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Background: Vedolizumab (VDZ), a gut-selective anti-lymphocyte trafficking integrin antibody, is effective in treating patients with moderately to severely active Crohn's disease (CD). In this study, we examined the real-world effectiveness and safety of induction therapy using VDZ alone or in combination with budesonide (VDZ + BUD) among patients with CD in Belgium, Israel, and Switzerland., Methods: This retrospective chart review analysis included adult patients with moderately to severely active CD who started induction treatment with VDZ or VDZ + BUD (January 2015 through January 2019). The primary objective of this study was to assess the effectiveness in terms of clinical remission of VDZ alone or VDZ + BUD using patient-reported outcomes (PRO) of abdominal pain (AP) and/or loose stool frequency (LSF) (PRO-2) at weeks 0, 2, 6, 10, and 14. Regression models were used to assess differences and associations between the treatment groups., Results: Overall, 123 patients were included (VDZ, n = 73; VDZ + BUD, n = 50). Clinical remission rates at week 14 were 71.4% (50/70) and 68.0% (34/50) with VDZ and VDZ + BUD, respectively. Mean percentage change in AP and LSF from baseline to week 14 was comparable between the groups. Median (95% confidence interval [CI]) time to clinical remission was 91 [70.0-98.0] and 95 [70.0-98.0] days, respectively. One patient in each group discontinued VDZ and 68.0% of patients in the VDZ + BUD group discontinued BUD before week 14. The rates of overall adverse events were similar between the groups (VDZ, 23.3%; VDZ + BUD, 26.0%)., Conclusions: In this retrospective study, VDZ alone and VDZ + BUD showed similar high remission rates in patients with moderately to severely active CD. Prospective randomized studies are needed to conclude on the role of combining VDZ with BUD., Trial Registration: Not applicable., (© 2023. The Author(s).)

Rotaviruses (RVs) are the most common cause of severe diarrheal disease. To date two rotavirus oral vaccines are licensed: Rotarix and Rotateq. Our aim was to contribute to the post-marketing evaluation of these vaccines safety profile. We collected all RV vaccines-related reports of Adverse Events Following Immunization (AEFI) in US Vaccine Adverse Events Reporting System (VAERS) and VigiBase between January 2007 and December 2017. A disproportionality analysis using Reporting Odds Ratio (ROR) was performed. A total of 17,750 reports in VAERS and 6,358 in VigiBase were retrieved. In VAERS, 86.2% of the reports concerned RotaTeq, whereas in VigiBase 67.7% of them involved Rotarix. Across the databases, diarrhea (1,672 events in VAERS, 1,961 in VigiBase) and vomiting (1,746 in VAERS, 1,508 in VigiBase) were the most reported AEFIs. Noteworthy, the RV vaccines-intussusception pair showed a ROR greater than 20 in both databases. Some new potential safety signals emerged such as fontanelle bulging, hypotonic-hyporesponsive episode, livedo reticularis, and opisthotonus. Overall, our data show that most of the reported AEFIs are listed in the Summary of Product Characteristics (SPCs). However, there remains the need to investigate the potential safety signals arose from this analysis, in order to complete the description of the AEFIs.

Objectives: Data concerning rates of gastrointestinal (GI) events in non-steroidal anti-inflammatory drug (NSAID) users derive mainly from clinical trials. The EVIDENCE study quantified the incidence of symptomatic uncomplicated and/or complicated GI events in at-risk European patients treated with NSAIDs in real-life practice., Methods: This non-interventional study assessed 4144 adults with at least one GI risk factor who recently initiated NSAID therapy for osteoarthritis (85%), rheumatoid arthritis (11%), ankylosing spondylitis (3%) or a combination (1%). Patient characteristics and medical history were collected from medical records. GI events (upper and lower) were recorded at in-clinic visits during 6 months' follow-up., Results: Mean time on index NSAID at enrolment was 33 days. The incidence (per 100 person-years) was 18.5 per 100 person-years for uncomplicated GI events and 0.7 per 100 person-years for complicated GI events. Upper GI events were far more common (12%) than lower GI events (1%) during study follow-up (median 182 days (range 61-320)). Other reported rates for cardiovascular, anaemia or non-GI events were much less frequent. A minority (28%) of patients had ongoing proton pump inhibitor use at enrolment, with strong variation by practice and country., Conclusions: EVIDENCE is the largest prospective study of the real-life management of European patients treated with NSAIDs for rheumatic diseases and at increased GI risk. It shows that GI events from the upper GI tract are far more common than those from the lower GI tract. It also shows adherence to guidelines for gastroprotection is generally low., Clinicaltrialsgov Identifier: NCT01176682., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose: Information about symptomatic toxicities of anticancer treatments is not based on direct report by patients, but rather on reports by clinicians in trials. Given the potential for under-reporting, our aim was to compare reporting by patients and physicians of six toxicities (anorexia, nausea, vomiting, constipation, diarrhea, and hair loss) within three randomized trials., Patients and Methods: In one trial, elderly patients with breast cancer received adjuvant chemotherapy; in two trials, patients with advanced non-small-cell lung cancer received first-line treatment. Toxicity was prospectively collected by investigators (graded by National Cancer Institute Common Toxicity Criteria [version 2.0] or Common Terminology Criteria for Adverse Events [version 3]). At the end of each cycle, patients completed the European Organisation for Research and Treatment of Cancer quality-of-life questionnaires, including toxicity-related symptom items. Possible answers were "not at all," "a little," "quite a bit," and "very much." Analysis was limited to the first three cycles. For each toxicity, agreement between patients and physicians and under-reporting by physicians (ie, toxicity reported by patients but not reported by physicians) were calculated., Results: Overall, 1,090 patients (2,482 cycles) were included. Agreement between patients and physicians was low for all toxicities. Toxicity rates reported by physicians were always lower than those reported by patients. For patients who reported toxicity (any severity), under-reporting by physicians ranged from 40.7% to 74.4%. Examining only patients who reported "very much" toxicity, under-reporting by physicians ranged from 13.0% to 50.0%., Conclusion: Subjective toxicities are at high risk of under-reporting by physicians, even when prospectively collected within randomized trials. This strongly supports the incorporation of patient-reported outcomes into toxicity reporting in clinical trials., (© 2015 by American Society of Clinical Oncology.)

Background: Diarrhea is a common toxicity of chemotherapy, but the practice of reporting only severe grades (≥ 3) in clinical trials results in misleading conclusions of significance. Epidemiology remains poorly described, and effects of multi-cycle regimens have not been investigated. To better understand the risks, symptom burden and consequences of CID, we studied patients receiving chemotherapy for colorectal cancer (CRC)., Methods: One hundred and fourteen patients receiving FOLFOX (95 patients, 530 cycles), FOLFOX + monoclonal antibodies (10 patients, 49 cycles) or FOLFIRI (9 patients, 50 cycles) were enrolled. CID was identified from diaries at baseline and daily during up to 8 chemotherapy cycles using supplemental questions on the Oral Mucositis Daily Questionnaire, a valid tool for collecting patient-reported outcomes of regimen-related mucosal injury. Patients scored CID severity from 0 "none" to 10 "worst possible," and quantity from "little" to "severe" on a 5-point scale. Quality of life was measured using the FACT-G, and fatigue using the FACIT fatigue scale., Results: CID occurred in 89% of patients on FOLFIRI, 50% on FOLFOX + monoclonal antibodies and 56% on FOLFOX alone. The risk of a first episode was highest during Cycle 1 (35 %) and dropped to <10% during Cycles 3-5. Patients with CID reported poorer quality of life scores than those without CID (77.1 vs 80.7)., Conclusions: Diarrhea occurs more commonly than typically appreciated during chemotherapy for CRC. Risk is highest during first exposure, suggesting variable susceptibility. Identification of this high-risk subgroup for prophylaxis could improve the quality of life.

Background: Cabazitaxel/prednisone has been shown to prolong survival versus mitoxantrone/prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or after docetaxel. Subsequently, compassionate-use programmes (CUPs) and expanded-access programmes (EAPs) were established worldwide, allowing access to cabazitaxel before its commercial availability. Preliminary results of the European CUP/EAP, focusing on the elderly population (aged > or =70 years), are reported., Patients and Methods: Enrolled patients with progressive mCRPC received cabazitaxel (25 mg/m2) plus 10mg oral prednisone/prednisolone every 3 weeks until disease progression, death, unacceptable toxicity or physician/patient decision. Safety was analysed by age group (<70, 70-74 and > or =75 years). The influence of selected variables on grade > or =3 neutropenia and/or neutropenic complications was analysed in multivariate analysis., Results: 746 men were enrolled (<70 years, n=421; 70-74, n=180, > or =75 years, n=145). Number of cabazitaxel cycles, dose reductions for any cause, dose delays possibly related to cabazitaxel adverse events, and tolerability were similar in the three age groups. Prophylactic granulocyte colony-stimulating factor (G-CSF) use was more common in men aged > or =0 years. In multivariate analysis, age > or =75 years, treatment cycle 1, and neutrophil count <4000/mm3 before cabazitaxel injection were associated with increased risk of developing grade > or =3 neutropenia and/or neutropenic complications. Prophylactic use of G-CSF at a given cycle significantly reduced this risk by 30% (odds ratio 0.70, p=0.04)., Conclusion: The results suggest that cabazitaxel has a manageable safety profile in everyday clinical practice. Prophylactic use of G-CSF, especially at cycle 1 and in men aged > or =75 years, is important and improves tolerability in senior adults treated with cabazitaxel., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: To investigate whether infusional high-dose 5-flurouracil (HD-FU) provides a significant improvement in recurrence-free survival (RFS) and overall survival (OS) compared with a standard bolus 5-FU regimen (Mayo Clinic) in patients with curatively resectable stage III colon cancer., Methods: Patients (n=1601) were randomised to receive either the Mayo Clinic regimen or one of the three HD-FU regimens; LV5FU2, the Arbeitsgemeinschaft Internistische Onkologie (AIO) or the Grupo Espaňol para el Tratamiento Digestivos (TTD), the data from which were combined to provide the HD-FU arm for final analysis., Results: Patients were evenly balanced for age, TMN, tumor grade and vascular and lymphatic invasion. Median follow-up was approximately 42months, RFS (hazard ratio [HR]=0.997) and OS (HR=0.96) (primary end-point) were not statistically different between the two treatment arms. Infusional HD-FU was generally better tolerated than bolus 5-FU regimen., Conclusions: Infusional HD-FU does not improve RFS and OS in curatively resected stage III colon cancer patients compared to the Mayo Clinic regimen, but is less toxic., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

After a short overview of the history of probiotics, the author presents the development of human intestinal microflora based on the newest genetic data and the microbiological features of main probiotics. The indications of probiotic administration have been defined and extended in recent years. The author reviews significant results of probiotic treatment in some gastrointestinal diseases based on meta-analytical data. Probiotics are useful in preventing and treating diarrhoea caused by antibiotics and Clostridium difficile caused diarrhoea. In the treatment of Helicobacter pylori infection, preparations containing certain Lactobacillus,Bifidobacterium strains or Saccaromyces boulardii could enhance by 5-10% the rate of successful eradication and reduce the incidence and severity of the side effects. Some symptoms of irritable bowel syndrome and thus the quality of life can be improved by probiotics. Their beneficial effect in ulcerative colitis was proven, while in Crohn's disease has not yet been defined. The use of probiotics is not included in guidelines, with the exception of the Maastricht IV/Florence consensus. For each disease it is advisable to use probiotics containing strains only with proven beneficial effect. The efficiency of preparations containing mixed strains has not yet been properly investigated. The author reviews the rare but potentially serious side effects of probiotics. In Hungary, there are many probiotic preparations available which can be purchased in pharmacies without prescription: their use is more empirical than evidence-based. The European Food Safety Authority has recently rejected claims for probiotics to be classed as medicines given the lack of convincing evidence on the effects of probiotics on human health and well-being. Clearly, further research is needed to collect evidence which could be incorporated into the international guidelines.

Background: The standard of chemotherapy regimens for advanced or metastatic gastric cancer and the clinical outcome were heterogeneous in Asian versus non-Asian countries. This study aimed to explore predictors of safety and efficacy of chemotherapy for patients with advanced or metastatic gastric cancer., Methods: Treatment group-based meta-analysis and met a regression were performed to analyze results of randomized trials published since 2005 for advanced or metastatic gastric cancer patients who received systemic chemotherapy as first-line treatment. Data were extracted and synthesized according to the Cochrane guidelines., Results: Twenty-five trials (8 Asian, 17 Western or international) with 56 treatment groups were analyzed. Asian trials reported a lower percentage of gastroesophageal junctional carcinoma, higher percentage of diffuse type histology, and more frequent use of second-line chemotherapy. Meta-analysis revealed significant heterogeneity both in treatment safety (grade 3–4 neutropenia and diarrhea) and efficacy [6-month progression-free survival(PFS) and 1-year overall survival (OS)]. Meta-regression analyses indicate that Asian trials are associated with an 8.2% lower incidence of grade 3–4 neutropenia and 2.1%lower incidence of grade 3–4 diarrhea. A lower percentage of patients with gastroesophageal junction carcinoma and the use of combination regimens predicted better PFS. The use of second-line chemotherapy predicts better 1-year OS,which will increase by 10% for every 10% increase inpatients who received second-line chemotherapy., Conclusion: Geographic region (Asian vs. non-Asian) is an independent predictor of safety in systemic therapy for gastric cancer.

Objectives: To evaluate the efficacy and safety of oral ganciclovir for the maintenance treatment of cytomegalovirus (CMV) retinitis in patients with AIDS., Design: A 20-week, randomized, multicentre, open-label study. Progression of retinitis was assessed by funduscopy and masked reading of fundus photographs., Methods: Adult patients with AIDS and stable CMV retinitis following a 2-3 week induction course of intravenous ganciclovir (5 mg/kg every 12 h) were randomized 2:1 to receive maintenance therapy with oral ganciclovir 500 mg six times daily, or 5 mg/kg intravenous ganciclovir once daily infused over 1 h. The primary efficacy variable was time to progression of CMV retinitis from initiation of maintenance therapy., Results: A total of 159 patients were enrolled; 112 received oral ganciclovir and 47 intravenous ganciclovir. By masked assessment of fundus photographs, CMV retinitis progressed in 72% of patients in the oral group and 76% in the intravenous group. Mean time to progression was 51 days with oral ganciclovir and 62 days with intravenous ganciclovir (P = 0.15). By funduscopy, CMV retinitis progressed in 59% of oral ganciclovir patients and 43% of intravenous ganciclovir patinets. Mean time to progression was 86 and 109 days, respectively (P = 0.02). Diarrhoea and neutropenia (absolute neutrophil count < 500 x 10(6)/l) were the most frequently reported adverse events in both groups. The incidence of spesis for the oral and intravenous ganciclovir patients was 3 and 8.5%, respectively. Infection at the intravenous site occurred in 0 and 9% of patients, respectively., Conclusions: Oral ganciclovir offers an effective and safe alternative to intravenous ganciclovir in the maintenance therapy of CMV retinitis.

Two controlled clinical trials compared loracarbef (LY163892 with amoxicillin/clavulanate or amoxicillin in the treatment of acute exacerbations of chronic bronchitis. Collectively, of 1,057 patients enrolled, 390 qualified for analysis: group 1 comprised 200 patients treated with loracarbef (400 mg twice daily); group 2, 120 patients treated with amoxicillin/clavulanate (500 mg three times daily); and group 3, 70 patients treated with amoxicillin (500 mg three times daily). Symptomatic and bacteriologic outcomes were assessed at post-therapy (within 72 hours of therapy completion), and at late-posttherapy (10-14 days after therapy completion). These evaluations were combined to provide an "overall" evaluation that accounted for all unfavorable outcomes occurring at either the posttherapy or late-posttherapy visit. At the posttherapy evaluation, 93.0% of group 1 patients, 95.0% of group 2 patients, and 88.6% of group 3 patients demonstrated favorable clinical outcomes (cure or improvement). "Overall" favorable clinical outcomes were achieved in 88.0% of group 1 patients, 90.0% of group 2 patients, and 81.4% of group 3 patients. Bacteriologic results from the two studies could not be merged due to marked differences in how posttherapy bacteriologic results were assessed. The clinical significance of positive posttherapy sputum cultures was doubtful: 90% of patients with a positive sputum culture at the posttherapy visit who returned for the late-posttherapy visit had successful clinical outcomes documented at the late-posttherapy evaluation. Loracarbef was associated with a lower incidence of diarrhea and a higher incidence of headache as compared with amoxicillin/clavulanate. These results suggest that 400 mg loracarbef twice daily for 7 days is effective and safe in the treatment of acute exacerbations of chronic bronchitis.

Optimal therapy for pyelonephritis requires the immediate administration of an effective broad-spectrum antibiotic. Because conventional oral antibiotics such as the sulfonamides and the aminopenicillins are limited by the development of resistant bacteria associated with this common disease, the therapeutic effectiveness of a new oral carbacephem antibiotic was investigated. Two double-blind, randomized clinical trials of loracarbef (LY163892) were conducted. A total of 245 patients (greater than or equal to 18 years old) with uncomplicated pyelonephritis were enrolled in parallel studies. One study compared loracarbef with cefaclor; the other compared loracarbef with norfloxacin. In the combined patient population, 119 patients were treated with loracarbef (400 mg twice daily), 43 with cefaclor (500 mg three times daily), and 83 with norfloxacin (400 mg twice daily). All treatment regimens continued for greater than or equal to 14 days. A total of 68 patients in the loracarbef group, 25 in the cefaclor group, and 43 in the norfloxacin group qualified for efficacy analysis. Escherichia coli was the causative pathogen in 85.0% of these patients. Successful posttherapy clinical and bacteriologic responses were similar for all three study drugs: 94.1 and 86.8%, 96.0 and 80.0%, 97.7 and 88.4% for loracarbef, cefaclor, and norfloxacin, respectively. Late posttherapy clinical responses were 87.4, 83.3, and 91.7% for the loracarbef, cefaclor, and norfloxacin groups, respectively. Bacteriologic responses for the three groups were 79.6, 60.0, and 88.9%. The most frequent adverse effects (headache, diarrhea, and nausea) were experienced by three patients (2.5%) in the loracarbef group; headaches were noted in two (4.7%) cefaclor patients, diarrhea was noted in three (7.0%) patients in the cefaclor group, and nausea was noted in four (9.3%). Gastrointestinal events were noted in four patients (4.8%) in the norfloxacin group. The data demonstrate that loracarbef is comparable in efficacy and safety to both cefaclor and norfloxacin as oral therapy for uncomplicated pyelonephritis.