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Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and risk of malnutrition can coexist in patients with inflammatory bowel disease (IBD). We performed a malnutrition risk assessment as part of the standard follow-up of IBD patients and studied the potential risk factors for being at risk of malnutrition based on the presence or absence of MASLD., Methods: The Malnutrition Universal Screening Tool (MUST) was used to screen malnutrition risk (MUST ≥1) and controlled attenuation parameter (CAP ≥248 dB/min) to assess MASLD. Adherence to a Mediterranean diet, physical activity, and quality of life were also assessed., Results: Of 686 evaluated IBD patients, 130 (18.9 %) were identified as being at risk of malnutrition. Patients without MASLD (n = 89 [68.5 %]) were more likely to be at risk than those with MASLD (n = 41 [31.5 %], p = 0.005). However, among patients at risk of malnutrition, those with MASLD were more likely to have active IBD (82.9 %) than patients without MASLD (39.3 %, p < 0.001). Female sex (OR 1.984, p = 0.027) and young age (OR 1.014, p = 0.006) were associated with malnutrition risk only in patients with IBD without MASLD. Being at risk of malnutrition was associated with worse quality of life (p < 0.001), especially in IBD patients with MASLD., Conclusions: Malnutrition risk and quality of life are modified by the presence of MASLD in IBD patients., Competing Interests: Declaration of competing interest Professor Gomollón has received payments for lectures from Abbvie, Janssen, Takeda, MSD, and Pfizer. His research group has received unrestricted grants for research from Janssen, Abbvie, and GETECCU., (Copyright © 2024. Published by Elsevier Inc.)

Background: Despite classical association between metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity, there is increasing evidence on the development of MASLD in lean individuals. The aim of the study was to assess the prevalence and risk factors of MASLD and significant liver fibrosis in lean participants with inflammatory bowel disease (IBD)., Methods: This was a cross-sectional, case-control study including 300 lean cases with IBD and 80 lean controls without IBD, matched by sex and age. All participants underwent a liver ultrasound, transient elastography, and laboratory tests., Results: The lean IBD group showed a significantly higher prevalence of MASLD compared with lean non-IBD group (21.3% vs 10%; P = .022), but no differences were observed in the prevalence of significant liver fibrosis (4.7% vs 0.0%; P = 1.000). No differences were found between the prevalence of MASLD in IBD and non-IBD participants who were overweight/obese (66.8% vs 70.8%; P = .442). In addition, the prevalence of MASLD was significantly higher in the overweight/obese IBD group compared with the lean IBD group (P < .001). IBD was an independent risk factor for MASLD in lean participants (odds ratio [OR], 2.71; 95% confidence interval [CI], 1.05-7.01; P = .04), after adjusting for classic metabolic risk factors and prior history of systemic steroid use. Nevertheless, no association between IBD related factors and MASLD was identified in lean IBD participants. When the overweight/obese and lean IBD groups with MASLD were compared, the overweight/obese IBD group with MASLD showed higher levels of the homeostatic model assessment of insulin resistance (OR, 1.49; 95% CI, 1.11-1.98; P = .007) and history of smoking (OR, 4.66; 95% CI, 1.17-18.49; P = .029)., Conclusions: MASLD prevalence was higher in the lean IBD group compared with lean non-IBD group, independent of classic metabolic risk factors., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Introduction and Aim: The aim of this systematic review was to assess the role of vitamin C in the prevention of pancreatic cancer (PC)., Methods: A comprehensive literature search was performed in PubMed, Embase and Web of Science up to August 2023, to identify randomized controlled trials (RCT), cohort studies and mendelian randomization studies based on prospective databases assessing the role of vitamin C in PC prevention., Results: A total of twelve studies including European and North-American participants were included: two RCT, three mendelian randomization (MR) studies and seven cohort studies. Both RCT showed high quality in Cochrane risk of bias tool. Only one cohort study had <7 points in Newcastle Ottawa Scale. Both RCT found no association between the intake of 500 mg/day of vitamin C and the incidence of PC. Only one prospective cohort study found an association between vitamin C serum levels and a lower incidence of PC. The remaining cohort studies and MR studies found no association between dietary/supplements intake of vitamin C or circulating vitamin C levels and the incidence of PC., Conclusion: There is no supporting evidence that vitamin C prevents PC development. Future prospective quality studies including high-risk populations are needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Martínez-Domínguez, Laredo and García-Rayado.)

Background: The influence of indications for Helicobacter pylori investigation on prescriptions and effectiveness is unknown. The aim of the study was to assess the impact of indications for H. pylori investigation on prescriptions, effectiveness, compliance, and tolerance., Methods: International, prospective, non-interventional registry of the management of H. pylori infection by European gastroenterologists (Hp-EuReg). Treatment-näive patients registered from 2013 to 2023 at e-CRF AEG-REDCap were analyzed. The effectiveness was assessed by modified intention-to-treat analysis., Results: Overall, 53,636 treatment-naïve cases from 34 countries were included. Most frequent indications were: dyspepsia with normal endoscopy (49%), non-investigated dyspepsia (20%), duodenal ulcer (11%), gastric ulcer (7.7%), and gastroesophageal reflux disease (GERD) (2.6%). Therapy effectiveness varied by indication: duodenal ulcer (91%), gastric ulcer (90%), preneoplastic lesions (90%), dyspepsia with normal endoscopy (89%), GERD (88%), and non-investigated dyspepsia (87%). Bismuth-metronidazole-tetracycline and clarithromycin-amoxicillin-bismuth quadruple therapies achieved 90% effectiveness in all indications except GERD. Concomitant clarithromycin-amoxicillin-tinidazole/metronidazole reached 90% cure rates except in patients with non-investigated dyspepsia; whereas sequential clarithromycin-amoxicillin-tinidazole/metronidazole proved optimal (≥90%) in patients with gastric ulcer only. Adverse events were higher in patients treated for dyspepsia with normal endoscopy and duodenal ulcer compared with the remaining indications (23% and 28%, p < 0.001). Therapeutic compliance was higher in patients with duodenal ulcer and preneoplastic lesions (98% and 99%, p < 0.001)., Conclusion: In Europe, patients with gastric or duodenal ulcers and preneoplastic lesions showed higher H. pylori treatment effectiveness. Bismuth and non-bismuth quadruple therapies achieved optimal results in almost all indications., Trial Registration: ClinicalTrials.gov identifier: NCT02328131., (© 2024 The Author(s). Helicobacter published by John Wiley & Sons Ltd.)

Background: Adherence to Helicobacter pylori (H. pylori) eradication treatment is a cornerstone for achieving adequate treatment efficacy., Objective: To determine which factors influence compliance with treatment., Methods: A systematic prospective non-interventional registry (Hp-EuReg) of the clinical practice of European gastroenterologists. Compliance was considered adequate if ≥90% drug intake. Data were collected until September 2021 using the AEG-REDCap e-CRF and were subjected to quality control. Modified intention-to-treat analyses were performed. Multivariate analysis carried out the factors associated with the effectiveness of treatment and compliance., Results: Compliance was inadequate in 646 (1.7%) of 38,698 patients. The non-compliance rate was higher in patients prescribed longer regimens (10-, 14-days) and rescue treatments, patients with uninvestigated dyspepsia/functional dyspepsia, and patients reporting adverse effects. Prevalence of non-adherence was lower for first-line treatment than for rescue treatment (1.5% vs. 2.2%; p < 0.001). Differences in non-adherence in the three most frequent first-line treatments were shown: 1.1% with proton pump inhibitor + clarithromycin + amoxicillin; 2.3% with proton pump inhibitor clarithromycin amoxicillin metronidazole; and 1.8% with bismuth quadruple therapy. These treatments were significantly more effective in compliant than in non-compliant patients: 86% versus 44%, 90% versus 71%, and 93% versus 64%, respectively (p < 0.001). In the multivariate analysis, the variable most significantly associated with higher effectiveness was adequate compliance (odds ratio, 6.3 [95%CI, 5.2-7.7]; p < 0.001)., Conclusions: Compliance with Helicobacter pylori eradication treatment is very good. Factors associated with poor compliance include uninvestigated/functional dyspepsia, rescue-treatment, prolonged treatment regimens, the presence of adverse events, and the use of non-bismuth sequential and concomitant treatment. Adequate treatment compliance was the variable most closely associated with successful eradication., (© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background and Aims: Inflammatory bowel disease (IBD) has been reported to increase the risk of early atherosclerosis even in young patients. Moreover, metabolic dysfunction-associated steatotic liver disease (MASLD), which has been linked to IBD, is a well-recognized but underdiagnosis entity related to cardiovascular risk. We analyze the impact of MASLD in IBD patients' cardiovascular risk through both advanced lipoprotein profile sorted by nuclear magnetic resonance spectroscopy, and carotid artery intima-media thickness (CIMT)., Methods: Cross-sectional cohort study which involves 941 IBD adult outpatients. Of them, 50 patients with IBD who met criteria for MASLD and 50 with IBD without MASLD, matched by sex and age were included. Alterations in CIMT were evaluated considering abnormal measures above the 75th percentile adjusted for sex and age. Specific advanced lipoprotein profile was also carried out., Results: Most of the patients had an abnormal CIMT (58%). MASLD (OR=5.05, CI 95%=1.71-14.92) and female sex (OR=3.32, CI 95%=1.03-10) were significantly associated with CIMT alterations. Dense LDL particles (with high cholesterol composition in general cohort (OR=3.62, 95% CI=1.07-12.19) and high triglycerides density in young subgroup (OR=6.25, 95% CI=1.04-50) but not total LDL cholesterol were associated with CIMT alterations., Conclusions: MASLD and female sex are associated with early atherosclerosis in IBD patients. Dense LDL particle in combination with vascular imaging findings should be evaluated as non-invasive tools in the management of cardiovascular risk in IBD patients., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

Background: Delayed cholecystectomy in patients with symptomatic gallstone disease is associated with recurrence. Limited data on the recurrence patterns and the factors that determine them are available., Objective: We aimed to determine the pattern of relapse in each symptomatic gallstone disease (acute pancreatitis, cholecystitis, cholangitis, symptomatic choledocholithiasis, and biliary colic) and determine the associated factors., Methods: RELAPSTONE was an international multicenter retrospective cohort study. Patients (n = 3016) from 18 tertiary centers who suffered a first episode of symptomatic gallstone disease from 2018 to 2020 and had not undergone cholecystectomy during admission were included. The main outcome was relapse-free survival. Kaplan-Meier curves were used in the bivariate analysis. Multivariable Cox regression models were used to identify prognostic factors associated with relapses., Results: Mean age was 76.6 [IQR: 59.7-84.1], and 51% were male. The median follow-up was 5.3 months [IQR 2.1-12.4]. Relapse-free survival was 0.79 (95% CI: 0.77-0.80) at 3 months, 0.71 (95% CI: 0.69-0.73) at 6 months, and 0.63 (95% CI: 0.61-0.65) at 12 months. In multivariable analysis, older age (HR = 0.57; 95% CI: 0.49-0.66), sphincterotomy (HR = 0.58, 95% CI: 0.49-0.68) and higher leukocyte count (HR = 0.79; 95% CI: 0.70-0.90) were independently associated with lower risk of relapse, whereas higher levels of alanine aminotransferase (HR = 1.22; 95% CI: 1.02-1.46) and multiple cholelithiasis (HR = 1.19, 95% CI: 1.05-1.34) were associated with higher relapse rates., Conclusion: The relapse rate is high and different in each symptomatic gallstone disease. Our independent predictors could be useful for prioritizing patients on the waiting list for cholecystectomies., (© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: A healthy lifestyle, including good adherence to a Mediterranean diet (MD) and regular physical exercise, may be an important factor during the course of inflammatory bowel disease (IBD). Our aim is to determine whether adherence to MD, physical activity, and the combination of both can impact on IBD course., Methods: This prospective cohort study includes 693 IBD outpatients who were in remission with a median follow-up time of 27 months (interquartile range 22-29 months). Each patient completed a survey to assess their adherence to the MD and physical activity. Healthy lifestyle was considered to be a proper adherence to both MD and an active lifestyle. Relapse during follow-up, severity of relapses, need for systemic steroids, and therapy changes were recorded., Results: During the follow-up period, 188 patients (27.1%) experienced relapse, of which 56.1% were moderate or severe. Among patients with relapse, 85 (45%) required treatment with corticosteroids, and 15 (7.9%) were hospitalized. Patients with ulcerative colitis (CU) were more adherent to healthy lifestyle than patients with Crohn's disease (P = .011). Healthy lifestyle was associated with lower risk of moderate and severe relapses (adjusted Hazard ratio [aHR], 0.250; 95% confidence interval [CI], 0.093-0.670) and steroids use (aHR 0.292; 95% CI, 0.103-0.828) in IBD patients and with lower risk of moderate and severe relapses (aHR 0.270; 95% CI, 0.093-0.789) in UC patients., Conclusions: Healthy lifestyle has a favorable influence on promoting a milder disease course, and thus should be a crucial part of clinical management of patients with IBD., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Management of Helicobacter pylori (H. pylori) infection requires co-treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful eradication., Aim: To evaluate the role of dosage of PPIs and the duration of therapy in the effectiveness of H. pylori eradication treatments based on the 'European Registry on Helicobacter pylori management' (Hp-EuReg)., Methods: Hp-EuReg is a multicentre, prospective, non-interventionist, international registry on the routine clinical practice of H. pylori management by European gastroenterologists. All infected adult patients were systematically registered from 2013 to 2022., Results: Overall, 36,579 patients from five countries with more than 1000 patients were analysed. Optimal (≥90%) first-line-modified intention-to-treat effectiveness was achieved with the following treatments: (1) 14-day therapies with clarithromycin-amoxicillin-bismuth and metronidazole-tetracycline-bismuth, both independently of the PPI dose prescribed; (2) All 10-day (except 10-day standard triple therapy) and 14-day therapies with high-dose PPIs; and (3) 10-day quadruple therapies with clarithromycin-amoxicillin-bismuth, metronidazole-tetracycline-bismuth, and clarithromycin-amoxicillin-metronidazole (sequential), all with standard-dose PPIs. In first-line treatment, optimal effectiveness was obtained with high-dose PPIs in all 14-day treatments, in 10- and 14-day bismuth quadruple therapies and in 10-day sequential with standard-dose PPIs. Optimal second-line effectiveness was achieved with (1) metronidazole-tetracycline-bismuth quadruple therapy for 14- and 10 days with standard and high-dose PPIs, respectively; and (2) levofloxacin-amoxicillin triple therapy for 14 days with high-dose PPIs. None of the 7-day therapies in both treatment lines achieved optimal effectiveness., Conclusions: We recommend, in first-line treatment, the use of high-dose PPIs in 14-day triple therapy and in 10-or 14-day quadruple concomitant therapy in first-line treatment, while standard-dose PPIs would be sufficient in 10-day bismuth quadruple therapies. On the other hand, in second-line treatment, high-dose PPIs would be more beneficial in 14-day triple therapy with levofloxacin and amoxicillin or in 10-day bismuth quadruple therapy either as a three-in-one single capsule or in the traditional scheme., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Background and Aims: Controversial data have been reported regarding the prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) in Inflammatory Bowel Disease (IBD) population and IBD-related risk factors. The aim of the study was to assess the prevalence and risk factors associated with NAFLD and liver fibrosis in IBD participants compared with non-IBD controls., Methods: Cross-sectional, case-control study including 741 IBD cases and 170 non-IBD controls, matched by sex and age. All participants underwent liver ultrasound, transient elastography and laboratory tests. A logistic regression multivariable analysis was performed adjusting for classic metabolic risk factors and history of systemic steroid use., Results: The prevalence of NAFLD and significant liver fibrosis was 45 % and 10 % in IBD group, and 40 % and 2.9 % in non-IBD group (p = 0.255 and 0.062, respectively). Longer IBD duration (aOR 1.02 95% CI (1.001-1.04)) and older age at IBD diagnosis (aOR 1.02 95 % CI (1.001-1.04)) were independent risk factors for NAFLD in IBD group. Crohn´s Disease was an independent risk factor for significant liver fibrosis in participants with IBD and NAFLD (aOR 3.97 95 % CI (1.78-8.96)). NAFLD occurred at lower BMI levels in IBD group with NAFLD compared to non-IBD group with NAFLD (aOR 0.92 95 % CI (0.87-0.98))., Conclusions: Although we found no differences in the prevalence of NAFLD and liver fibrosis between IBD group and non-IBD group, our findings suggest that liver fibrosis progression should be closely monitored in patients with concomitant CD and NAFLD, more in particular in those with long standing active disease., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest regarding this project., (Copyright © 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Suboptimal vaccine response is a significant concern in patients with Inflammatory Bowel Disease (IBD) receiving biologic drugs. This single-center observational study involved 754 patients with IBD. In Phase I (October 2020-April 2021), 754 IBD participants who had not previously received the SARS-CoV-2 vaccine, underwent blood extraction to assess the seroprevalence of SARS-CoV-2 infection and IBD-related factors. Phase II (May 2021-October 2021) included a subgroup of 52 IBD participants with confirmed previous SARS-CoV-2 infection, who were studied for humoral and cellular response to the SARS-CoV-2 vaccine. In Phase I, treatment with anti-TNF was associated with lower rates of seroconversion (aOR 0.25 95% CI [0.10-0.61]). In Phase II, a significant increase in post-vaccination IgG levels was observed regardless of biologic treatment. However, patients treated with anti-TNF exhibited significantly lower IgG levels compared to those without IBD therapy (5.32 ± 2.47 vs. 7.99 ± 2.59 U/ml, p = 0.042). Following vaccination, a lymphocyte, monocyte, and NK cell activation pattern was observed, with no significant differences between patients receiving biologic drugs and those without IBD treatment. Despite lower seroprevalence and humoral response to the SARS-CoV-2 vaccine in patients treated with anti-TNF, the cellular response to the vaccine did not differ significantly from that patients without IBD therapy., (© 2024. The Author(s).)

Background: The recommended schedule for single capsule bismuth quadruple therapy (scBQT, Pylera) includes a proton pump inhibitor (PPI) two times a day and three scBQT capsules four times a day. Four times a day treatments are inconvenient and reduce adherence. In contrast, adherence improves with three times a day schedules. In clinical practice, many gastroenterologists use four capsule scBQT three times a day. However, the effectiveness and safety of this latter approach remain uncertain., Aim: To assess the effectiveness and safety of scBQT administered three times a day in the patients included in the European Registry on Helicobacter pylori Management (Hp-EuReg)., Methods: All Spanish adult patients registered in the Asociación Española de Gastroenterología Research Electronic Data Capture (REDCap) database from June 2013 to March 2021 receiving 10-day scBQT were analysed. Modified intention-to-treat effectiveness, adherence and the safety of scBQT given three times a day were calculated and compared with the four times a day schedule. A multivariate analysis was performed to determine independent factors predicting cure of the infection., Results: Of the 3712 cases, 2516 (68%) were four times a day and 1196 (32%) three times a day. Mean age was 51 years, 63% were women and 15% had a peptic ulcer. The three times a day schedule showed significantly better overall cure rates than four times a day (1047/1112, 94%; 95% CI 92.7 to 95.6 vs 2207/2423, 91%; 95% CI 89.9 to 92.2, respectively, p=0.002). Adherence and safety data were similar for both regimens. In the multivariate analysis, three times a day dosage, first-line therapy, use of standard or high-dose PPIs and adherence over 90% were significantly associated with cure of the infection., Conclusions: ScBQT prescribed three times a day was more effective than the traditional four times a day schedule. No differences were observed in treatment adherence or safety., Competing Interests: Competing interests: XC has received research grants and fees for lectures from Allergan. JPG has served as speaker, consultant and advisory member for or has received research funding from Mayoly Spindler, Allergan, Diasorin, Gebro Pharma and Richen. OPN received research funding from Allergan and Mayoly Spindler. Dr Bordin served as a lecturer for Astellas, AstraZeneca, KRKA, and Abbott. FM is a consultant for PHATHOM and DaVoltera and has received grants from Allergan, bioMerieux and Mobidiag. The remaining authors declare no conflict of interest., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

The prevalence of Helicobacter pylori remains high in the older population. Specific age-related peculiarities may impact the outcomes of H. pylori treatment. The aim of the study was to evaluate the diagnostics and effectiveness of H. pylori eradication between the younger and older European populations. "European Registry on H. pylori Management (Hp-EuReg)" data from 2013 to 2022 were analyzed. Patients were divided into older (≥ 60 years) and younger (18-59 years) groups. Modified intention-to-treat (mITT) and per-protocol (PP) analysis was performed. 49,461 patients included of which 14,467 (29%) were older-aged. Concomitant medications and penicillin allergy were more frequent among the older patients. Differences between younger and older populations were observed in treatment duration in first-line treatment and in proton pump inhibitors (PPIs) doses in second-line treatment. The overall incidence of adverse events was lower in the older adults group. The overall first-line treatment mITT effectiveness was 88% in younger and 90% in the older patients (p < 0.05). The overall second-line mITT treatment effectiveness was 84% in both groups. The effectiveness of the most frequent first- and second-line triple therapies was suboptimal (< 90%) in both groups. Optimal efficacy (≥ 90%) was achieved by using bismuth and non-bismuth-based quadruple therapies. In conclusion, the approach to the diagnostics and treatment of H. pylori infection did not generally differ between younger and older patients. Main differences were reported in the concurrent medications, allergy to penicillin and adverse events both in first- and second-line treatment. Optimal effectiveness rates were mostly achieved by using bismuth and non-bismuth-based quadruple therapies. No clinically relevant differences in the effectiveness between the age groups were observed., (© 2023. Springer Nature Limited.)

Inflammatory bowel diseases (IBDs) are associated with an increased risk of metabolic comorbidities. There is a lack of data regarding the relationship between lifestyle and metabolic diseases in IBD patients. A cross-sectional study on consecutive IBD outpatients was conducted. Adherence to the Mediterranean diet (MD) was assessed using a 14-item questionnaire from the PREDIMED study, and physical activity was evaluated using the GODIN-Leisure score. Body composition was studied based on body mass index and waist-hip ratio (WHR), while quality of life was assessed using a nine-item short questionnaire. Among the 688 evaluated IBD patients, 66% were overweight or obese, 72.7% did not lead an active lifestyle and 70.1% did not adhere to the MD. Metabolic syndrome was associated with age (OR = 1.07, p = 0.019), overweight/obesity (OR = 12.987, p < 0.001) and the inflammatory behavior of Crohn's disease (OR = 6.172, p = 0.001). Type 2 diabetes mellitus or prediabetes was associated with age (OR = 1.063 p = 0.016), overweight/obesity (OR = 3.861, p < 0.001) and the inflammatory behavior of Crohn's disease (OR = 4.716, p = 0.001). Overweight /obesity (OR = 5.494, p < 0.001), a high WHR (OR = 2.564, p = 0.005) and a non-active lifestyle (OR = 2.202, p = 0.0003) were associated with metabolic dysfunction-associated steatotic liver disease. Lifestyle, body composition and not solely systemic inflammation might exert a significant influence on the emergence of metabolic comorbidities such as MASLD, type 2 diabetes mellitus and metabolic syndrome in patients with IBD.

The segmentation of patients into homogeneous groups could help to improve eradication therapy effectiveness. Our aim was to determine the most important treatment strategies used in Europe, to evaluate first-line treatment effectiveness according to year and country. Data collection : All first-line empirical treatments registered at AEGREDCap in the European Registry on Helicobacter pylori management (Hp-EuReg) from June 2013 to November 2022. A Boruta method determined the "most important" variables related to treatment effectiveness. Data clustering was performed through multi-correspondence analysis of the resulting six most important variables for every year in the 2013-2022 period. Based on 35,852 patients, the average overall treatment effectiveness increased from 87% in 2013 to 93% in 2022. The lowest effectiveness (80%) was obtained in 2016 in cluster #3 encompassing Slovenia, Lithuania, Latvia, and Russia, treated with 7-day triple therapy with amoxicillin-clarithromycin (92% of cases). The highest effectiveness (95%) was achieved in 2022, mostly in Spain (81%), with the bismuth-quadruple therapy, including the single-capsule (64%) and the concomitant treatment with clarithromycin-amoxicillin-metronidazole/tinidazole (34%) with 10 (69%) and 14 (32%) days. Cluster analysis allowed for the identification of patients in homogeneous treatment groups assessing the effectiveness of different first-line treatments depending on therapy scheme, adherence, country, and prescription year.

Background: An adequate diagnostic and therapeutic approach to Helicobacter pylori (H. pylori) infection is the cornerstone to avoid overdiagnosis, overuse of health resources, and increase in antibiotic resistances. The aim of the study was to evaluate the most common errors in clinical practice and the associated risk factors., Materials and Methods: This is a retrospective observational study including patients with H. pylori infection and no previous treatment belonging to two defined areas of the National Health System in Spain; some of them were enrolled in the European Registry on H. pylori management (Hp-EuReg). Patients were attended by gastroenterologists between 2010 and 2019. According to current guidelines, we evaluated indications for H. pylori investigation, appropriateness of diagnostic test used in dyspeptic patients and discontinuation of surveillance after treatment., Results: A total of 1730 patients were included, receiving 2260 eradication regimens. H. pylori infection was investigated in 1.7% cases in absence of a formal indication. Oral endoscopy was incorrectly used in 56% of patients with dyspepsia under 55 years without alarm signs, and urea breath test (UBT) was incorrectly used in 22.4% of patients with dyspepsia ≥55 years or red flags. Levofloxacin containing regimens were used as first-line therapy in 7.5% of non-allergic to penicillin patients. After first-line failure, clarithromycin was repeated in 2.6% of the patients who received second-line therapy. Confirmatory test of H. pylori status was absent in 2.5% cases. Men, patients under 55 years, and patients diagnosed by UBT had a higher risk of not undergoing a confirmatory test., Conclusions: Investigation of H. pylori infection by gastroenterologists is rare in absence of a formal indication; however, endoscopy is commonly used for dyspeptic patients <55 years without red flags and non-invasive tests are still used for dyspeptic patients ≥55 years or presenting alarm signs. Men, patients under 55 years, and patients diagnosed by UBT have an increased risk of being lost to follow-up after eradication treatment., (© 2023 John Wiley & Sons Ltd.)

Background and Aims: Several methods are available to diagnose Helicobacter pylori infection. Our objective was to evaluate the tests used for both the initial diagnosis and the confirmation of eradication after treatment in Europe., Methods: The European Registry on the management of Helicobacter pylori infection is an international, multicentre, prospective, non-interventional registry aiming to evaluate the management of Helicobacter pylori -infected patients in Europe. Countries with at least 100 cases registered from June 2013 to April 2021, and with a validated diagnostic method were analysed. Data were quality reviewed., Results: A total of 34,920 adult patients from 20 countries were included (mean age 51 years; 61% women). To establish the initial diagnosis, invasive tests were performed in 19,801 (71%) patients, non-invasive in 11,369 (41%), and both in 3437 (12%). The most frequent were histology (n = 11,885; 43%), a rapid urease test (n = 10,636; 38%) and an urea breath test (n = 7577; 27%). According to the age, invasive tests were indicated in 11,179 (77%) ≥50 years, and in 8603 (65%) <50 years. Depending on the country, the use of invasive tests ranged from 29-99% in <50 years to 60-99% in ≥50. Most of the tests used to confirm eradication were non-invasive (n = 32,540; 93%), with the urea breath test being the most frequent (n = 32,540; 78%). In 2983 (9%) post-treatment tests, histology (n = 1887; 5%) or a rapid urease test (n = 1223; 4%) were performed., Conclusion: A great heterogeneity was observed for the initial diagnosis and confirmation of the eradication. The reasons for the apparent lack of adherence to the clinical guidelines should be further explored.

The aim of the systematic review is to assess the prevalence and risk factors of liver fibrosis in patients with Inflammatory Bowel Disease (IBD) and Non-Alcoholic Fatty Liver Disease (NAFLD) and to discuss the role of liver fibrosis in the progression to hepatocellular carcinoma (HCC). We performed a structured search in PubMed, Web of Science, Embase, and Scopus up to 3 March 2023 to identify observational studies reporting liver fibrosis in patients with NAFLD and IBD. Quality of studies was assessed using the Newcastle-Ottawa Scale (NOS) score. A total of 23 studies met our inclusion criteria, including 629,781 patients. A total of 10 cross-sectional, 3 case-control, and 10 cohort studies were included. Fourteen studies had a NOS score ≥ 7 points. NAFLD was diagnosed in 2162/6332 (34.1%) IBD participants. However, NAFLD diagnosis was established in 924/2962 (31.2%) healthy individuals without IBD. Advanced liver fibrosis was found in 116 (11.6%) of 992 IBD patients with NAFLD. Most studies found an association between NAFLD and classic cardiovascular risk factors such as older age, male sex, higher BMI, diabetes, hypertension and dyslipidemia. In addition, metabolic syndrome features were also associated with an increased risk of significant and advanced liver fibrosis. Although no strong association between NAFLD and IBD therapy was reported, some studies associated NAFLD with IBD diagnosis, Crohn's Disease, a complicated course of IBD, disease activity, and IBD duration. Advanced liver fibrosis was also associated with Crohn's disease in several studies. In conclusion, NAFLD and advanced liver fibrosis are prevalent and clinically relevant extraintestinal manifestations, so its diagnosis and potential progression to HCC should be carefully considered in daily clinical practice.

Chronic inflammation in patients with Inflammatory Bowel Disease (IBD) leads to an increased risk of colorectal cancer, small bowel cancer, intestinal lymphoma and cholangiocarcinoma. However, treatments for IBD have also been associated with an increased risk of neoplasms. Patients receiving Thiopurines (TPs) have an increased risk of hematologic malignancies, non-melanoma skin cancer, urinary tract neoplasms and cervical cancer. Anti-TNFs have been associated with a higher risk of neoplasms, mainly lymphomas and melanomas; however, the data are controversial, and some recent studies do not confirm the association. Nevertheless, other biologic agents, such as ustekinumab and vedolizumab, have not shown an increased risk of any neoplasm to date. The risk of malignancies with tofacitinib exists, but its magnitude and relationship with previous treatment with TPs is not defined, so more studies from daily clinical practice are needed. Although biologic therapy seems to be safe for patients with current cancer or a prior history of cancer, as has been demonstrated in other chronic inflammatory conditions, prospective studies in this specific population are needed. Until that time, it is crucial to manage such conditions via the combined clinical expertise of the gastroenterologist and oncologist.

Helicobacter pylori infection ( H. pylori ) is mainly managed at the primary care level. Our group previously performed a study demonstrating that providing specific counselling (SC) to primary care practitioners (PCPs) who requested a urea breath test (UBT) improved treatment management but not indications for H. pylori tests. SC was given in the form of a personal letter addressed to PCPs with UBT results which contained information about accepted UBT indications and a Helicobacter pylori treatment algorithm. The purpose of the present study was to evaluate the effect of training sessions (TS) on UBT indications, antibiotic prescriptions and eradication rates. This was a quasi-experimental study performed at primary care centres (PCCs). Phase I included 399 patients diagnosed with H. pylori infection after providing SC to PCPs. Phase II included 400 H. pylori -positive patients after giving TS to PCPs who had already received SC (100 from PCCs with TS and 300 from PCCs without TS). An improved trend in the appropriate indication of H. pylori diagnosis was observed between Phase I and PCCs with TS in Phase II (57.5% vs. 67%; p = 0.06). TS improved appropriate prescriptions in PCCs with TS compared to PCCs that only received SC in Phase I and II (94% vs. 75.3%, p = 0.01; 94% vs. 85.6%, p = 0.04, respectively). Eradication rates showed no differences between groups. In conclusion, training sessions after specific counselling improved antibiotic prescription appropriateness but not eradication rates.

The stool antigen test (SAT) represents an attractive alternative for detection of Helicobacter pylori. The aim of this study was to assess the accuracy of a new SAT, the automated LIAISON® Meridian H. pylori SA based on monoclonal antibodies, compared to the defined gold standard 13C-urea breath test (UBT). This prospective multicentre study (nine Spanish centres) enrolled patients ≥18 years of age with clinical indication to perform UBT for the initial diagnosis and for confirmation of bacterial eradication. Two UBT methods were used: mass spectrometry (MS) including citric acid (CA) or infrared spectrophotometry (IRS) without CA. Overall, 307 patients (145 naïve, 162 with confirmation of eradication) were analysed. Using recommended cut-off values (negative SAT < 0.90, positive ≥ 1.10) the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 67%, 97%, 86%, 92% and 91%, respectively, obtaining an area under the receiver operating characteristic (ROC) curve (AUC) of 0.85. Twenty-eight patients, including seven false positives and 21 false negatives, presented a discordant result between SAT and UBT. Among the 21 false negatives, four of six tested with MS and 11 of 15 tested with IRS presented a borderline UBT delta value. In 25 discordant samples, PCR targeting H. pylori DNA was performed to re-assess positivity and SAT accuracy was re-analysed: sensitivity, specificity, positive predictive value, negative predictive value, accuracy and AUC were 94%, 97%, 86%, 99%, 97% and 0.96, respectively. The new LIAISON® Meridian H. pylori SA SAT showed a good accuracy for diagnosis of H. pylori infection.

The main clinical relevance of Barrett's esophagus (BE), a result of chronic exposure to gastroesophageal reflux, is its potential progression to esophageal adenocarcinoma (EAC). Although screening for BE is not recommended in the general population, after diagnosis of BE, a surveillance strategy for early detection of dysplasia or neoplasia is needed. The gold standard for diagnosis and surveillance is high-definition oral endoscopy with random biopsies. In addition, any visible lesion should be completely resected, which will be considered curative in the presence of low grade dysplasia (LGD), high-grade dysplasia (HGD) or EAC confined to the mucosa (T1a), followed by eradication of residual BE by endoscopic ablation. In the absence of a visible lesion, radiofrequency ablation should be performed to eradicate BE with LGD, HGD or intramucosal EAC., (Copyright © 2022 Elsevier España, S.L.U. All rights reserved.)

The management and effectiveness of the treatment of Helicobacter pylori infection are heterogeneous worldwide, despite the publication of international consensus conferences and guidelines, which have been widely available for years. The aim of the study was to describe the clinical management and the eradication rates in a region of Southern Europe (Spain). Between 2010 and 2019, we conducted a retrospective analysis of patients with H. pylori infection attended by gastroenterologists in two defined areas of the National Health System in Aragón. We compared the appropriateness of therapies according to guidelines, and described the effectiveness of each treatment. A total of 1644 penicillin non-allergic patients were included. The most prescribed therapy between 2010 and 2013 was the 'classic' triple therapy PCA (80%), whereas the 'concomitant' therapy PCAM was chosen by 90% of the gastroenterologists in 2015. After 2016, the use of the quadruple bismuth-containing therapy in a single capsule (Pylera ® ) quickly increased, representing almost half of the overall prescriptions in 2019. Throughout the decade, adherence to guidelines was 76.4% and global efficacy was 70.7% (ITT). Triple therapies' eradication rates were lower than 70% (ITT), whereas eradication rates with quadruple therapies achieved or were over 80% (ITT). In conclusion, despite the use of quadruple therapies and optimized treatments, the effectiveness of H. pylori management in daily clinical practice is far from the target of 90%.

Introduction: The lockdown period due to the coronavirus disease 2019 (COVID-19) in Spain probably had a significant emotional impact on chronic patients and hence on those who are suffering from inflammatory bowel disease (IBD) due to their high risk of emotional disorders. The aim of this study was to learn how COVID-19 influenced patients suffering from IBD during the quarantine period, focusing in particular on psychological distress through the Perceived Stress Scale-10 (PSS-10) and also the impact of the pandemic on therapeutic adherence using the Visual Analogue Scale (VAS)., Patients and Methods: A prospective, single-centre and analytical observational study was carried out in the IBD unit in August 2020. Patients were contacted and interviewed by phone. A descriptive analysis was carried out and subsequently the factors associated with the loss of therapeutic adherence and higher-moderate levels of stress were analyzed through logistic regression multivariate analyses., Results: A total of 426 patients were included with a median PSS-10 score of 12 (10-16). A higher level of stress was reported by those who were not married, women and those who experienced an increase in IBD-related symptoms. Adherence to treatment was not associated with stress based on the PSS-10 questionnaire., Conclusions: Although the lockdown period due to the COVID-19 pandemic has probably had a significant emotional impact on Spaniards with IBD, IBD patients in general had lower PSS-10 scores., (Copyright © 2021 Elsevier España, S.L.U. All rights reserved.)

Statins could increase the effectiveness of Helicobacter pylori eradication therapies due to their anti-inflammatory effect. The aim of this study was to analyze the impact of this therapeutic association in real life. This is a multicenter, prospective, non-interventional study aimed at evaluating the management of H. pylori by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap from 2013 to 2020. The association between statin use and H. pylori eradication effectiveness was evaluated through multivariate analysis. Overall, 9988 and 705 patients received empirical and culture-guided treatment, respectively. Overall, statin use was associated with higher effectiveness in the empirical group (OR = 1.3; 95%CI = 1.1-1.5), but no association was found with first-line treatment effectiveness (N = 7738); as an exception, statin use was specifically associated with lower effectiveness of standard triple therapy (OR = 0.76; 95%CI = 0.59-0.99). In the rescue therapy empirical group (N = 2228), statins were associated with higher overall effectiveness (OR = 1.9; 95%CI = 1.4-2.6). However, sub-analyses by treatment schemes only confirmed this association for the single-capsule bismuth quadruple therapy (OR = 2.8; 95%CI = 1.3-5.7). No consistent association was found between statin use and H. pylori therapy effectiveness. Therefore, the addition of statins to the usual H. pylori treatment cannot be currently recommended to improve cure rates.

Objective: To assess the efficacy of cervical pessary application for the prevention of spontaneous preterm birth (SPB) in singleton pregnancies with a sonographically measured short cervix., Methods: Searches were conducted in PubMed-Medline, Embase, Scopus, Web of Science, and Cochrane Library, and clinical trial registries for randomized controlled trials (RCTs) published in all languages from inception through 28 July 2018. Inclusion criteria were registered RCTs of singleton pregnants with a short cervix (≤ 25 mm) measured at 22-24 weeks comparing the use of a cervical pessary versus controls over the risk of SPB. Risk of bias was evaluated with the Cochrane tool. Risk ratios (RRs) and mean differences and 95% confidence intervals (CIs) were calculated., Results: We identified three RCTs meeting defined inclusion criteria, including a total of 1612 pregnancies (805 used a cervical pessary). SPB risk at < 37 was lower for participants using the pessary (RR  0.46; 95% CI 0.28-0.77). Pessary application was associated with a higher risk of presenting vaginal discharge (RR 2.05; 95% CI 1.82-2.31). There were no significant differences between pessary users and controls in terms of SPB at < 28 and < 34 weeks, and for any type of preterm birth < 34 weeks; mean gestational age and infant weight at delivery; and the risks of chorioamnionitis, cesarean delivery, and perinatal or neonatal outcomes. Sub-analysis by risk of bias showed that there was a lower risk of SPB < 34 weeks (RR 0.33; 95% CI 0.16-0.66) in two RCTs with low risk of bias., Conclusion: Cervical pessary application was associated with a reduced risk of SPB at  < 37 weeks and a higher risk of vaginal discharge.

Objective: This systematic review and meta-analysis of Spanish studies assessed the association of maternal 25-hydroxyvitamin D [25(OH)D] levels on perinatal outcomes. Methods: PubMed, Cochrane Library, Embase, Scielo, Scopus, and Web of Science research databases were searched from inception through December 30 2017 using the terms 'vitamin D', 'pregnancy', and 'Spain'. Studies that compared first or second half of pregnancy normal 25(OH)D (≥30.0 ng/mL) versus insufficient (20.0-29.9 ng/mL) or deficient (<20.0 ng/mL) circulating levels and perinatal outcomes were systematically extracted. Data are presented as pooled odds ratios and their 95% confidence intervals (CIs) for categorical variables or mean differences and CIs for continuous variables. Risk of bias was evaluated with the Newcastle-Ottawa Scale. Results: Five cohort studies met inclusion criteria. The risk of gestational diabetes mellitus, preeclampsia, preterm birth, and small-for-gestational-age infants, and birthweight was not influenced by first half of pregnancy maternal 25(OH)D levels. In addition, second half of pregnancy 25(OH) levels did not affect birthweight. Conclusion: Maternal 25(OH)D levels during pregnancy did not affect studied perinatal outcomes and birthweight.

Objective: To investigate the association between endometriosis and preeclampsia and/or its severe forms (eclampsia and/or the hemolysis, elevated liver enzymes and low platelet count [HELLP] syndrome) in pregnancies conceived either spontaneously or by assisted reproductive technology (ART)., Design and Methods: Systematic review and meta-analysis of observational studies. Search in PubMed-Medline, Scopus, Web of Science, Cochrane Library, Clinicaltrials.gov, the UK Clinical Trials Gateway, and the Australian New Zealand Clinical Trials Registry was conducted from inception through 21 June 2017, without language restrictions. Primary outcome was preeclampsia and/or its severe forms (eclampsia and/or HELLP syndrome) in pregnant women. Random-effects models were used for meta-analyses. Endometriosis effect was estimated as odds ratio (OR) with 95% confidence interval (CI)., Results: A total of 9 cohort and 4 case-control studies were eligible for data analysis, including 39,816 pregnancies with endometriosis and 2,831,065 without. Women with endometriosis diagnosed through biopsy did not have a higher preeclampsia, eclampsia and HELLP syndrome risk as compared to those without (OR 1.01, 95% CI 0.56-1.82); this was found the same even if endometriosis was diagnosed using other procedures (OR 1.15, 95% CI 0.94-1.40). Preeclampsia, eclampsia and HELLP syndrome risk was also not increased in women with endometriosis conceiving spontaneously (OR 1.21; 95% CI 0.94-1.56) or through ART (OR 0.74; 95% CI 0.41-1.35)., Conclusion: This meta-analysis evidences that endometriosis was not associated to a higher risk of preeclampsia and/or its severe forms in pregnancies either conceived spontaneously or through ART., (Copyright © 2018. Published by Elsevier B.V.)

Objective: To clarify the effect of programmed exercise (PE), performed for at least six weeks, on perceived stress (PS) in middle aged and old women., Methods: A structured search was carried out in PubMed, Embase, Cochrane Library, Scielo, Web of Science and Scopus, from database inception through January 10, 2018, without language restriction. The US, UK, and Australian clinical trials databases were also searched. The search included a combination of the terms "programmed exercise", "perceived stress", "menopausal women" and "randomized controlled trial" (RCTs). PE was classified according to duration as "mid-term exercise intervention" (MTEI; mean duration 6 months), and "long-term exercise intervention" (LTEI; mean duration 12 months). Mean ± standard deviations of changes in PS scores, as assessed with different questionnaires, were calculated as standardized mean differences (SMDs) and used as effect size for meta-analysis. SMDs of PS after intervention were pooled using a random-effects model. Study quality and bias risk were assessed with the Cochrane tool., Results: Five RCTs that studied midlife and older women (mean age 47.0 ± 1.7 years minimum to 71.8 ± 5.6 maximum) were included in the meta-analysis. There was no significant effect of PE on PS score (SMD: -0.16; 95% CI: -0.43 to 0.11). In subgroup analyses, there was no significant effect of PE on PS with mid-term interventions (SMD: - 0.17; 95% CI: -0.59 to 0.25) nor with long-term interventions (SMD: -0.02; 95% CI: -0.42 to 0.38) as compared with controls., Conclusion: PE of low to moderate intensity does not improve PS in midlife and older women., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To compare the efficacy of single- versus double-balloon catheter (SBC vs. DBC) for cervical ripening and labor induction with an unfavorable cervix., Methods: Systematic review and meta-analysis of randomized controlled trials (RCTs) or quasi-RCTs (qRCT) regarding the use of SBC or DBC for labor induction of live singleton cephalic pregnancies (≥ 35 weeks) of any parity with an unripe cervix (Bishop score ≤ 6). Nine research databases were searched for original articles published in all languages up to November 2017 comparing both devices for labor induction. Five RCTs and one qRCT were included. Primary outcome measures were time from intervention (device placement) to birth time, vaginal delivery and cesarean section rates, and maternal satisfaction with the procedure. Risk of bias was evaluated with the Cochrane tool. Random effects models were used to combine data for meta-analyses. Summary measures were reported as mean differences and risk ratios (RR) with 95% confidence intervals., Results: Regardless of parity, pooled analyses of the six trials (n = 1060 women) found that mean intervention to birth time, vaginal delivery and cesarean section rates, and maternal satisfaction to the procedure were similar for both studied groups (SBC vs. DBC)., Conclusion: Measured primary outcome measures were similar regardless of the type of device used for labor induction of singleton pregnancies.

Objective: To perform a systematic review and meta-analysis regarding endometriosis and the risk of gestational diabetes mellitus (GDM)., Methods: We carried out a search of the following databases: Medline, Embase, Web of Science, Cochrane Library, Scopus, Scielo, Clinicaltrials.gov, the UK Clinical Trials Gateway, and the Australian New Zealand Clinical Trials Registry, from inception through April 28 2017, without language restrictions, in order to evaluate the effect of endometriosis over GDM risk, in women with and without endometriosis. Odds ratios (ORs) and their 95% confidence intervals (CIs) or mean differences (MDs) were calculated as effects. Methodological quality of evidence was assessed with the Newcastle-Ottawa Scale, and heterogeneity among studies with the I 2 statistic. Random-effects models were used for meta-analyses, and publication bias was assessed with Egger's test., Results: We identified 12 studies (10 cohort and two case control studies) with a total of 48,762 pregnancies, including 3,461 with endometriosis. Endometriosis had no significant effect on GDM risk (OR =1.14; 95% CI: 0.86, 1.51; p = .35, I 2  = 56%, Egger's test p = .45). Secondary outcomes (gestational age at delivery, birthweight, and Neonatal Intensive Care Unit admission) were statistically similar in women with and without endometriosis., Conclusions: Better-designed studies are needed to confirm our results.

We aimed to perform a systematic review and meta-analysis in order to clarify the effect of programmed exercise over mild-to-moderate anxiety symptoms (ASs) in midlife and older women. A structured search of PubMed, Medline, Web of Science, Scopus, Embase, Cochrane Library, Scielo, and the US, UK and Australian Clinical Trials databases (from inception through July 27, 2017) was performed, with no language restriction using the following terms: 'anxiety', 'anxiety symptoms', 'exercise', 'physical activity', 'menopause', and 'randomized controlled trial' (RCTs) in mid-aged and older women. We assessed RCTs that compared the effect of exercise for at least 6 weeks versus no intervention over ASs as outcome (as defined by trial authors). Exercise was classified according to duration as 'mid-term exercise intervention' (MTEI; for 12 weeks to 4 months), and 'long-term exercise intervention' (LTEI; for 6-14 months). Mean ± standard deviations of changes for ASs, as assessed with different questionnaires, were extracted to calculate Hedges' g and then used as effect size for meta-analyses. Standardized mean differences (SMDs) of ASs after intervention were pooled using a random-effects model. Ten publications were included for analysis related to 1463 midlife and older women (minimum age 54.2 ± 3.5 and maximum age 77.6 ± 5.4 years). Eight MTEIs were associated with a significant reduction of ASs (SMD = -0.42; 95% CI -0.81 to -0.02) as compared to controls. There was no reduction of ASs in seven LTEIs (SMD = -0.03; 95% CI -0.18 to 0.13). It can be concluded that MTEIs of low-to-moderate intensity seem to improve mild-moderate ASs in midlife and older women.

Objective: To perform a systematic review and meta-analysis to clarify the effect of programmed exercise on depressive symptoms (DSs) in midlife and older women., Methods: We carried out a structured search of PubMed-Medline, Web of Science, Scopus, Embase, Cochrane Library and Scielo, from database inception through June 29, 2017, without language restriction. The search included the following terms: "depression", "depressive symptoms", "exercise", "physical activity", "menopause", and "randomized controlled trial" (RCTs) in midlife and older women. The US, UK and Australian Clinical Trials databases were also searched. We assessed randomized controlled trials (RCTs) that compared the effect of exercise for at least 6 weeks versus no intervention on DSs as the outcome (as defined by trial authors). Exercise was classified according to duration as "mid-term exercise intervention" (MTEI; lasting for 12 weeks to 4 months), and "long-term exercise intervention" (LTEI; lasting for 6-12 months). Mean changes (±standard deviations) in DSs, as assessed with different questionnaires, were extracted to calculate Hedges' g and then used as the effect size for meta-analysis. Standardized mean differences (SMDs) of DSs after intervention were pooled using a random-effects model., Results: Eleven publications were included for analysis related to 1943 midlife and older women (age range 44-55 years minimum to 65.5±4.0 maximum), none of whom was using a hormone therapy. Seven MTEIs were associated with a significant reduction in DSs (SMD=-0.44; 95% CI -0.69, -0.18; p=0.0008) compared with controls. The reduction in DSs was also significant in six LTEIs (SMD=- 0.29; 95% CI -0.49; -0.09; p=0.005). Heterogeneity of effects among studies was moderate to high. Less perceived stress and insomnia (after exercise) were also found as secondary outcomes., Conclusion: Exercise of low to moderate intensity reduces depressive symptoms in midlife and older women., (Copyright © 2017. Published by Elsevier B.V.)