Journal articleIFPRI3; ISI; CRP2; CRP5; E Building ResilienceEPTD; PIMPRCGIAR Research Program on Policies, Institutions, and Markets (PIM); CGIAR Research Program on Water, Land and Ecosystems (WLE

The quality of life of patients who have had rectal cancer is closely associated with the severity of the low anterior resection syndrome. Therefore, it is important that clinicians and researchers focus on this syndrome to improve the prevention and the treatment of bowel dysfunction and the information given to patients.

NCT02175901.

No abstract

Background:Increasing Helicobacter pylori resistance has led to decreases in treatment effectiveness.Aim: To test the effectiveness of susceptibility-guided therapy vs a locally highly effective empiric modified bismuth quadruple therapy for first-line H pylori treatment in a region with high antimicrobial resistance. Methods:We compared 14-day susceptibility-guided with empiric therapy using a multicentre superiority-design trial, which randomised H pylori infected subjects 3:1 to (a) susceptibility-guided therapies contained esomeprazole 20 mg and amoxicillin 1 g b.d. plus clarithromycin 500 mg, metronidazole 400 mg b.d., or levofloxacin 500 mg daily for susceptible infections or bismuth 220 mg b.d. and metronidazole 400 mg q.d.s. for triple-resistant infections; (b) Empiric therapy contained esomeprazole 20 mg, bismuth 220 mg b.d., amoxicillin 1 g and metronidazole 400 mg t.d.s.Primary outcome was H pylori eradication. Results: Between February 2017 and March 2018, 491 subjects were screened and 382 were randomised. Both the susceptibility-guided and the empiric regimens were highly successful with per-protocol eradication rates of 97.7% (250/256) vs 97.6% (81/83, P = 1.00) and intent-to-treat eradication rates of 91.6% (262/286) vs 85.4%(82/96, P = 0.12). Overall, susceptibility-guided therapy was not superior to empiric therapy with 0.1% per-protocol (95% CI −3.1% to 3.2%) and 6.2% intent-to-treat (−0.3% to 12.7%) eradication difference. Both approaches had high adherence and low adverse event rates.Conclusions: Both susceptibility-guided and empiric therapies provided excellent eradication rates. Clinically, the choice would hinge on availability of susceptibility testing and/or a locally highly effective empiric therapy. S U PP O RTI N G I N FO R M ATI O NAdditional supporting information will be found online in the Supporting Information section at the end of the article.How to cite this article: Chen Q, Long X, Ji Y, et al.Randomised controlled trial: susceptibility-guided therapy versus empiric bismuth quadruple therapy for first-line Helicobacter pylori treatment. Aliment Pharmacol Ther.

Objective Antimicrobial resistance has continued to undermine many popular anti-Helicobacter pylori therapies. Antibiotic resistance to commonly used anti-H. pylori drugs in China has increased remarkably making China an ideal site to identify regimens that remain effective despite widespread antimicrobial resistance. Bismuth is one of the few antimicrobials to which resistance does not develop. Factors contributing to H. pylori treatment success include host factors (e.g., genetic differences in metabolism of the drugs used), bacterial factors (e.g., susceptibility) and details of the regimen (e.g., doses, dosing interval, dosing in relation of meals, formulation, etc). Methods We reviewed the recent experience in China with bismuth-containing quadruple therapies. The experience consists of 16 studies with 25 arms involving 1,971 patients to identify successful regimens (defined as reliably obtaining 90% or greater eradication per protocol) deserving of further study. Results Despite high rates of resistance to commonly used antimicrobials, several regimens were able to achieve high success. These were characteristically 14 day regimens containing a proton pump inhibitor and either tetracycline and metronidazole or furazolidone and amoxicillin. Conclusions We propose approaches for further development including for optimization and simplification relation to convenience and side effects (e.g., twice rather than three or 4 times daily or administration at the noon and evening meal instead of at breakfast and evening) while maintaining effectiveness ≥ 90%. Studies in China identified regimens that were highly effective despite the high prevalence of resistance to metronidazole, fluoroquinolones, and macrolides. Multicenter randomized studies will be required to confirm which is best.

Robust and clinically convenient biomarkers for cancer diagnosis, early detection, and prognosis have great potential to improve patient survival and are the key to precision medicine. The advent of next-generation sequencing technologies enables a more sensitive and comprehensive profiling of genetic and epigenetic information in tumor-derived materials. Researchers are now able to monitor the dynamics of tumorigenesis in new dimensions, such as using circulating cell-free DNA (cfDNA) and tumor DNA (ctDNA). Mutation-based assays in liquid biopsy cannot always provide consistent results across studies due partly to intra- and inter-tumoral heterogeneity as well as technical limitations. In contrast, epigenetic analysis of patient-derived cfDNA is a promising alternative, especially for early detection and disease surveillance, because epigenetic modifications are tissue-specific and reflect the dynamic process of cancer progression. Therefore, cfDNA-based epigenetic assays are emerging to be a highly sensitive, minimally invasive tool for cancer diagnosis and prognosis with great potential in future precise care of cancer patients. The major obstacle for applying epigenetic analysis of cfDNA, however, has been the lack of enabling techniques with high sensitivity and technical robustness. In this review, we summarized the advances in epigenome-wide profiling of 5-hydroxymethylcytosine (5hmC) in cfDNA, focusing on the detection approaches and potential role as biomarkers in different cancer types.

To study the impact of donepezil, rivastigmine, galantamine, and memantine on cognitive, functional, behavioral, global changes and adverse effects in patients with mild, moderate and severe Alzheimer’s disease (AD), we screened the literature published before September 2017 in the Pubmed, Embase, Cochrane library and Web of Science Electronic databases according to the inclusion criteria. Thirty-six studies were finally determined from 1560 preliminary screened articles. The AD Assessment Scale-cognitive Subscale (ADAS-cog), AD Cooperative Study-Activities of Daily Living (ADCS-ADL), Neuropsychiatric Inventory (NPI), and Clinician’s Interview-Based Impression of Change Plus Caregiver Input scale (CIBIC+) were used as valid endpoints. Of the 36 trials included, meta-analyses of these placebo-control trials showed that there were significant differences between the donepezil, rivastigmine and placebo groups using ADAS-cog, ADCS-ADL, and CIBIC+. Meta-analyses of these placebo-controlled trials showed that there were significant differences between the galantamine and placebo groups using ADAS-cog, ADCS-ADL, NPI, and CIBIC+. These observations suggest that memantine is beneficial for stabilizing or slowing the decline in ADAS-cog and ADCS-ADL 19 changes in AD patients. However, there was no significant effect according to the ADCS-ADL 23 , NPI, and CIBIC+ tests, which indicated that memantine treatment has no significant effect on these cognitive aspects of AD patients. Different effects of donepezil, rivastigmine, galantamine, or memantine on AD were found in this study. According to the results, we conclude that galantamine is effective in treating all aspects of AD and is the first choice for the treatment of AD. However, due to limited data, we should consider additional data to obtain more stable results.