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Biomedical subjects

Yuhong Yuan

Publications and source records attributed to Yuhong Yuan.

8 recordsLinked to original sources

Efficacy of Advanced Therapies in Achieving Remission by Disease Location in Crohn's Disease: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: We compared the efficacy of different advanced therapies by disease location in patients with Crohn's disease (CD) through a systematic review and meta-analysis. METHODS: Through a systematic review, we identified 14 randomized controlled trials in 3139 patients with moderate-to-severe CD who were treated with different advanced therapies vs placebo, and reported efficacy in inducing clinical remission, stratified by disease location (isolated colonic vs ileal disease, excluding ileocolonic disease). We grouped advanced therapies based on the primary mechanism of action: anti-interleukins, Janus kinase inhibitors (JAK inhibitors), anti-integrins, and tumor necrosis factor (TNF) antagonists. We calculated treatment efficacy (drug vs placebo), overall and by drug class, for colonic vs ileal disease. RESULTS: Overall treatment efficacy of advanced therapies vs placebo was higher in patients with colonic (odds ratio [OR], 4.09; 95% confidence interval [CI], 3.02-5.54) vs ileal CD (OR, 1.80; 95% CI, 1.23-2.63; P < .001). By drug class, anti-interleukins demonstrated a higher efficacy in colonic disease (OR, 4.29; 95% CI, 2.77-6.64) vs ileal disease (OR, 2.31; 95% CI, 1.44-3.70; P = .059), whereas no difference in efficacy was observed with anti-integrins (colonic vs ileal: OR, 1.79; 95% CI, 0.55-5.87 vs 2.10; 95% CI, 0.80-5.53; P = .84). For JAK inhibitors, efficacy was observed only in patients with isolated colonic disease (OR, 4.37; 95% CI, 2.67-7.15), but not in ileal disease (OR, 1.01; 95% CI, 0.54-1.89; P < .001). All analyses had minimal to moderate heterogeneity. CONCLUSIONS: The magnitude of efficacy of advanced therapies for ileal CD is generally lower compared with isolated colonic CD, with JAK inhibitors showing particularly limited efficacy for ileal disease. These results may help inform treatment selection.

Humans↗

Selective serotonin reuptake inhibitors and risk of upper GI bleeding: confusion or confounding?

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) represent a relatively new class of antidepressants. Several studies have reported bleeding disorders associated with the use of SSRIs, which are considered the result of a decrease in platelet serotonin leading to a defect in platelet aggregation. To what extent the use of SSRIs increases the risk of gastrointestinal bleeding is unclear. METHODS: A comprehensive literature search for studies addressing SSRI use and upper gastrointestinal tract bleeding (UGIB) was conducted using Medline, EMBASE, and Cochrane databases with a recursive manual reference search up to May 2005. Any observational and interventional studies were systematically reviewed, and critical appraisal was conducted on available studies. RESULTS: Published clinical evidence on the relationship between SSRI use and gastrointestinal bleeding is limited to observational studies without any clinical trials. Three cohort studies and one case-control study met inclusion criteria. These studies combined different affinity SSRIs in the class and had differing control groups with conflicting conclusions. Both a cohort study and a case-control study investigating the concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin found that combined use with an SSRI increased the risk of UGIB. CONCLUSIONS: Only a few epidemiology studies have investigated the association between SSRIs and UGIB. They provide weak evidence to support the hypothesis of a link between SSRIs and UGIB at a population level. Available evidence shows that concurrent use of NSAIDs or aspirin with SSRIs greatly increases the risk of UGIB. The preventive strategy should be considered in those SSRI users at high risk, especially the elderly or those with a history of UGIB and taking nonselective NSAIDs or aspirin.

Antidepressive Agents↗

Peptic ulcer disease today.

Over the past few decades, since the introduction of histamine H(2)-receptor antagonists, proton-pump inhibitors, cyclo-oxygenase-2-selective anti-inflammatory drugs (coxibs), and eradication of Helicobacter pylori infection, the incidence of peptic ulcer disease and ulcer complications has decreased. There has, however, been an increase in ulcer bleeding, especially in elderly patients. At present, there are several management issues that need to be solved: how to manage H. pylori infection when eradication failure rates are high; how best to prevent ulcers developing and recurring in nonsteroidal anti-inflammatory drug (NSAID) and aspirin users; and how to treat non-NSAID, non-H. pylori-associated peptic ulcers. Looking for H. pylori infection, the overt or surreptitious use of NSAIDs and/or aspirin, and the possibility of an acid hypersecretory state are important diagnostic considerations that determine the therapeutic approach. Combined treatment with antisecretory therapy and antibiotics for 1-2 weeks is the first-line choice for H. pylori eradication therapy. For patients at risk of developing an ulcer or ulcer complications, it is important to choose carefully which anti-inflammatory drugs, nonselective NSAIDs or coxibs to use, based on a risk assessment of the patient, especially if the high-risk patient also requires aspirin. Testing for and eradicating H. pylori infection in patients is recommended before starting NSAID therapy, and for those currently taking NSAIDs, when there is a history of ulcers or ulcer complications. Understanding the pathophysiology and best treatment strategies for non-NSAID, non-H. pylori-associated peptic ulcers presents a challenge.

Anti-Bacterial Agents↗

The effect of CYP2C19 polymorphisms on H. pylori eradication rate in dual and triple first-line PPI therapies: a meta-analysis.

PREMISE: It has been suggested that proton pump inhibitor (PPI)-related differences in Helicobacter pylori eradication rates are partly because of CYP2C19 polymorphisms and there have been conflicting data in this area. We conducted a meta-analysis to investigate the evidence relating CYP2C19 to first-line H. pylori eradication rates. METHODS: A search of the literature was conducted up to June 2005 using Medline, EMBase, and Cochrane Register of Controlled Trials (CENTRAL). Twenty-eight arms from 17 papers were extracted for omeprazole, lansoprazole, and rabeprazole, collectively. Review Manager 4.2.8 was used for analysis. RESULTS: When all eradication rates, regardless of PPI used, were combined there was no significant difference between poor metabolizers (PM) and heterozygous extensive metabolizers (HetEMs) (odds ratio [OR]= 1.35, 95% confidence interval [CI] 0.89-2.07, p = 0.15); however, there was a significant difference between HetEM and homozygous extensive metabolizers (HomEMs) (OR = 1.90, 95% CI 1.38-2.60, p < 0.0001). Significant heterogeneity was observed in a HomEM and PM comparison, hence additional subanalysis of individual PPIs revealed that dual and triple omeprazole therapies significantly favored higher H. pylori eradication rates in PM over HomEM (OR = 4.03, 95% CI 1.97-8.28, p = 0.0001), and also over HetEM (OR = 2.24, 95% CI 1.09-4.61, p = 0.03). Dual and triple rabeprazole and triple lansoprazole therapies did not show significantly different H. pylori eradication rates between PM and HomEM (OR = 1.04, 95% CI 0.44-2.46, p = 0.25) and (OR = 1.80, 95% CI 0.67-4.85, p = 0.93), respectively. CONCLUSIONS: The impact of CYP2C19 polymorphisms on H. pylori eradication rates in studied populations appears clinically relevant in patients prescribed omeprazole as a component of their dual- or triple-drug therapy, whereas regimens that include lansoprazole or rabeprazole are unaffected. The choice of PPI and/or dose rather than CYP2C19 genotyping could be a more practical approach to assure the highest H. pylori eradication rates in clinical settings.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Time course and pattern of blood loss with ibuprofen treatment in healthy subjects.

BACKGROUND & AIMS: Nonselective nonsteroidal anti-inflammatory drug (NSAID) users are at increased risk of gastrointestinal bleeding. We aimed to assess the pattern and extent of fecal blood loss (FBL) with ibuprofen, which is considered to have a favorable gastrointestinal safety profile. METHODS: We conducted a post hoc analysis of 2 separate randomized, parallel-group, double-blind studies, in which ibuprofen was used as a positive control. FBL was measured by radioactive analysis of chromium-51 labeled red cells in stools during baseline and then followed by 4 weeks of treatment with ibuprofen (800 mg 3 times daily) or placebo in 68 healthy volunteers. FBL was considered significant when blood loss was >2 mL daily. RESULTS: The baseline period was identical for all subjects, with an average FBL of 0.36 mL (standard deviation, +/-0.075) per day. During the study period, all subjects receiving ibuprofen had a daily mean FBL >2 mL, with a group daily mean loss 3.64-fold greater than in the placebo group (2.55 mL [+/-3.2] vs 0.7 mL [+/-0.37], P < .001). In the ibuprofen group (n = 31), 26 subjects had between 1 and 7 random episodes of microbleeding with FBL >3 mL. Nine had a maximum FBL >10 mL (29.35 +/- 23.32 mL), and in 2 subjects blood loss reached 73 mL and 66 mL, respectively. CONCLUSIONS: Treatment with a therapeutic dose of ibuprofen, a commonly used nonselective NSAID, in healthy subjects is associated with significant FBL, which occurs randomly with spikes of bleeding, sometimes exceeding 66 mL in a single day. Chronic anemia or gastrointestinal bleeding in patients taking nonselective NSAIDs should be thoroughly investigated.

Adult↗

Effect on intragastric pH of a PPI with a prolonged plasma half-life: comparison between tenatoprazole and esomeprazole on the duration of acid suppression in healthy male volunteers.

OBJECTIVE: To compare the inhibitory effect of a novel proton pump inhibitor (PPI), tenatoprazole 40 mg once daily, with esomeprazole 40 mg once daily on intragastric acidity. METHODS: A randomized, investigator-blind, two-way, crossover study was conducted in 30 healthy Helicobacter pylori negative male volunteers. Tenatoprazole 40 mg or esomeprazole 40 mg was administered once daily for 7 consecutive days with a 4-wk washout period between treatments. Ambulatory 24-h intragastric pH was recorded at baseline, after 7 days' treatment, and 3 and 5 days after treatment was stopped. RESULTS: At presumed steady-state (day 7), median 24-h pH values were 5.02 and 4.79 for tenatoprazole and esomeprazole, respectively. There was a significant difference between tenatoprazole and esomeprazole during the nocturnal period when mean pH was 4.64 +/- 0.67 versus 3.61 +/- 0.90, respectively (p < 0.0001), as well as a significantly higher mean percentage of time with pH >4 on tenatoprazole (72.5 +/- 14.9 vs 62.2 +/- 13.6, p < 0.0001). The effect of tenatoprazole was still present 5 days after treatment withdrawal especially during the night-time. The mean area under the plasma concentration-time curve and elimination half-time was significantly higher in the tenatoprazole group as compared with the esomeprazole group. CONCLUSION: Tenatoprazole 40 mg daily provides a prolonged duration of acid suppression and a shorter nocturnal acid breakthrough in healthy volunteers, even after stopping the drug. Thus, tenatoprazole may provide greater clinical efficacy for patients in whom a once daily PPI is ineffective. Further studies are indicated.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Assessment of the safety of selective cyclo-oxygenase-2 inhibitors: where are we in 2003?

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs worldwide despite their well-documented adverse gastrointestinal (GI) effects. The risk of developing a severe GI event varies from patient to patient and NSAID to NSAID. Selective cyclo-oxygenase-2 inhibitors (coxibs) have been designed to have similar efficacy but less GI toxicity than traditional NSAIDs, and have been shown to have an improved GI tolerability and less adverse events across a range of different GI safety assessments. In clinical trials, particularly VIGOR and CLASS, rofecoxib and celecoxib, respectively, significantly reduce the risk of ulcers and ulcer complications than nonselective NSAID comparators with ulcer rates comparable to placebo. The real benefit of a coxib comes from the sparing of the thromboxane and hence preservation of normal platelet function. Thus, there is less risk of bleeding with selective inhibition of COX-2, which is the most common and serious complication of non-selective NSAIDs. Moreover, bleeding can occur anywhere in the GI tract. Although some concern has been raised about the cardiovascular safety of coxibs, when used in recommended doses, there is no convincing evidence that patients treated with a coxib have an increased risk of cardiovascular thrombotic events. Different approaches have been advocated to minimize NSAID-related GI toxicity. Choice of less harmful NSAIDs such as coxib has been one of the strategies promoted in guidelines. The introduction of coxibs with a higher benefit-risk ratio has dramatically changed the therapeutic scenario for anti-inflammatory treatment in the clinical practice.

Journal Article↗