BACKGROUND A dual therapy regimen containing amoxicillin is a common treatment option for the eradication of Helicobacter pylori(H.pylori).While substantial research supports the efficacy and safety of vonoprazan and ...BACKGROUND A dual therapy regimen containing amoxicillin is a common treatment option for the eradication of Helicobacter pylori(H.pylori).While substantial research supports the efficacy and safety of vonoprazan and amoxicillin(VA)dual therapy in the general population,there is still a lack of studies specifically focusing on its safety in elderly patients.AIM To evaluate efficacy and safety of VA dual therapy as first-line or rescue treatment for H.pylori in elderly patients.METHODS As a real-world retrospective study,data were collected from elderly patients aged 60 years and above who accepted VA dual therapy(vonoprazan 20 mg twice daily+amoxicillin 1000 mg thrice daily for 14 days)for H.pylori eradication in the Department of Gastroenterology at Peking University First Hospital between June 2020 and January 2024.H.pylori status was evaluated by^(13)C-urease breath test 6 weeks after treatment.All adverse events(AEs)during treatment were recorded.RESULTS In total,401 cases were screened.Twenty-one cases were excluded due to loss to follow-up,lack of re-examination,or unwillingness to take medication.The total of 380 included cases comprised 250 who received VA dual therapy as first-line treatment and 130 who received VA dual therapy as rescue treatment.H.pylori was successfully eradicated in 239 cases(95.6%)in the first-line treatment group and 116 cases(89.2%)in the rescue treatment group.The overall incidence of AEs was 9.5%for both groups.Specifically,9.2%of patients experienced an AE in the first-line treatment group and 10.0%in the rescue treatment group.Five patients discontinued treatment due to AE,with a discontinuation rate of 1.3%.No serious AE occurred.CONCLUSION The VA dual therapy regimen as a first-line treatment and a rescue therapy was effective and safe for elderly patients aged 60 and older.展开更多
BACKGROUND The efficacy of Vonoprazan-amoxicillin dual therapy(VAT)in the treatment of Helicobacter pylori(H.pylori)is controversial.AIM To evaluate the efficacy of VAT in the Chinese population.METHODS This prospecti...BACKGROUND The efficacy of Vonoprazan-amoxicillin dual therapy(VAT)in the treatment of Helicobacter pylori(H.pylori)is controversial.AIM To evaluate the efficacy of VAT in the Chinese population.METHODS This prospective,multicenter,randomized,open-label,and two-stage study was conducted at 23 centers in Fujian,China(May 2021-April 2022).H.pylori-infected patients were randomized to bismuth quadruple therapy(BQT),BQT-Vonoprazan(BQT-V),seven-day VAT(VAT-7),ten-day VAT(VAT-10),and fourteen-day VAT(VAT-14)groups.The primary endpoint was the H.pylori eradication rate.The secondary endpoint was the frequency of adverse events.This study was registered with the Chinese Clinical Trial Registry,ChiCTR2100045778.RESULTS In the first stage,VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated.In the second stage,the eradication rates for BQT,VAT-10,and VA-14 were 80.2%[95%confidence interval(95%CI):71.4%-86.8%],93.2%(86.6%-96.7%),92.2%(85.3%-96.0%)in the intention-to-treat(ITT)analysis,and 80.9%(95%CI:71.7%-87.5%),94.0%(87.5%-97.2%),and 93.9%(87.4%-97.2%)in the per-protocol analysis.The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group(P=0.022 and P=0.046,respectively).The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group(25.27%and 13.73%vs 37.62%,respectively;P<0.001).CONCLUSION VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT,with a more tolerable safety profile in H.pylori-infected patients in Fujian.Huang XP et al.VAT for H.pylori eradication.展开更多
Helicobacter pylori(H.pylori)infections may cause chronic gastritis,peptic ulcer disease,gastric cancers,and other conditions outside of the gastrointestinal tract.Hence,it is important to diagnose and treat it early....Helicobacter pylori(H.pylori)infections may cause chronic gastritis,peptic ulcer disease,gastric cancers,and other conditions outside of the gastrointestinal tract.Hence,it is important to diagnose and treat it early.H.pylori is resistant to certain drugs in traditional eradication therapy,so alternative therapy protocols are needed,such as high-dose amoxicillin dual therapy(HDADT).This article aims to comment on a recent paper by Costigan et al in the World Journal of Clinical Cases.In this study,the authors recruited 139 patients diagnosed with H.pylori,all treated with HDADT.Of these,93 were treatment-naïve and 46 had received at least one alternative treatment in the past.Four weeks after the end of the treatment,the urea breath test was administered to estimate the eradication rate.The total eradication rate was 56%(78/139),62%for the treatment-naïve arm and 43%for the previous treatment arm,thus indicating a lower success rate for the arm that had previously received a different treatment regimen.In conclusion,a therapeutic approach with first-line HDADT may potentially be a better treat-ment,but the results are not sufficient to recommend the use of this regimen in a country with high levels of dual resistance.展开更多
Atrial fibrillation(AF)is a very common arrhythmia in clinical practice.Its incidence and prevalence are age-related and are growing in the last years.Age is a risk factor also for coronary artery disease(CAD),and wit...Atrial fibrillation(AF)is a very common arrhythmia in clinical practice.Its incidence and prevalence are age-related and are growing in the last years.Age is a risk factor also for coronary artery disease(CAD),and with the evolution of preventive care,the first event(acute coronary syndrome(ACS)or percutaneous coronary intervention(PCI))takes place at a later age.If elderly patients with AF and CAD undergo ACS or PCI,they have indication to assume triple therapy.Triple therapy(oral anticoagulation(OAC)plus dual antiplatelet therapy(DAPT))exposes patients to high bleeding risk.In the last 10 years,several clinical trials have tested dual therapy(OAC plus single antiplatelet therapy)in AF patients who undergo ACS or elective PCI.WOEST trial has tested warfarin+clopidogrel against triple therapy.PIONEER AF-PCI trial has tested low-dose rivaroxaban+P2Y12 inhibitor or very low-dose rivaroxaban+DAPT against standard triple therapy with warfarin.RE-DUAL PCI trial has tested two doses of dabigatran+P2Y12 inhibitor against standard triple therapy with Warfarin.AUGUSTUS trial has tested apixaban against warfarin both in dual therapy with P2Y12 inhibitor and in triple therapy with a P2Y12 inhibitor and aspirin.ENTRUST-AF PCI,last published study,has tested edoxaban+P2Y12 inhibitor against triple therapy.All these trials show dual therapy reduces significantly bleeding risk than triple therapy.In this paper,we analyze these clinical trials to understand if dual therapy results can be applied to elderly patients and what is probably the better approach in elderly AF patients undergo to ACS or PCI.展开更多
We evaluated the efficacy and tolerability of a dual therapy with rabeprazole and amoxicillin (AMX) as an empiric third-line rescue therapy. In patients with failure of first-line treatment with a proton pump inhibito...We evaluated the efficacy and tolerability of a dual therapy with rabeprazole and amoxicillin (AMX) as an empiric third-line rescue therapy. In patients with failure of first-line treatment with a proton pump inhibitor (PPI)- AMX-clarithromycin regimen and second-line treatment with the PPI-AMX-metronidazole regimen, a third-line eradication regimen with rabeprazole (10 mg q.i.d.) and AMX (500 mg q.i.d.) was prescribed for 2 wk. Eradication was confirmed by the results of the 13C-urea breath test (UBT) at 12 wk after the therapy. A total of 46 patients were included; however, two were lost to followup. The eradication rates as determined by per-protocol and intention-to-treat analyses were 65.9% and 63.0%,respectively. The pretreatment UBT results in the subjects showing eradication failure; those patients showing successful eradication comprised 32.9 ± 28.8 permil and 14.8 ± 12.8 permil, respectively. The pretreatment UBT results in the subjects with eradication failure were significantly higher than those in the patients with successful eradication (P = 0.019). A low pretreatment UBT result (≤ 28.5 permil) predicted the success of the eradication therapy with a positive predictive value of 81.3% and a sensitivity of 89.7%. Adverse effects were reported in 18.2% of the patients, mainly diarrhea and stomatitis. Dual therapy with rabeprazole and AMX appears to serve as a potential empirical third-line strategy for patients with low values on pretreatment UBT.展开更多
To survey the efficacy and safety of dual therapy with daclatasvir and asunaprevir in the elderly hepatitis C virus (HCV) patients multicentricity. METHODSInterferon-ineligible/intolerant patients and non-responders t...To survey the efficacy and safety of dual therapy with daclatasvir and asunaprevir in the elderly hepatitis C virus (HCV) patients multicentricity. METHODSInterferon-ineligible/intolerant patients and non-responders to previous pegylated-interferon/ribavirin therapy with chronic HCV genotype 1b infection were enrolled. Child B, C cirrhotic patients were excluded. Patients received oral direct acting antiviral treatment consisting of 60 mg daclatasvir once daily plus 200 mg asunaprevir twice daily for 24 wk. We divided the patients into two groups of 56 elderly patients (≥ 75 years-old) and 141 non-elderly patients (< 75 years old) and compared the efficacy and safety. RESULTSNinety-one point one percent of elderly patients and 90.1% of non-elderly patients achieved sustained virological response at 24 wk (SVR<sub>24</sub>). In the former, 1.8% experienced viral breakthrough, as compared with 3.5% in the latter (not significant). Adverse events occurred in 55.4% of the former and 56.0% of the latter. In the former, 7 cases (12.5%) were discontinued due to adverse events, and in the latter 9 cases were discontinued (6.4%, not significant). CONCLUSIONDual therapy with daclatasvir and asunaprevir achieved the same high rates of SVR<sub>24</sub> in HCV elderly patients without more adverse events than in the non-elderly patients.展开更多
BACKGROUND Ulcerative colitis(UC)is an idiopathic,chronic inflammatory bowel disease(IBD)most often located in the rectum,but may involve the entire colon.Extra intestinal manifestations(EIMs)occur with varying freque...BACKGROUND Ulcerative colitis(UC)is an idiopathic,chronic inflammatory bowel disease(IBD)most often located in the rectum,but may involve the entire colon.Extra intestinal manifestations(EIMs)occur with varying frequency depending on the affected organ.The most common ones are musculoskeletal EIMs,affecting up to 33%-40%of IBD patients.These include,among others,inflammatory back pain,tendinitis,plantar fasciitis and arthritis.Only a few case reports in literature discuss Achilles tendinitis.CASE SUMMARY This report describes a patient with UC and Achilles tendinitis in whom after many unsuccessful attempts of treatment with sulfasalazine,mesalazine,glucocorticosteroids,infliximab and tofacitinib,a complete UC remission and resolution of Achilles tendinitis were achieved with the use of dual biologic therapy(DBT)-ustekinumab and adalimumab(ADA).CONCLUSION This case mentions rare EIMs of UC and suggests that DBT may be an alternative for patient with ulcerative colitis and EIMs.展开更多
Background:High-dose dual therapy(HDDT)with proton pump inhibitors(PPIs)and amoxicillin has attracted widespread attention due to its favorable efficacy in eradicating Helicobacter pylori(H.pylori).This study aimed to...Background:High-dose dual therapy(HDDT)with proton pump inhibitors(PPIs)and amoxicillin has attracted widespread attention due to its favorable efficacy in eradicating Helicobacter pylori(H.pylori).This study aimed to compare the efficacy and safety of high-dose PPI-amoxicillin dual therapy and bismuth-containing quadruple therapy for H.pylori rescue treatment.Methods:This was a prospective,randomized,multicenter,non-inferiority trial.Patients recruited from eight centers who had failed previous treatment were randomly(1:1)allocated to two eradication groups:HDDT(esomeprazole 40 mg and amoxicillin 1000 mg three times daily;theHDDTgroup)and bismuth-containing quadruple therapy(esomeprazole 40 mg,bismuth potassium citrate 220 mg,and furazolidone 100 mg twice daily,combined with tetracycline 500 mg three times daily;the tetracycline,furazolidone,esomeprazole,and bismuth[TFEB]group)for 14 days.The primary endpoint was the H.pylori eradication rate.The secondary endpoints were adverse effects,symptom improvement rates,and patient compliance.Results:A total of 658 patients who met the criteria were enrolled in this study.The HDDT group achieved eradication rates of 75.4%(248/329),81.0%(248/306),and 81.3%(248/305)asdetermined by the intention-to-treat(ITT),modified intention-totreat(MITT),and per-protocol(PP)analyses,respectively.The eradication rates were similar to those in the TFEB group:78.1%(257/329),84.2%(257/305),and 85.1%(257/302).The lower 95%confidence interval boundary(9.19%in the ITT analysis,9.21%in the MITT analysis,and9.73%in the PP analysis)was greater than the predefined non-inferiority margin of10%,establishing a non-inferiority of the HDDT group vs.the TFEB group.The incidence of adverse events in the HDDT group was significantly lower than that in the TFEB group(11.1%vs.26.8%,P<0.001).Symptom improvement rates and patients’compliance were similar between the two groups.Conclusions:Fourteen-day HDDT is non-inferior to bismuth-containing quadruple therapy,with fewer adverse effects and good treatment compliance,suggesting HDDT as an alternative for H.pylori rescue treatment in the local region.Trial registration:Clinicaltrials.gov,NCT04678492.展开更多
Bismuth-containing quadruple therapy(BQT)has long been recommended for Helicobacter pylori(H.pylori)eradication in China.Meanwhile,in the latest national consensus in China,dual therapy(DT)comprising an acid suppresso...Bismuth-containing quadruple therapy(BQT)has long been recommended for Helicobacter pylori(H.pylori)eradication in China.Meanwhile,in the latest national consensus in China,dual therapy(DT)comprising an acid suppressor and amoxicillin has also been recommended.In recent years,the eradication rate of H.pylori has reached>90%using DT,which has been used not only as a first-line treatment but also as a rescue treatment.Compared with BQT,DT has great potential for H.pylori eradication;however,it has some limitations.This review summarizes the development of DT and its application in H.pylori eradication.The H.pylori eradication rates of DT were comparable to or even higher than those of BQT or standard triple therapy,especially in the first-line treatment.The incidence of adverse events associated with DT was lower than that with other therapies.Furthermore,there were no significant differences in the effects of dual and quadruple therapies on gastrointestinal microecology.In the short term,H.pylori eradication causes certain fluctuations in the gastrointestinal microbiota;however,in the long term,the gastrointestinal microbiota eventually returns to its normal state.In the penicillin-naïve population,patients receiving DT have a high eradiation rate,better compliance,lower incidence of adverse reactions,and lower primary and secondary resistance to amoxicillin.These findings suggest the safety,efficacy,and potential of DT for H.pylori eradication.展开更多
Objective The main aim of this meta-analysis is to compare the efficacy and safety of dual versus single antiplatelet therapy for pa- tients taking oral anticoagulation (OAC) after coronary intervention. Background ...Objective The main aim of this meta-analysis is to compare the efficacy and safety of dual versus single antiplatelet therapy for pa- tients taking oral anticoagulation (OAC) after coronary intervention. Background The optimal regimen remains controversial for patients taking OAC after coronary intervention. Methods PubMed, Embase and Cochrane Central Register of Controlled Trials were searched for eligible studies including data of triple therapy (TT) versus OAC plus single antiplatelet therapy for patients requiring OAC after coronary intervention. The primary outcome was major adverse cardiac and cerebrovascular event (MACCE). The safety outcome was major bleeding. Results Fourteen studies with 32,825 patients were included. Among prospective studies, patients with TT had a trend toward a higher risk of major bleeding [odds ratios (OR): 1.56, 95% confidence interval (CI): 0.98-2.49, P = 0.06] and a markedly higher risk of all-cause death (OR; 2.11, 95% CI: 1.10-4.06 P = 0.02) compared with OAC plus clopidogrel. Meanwhile, TT was associated with decreased risks of MACCE (OR: 0.63, 95% CI: 051-0.77 P 〈 0.0001), all-cause death (OR: 0.45, 95% CI: 0.20-0.97, P = 0.04), and stroke/transient ischemic attack (TIA)/peripheral embolism (PE) (OR= 0.29, 95% CI: 0.09~3.96, P = 0.04) compared with OAC plus aspirin. Conclusions For pa- tients requiring OAC after coronary intervention, OAC plus clopidogrel may bring more clinical net benefit than TT, whereas OAC plus aspirin should be the last choice. More large-size randomized control trials are needed to confirm these findings.展开更多
Objective To assess the prevalence of the bleeding complications in pacemaker implanted patients receiving different antiplatelet regimens, and the influence of each regimen on hospital stays after device implantation...Objective To assess the prevalence of the bleeding complications in pacemaker implanted patients receiving different antiplatelet regimens, and the influence of each regimen on hospital stays after device implantation. Methods We prospectively enrolled 364 patients receiving the cardiac rhythm device implantations in Fuwai Hospital from July 2012 to December 2013. Bleeding complications including pocket hematoma, hemothorax, cardiac tamponade and blood transfusion requirement were measured as endpoints. Post operation hospital stay was also included in the endpoints. Results Bleeding complications were detected in 15 patients (14 with hematoma, one with hemothorax) out of all 364 patients (4.12%). Dual antiplatelet therapy (DAT) significantly increased hematoma (19.3%) compared with aspi- fin treatment (ASA) (3.2%, P = 0.001) and no antiplatelet therapy (1.9%, P 〈 0.001). There was no significant difference in incidence of pocket hematoma between the ASA group and the control group (P = 0.45). The post procedure hospital stay was longer in DAT group (5.45 ± 2.01 days) compared to those in the ASA group (3.65 ± 1.37 days, P 〈 0.05) or control group (3.99 ± 2.27 days, P 〈 0.05). Pocket hema- toma was considered an independent predictor of hospital stay prolongation (OR: 5.26; 95% CI: 1.56-16.64; P = 0.007). Conclusions Among the Chinese patients undergoing device implantation in this study, the use of dual antiplatelet agents significantly increased the risk of pocket hematoma complications and led to a longer hospital stay. Use of aspirin alone did not increase the risk.展开更多
Objective The alpha 2A-adrenergic receptor gene (ADRA2A) polymorphism in individuals antiplatelet response to sympathetic stimulation. The aim of this study was to investigate ADRA2A variants on platelet reactivity ...Objective The alpha 2A-adrenergic receptor gene (ADRA2A) polymorphism in individuals antiplatelet response to sympathetic stimulation. The aim of this study was to investigate ADRA2A variants on platelet reactivity in Chinese patients on dual antiplatelet therapy undergoing percutaneous coronary intervention (PCI). modifies the the effect of (DAPT) after Methods From March 2011 to March 2013, 1,024 patients were enrolled in this prospective, single-center, observational study in China. Four single nucleotide polymorphisms (SNPs) of ADRA2A gene (rs11195419, rs3750625, rs13306146, and rs553668) and CYP2C19^*2 were detected by ligase detection reaction (LDR), and adenosine diphosphate (ADP) inhibition was detected by thromboelastography (TEG). Results The minor allele frequencies of ADRA2A SNPs were common. Platelet ADP inhibition was significantly different among patients carrying rs11195419 (adjusted P = 0.022) and rs3750625 (adjusted P = 0.016). The homozygous allele carriers had the lowest ADP inhibition. However, ADP inhibition was not significantly different in rs553668 and rs13306146. At the multivariate analysis, rs11195419 (P = 0.033), rs3750625 (P = 0.020) and CYP2C19"2 (P = 0.002) were independent predictors of ADP inhibition. Subgroups analysis based on sex showed rs11195419 (P = 0.003) and rs3750625 (P = 0.002) were significantly associated with ADP inhibition in males, but not in females. Conclusion ADRA2A genetic variations were associated with ADP-induced platelet aggregation during DAPT in Chinese patients undergoing PCI, and the effect was particularly more pronounced in males.展开更多
BACKGROUND:To investigate the most appropriate dual antiplatelet therapy(DAPT)duration for patients with acute coronary syndrome(ACS)after drug-eluting stent(DES)implantation in the largest cardiovascular center of Ch...BACKGROUND:To investigate the most appropriate dual antiplatelet therapy(DAPT)duration for patients with acute coronary syndrome(ACS)after drug-eluting stent(DES)implantation in the largest cardiovascular center of China.METHODS:We enrolled 5,187 consecutive patients with ACS who received DES from January to December 2013.Patients were divided into four groups based on DAPT duration:standard DAPT group(11-13 months,n=1,568)and prolonged DAPT groups(13-18 months[n=308],18-24 months[n=2,125],and>24 months[n=1,186]).Baseline characteristics and 5-year clinical outcomes were recorded.RESULTS:Baseline characteristics were similar across the four groups.Among the four groups,those with prolonged DAPT(18-24 months)had the lowest incidence of major adverse cardiovascular and cerebrovascular events(MACCEs)(14.1%vs.11.7%vs.9.6%vs.24.2%,P<0.001),all-cause death(4.8%vs.3.9%vs.2.1%vs.2.6%,P<0.001),cardiac death(3.1%vs.2.6%vs.1.4%vs.1.9%,P=0.004),and myocardial infarction(MI)(3.8%vs.4.2%vs.2.5%vs.5.8%,P<0.001).The incidence of bleeding was not different among the four groups(9.9%vs.9.4%vs.11.0%vs.9.4%,P=0.449).Cox multivariable analysis showed that prolonged DAPT(18-24 months)was an independent protective factor for MACCEs(hazard ratio[HR]0.802,95%confidence interval[CI]0.729-0.882,P<0.001),all-cause death(HR 0.660,95%CI 0.547-0.795,P<0.001),cardiac death(HR 0.663,95%CI 0.526-0.835,P<0.001),MI(HR 0.796,95%CI 0.662-0.957,P=0.015),and target vessel revascularization(HR 0.867,95%CI 0.755-0.996,P=0.044).Subgroup analysis for high bleeding risk showed that prolonged DAPT remained an independent protective factor for all-cause death and MACCEs.CONCLUSION:For patients with ACS after DES,appropriately prolonging the DAPT duration may be associated with a reduced risk of adverse ischemic events without increasing the bleeding risk.展开更多
Biologic agents have now been used in the management of inflammatory bowel disease(IBD)for many years where experience,expertise and confidence in their use has developed over time.In the United Kingdom,there are well...Biologic agents have now been used in the management of inflammatory bowel disease(IBD)for many years where experience,expertise and confidence in their use has developed over time.In the United Kingdom,there are well established guidelines and recommendations for both single agent biologic treatments,and with combination therapy of a biologic agent with a small molecule agent in maintenance therapy.In recent times,there has been increasing interest and experience using dual biologic therapy(DBT)in IBD,primarily in difficult to treat and refractory cases with high disease burden.However,published data on use,experience and safety profiles is limited and large-scale studies remain low in number in this developing area.We therefore aim to present a summary and review of the available published data in this area to help us better understand the emerging role of DBT in IBD.展开更多
BACKGROUND Little is known about the safety and efficacy of using two or more biologics for the treatment of immune-mediated diseases,including Crohn’s disease(CD).CASE SUMMARY This case report and narrative review d...BACKGROUND Little is known about the safety and efficacy of using two or more biologics for the treatment of immune-mediated diseases,including Crohn’s disease(CD).CASE SUMMARY This case report and narrative review demonstrate the potential safety of dual biologic therapy(DBT)in a 45-year-old female with two separate immunemediated diseases.She had a history of multiple sclerosis for which she was receiving treatment with ocrelizumab,and she had been recently diagnosed with CD after presenting with diarrhoea.The CD diagnosis was confirmed radiologically,endoscopically,histologically,and biochemically.The patient received treatment with vedolizumab,a gut-specific inhibitor of theα4β7 integrin on leukocytes.No adverse reactions were observed for the duration of treatment.The safety of ocrelizumab and vedolizumab for the treatment of different immune-mediated diseases was demonstrated.CONCLUSION DBT may be a safe and effective option for the treatment of refractory disease or multiple immunemediated diseases.Newer biologics,which have improved safety profiles and gut specificity,may provide promising avenues for treatment.However,caution must be exercised in the appropriate selection of biologics given their inherent immunosuppressive properties,side effects,and efficacy profiles.Current evidence suggests that biologic therapy is not associated with a worse prognosis in patients with coronavirus disease 2019,but treatment decisions should be made in a multidisciplinary setting.Further research from controlled trials is needed to better understand the safety profile of DBT in CD.The immunopathological mechanisms underlying DBT also remain to be clarified.展开更多
Percutaneous coronary intervention with stenting is followed by a duration of dual antiplatelet therapy(DAPT)to reduce stent thrombosis and avoid target lesion failure.The period of DAPT recommended in international g...Percutaneous coronary intervention with stenting is followed by a duration of dual antiplatelet therapy(DAPT)to reduce stent thrombosis and avoid target lesion failure.The period of DAPT recommended in international guidelines following drug-eluting stent implantation is 12 mo for most patients with acute coronary syndrome,and 6 mo for patients with chronic coronary syndrome or high bleeding risk.The new generation of drug-eluting stents have metallic platforms with thinner struts,associated with significantly less stent thrombosis.Shortened DAPT has been investigated with these stents,with evidence from randomised clinical trials for some individual stents showing non-inferior safety and efficacy outcomes.This has to be balanced by the effect of DAPT on secondary prevention of systemic cardiovascular disease especially in high-risk populations.This review will outline the current evidence for individual stents with regards to DAPT duration for both acute coronary syndrome and chronic coronary syndrome and discuss further directions for research and personalised medicine in this contemporary percutaneous coronary intervention era.展开更多
Treatment strategies for inflammatory bowel disease(IBD)are rapidly evolving with the development of biologics and small molecule drugs(SMDs).However,these drugs are not guaranteed to be effective in all patients,and ...Treatment strategies for inflammatory bowel disease(IBD)are rapidly evolving with the development of biologics and small molecule drugs(SMDs).However,these drugs are not guaranteed to be effective in all patients,and a“ceiling effect”of biologic monotherapy may occur.This issue highlights an unmet need for optimizing the use of biologics and predicting therapeutic responses.Thus,the development of new drugs with novel mechanisms of action is urgently needed for patients with primary nonresponse and secondary loss of response to conventional biologics and SMDs.In addition,combining different biologics or SMDs has been proposed as a novel strategy to enhance treatment efficacy in IBD,which theoretically has multidimensional anti-inflammatory potential.Based on the current evidence available for IBD,dual targeted therapy may be a promising strategy for refractory IBD patients who have failed in multiple biologic treatments or who have extraintestinal manifestation.Additionally,identifying the subgroup of IBD patients who are responding to biological combination therapies is also equally important in stable disease remission.In this review,we summarize the newly developed biologics and SMDs and the current status of biologics/SMDs to highlight the development of individualized treatment in IBD.展开更多
BACKGROUND Helicobacter pylori(H.pylori)eradication rates have fallen globally,likely in large part due to increasing antibiotic resistance to traditional therapy.In areas of high clarithromycin and metronidazole resi...BACKGROUND Helicobacter pylori(H.pylori)eradication rates have fallen globally,likely in large part due to increasing antibiotic resistance to traditional therapy.In areas of high clarithromycin and metronidazole resistance such as ours,Maastricht VI guidelines suggest high dose amoxicillin dual therapy(HDADT)can be considered,subject to evidence for local efficacy.In this study we assess efficacy of HDADT therapy for H.pylori eradication in an Irish cohort.AIM To assess the efficacy of HDADT therapy for H.pylori eradication in an Irish cohort as both first line,and subsequent therapy for patients diagnosed with H.pylori.METHODS All patients testing positive for H.pylori in a tertiary centre were treated prospectively with HDADT(amoxicillin 1 g tid and esomeprazole 40 mg bid×14 d)over a period of 8 months.Eradication was confirmed with Urea Breath Test at least 4 wk after cessation of therapy.A delta-over-baseline>4%was considered positive.Patient demographics and treatment outcomes were recorded,analysed and controlled for basic demographics and prior H.pylori treatment.RESULTS One hundred and ninety-eight patients were identified with H.pylori infection,10 patients were excluded due to penicillin allergy and 38 patients refused follow up testing.In all 139 were included in the analysis,55%(n=76)were female,mean age was 46.6 years.Overall,93(67%)of patients were treatment-naïve and 46(33%)had received at least one previous course of treatment.The groups were statistically similar.Self-reported compliance with HDADT was 97%,mild side-effects occurred in 7%.There were no serious adverse drug reactions.Overall the eradication rate for our cohort was 56%(78/139).Eradication rates were worse for those with previous treatment[43%(20/46)vs 62%(58/93),P=0.0458,odds ratio=2.15].Age and Gender had no effect on eradication status.CONCLUSION Overall eradication rates with HDADT were disappointing.Despite being a simple and possibly better tolerated regime,these results do not support its routine use in a high dual resistance country.Further investigation of other regimens to achieve the>90%eradication target is needed.展开更多
For a long time, a combination of interferon and ribavirin has been used to treat viral hepatitis C, but the sustained virological response was only achieved in 45% of cases and side effects were serious [1]. Dir...For a long time, a combination of interferon and ribavirin has been used to treat viral hepatitis C, but the sustained virological response was only achieved in 45% of cases and side effects were serious [1]. Direct acting antivirals (DAA) have provided a cure for almost everyone with hepatitis C, with few side effects. The Purpose of Our Work is to compare the results of treatment for viral hepatitis C before and after DAA. Patients and Methods: This is a retrospective study, bringing together all patients with chronic viral hepatitis C treated between January 2009 and March 2020 at the University Hospital Hassan II in Fez, Morocco. The epidemiological, clinical, biological, virological characteristics of the included patients were collected from the two groups: A, treated with interferon and ribavirin or by triple therapy and B, treated with DAA. Results: 162 patients were included, the average age was 55 y/o, with 90 women and 72 men. 88 patients (54.3%) were already cirrhotic, of which 61 were compensated and 27 were decompensated. Genotype 1 was dominant with a frequency of 71.6%, 107 patients (66%) initially treated with old HCV treatments and 55 (34%) treated with DAA. Sustained viral response was obtained in 59 cases (55.14%) in group A versus 54 cases (98.18%) in group B with a very significant difference (p < 0.0001). Treatment failure was observed in 14 patients (13.1%) in group A and only one patient, i.e. 2% in group B (p = 0.019). 14 patients relapsed in group A (13.1%) versus 0 patient in group B (p = 0.003). The tolerance of the treatment was excellent in group B as a whole with only five patients (9%) reported side effects which were minor, not leading to the discontinuation of treatment while the side effects were major in 49 patients (45.7%) in group A with led to the permanent discontinuation of treatment in 6 patients. The difference in side effects between the two groups was very significant with (p Conclusion: Our study has shown the superiority of DAA in terms of efficacy and tolerance compared to the old treatments for chronic hepatitis C. In addition, these treatments allow almost systematic viral elimination and therefore consequently a reduction in the risk of complications hepatic with a short time of treatment.展开更多
Objective: To evaluate the efficacy of dual antiplatelet therapy combined with Naoxintong Capsule (脑心通胶囊, NXTC) in a rat model of coronary microembolization (CME). Methods: A total of 95 rats were randomly ...Objective: To evaluate the efficacy of dual antiplatelet therapy combined with Naoxintong Capsule (脑心通胶囊, NXTC) in a rat model of coronary microembolization (CME). Methods: A total of 95 rats were randomly divided into 6 groups: control, sham-operation, CME model, NXTC, dual antiplatelet (clopidogrel and aspirin) intervention (DA), and NXTC combined with DA (NDA) groups. The complete data in 69 rats were obtained. The number of CME, myocardial apoptosis rate, bleeding time, clotting time, and adensosine diphosphate (ADP)-induced platelet aggregation were assessed. Results: Compared with the CME group, the number of CME and myocardial apoptosis rates were significantly decreased in the NXTC, DA, and NDA groups (P〈0.01). Compared with other intervention groups, the number of CME and myocardial apoptosis rates were the least in the NDA group (P〈0.01), and the incidence of surgical bleeding was the highest in the DA group (P〈0.01). Compared with the CME group, ADP-induced maximum platelet aggregation rate was significantly inhibited in the NXTC, DA, and NDA groups (P〈0.01), both bleeding time and clotting time were significantly increased in the NXTC, DA, and NDA groups (P〈0.01), while the above parameters were the highest in the DA group (P〈0.05). Conclusion: The combination therapy of NXTC and DA enhanced the anti-CME effect of either therapy alone and reduced the risk of the DA therapy-associated bleeding, demonstrating an improved benefit/ risk ratio in the rat model of CME.展开更多
基金Supported by National High Level Hospital Clinical Research Funding(Youth Clinical Research Project of Peking University First Hospital),No.2023YC27Capital’s Funds for Health Improvement and Research,No.2022-2-40711National High Level Hospital Clinical Research Funding(Interdepartmental Research Project of Peking University First Hospital),No.2024IR20.
文摘BACKGROUND A dual therapy regimen containing amoxicillin is a common treatment option for the eradication of Helicobacter pylori(H.pylori).While substantial research supports the efficacy and safety of vonoprazan and amoxicillin(VA)dual therapy in the general population,there is still a lack of studies specifically focusing on its safety in elderly patients.AIM To evaluate efficacy and safety of VA dual therapy as first-line or rescue treatment for H.pylori in elderly patients.METHODS As a real-world retrospective study,data were collected from elderly patients aged 60 years and above who accepted VA dual therapy(vonoprazan 20 mg twice daily+amoxicillin 1000 mg thrice daily for 14 days)for H.pylori eradication in the Department of Gastroenterology at Peking University First Hospital between June 2020 and January 2024.H.pylori status was evaluated by^(13)C-urease breath test 6 weeks after treatment.All adverse events(AEs)during treatment were recorded.RESULTS In total,401 cases were screened.Twenty-one cases were excluded due to loss to follow-up,lack of re-examination,or unwillingness to take medication.The total of 380 included cases comprised 250 who received VA dual therapy as first-line treatment and 130 who received VA dual therapy as rescue treatment.H.pylori was successfully eradicated in 239 cases(95.6%)in the first-line treatment group and 116 cases(89.2%)in the rescue treatment group.The overall incidence of AEs was 9.5%for both groups.Specifically,9.2%of patients experienced an AE in the first-line treatment group and 10.0%in the rescue treatment group.Five patients discontinued treatment due to AE,with a discontinuation rate of 1.3%.No serious AE occurred.CONCLUSION The VA dual therapy regimen as a first-line treatment and a rescue therapy was effective and safe for elderly patients aged 60 and older.
基金Supported by the Natural Science Foundation of Fujian Province,No.2020J011087 and No.2022J011025Medical Innovation Project of Fujian Provincial Health Commission,No.2020CXA006Zhuhai Science and Technology Project,No.20181117E030040.
文摘BACKGROUND The efficacy of Vonoprazan-amoxicillin dual therapy(VAT)in the treatment of Helicobacter pylori(H.pylori)is controversial.AIM To evaluate the efficacy of VAT in the Chinese population.METHODS This prospective,multicenter,randomized,open-label,and two-stage study was conducted at 23 centers in Fujian,China(May 2021-April 2022).H.pylori-infected patients were randomized to bismuth quadruple therapy(BQT),BQT-Vonoprazan(BQT-V),seven-day VAT(VAT-7),ten-day VAT(VAT-10),and fourteen-day VAT(VAT-14)groups.The primary endpoint was the H.pylori eradication rate.The secondary endpoint was the frequency of adverse events.This study was registered with the Chinese Clinical Trial Registry,ChiCTR2100045778.RESULTS In the first stage,VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated.In the second stage,the eradication rates for BQT,VAT-10,and VA-14 were 80.2%[95%confidence interval(95%CI):71.4%-86.8%],93.2%(86.6%-96.7%),92.2%(85.3%-96.0%)in the intention-to-treat(ITT)analysis,and 80.9%(95%CI:71.7%-87.5%),94.0%(87.5%-97.2%),and 93.9%(87.4%-97.2%)in the per-protocol analysis.The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group(P=0.022 and P=0.046,respectively).The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group(25.27%and 13.73%vs 37.62%,respectively;P<0.001).CONCLUSION VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT,with a more tolerable safety profile in H.pylori-infected patients in Fujian.Huang XP et al.VAT for H.pylori eradication.
文摘Helicobacter pylori(H.pylori)infections may cause chronic gastritis,peptic ulcer disease,gastric cancers,and other conditions outside of the gastrointestinal tract.Hence,it is important to diagnose and treat it early.H.pylori is resistant to certain drugs in traditional eradication therapy,so alternative therapy protocols are needed,such as high-dose amoxicillin dual therapy(HDADT).This article aims to comment on a recent paper by Costigan et al in the World Journal of Clinical Cases.In this study,the authors recruited 139 patients diagnosed with H.pylori,all treated with HDADT.Of these,93 were treatment-naïve and 46 had received at least one alternative treatment in the past.Four weeks after the end of the treatment,the urea breath test was administered to estimate the eradication rate.The total eradication rate was 56%(78/139),62%for the treatment-naïve arm and 43%for the previous treatment arm,thus indicating a lower success rate for the arm that had previously received a different treatment regimen.In conclusion,a therapeutic approach with first-line HDADT may potentially be a better treat-ment,but the results are not sufficient to recommend the use of this regimen in a country with high levels of dual resistance.
文摘Atrial fibrillation(AF)is a very common arrhythmia in clinical practice.Its incidence and prevalence are age-related and are growing in the last years.Age is a risk factor also for coronary artery disease(CAD),and with the evolution of preventive care,the first event(acute coronary syndrome(ACS)or percutaneous coronary intervention(PCI))takes place at a later age.If elderly patients with AF and CAD undergo ACS or PCI,they have indication to assume triple therapy.Triple therapy(oral anticoagulation(OAC)plus dual antiplatelet therapy(DAPT))exposes patients to high bleeding risk.In the last 10 years,several clinical trials have tested dual therapy(OAC plus single antiplatelet therapy)in AF patients who undergo ACS or elective PCI.WOEST trial has tested warfarin+clopidogrel against triple therapy.PIONEER AF-PCI trial has tested low-dose rivaroxaban+P2Y12 inhibitor or very low-dose rivaroxaban+DAPT against standard triple therapy with warfarin.RE-DUAL PCI trial has tested two doses of dabigatran+P2Y12 inhibitor against standard triple therapy with Warfarin.AUGUSTUS trial has tested apixaban against warfarin both in dual therapy with P2Y12 inhibitor and in triple therapy with a P2Y12 inhibitor and aspirin.ENTRUST-AF PCI,last published study,has tested edoxaban+P2Y12 inhibitor against triple therapy.All these trials show dual therapy reduces significantly bleeding risk than triple therapy.In this paper,we analyze these clinical trials to understand if dual therapy results can be applied to elderly patients and what is probably the better approach in elderly AF patients undergo to ACS or PCI.
基金Supported by A grant from the National Hospital Organization,No. H21-NHO-01
文摘We evaluated the efficacy and tolerability of a dual therapy with rabeprazole and amoxicillin (AMX) as an empiric third-line rescue therapy. In patients with failure of first-line treatment with a proton pump inhibitor (PPI)- AMX-clarithromycin regimen and second-line treatment with the PPI-AMX-metronidazole regimen, a third-line eradication regimen with rabeprazole (10 mg q.i.d.) and AMX (500 mg q.i.d.) was prescribed for 2 wk. Eradication was confirmed by the results of the 13C-urea breath test (UBT) at 12 wk after the therapy. A total of 46 patients were included; however, two were lost to followup. The eradication rates as determined by per-protocol and intention-to-treat analyses were 65.9% and 63.0%,respectively. The pretreatment UBT results in the subjects showing eradication failure; those patients showing successful eradication comprised 32.9 ± 28.8 permil and 14.8 ± 12.8 permil, respectively. The pretreatment UBT results in the subjects with eradication failure were significantly higher than those in the patients with successful eradication (P = 0.019). A low pretreatment UBT result (≤ 28.5 permil) predicted the success of the eradication therapy with a positive predictive value of 81.3% and a sensitivity of 89.7%. Adverse effects were reported in 18.2% of the patients, mainly diarrhea and stomatitis. Dual therapy with rabeprazole and AMX appears to serve as a potential empirical third-line strategy for patients with low values on pretreatment UBT.
文摘To survey the efficacy and safety of dual therapy with daclatasvir and asunaprevir in the elderly hepatitis C virus (HCV) patients multicentricity. METHODSInterferon-ineligible/intolerant patients and non-responders to previous pegylated-interferon/ribavirin therapy with chronic HCV genotype 1b infection were enrolled. Child B, C cirrhotic patients were excluded. Patients received oral direct acting antiviral treatment consisting of 60 mg daclatasvir once daily plus 200 mg asunaprevir twice daily for 24 wk. We divided the patients into two groups of 56 elderly patients (≥ 75 years-old) and 141 non-elderly patients (< 75 years old) and compared the efficacy and safety. RESULTSNinety-one point one percent of elderly patients and 90.1% of non-elderly patients achieved sustained virological response at 24 wk (SVR<sub>24</sub>). In the former, 1.8% experienced viral breakthrough, as compared with 3.5% in the latter (not significant). Adverse events occurred in 55.4% of the former and 56.0% of the latter. In the former, 7 cases (12.5%) were discontinued due to adverse events, and in the latter 9 cases were discontinued (6.4%, not significant). CONCLUSIONDual therapy with daclatasvir and asunaprevir achieved the same high rates of SVR<sub>24</sub> in HCV elderly patients without more adverse events than in the non-elderly patients.
文摘BACKGROUND Ulcerative colitis(UC)is an idiopathic,chronic inflammatory bowel disease(IBD)most often located in the rectum,but may involve the entire colon.Extra intestinal manifestations(EIMs)occur with varying frequency depending on the affected organ.The most common ones are musculoskeletal EIMs,affecting up to 33%-40%of IBD patients.These include,among others,inflammatory back pain,tendinitis,plantar fasciitis and arthritis.Only a few case reports in literature discuss Achilles tendinitis.CASE SUMMARY This report describes a patient with UC and Achilles tendinitis in whom after many unsuccessful attempts of treatment with sulfasalazine,mesalazine,glucocorticosteroids,infliximab and tofacitinib,a complete UC remission and resolution of Achilles tendinitis were achieved with the use of dual biologic therapy(DBT)-ustekinumab and adalimumab(ADA).CONCLUSION This case mentions rare EIMs of UC and suggests that DBT may be an alternative for patient with ulcerative colitis and EIMs.
基金partially supported by the grant of the Project from the State Key Laboratory of Cancer Biology(No.CBSKL2019ZZ07).
文摘Background:High-dose dual therapy(HDDT)with proton pump inhibitors(PPIs)and amoxicillin has attracted widespread attention due to its favorable efficacy in eradicating Helicobacter pylori(H.pylori).This study aimed to compare the efficacy and safety of high-dose PPI-amoxicillin dual therapy and bismuth-containing quadruple therapy for H.pylori rescue treatment.Methods:This was a prospective,randomized,multicenter,non-inferiority trial.Patients recruited from eight centers who had failed previous treatment were randomly(1:1)allocated to two eradication groups:HDDT(esomeprazole 40 mg and amoxicillin 1000 mg three times daily;theHDDTgroup)and bismuth-containing quadruple therapy(esomeprazole 40 mg,bismuth potassium citrate 220 mg,and furazolidone 100 mg twice daily,combined with tetracycline 500 mg three times daily;the tetracycline,furazolidone,esomeprazole,and bismuth[TFEB]group)for 14 days.The primary endpoint was the H.pylori eradication rate.The secondary endpoints were adverse effects,symptom improvement rates,and patient compliance.Results:A total of 658 patients who met the criteria were enrolled in this study.The HDDT group achieved eradication rates of 75.4%(248/329),81.0%(248/306),and 81.3%(248/305)asdetermined by the intention-to-treat(ITT),modified intention-totreat(MITT),and per-protocol(PP)analyses,respectively.The eradication rates were similar to those in the TFEB group:78.1%(257/329),84.2%(257/305),and 85.1%(257/302).The lower 95%confidence interval boundary(9.19%in the ITT analysis,9.21%in the MITT analysis,and9.73%in the PP analysis)was greater than the predefined non-inferiority margin of10%,establishing a non-inferiority of the HDDT group vs.the TFEB group.The incidence of adverse events in the HDDT group was significantly lower than that in the TFEB group(11.1%vs.26.8%,P<0.001).Symptom improvement rates and patients’compliance were similar between the two groups.Conclusions:Fourteen-day HDDT is non-inferior to bismuth-containing quadruple therapy,with fewer adverse effects and good treatment compliance,suggesting HDDT as an alternative for H.pylori rescue treatment in the local region.Trial registration:Clinicaltrials.gov,NCT04678492.
基金National Nature Science Foundation of China(No.82270570)
文摘Bismuth-containing quadruple therapy(BQT)has long been recommended for Helicobacter pylori(H.pylori)eradication in China.Meanwhile,in the latest national consensus in China,dual therapy(DT)comprising an acid suppressor and amoxicillin has also been recommended.In recent years,the eradication rate of H.pylori has reached>90%using DT,which has been used not only as a first-line treatment but also as a rescue treatment.Compared with BQT,DT has great potential for H.pylori eradication;however,it has some limitations.This review summarizes the development of DT and its application in H.pylori eradication.The H.pylori eradication rates of DT were comparable to or even higher than those of BQT or standard triple therapy,especially in the first-line treatment.The incidence of adverse events associated with DT was lower than that with other therapies.Furthermore,there were no significant differences in the effects of dual and quadruple therapies on gastrointestinal microecology.In the short term,H.pylori eradication causes certain fluctuations in the gastrointestinal microbiota;however,in the long term,the gastrointestinal microbiota eventually returns to its normal state.In the penicillin-naïve population,patients receiving DT have a high eradiation rate,better compliance,lower incidence of adverse reactions,and lower primary and secondary resistance to amoxicillin.These findings suggest the safety,efficacy,and potential of DT for H.pylori eradication.
文摘Objective The main aim of this meta-analysis is to compare the efficacy and safety of dual versus single antiplatelet therapy for pa- tients taking oral anticoagulation (OAC) after coronary intervention. Background The optimal regimen remains controversial for patients taking OAC after coronary intervention. Methods PubMed, Embase and Cochrane Central Register of Controlled Trials were searched for eligible studies including data of triple therapy (TT) versus OAC plus single antiplatelet therapy for patients requiring OAC after coronary intervention. The primary outcome was major adverse cardiac and cerebrovascular event (MACCE). The safety outcome was major bleeding. Results Fourteen studies with 32,825 patients were included. Among prospective studies, patients with TT had a trend toward a higher risk of major bleeding [odds ratios (OR): 1.56, 95% confidence interval (CI): 0.98-2.49, P = 0.06] and a markedly higher risk of all-cause death (OR; 2.11, 95% CI: 1.10-4.06 P = 0.02) compared with OAC plus clopidogrel. Meanwhile, TT was associated with decreased risks of MACCE (OR: 0.63, 95% CI: 051-0.77 P 〈 0.0001), all-cause death (OR: 0.45, 95% CI: 0.20-0.97, P = 0.04), and stroke/transient ischemic attack (TIA)/peripheral embolism (PE) (OR= 0.29, 95% CI: 0.09~3.96, P = 0.04) compared with OAC plus aspirin. Conclusions For pa- tients requiring OAC after coronary intervention, OAC plus clopidogrel may bring more clinical net benefit than TT, whereas OAC plus aspirin should be the last choice. More large-size randomized control trials are needed to confirm these findings.
文摘Objective To assess the prevalence of the bleeding complications in pacemaker implanted patients receiving different antiplatelet regimens, and the influence of each regimen on hospital stays after device implantation. Methods We prospectively enrolled 364 patients receiving the cardiac rhythm device implantations in Fuwai Hospital from July 2012 to December 2013. Bleeding complications including pocket hematoma, hemothorax, cardiac tamponade and blood transfusion requirement were measured as endpoints. Post operation hospital stay was also included in the endpoints. Results Bleeding complications were detected in 15 patients (14 with hematoma, one with hemothorax) out of all 364 patients (4.12%). Dual antiplatelet therapy (DAT) significantly increased hematoma (19.3%) compared with aspi- fin treatment (ASA) (3.2%, P = 0.001) and no antiplatelet therapy (1.9%, P 〈 0.001). There was no significant difference in incidence of pocket hematoma between the ASA group and the control group (P = 0.45). The post procedure hospital stay was longer in DAT group (5.45 ± 2.01 days) compared to those in the ASA group (3.65 ± 1.37 days, P 〈 0.05) or control group (3.99 ± 2.27 days, P 〈 0.05). Pocket hema- toma was considered an independent predictor of hospital stay prolongation (OR: 5.26; 95% CI: 1.56-16.64; P = 0.007). Conclusions Among the Chinese patients undergoing device implantation in this study, the use of dual antiplatelet agents significantly increased the risk of pocket hematoma complications and led to a longer hospital stay. Use of aspirin alone did not increase the risk.
基金supported by grant from the National Natural Science Foundation of China[81470486]
文摘Objective The alpha 2A-adrenergic receptor gene (ADRA2A) polymorphism in individuals antiplatelet response to sympathetic stimulation. The aim of this study was to investigate ADRA2A variants on platelet reactivity in Chinese patients on dual antiplatelet therapy undergoing percutaneous coronary intervention (PCI). modifies the the effect of (DAPT) after Methods From March 2011 to March 2013, 1,024 patients were enrolled in this prospective, single-center, observational study in China. Four single nucleotide polymorphisms (SNPs) of ADRA2A gene (rs11195419, rs3750625, rs13306146, and rs553668) and CYP2C19^*2 were detected by ligase detection reaction (LDR), and adenosine diphosphate (ADP) inhibition was detected by thromboelastography (TEG). Results The minor allele frequencies of ADRA2A SNPs were common. Platelet ADP inhibition was significantly different among patients carrying rs11195419 (adjusted P = 0.022) and rs3750625 (adjusted P = 0.016). The homozygous allele carriers had the lowest ADP inhibition. However, ADP inhibition was not significantly different in rs553668 and rs13306146. At the multivariate analysis, rs11195419 (P = 0.033), rs3750625 (P = 0.020) and CYP2C19"2 (P = 0.002) were independent predictors of ADP inhibition. Subgroups analysis based on sex showed rs11195419 (P = 0.003) and rs3750625 (P = 0.002) were significantly associated with ADP inhibition in males, but not in females. Conclusion ADRA2A genetic variations were associated with ADP-induced platelet aggregation during DAPT in Chinese patients undergoing PCI, and the effect was particularly more pronounced in males.
基金supported by the National High Level Hospital Clinical Research Funding(2022-GSP-QN-1)the National Clinical Research Center for Cardiovascular Diseases,Fuwai Hospital,Chinese Academy of Medical Sciences(NCRC2020013)+1 种基金the National Natural Science Foundation of China(81900323)China International Exchange and Promotion Association for Medical and Healthcare Investigator Sponsored Study(CN174125,DIREGL08735-DAPT)。
文摘BACKGROUND:To investigate the most appropriate dual antiplatelet therapy(DAPT)duration for patients with acute coronary syndrome(ACS)after drug-eluting stent(DES)implantation in the largest cardiovascular center of China.METHODS:We enrolled 5,187 consecutive patients with ACS who received DES from January to December 2013.Patients were divided into four groups based on DAPT duration:standard DAPT group(11-13 months,n=1,568)and prolonged DAPT groups(13-18 months[n=308],18-24 months[n=2,125],and>24 months[n=1,186]).Baseline characteristics and 5-year clinical outcomes were recorded.RESULTS:Baseline characteristics were similar across the four groups.Among the four groups,those with prolonged DAPT(18-24 months)had the lowest incidence of major adverse cardiovascular and cerebrovascular events(MACCEs)(14.1%vs.11.7%vs.9.6%vs.24.2%,P<0.001),all-cause death(4.8%vs.3.9%vs.2.1%vs.2.6%,P<0.001),cardiac death(3.1%vs.2.6%vs.1.4%vs.1.9%,P=0.004),and myocardial infarction(MI)(3.8%vs.4.2%vs.2.5%vs.5.8%,P<0.001).The incidence of bleeding was not different among the four groups(9.9%vs.9.4%vs.11.0%vs.9.4%,P=0.449).Cox multivariable analysis showed that prolonged DAPT(18-24 months)was an independent protective factor for MACCEs(hazard ratio[HR]0.802,95%confidence interval[CI]0.729-0.882,P<0.001),all-cause death(HR 0.660,95%CI 0.547-0.795,P<0.001),cardiac death(HR 0.663,95%CI 0.526-0.835,P<0.001),MI(HR 0.796,95%CI 0.662-0.957,P=0.015),and target vessel revascularization(HR 0.867,95%CI 0.755-0.996,P=0.044).Subgroup analysis for high bleeding risk showed that prolonged DAPT remained an independent protective factor for all-cause death and MACCEs.CONCLUSION:For patients with ACS after DES,appropriately prolonging the DAPT duration may be associated with a reduced risk of adverse ischemic events without increasing the bleeding risk.
文摘Biologic agents have now been used in the management of inflammatory bowel disease(IBD)for many years where experience,expertise and confidence in their use has developed over time.In the United Kingdom,there are well established guidelines and recommendations for both single agent biologic treatments,and with combination therapy of a biologic agent with a small molecule agent in maintenance therapy.In recent times,there has been increasing interest and experience using dual biologic therapy(DBT)in IBD,primarily in difficult to treat and refractory cases with high disease burden.However,published data on use,experience and safety profiles is limited and large-scale studies remain low in number in this developing area.We therefore aim to present a summary and review of the available published data in this area to help us better understand the emerging role of DBT in IBD.
文摘BACKGROUND Little is known about the safety and efficacy of using two or more biologics for the treatment of immune-mediated diseases,including Crohn’s disease(CD).CASE SUMMARY This case report and narrative review demonstrate the potential safety of dual biologic therapy(DBT)in a 45-year-old female with two separate immunemediated diseases.She had a history of multiple sclerosis for which she was receiving treatment with ocrelizumab,and she had been recently diagnosed with CD after presenting with diarrhoea.The CD diagnosis was confirmed radiologically,endoscopically,histologically,and biochemically.The patient received treatment with vedolizumab,a gut-specific inhibitor of theα4β7 integrin on leukocytes.No adverse reactions were observed for the duration of treatment.The safety of ocrelizumab and vedolizumab for the treatment of different immune-mediated diseases was demonstrated.CONCLUSION DBT may be a safe and effective option for the treatment of refractory disease or multiple immunemediated diseases.Newer biologics,which have improved safety profiles and gut specificity,may provide promising avenues for treatment.However,caution must be exercised in the appropriate selection of biologics given their inherent immunosuppressive properties,side effects,and efficacy profiles.Current evidence suggests that biologic therapy is not associated with a worse prognosis in patients with coronavirus disease 2019,but treatment decisions should be made in a multidisciplinary setting.Further research from controlled trials is needed to better understand the safety profile of DBT in CD.The immunopathological mechanisms underlying DBT also remain to be clarified.
文摘Percutaneous coronary intervention with stenting is followed by a duration of dual antiplatelet therapy(DAPT)to reduce stent thrombosis and avoid target lesion failure.The period of DAPT recommended in international guidelines following drug-eluting stent implantation is 12 mo for most patients with acute coronary syndrome,and 6 mo for patients with chronic coronary syndrome or high bleeding risk.The new generation of drug-eluting stents have metallic platforms with thinner struts,associated with significantly less stent thrombosis.Shortened DAPT has been investigated with these stents,with evidence from randomised clinical trials for some individual stents showing non-inferior safety and efficacy outcomes.This has to be balanced by the effect of DAPT on secondary prevention of systemic cardiovascular disease especially in high-risk populations.This review will outline the current evidence for individual stents with regards to DAPT duration for both acute coronary syndrome and chronic coronary syndrome and discuss further directions for research and personalised medicine in this contemporary percutaneous coronary intervention era.
基金Jiangsu Provincial Health Commission,No.M2021013the Science Foundation of Jinling Hospital,No.YYMS2021035.
文摘Treatment strategies for inflammatory bowel disease(IBD)are rapidly evolving with the development of biologics and small molecule drugs(SMDs).However,these drugs are not guaranteed to be effective in all patients,and a“ceiling effect”of biologic monotherapy may occur.This issue highlights an unmet need for optimizing the use of biologics and predicting therapeutic responses.Thus,the development of new drugs with novel mechanisms of action is urgently needed for patients with primary nonresponse and secondary loss of response to conventional biologics and SMDs.In addition,combining different biologics or SMDs has been proposed as a novel strategy to enhance treatment efficacy in IBD,which theoretically has multidimensional anti-inflammatory potential.Based on the current evidence available for IBD,dual targeted therapy may be a promising strategy for refractory IBD patients who have failed in multiple biologic treatments or who have extraintestinal manifestation.Additionally,identifying the subgroup of IBD patients who are responding to biological combination therapies is also equally important in stable disease remission.In this review,we summarize the newly developed biologics and SMDs and the current status of biologics/SMDs to highlight the development of individualized treatment in IBD.
文摘BACKGROUND Helicobacter pylori(H.pylori)eradication rates have fallen globally,likely in large part due to increasing antibiotic resistance to traditional therapy.In areas of high clarithromycin and metronidazole resistance such as ours,Maastricht VI guidelines suggest high dose amoxicillin dual therapy(HDADT)can be considered,subject to evidence for local efficacy.In this study we assess efficacy of HDADT therapy for H.pylori eradication in an Irish cohort.AIM To assess the efficacy of HDADT therapy for H.pylori eradication in an Irish cohort as both first line,and subsequent therapy for patients diagnosed with H.pylori.METHODS All patients testing positive for H.pylori in a tertiary centre were treated prospectively with HDADT(amoxicillin 1 g tid and esomeprazole 40 mg bid×14 d)over a period of 8 months.Eradication was confirmed with Urea Breath Test at least 4 wk after cessation of therapy.A delta-over-baseline>4%was considered positive.Patient demographics and treatment outcomes were recorded,analysed and controlled for basic demographics and prior H.pylori treatment.RESULTS One hundred and ninety-eight patients were identified with H.pylori infection,10 patients were excluded due to penicillin allergy and 38 patients refused follow up testing.In all 139 were included in the analysis,55%(n=76)were female,mean age was 46.6 years.Overall,93(67%)of patients were treatment-naïve and 46(33%)had received at least one previous course of treatment.The groups were statistically similar.Self-reported compliance with HDADT was 97%,mild side-effects occurred in 7%.There were no serious adverse drug reactions.Overall the eradication rate for our cohort was 56%(78/139).Eradication rates were worse for those with previous treatment[43%(20/46)vs 62%(58/93),P=0.0458,odds ratio=2.15].Age and Gender had no effect on eradication status.CONCLUSION Overall eradication rates with HDADT were disappointing.Despite being a simple and possibly better tolerated regime,these results do not support its routine use in a high dual resistance country.Further investigation of other regimens to achieve the>90%eradication target is needed.
文摘For a long time, a combination of interferon and ribavirin has been used to treat viral hepatitis C, but the sustained virological response was only achieved in 45% of cases and side effects were serious [1]. Direct acting antivirals (DAA) have provided a cure for almost everyone with hepatitis C, with few side effects. The Purpose of Our Work is to compare the results of treatment for viral hepatitis C before and after DAA. Patients and Methods: This is a retrospective study, bringing together all patients with chronic viral hepatitis C treated between January 2009 and March 2020 at the University Hospital Hassan II in Fez, Morocco. The epidemiological, clinical, biological, virological characteristics of the included patients were collected from the two groups: A, treated with interferon and ribavirin or by triple therapy and B, treated with DAA. Results: 162 patients were included, the average age was 55 y/o, with 90 women and 72 men. 88 patients (54.3%) were already cirrhotic, of which 61 were compensated and 27 were decompensated. Genotype 1 was dominant with a frequency of 71.6%, 107 patients (66%) initially treated with old HCV treatments and 55 (34%) treated with DAA. Sustained viral response was obtained in 59 cases (55.14%) in group A versus 54 cases (98.18%) in group B with a very significant difference (p < 0.0001). Treatment failure was observed in 14 patients (13.1%) in group A and only one patient, i.e. 2% in group B (p = 0.019). 14 patients relapsed in group A (13.1%) versus 0 patient in group B (p = 0.003). The tolerance of the treatment was excellent in group B as a whole with only five patients (9%) reported side effects which were minor, not leading to the discontinuation of treatment while the side effects were major in 49 patients (45.7%) in group A with led to the permanent discontinuation of treatment in 6 patients. The difference in side effects between the two groups was very significant with (p Conclusion: Our study has shown the superiority of DAA in terms of efficacy and tolerance compared to the old treatments for chronic hepatitis C. In addition, these treatments allow almost systematic viral elimination and therefore consequently a reduction in the risk of complications hepatic with a short time of treatment.
基金Supported by the Grants of Fujian Province Health Education Union Scientific,Ministry of Health of the People's Republic of China(WKJ 2008-2-59)
文摘Objective: To evaluate the efficacy of dual antiplatelet therapy combined with Naoxintong Capsule (脑心通胶囊, NXTC) in a rat model of coronary microembolization (CME). Methods: A total of 95 rats were randomly divided into 6 groups: control, sham-operation, CME model, NXTC, dual antiplatelet (clopidogrel and aspirin) intervention (DA), and NXTC combined with DA (NDA) groups. The complete data in 69 rats were obtained. The number of CME, myocardial apoptosis rate, bleeding time, clotting time, and adensosine diphosphate (ADP)-induced platelet aggregation were assessed. Results: Compared with the CME group, the number of CME and myocardial apoptosis rates were significantly decreased in the NXTC, DA, and NDA groups (P〈0.01). Compared with other intervention groups, the number of CME and myocardial apoptosis rates were the least in the NDA group (P〈0.01), and the incidence of surgical bleeding was the highest in the DA group (P〈0.01). Compared with the CME group, ADP-induced maximum platelet aggregation rate was significantly inhibited in the NXTC, DA, and NDA groups (P〈0.01), both bleeding time and clotting time were significantly increased in the NXTC, DA, and NDA groups (P〈0.01), while the above parameters were the highest in the DA group (P〈0.05). Conclusion: The combination therapy of NXTC and DA enhanced the anti-CME effect of either therapy alone and reduced the risk of the DA therapy-associated bleeding, demonstrating an improved benefit/ risk ratio in the rat model of CME.