rush. CONCLUSIONS: Pylera® achieved a remarkable eradication rate in real life both as first treatment and as a rescue therapy, with a good safety profile.

New bismuth-containing quadruple therapy in patients infected with Helicobacter pylori: A first Italian experience in clinical practice.

BACKGROUND: Rising antibiotic resistance requires the evaluation of new and effective therapies. AIMS: To test the efficacy and safety of the new bismuth-containing quadruple therapy in patients infected with Helicobacter pylori. MATERIAL AND METHODS: Consecutive H. pylori-positive dyspeptic patients were enrolled, either naïve or with previous failure treatment. Patients were treated with Pylera® (three-in-one capsules containing bismuth subcitrate potassium 140 mg, metronidazole 125 mg, and tetracycline 125 mg) three capsules q.i.d. plus omeprazole 20 mg or esomeprazole 40 mg b.i.d. for 10 days. Eradication was confirmed using an urea breath test (at least 30 days after the end of treatment). Efficacy was assessed by UBT and safety by means of treatment-emergent adverse events. RESULTS: One hundred and thirty-one patients were included in the study: 42% of patients were naïve, and 58%, with previous failure treatment. H. pylori eradication was achieved in 124 patients (94.7%, 95% confidence intervals (CIs) 89.3-97.8) in ITT population. In the PP population, the percentage was 97.6% (95%, CIs 93.3-99.2). No difference in eradication rate was found either between naïve and previously treated patients (92.7% vs 96.0%, P=.383), or smoking and nonsmoking ones, or in patients taking omeprazole or esomeprazole. Treatment-emergent adverse events occurred in 35 patients (26.7%, 95% CIs 19.9-34.9). They were mild in all cases except in four, who discontinued the study due to diarrhea (three patients) and diffuse urticarial rush (one patient). CONCLUSIONS: Pylera® achieved a remarkable eradication rate in clinical practice, irrespective if it was used as first treatment or as a rescue therapy. Treatment-emergent adverse events were uncommon generally mild.

The Management of Patients With Diverticulosis and Diverticular Disease in Primary Care: An Online Survey Among Italian General Pratictioners.

GOALS: To investigate the current opinion of Italian general practitioners (GPs) on the management of patients with diverticular disease (DD) of the colon. BACKGROUND: The management of DD remains a point of debate, and guidelines are not uniform in their advice. STUDY: A web-based survey was conducted among Italian GPs. Twelve questions were aimed at the diagnosis, treatment, and management options for diverticulosis and symptomatic DD. RESULTS: In total, 245 surveys were filled out. A high-fiber diet was prescribed widely in diverticulosis (44%), together with advice to allow seeds (30%). Rifaximin (26%) and probiotics (25%) were the most frequently prescribed drugs in this population. Colonoscopy was the most prescribed instrumental tool in the diagnosis (77%) and follow-up (21%) of symptomatic uncomplicated diverticular disease patients. Rifaximin, probiotics, and mesalazine were the most frequently prescribed drugs in symptomatic uncomplicated diverticular disease patients (82.8, 59.5%, and 36.3%, respectively). Finally, 77% of the Italian GPs prescribed laboratory exams in the follow-up of these patients. The vast majority of the Italian GPs (83%) managed suspected acute diverticulitis at home, and did not consider two episodes of acute diverticulitis as a strict surgical indication (86%). Rifaximin, probiotics, and mesalazine were the most frequently prescribed drugs to prevent recurrence of the disease (42.5%, 28.2%, and 12.4%, respectively). Finally, 87% of the Italian GPs prescribed laboratory examinations in the follow-up of these patients. CONCLUSIONS: This survey shows that the current management of DD in primary care by Italian GPs is not fully in line with current guidelines and more recent literature data.

Predictive value of the Diverticular Inflammation and Complication Assessment (DICA) endoscopic classification on the outcome of diverticular disease of the colon: An international study.

BACKGROUND: Diverticular Inflammation and Complication Assessment (DICA) endoscopic classification has been recently developed for patients suffering from diverticulosis and diverticular disease. AIMS: We assessed retrospectively the predictive value of DICA in patients for whom endoscopic data and clinical follow-up were available. METHODS: For each patient, we recorded: age, severity of DICA, presence of abdominal pain, C-reactive protein and faecal calprotectin test (if available) at the time of diagnosis; months of follow-up; therapy taken during the follow-up to maintain remission (if any); occurrence/recurrence of diverticulitis; need of surgery. RESULTS: We enrolled 1651 patients (793 M, 858 F, mean age 66.6 ± 11.1 years): 939 (56.9%) patients were classified as DICA 1, 501 (30.3%) patients as DICA 2 and 211 (12.8%) patients as DICA 3. The median follow-up was 24 (9-38) months. Acute diverticulitis (AD) occurred/recurred in 263 (15.9%) patients; surgery was necessary in 57 (21.7%) cases. DICA was the only factor significantly associated to the occurrence/recurrence of diverticulitis and surgery either at univariate (χ(2 )= 405.029; p < 0.0001) or multivariate analysis (hazard ratio = 4.319, 95% confidence interval (CI) 3.639-5.126; p < 0.0001). Only in DICA 2 patients was therapy effective for prevention of AD occurrence/recurrence with a hazard ratio (95% CI) of 0.598 (0.391-0.914) (p = 0.006, log rank test). Mesalazine-based therapies reduced the risk of AD occurrence/recurrence and needs of surgery with a hazard ratio (95% CI) of 0.2103 (0.122-0.364) and 0.459 (0.258-0.818), respectively. CONCLUSIONS: DICA classification is a valid parameter to predict the risk of diverticulitis occurrence/recurrence in patients suffering from diverticular disease of the colon.

Nickel sensitization in patients with gastro-esophageal reflux disease.

BACKGROUND: Gastro-esophageal reflux disease (GERD) leads to frequent medical visits, and available therapies fail in up to 40% of patients. Food allergies may be involved in GERD pathogenesis; however, allergens other than food have received little attention. Nickel allergy is common in the general population and some high-nickel foods are associated with GERD. However, the potential relationship between nickel allergy and GERD remains unaddressed. AIM: This study aimed to evaluate the prevalence of nickel sensitization in patients with and without GERD and to compare clinical and demographic features. METHODS: This prospective, multicenter study included 210 adult GERD patients and 140 patients without GERD who presented at the general practitioner. All GERD patients had undergone treatment with proton pump inhibitors and upper digestive endoscopy within the previous five years. Demographic and clinical data were collected by questionnaire and patients underwent a nickel patch allergy test. RESULTS: Patients with and without GERD presented similar characteristics, with the exception of nickel sensitization, which was significantly more prevalent among GERD patients than controls (39.5% vs. 16.4%; p = 0.001). Nickel-positive GERD patients were more frequently female (90.4% vs. 65.4%, p = 0.003) and asthmatic (18.1% vs. 4.7%; p = 0.038), compared to nickel-negative GERD patients. At six-month follow-up, most of the patients, with or without nickel sensitization, reported improved symptoms without differences in drug prescription. CONCLUSION: Nickel sensitization is particularly prevalent in GERD patients seen in general practice. Whether allergies other than food allergy play a role in GERD remains to be elucidated.

Association between coeliac disease and psoriasis: Italian primary care multicentre study.

BACKGROUND: Studies assessing the association between coeliac disease (CD) and psoriasis show conflicting results. OBJECTIVE: To assess in the primary care setting the prevalence of CD in patients with psoriasis and the response to a gluten-free diet (GFD) in subjects with psoriasis and CD. METHODS: We enrolled 218 patients with psoriasis and 264 controls. Coeliac screening was carried out in all subjects (Eurospital, Trieste, Italy). In subjects with a positive serology, the diagnosis of CD was confirmed histologically. RESULTS: Nine (4.1%) psoriatic patients had positive anti-tissue transglutaminase antibodies compared to only 1 among controls (0.4%, p < 0.05; OR 2.03, 95% CI 1.42-90.11). The diagnosis of CD was confirmed histologically in all 10 subjects. At 6 months GFD was associated with a great improvement of skin lesions in 7 out of 8 patients with psoriasis. CONCLUSION: Our multicentre primary care study showed an high prevalence of CD in psoriasis and an improvement of skin lesions in CD under GFD.