Efficacy Of Sequential Therapy Research Articles

Efficacy of Sequential Therapy as the First-Line Treatment in the Eradication of Helicobacter pylori.

The Helicobacter pylori infection is a significant issue in global health as it is associated with a range of gastrointestinal disorders and an elevated likelihood of developing stomach cancer. The declining efficacy of standard triple therapy (TT) as the recommended treatment can be attributed to the emergence of drug-resistant strains. Sequential therapy (ST) has been recognized as an alternative approach, wherein a combination of proton-pump inhibitor (PPI) and amoxicillin is administered for the initial five days, followed by a combination of PPI, clarithromycin, and metronidazole for the subsequent five days. In this comprehensive systematic review and meta-analysis, we have thoroughly assessed the effectiveness and tolerability of ST as a primary treatment option in comparison to TT for the eradication of H. pylori. The analysis comprised a total of 15 randomized controlled trials, encompassing a sample size of 5,219 patients. The collective findings indicate that ST exhibits promise as it achieves higher rates of eradication. Additionally, it is worth noting that this approach has the potential to yield cost savings and enhance treatment compliance when compared to TT. To summarize, this systematic review and meta-analysis provide evidence that ST is a viable option for the initial treatment of H. pylori eradication. It shows potential benefits compared to the standard TT, especially when there is resistance to clarithromycin.In order to establish ST as the preferred first-line treatment, it is imperative that additional research be conducted to address the aforementioned limitations and thoroughly investigate its long-term efficacy and safety profiles. Nevertheless, it is required that additional research be conducted in order to adequately tackle the constraints of the current studies and solidify its position as a favored treatment alternative. It is also essentialto consider ST as a viable approach to improve the rates of H. pylori eradication. This method should be thoroughly examined in clinical practice to gain a deeper understanding of its effectiveness.

Head-to-Head Comparison of Tazarotene and Calcitriol with or without Sequential Therapy in Mild-to-Moderate Psoriasis: A Randomized Open-label Study.

Psoriasis is an autoimmune disease that causes rapid turnover of skin cells. It is a chronic disease that affects a patient's quality of life significantly and frequently requires long-term treatment. The study on sequential therapy with tazarotene 0.1% and calcitriol 0.0003% has not been tried so far; hence, we designed this study to compare the safety and efficacy of sequential therapy with tazarotene 0.1% cream and calcitriol 0.0003% ointment versus monotherapy in mild-to-moderate stable plaque psoriasis (SPP). The objective of this study was to compare the safety and efficacy of topical sequential treatment with tazarotene followed by calcitriol, topical calcitriol followed by tazarotene, tazarotene monotherapy, calcitriol monotherapy, and compare the safety and efficacy of the sequential therapies with monotherapies. The study was a single center, prospective parallel-group, active control, randomized study of 16 weeks duration (treatment for 8 weeks and follow-up for 16 weeks), randomized to either of the four groups, i.e., tazarotene 0.1% for 4 weeks followed by calcitriol 0.0003% for 4 weeks or calcitriol 0.0003% for 4 weeks followed by tazarotene 0.1% for 4 weeks or tazarotene 0.1% for 8 weeks or calcitriol 0.0003% for 8 weeks. Both tazarotene and calcitriol were applied once daily in all the groups. There was no significant difference with regard to age and duration of illness among the four treatment groups. Statistically significant improvement was observed in erythema, scaling, and induration scores, and Physician`s global assessment scale at 8 weeks and 16 weeks as compared to baseline in tazarotene - calcitriol, calcitriol - tazarotene, and calcitriol versus tazarotene groups. This study concluded that topical treatment with tazarotene 0.1% and calcitriol 0.003% was efficacious in treating mild-to-moderate SPP as both sequential and monotherapy. However, topical treatment with tazarotene as monotherapy was the least efficacious.

Docetaxel versus abiraterone for metastatic hormone-sensitive prostate cancer with focus on efficacy of sequential therapy

Docetaxel versus abiraterone for metastatic hormone-sensitive prostate cancer with focus on efficacy of sequential therapy

Docetaxel versus abiraterone for metastatic hormone-sensitive prostate cancer with focus on efficacy of sequential therapy.

We aimed to assess the oncologic efficacy of combining docetaxel (DOC) versus abiraterone (ABI) with androgen deprivation therapy (ADT) in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC), with a focus on the efficacy of sequential therapy, in a real-world clinical practice setting. The records of 336 patients who harbored de novo high-risk mHSPC, based on the LATITUDE criteria, and had received ADT with either DOC (n = 109) or ABI (n = 227) were retrospectively analyzed. Overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), including time to castration-resistant prostate cancer (CRPC), time to 2nd-line progression (PFS2), and 2nd- and 3rd-line PFS, were compared. We used one-to-two propensity score matching to minimize the confounders. The differential efficacy of 2nd-line therapy based on agents in each arm was evaluated using the unmatched cohort as an additional interest. After propensity score matching, 86 patients treated with DOC + ADT and 172 with ABI + ADT were available for analyses. The 3-year OS and CSS for DOC versus ABI were 76.2% versus 75.1% (p = 0.8) and 78.2% versus 78.6% (p = 1), respectively. There was no difference in the median PFS2 (49 vs. 43 months, p = 0.39), while the median time to CRPC in patients treated with ABI was significantly longer compared to those treated with DOC (42 vs. 22 months; p = 0.006). The median 2nd-linePFS (14 vs. 4 months, p < 0.001) and 3rd-linePFS (4 vs. 2 months, p = 0.012) were significantly better in the DOC group than in the ABI group. Among the unmatched cohort, after ABI for mHSPC, the median 2nd-linePFS did not differ between the patients treated with DOC and those treated with enzalutamide as 2nd-line therapy (both 3 months, p = 0.8). ADT with DOC or ABI has comparable oncologic outcomes in terms of OS, CSS, and PFS2 in patients with de novo high-risk mHSPC. Compared to DOC, ABI resulted in longer time to CRPC but worse 2nd and 3rd-line PFS. Further studies are needed to clarify the optimal sequence of therapy in the upfront intensive treatment era.

Abiraterone, Orteronel, Enzalutamide and Docetaxel: Sequential or Combined Therapy?

Objective: To summarize the current therapeutic status using chemotherapeutic agent docetaxel and endocrine therapeutic agents (ARAT, abiraterone, orteronel or enzalutamide) for the treatment of metastatic castration-resistant prostate cancer (mCRPC), including sequential therapy and combined therapy, to promote the consensus on the optimal regimen for achieving superior treatment efficacy. Methods: Through literature search in PubMed, articles with the following relevant keywords were collected and anlyzed: CRPC, abiraterone, orteronel and enzalutamide, median survival, overall survival, prostate specific antigen (PSA), PSA response rate and median radiologic progression-free survival. Results: Fifty-eight articles were obtained and analyzed in this review. These articles included androgen axis-targeting agents after docetaxel, docetaxel after androgen axis-targeting agents, Triple sequential and combination therapy, covering four current drugs for mCRPC treatment: docetaxel, abiraterone, orteronel, and enzalutamide. It was found that there may be some cross-resistance between androgen axis-targeting agents, which will reduce the efficacy of subsequent drug treatment. Although neither of the studies of using combination therapy showed serious drug toxicity, the efficacy of sequential therapy was not as good as expected. Most adverse reactions after treatment were reported to be level 1–2. Conclusion: Based on the results of the current studies, abiraterone followed by enzalutamide treatment is the best sequential treatment for most docetaxel-naïve patients. This treatment achieves not only good OS, but also PFS and PSA response rates. In addition, for patients who have previously failed docetaxel treatment, enzalutamide is the best choice as the subsequent treatment.

Clinical Efficacy of Sequential Therapy of Statins in Treatment of Cardiovascular Diseases

Clinical Efficacy of Sequential Therapy of Statins in Treatment of Cardiovascular Diseases

Systemic immune-inflammation index predicts prognosis of sequential therapy with sorafenib and regorafenib in hepatocellular carcinoma

BackgroundRegorafenib has shown promising results as a second-line therapy for patients with hepatocellular carcinoma (HCC) who progressed on sorafenib. Although there have been several data regarding the efficacy of sequential therapy with sorafenib and that of regorafenib in real-life, specific inflammation markers for predicting the prognosis have not been studied. This study aimed to investigate prognostic value of systemic inflammatory markers in patients with HCC who received sorafenib-regorafenib sequential therapy.MethodsWe retrospectively analyzed medical data of patients who received regorafenib for the treatment of HCC after sorafenib failure. Progression free survival (PFS) and overall survival (OS) were assessed using the Kaplan–Meier survival curves. Univariate and multivariate analyses were performed to analyze the factors associated with survival.ResultsA total of 58 patients who received at least one dose of regroafenib and fulfilled the eligibility criteria, good performance status (Eastern Cooperative Oncology Group [ECOG] 0–1) and preserved liver function (Child-Pugh-A), were included in the analysis. The median PFS was 3 months (95% confidence interval [CI] = 0.981–5.019) and the median OS was 8 months (95% CI = 5.761–10.239). Elevated systemic immune-inflammation index (SII ≥340) was independently associated with poor OS. In multivariate analysis, the SII (hazard ratio [HR] = 2.211, 95% CI = 1.089–4.489, P = 0.028) and alpha-fetoprotein (AFP) (HR = 2.750, 95% CI = 1.259–6.010, P = 0.011) were independent predictors of OS.ConclusionElevated SII is associated with poor OS in patients with HCC who received sequential therapy with sorafenib and regorafenib. In addition, when selecting a treatment strategy, the SII can be used in combination with the AFP level as a promising prognostic tool for HCC.

Sequential Docetaxel in ≥7 Cycles Followed by Cabazitaxel Improves Oncological Outcomes in Patients with Metastatic Castration-Resistant Prostate Cancer

Background. Docetaxel (DOC) was the first regimen that increased the survival and became the standard-of-care in patients with metastatic castration-resistant prostate cancer (mCRPC). However, it is unclear whether switching to second-line chemotherapy or optimal sequencing of cabazitaxel (CBZ) ensures better clinical outcomes. We aimed to evaluate the efficacy of sequential therapy with DOC and CBZ and the effect of the number of prior DOC cycles on oncological outcomes in patients with mCRPC. Methods. We retrospectively included 46 mCRPC patients who received DOC followed by CBZ at quaternary hospitals in Japan between February 2015 and March 2019. Participants received intravenous DOC (40–75 mg/m2) every 3–4 weeks; CBZ (15–25 mg/m2) was administered every 3–4 weeks. Androgen-deprivation therapy and prednisolone 5 mg (twice daily) were administered throughout both regimens. The primary endpoints were overall (OS) and progression-free survival (PFS). The secondary endpoints were the rates of ≥30% and ≥50% reduction in prostate-specific antigen (PSA) levels at chemotherapy initiation. Results. Participants were divided into two groups according to DOC cycles (Groups A and B: ≤6 and ≥7 DOC cycles, respectively). The rates of ≥30% and ≥50% reduction in PSA levels were higher in Group B than in Group A, but there were no significant differences in both groups. Median OS in Groups A and B was 12.7 and 71.0 months, respectively P &lt; 0.001 ; median PFS in Groups A and B was 3 and 12 months, respectively P &lt; 0.001 . Conclusions. Administration of ≥7 cycles of DOC followed by CBZ may improve oncological outcomes in patients with mCRPC.

Treatment of Helicobacter pylori infection: a clinical practice update

Helicobacter pylori infection still represents a major health issue, especially in developing countries, with an estimate of 4 billion of infected subjects in 2015. The increase of antibiotic resistance has undermined the efficacy of standard triple therapy leading to more complex regimens. This review summarizes recommendations of international guidelines and reports the most recent evidence from meta-analyses and clinical trials on the treatment of Helicobacter pylori infection. The choice of H. pylori eradication regimen should be based on the local prevalence of clarithromycin resistance and the previous use of macrolides. Quadruple therapies (bismuth quadruple and concomitant) are the recommended regimens for the first-line treatment; a 14-day clarithromycin-containing triple therapy is suggested in areas with low prevalence of clarithromycin resistance and in patients without previous use of macrolides. Data on the efficacy of sequential therapy against clarithromycin resistant H. pylori strains are contradictory, and its use in the treatment of H. pylori infection is generally discouraged. Second-line treatments include levofloxacin-containing triple therapy and bismuth quadruple therapy. Probiotic supplementation should be used with the aim to reduce antibiotic-related adverse events. Recent evidence would support current guideline recommendations for the treatment of Helicobacter pylori infection.

Efficacy of sequential therapy comprising of docetaxel, abiraterone, enzalutamide, and cabazitaxel in patients with castration-resistant prostate cancer.

239 Background: The sequence of use of life-prolonging therapy (docetaxel, abiraterone, enzalutamide, and cabazitaxel) is unclear in patients with castration-resistant prostate cancer (CRPC). Methods: We retrospectively identified a total of 316 patients diagnosed with CRPC from September 2003 to April 2019 at Nagoya University and its affiliated hospitals. All patients were treated with &gt;2 life-prolonging therapies. We divided these patients into four groups based on the sequence of drug administration. The group of patients who were treated using the sequence of abiraterone to enzalutamide or enzalutamide to abiraterone was termed as AA. The group treated using the sequence of abiraterone or enzalutamide to docetaxel was termed as AD. The group treated using the sequence of docetaxel to abiraterone or enzalutamide was termed as DA. Lastly, the group treated using the sequence of docetaxel to cabazitaxel was termed as DC. We investigated the overall survival (OS) from the time of diagnosis of CRPC. In addition, we estimated combined progression-free survival (combined PFS) defined as the sum of the PFS of each agent. Results: The number of patients in AA, AD, DA, and DC was 106, 69, 130, and 11, respectively. Regarding AA, AD, DA, and DC, the median ages were 72, 70, 68, and 64 years, respectively. The proportion of patients who had de novo distant metastasis was 66%, 65%, 58%, and 73% in AA, AD, DA, and DC, respectively. Further, the median OS was 68.7, 54.5, 68.6, and 22.0 months for AA, AD, DA, and DC, respectively. Notably, no significant differences related to OS were observed between AA and AD ( p = 0.06), AA and DA ( p = 0.24), as well as AD and DA ( p = 0.46). The median combined PFS was 8.6, 10.1, 13.9, and 5.6 months for AA, AD, DA, and DC, respectively. In terms of combined PFS, a significant difference was observed between AA and DA ( p &lt; 0.001) as well as AD and DA ( p = 0.003). OS and combined PFS were significantly poor in DC compared with those in the other groups. Conclusions: No significant differences related to OS were observed regarding the sequence of use of docetaxel, abiraterone, and enzalutamide. Notably, combined PFS was comparatively better in DA than in any other group.

Sequential therapy with sorafenib and regorafenib for advanced hepatocellular carcinoma: a multicenter retrospective study in Japan.

Background Conversion from sorafenib to regorafenib is primarily an evidence-based treatment strategy in patients with advanced hepatocellular carcinoma (HCC). This study aimed to assess the safety and efficacy of sequential therapy with sorafenib and regorafenib in patients with advanced HCC by analysis of outcomes in clinical practice with the aim to complement phase III findings. Methods The medical records of patients with advanced HCC receiving regorafenib were retrieved to collect data on sorafenib administration at seven Japanese institutions. Radiological responses and adverse events were evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1 and the Common Terminology Criteria for Adverse Events version 4.0, respectively. Results Before March 2018, 44 patients were administered regorafenib for advanced HCC. The median sorafenib treatment duration was 8.4months. The most common adverse events were similar to those reported by the RESORCE trial. The median overall survival (OS) was 17.3months (95% confidence interval [CI] 11.4-22.9), and 17 of 37 patients (45.9%) discontinued regorafenib and received sequential systemic therapy after regorafenib. These patients had significantly longer OS than those who were treated by the best supportive care or sub-optimal therapy (not reached versus 8.7months [95% CI 5.8-11.7]; P < 0.001). Conclusion The results based on Japanese clinical practices verified the tolerability of regorafenib in advanced HCC. Major regorafenib-associated adverse events were similar to those related to sorafenib. OS was significantly longer than expected, which might be associated with the sequential systemic therapies after regorafenib, mainly lenvatinib.

Clinical efficacy of sequential therapy for butylphthalide combined with alteplase in the treatment of acute cerebral infarction

Objective To observe the effect of butylphthalide sequential therapy combined with injection of alteplase(injection with recombinant human collagenous tissue plasminogen activator) in the treatment of acute cerebral infarction (ACI). Methods 61 patients with ACI and within 4.5 hours of onset were selected, and they were divided into treatment group(butylphthalide combined with alteplase group, 31 cases) and the control group (alteplase only group, 30 cases) by random number table.The two groups were given glucose-lowering, statins for maintaining the blood pressure, as well as aspirin enteric tablets or clopidogrel for those without bleeding on the 24 hour review head CT in the acute phase.The treatment group was given alteplase for injection with sequential butylphthalide therapy (butylphthalide injection for 2 weeks followed by an oral administration of butylphthalide soft capsules for 3 months), and the control group was given only alteplase for injection.The National Institute of Health stroke scale (NIHSS) and Barthel index (BI) were used for evaluating the final clinical efficacy. Results The NIHSS scores of the treatment group compared with the control group at 24 hour, 14 days and 3.5 months after the treatment had statistically significant differences(t=-0.102, -1.964, -2.444, P=0.037, 0.018 and 0.012). The NIHSS scores of the treatment group had decreased 2%, 27% and 41% compared with the control group at 24 hour, 14 days and 3.5 months after the treatment, respectively.The BI score of the treatment group and control group at 3.5 months after treatment had statistically significant difference(t=-1.956, P=0.029). Conclusion The sequential butylphthalide therapy combined with injection of alteplase has good synergistic effect for the patients with onset of ACI less than 4.5 hours, and it is a safe and effective treatment method for ACI within 4.5 h and it is worthy of clinical promotion. Key words: Cerebral infarction, acute; Butylphthalide; Alteplase

The efficacy of sequential therapy in eradication of Helicobacter pylori in Turkey.

Most of the studies about sequential therapy that have been reported from Turkey were levofloxacin based. We aimed to compare the Helicobacter pylori (H. pylori) eradication rates of standard triple, sequential and quadruple therapies including claritromycin regimes in this study. A total of 160 patients with dyspeptic symptoms were enrolled to the study. The patients were randomized to four groups of treatment protocols. And 40 patients received standard triple therapy for 2 weeks, 40 patients received bismuth containing quadruple therapy for 2 weeks, 40 patients received 5 + 5 clarithromycin-based sequential therapy, and 40 patients received 7 + 7 clarithromycin-based sequential therapy. H. pylori eradication was assessed by C 14 urea breath test 4 weeks after therapy. Out of 160 patients with H. pylori infection, 131 (81.9%) were eradicated successfully and 29 (18.1%) failed to eradicate H. pylori infection. H. pylori eradication was achieved in 28 of 40 patients receiving standard triple therapy (70%), in 33 of 40 patients receiving quadruple therapy (82.5%), in 37 of 40 patients receiving 5 + 5 sequential therapy (92.5%), and in 33 of 40 patients receiving 7 + 7 sequential therapy (82. 5%). Statistics revealed that 5 + 5 sequential therapy led to significantly higher H. pylori eradication rates compared with that of standard triple therapy (P = 0.019). There was no statically difference between 5 + 5 sequential therapy and the other therapy groups' eradication rates, but it was higher than all of the protocols. H. pylori eradication rate with sequential therapy in our patients with nonulcer dyspepsia was higher than those of patients with standard therapy (93% versus 82%, respectively, P>0.05). 5 + 5 sequential therapy was associated with significantly higher eradication rate of H. pylori compared with standard triple therapy in our study cohort.

A Case of Alzheimer’s Disease Was Kept Relative Stable with Sequential Therapy for Eight Years

Background: Although Alzheimer’s disease (AD) has been intensively investigated for many years, the effective treatments are largely missing. Commonly used conventional therapy, such as cholinesterase inhibitors (ChEI) and N-methyl D-asparate receptor antagonist, have been generally considered as having symptom-relieving rather than disease-modifying effects. Thus, how to improve cognitive function beyond such effect & time limitations has become a serious challenge. Aim: In order to solve this challenge, a sequential therapy with the integration of conventional therapy and herbal therapy was applied to AD patients. Careful clinical observation was conducted in our outpatient setting. Case Presentation: A case of probable AD received the sequential therapy has achieved relative stable cognition and overall status in eight years. Conclusion: During the treatment of this AD case in eight years, sequential therapy showed great potential in stabilizing and improving cognition and overall status. Well designed preclinical and clinical studies are needed to investigate the efficacy of sequential therapy for AD and other type of dementia.

Treating idiopathic hypertrophic pyloric stenosis with sequential therapy: A clinical study.

The aim of this study was to explore the efficacy and safety of treating idiopathic hypertrophic pyloric stenosis with sequential therapy (ST). From January 2010 to June 2013, 49 children with idiopathic hypertrophic pyloric stenosis were divided into two groups to accept either atropine ST (ST group, n = 26) or laparoscopic surgery (operation group, n = 23). The remission rate of vomiting, complications, hospital stay and medical expenditure were compared between the two groups. The body weight and the thickness of the pyloric muscle at 6 months after the treatments were also compared. The remission rate of vomiting was lower in the ST group (88.5%; 23/26) than in the operation group (100%, 23/23). The difference in the incidence rate of complications, body weight and pyloric muscle thickness was not statistically significant between the two groups. However, the hospital stay was significantly longer, while the medical expenditure was significantly lower in the ST group than in the operation group. Atropine ST is safe, effective and cost-effective as compared with operation; however, the efficacy of ST is lower than operation.

Ten-day empirical sequential or concomitant therapy is more effective than triple therapy for Helicobacter pylori eradication: A multicenter, prospective study

BackgroundThe resistance of Helicobacter pylori to antibiotics has increased the need for new empirical, first-line treatments. However, the efficacy of sequential therapy (ST) and concomitant therapy (CT) compared with triple therapy (TT) has not been adequately evaluated. AimIn this study, we evaluated the efficacy of these empirical three regimens. MethodsThe 517 patients enrolled in the study were prospectively randomized to receive 10 days of TT (n=171), ST (n=170), and CT (n=176) at 5 university-affiliated hospitals from May 2013 to March 2015. The post-treatment H. pylori status was determined using the 13C-urea breath test. ResultsThe baseline characteristics were similar among the three groups. The intention-to-treat eradication rates were 62.6%, 70.6%, and 77.8% in the TT, ST, and CT groups, respectively (p<0.01). The corresponding per-protocol eradication rates were 82.8%, 89.5%, and 94.4%, respectively (p<0.01). There were no significant differences in the compliance, side effects, and follow-up loss rates. ConclusionA higher eradication rate was achieved with empirical 10-day ST, and CT than with the TT regimen, with similar rates of compliance and treatment side effects.

Comparative analysis of efficacy of sequential therapy combined with probiotics, pure sequential therapy and standard triple therapy for Helicobacter pylori eradication

Objective To compare the efficacy of sequential therapy combined with probiotics, pure sequential therapy and standard triple therapy for Helicobacter pylori eradication. Methods Selected the clinical data of 240 patients admitted. The 240 patients were randomly divided into 3 groups. Group A received standard triple therapy, group B received sequential therapy and Group C received sequential therapy in combination with probiotics. Then, we compared the eradication rate, the score of gastrointestinal tract symptoms before and after treatment, and the side effects among 3 groups. Results The eradication rate was 72.5%in group A,87.5%in group B,and 96.3%in group C. The eradication rate of group C was significantly better than group A and group B(χ2=18.531,P 0.05), but they all significantly decreased after treatment among 3 groups(P<0.05),with group C a better result(F=25.581,P<0.05).The side effects of 3 groups were 16.3%,13.8%,3.8%,respectively. There were a significantly differencec between group C and the other 2 groups(χ2=7.011,P=0.030). Conclusion Sequential therapy in combination with probiotics can achieve a higher eradication rate, improve the score of gastrointestinal tract symptoms, and decrease side effects. Key words: H.pylori; sequential therapy; probiotics

Su1191 Efficacy of Sequential Therapy for Eradication of Helicobacter pylori All Over the Word. Lessons From a Comparative Meta-Analysis

Su1191 Efficacy of Sequential Therapy for Eradication of Helicobacter pylori All Over the Word. Lessons From a Comparative Meta-Analysis

What is the Best Regimen forHelicobacter pyloriEradication in Canadian Arctic Aboriginals?

Canadian Aboriginal populations have a high prevalence of Helicobacter pylori infection and an increased risk for the development of gastric cancer (1). Thus, there is a need to identify effective H pylori eradication regimens in this at-risk population. In the current issue of the Journal, Morse et al (2) (pages 701–706) report results from a randomized controlled trial comparing sequential versus standard clarithromycin-containing triple therapy in H pylori-infected adults from the community of Aklavik (Northwest Territories) (2). The study was part of a participatory research project focusing on community-identified research goals investigating the burden of H pylori disease in Arctic Aboriginal communities. In the study by Morse et al (2), H pylori-infected patients >15 years of age were randomly assigned to either a 10-day treatment of standard triple therapy consisting of a proton pump inhibitor (rabeprazole), amoxillicin and clarithromycin, or sequential therapy. Antibiotic resistance rates to clarithromycin and metronidazole were available for almost one-half of the subjects, allowing tailored treatment. If clarithromycin resistance was detected, patients were randomly assigned to sequential therapy or quadruple therapy. Several important points are noteworthy in this study. First, as identified in other Canadian Aboriginal populations, the prevalence of H pylori infection remains high in this community despite a diminishing H pylori prevalence in most segments of the Canadian population. Second, the prevalence of precancerous lesions, gastric atrophy and intestinal metaplasia were high, supporting the increased risk for development of gastric cancer in this population and underscoring the need for effective H pylori eradication regimens. When outcomes were assessed by the more stringent intention-to-treat analysis, the effectiveness of both therapies was disappointing, with only 55% efficacy with triple therapy and 57% with sequential therapy. With these poor outcomes, it is important to consider why the results were suboptimal. The success of treatment for H pylori is determined, in large part, by the presence of antibiotic resistance and patient adherence (3). In the study by Morse et al (2), of the 50 subjects who underwent sensitivity testing, the rates of clarithromycin and metronidazole resistance were 10% and 26%, respectively. Thus, it is likely that similar resistance rates were present in the remaining subjects who were randomly assigned to triple versus sequential therapy. The updated Maastricht guidelines (4) do not recommend clarithromycin therapy if the local clarithromycin resistance rate is >15%. Thus, one potential explanation for the poor efficacy is antibiotic resistance. Poor adherence to therapy is an additional important determinant of efficacy (3). In the study by Morse et al, the overall adherence levels were suboptimal (60%). In fact, even in the group who underwent antibiotic sensitivity-directed therapy, the eradication rates were still low. However, in subjects with 100% compliance, treatment effectiveness increased in both the triple therapy and sequential therapy groups to 65% and 75%, respectively. Thus, the combination of antibiotic resistance and decreased adherence likely account for the poor efficacy of both triple therapy and sequential therapy. Although sequential therapy was initially regarded as superior to triple therapy, follow-up studies indicate that the efficacy of sequential therapy is not as good as the original studies suggested. Sequential therapy loses efficacy in the presence of clarithromycin and metronidaz-ole resistance (3). In the study by Morse et al, even when assessed by per-protocol analyses, efficacy of sequential therapy was well below the recommended cure rates of 80% to 90%, suggesting that this regimen is not an optimal choice in this particular community unless adherence can be improved. Morse et al should be commended for providing key information concerning H pylori infection in a Canadian Aboriginal Arctic community. This study shows that, in this at-risk population, the efficacies of two currently recommended eradication regimens are suboptimal, likely due to both antibiotic resistance and poor compliance. These findings support further studies aimed at identifying effective therapies by focusing on both optimized regimens based on known antibiotic susceptibility rates in the community and promoting adherence.

Efficacy of genotypic resistance-guided sequential therapy in the third-line treatment of refractory Helicobacter pylori infection: a multicentre clinical trial

The efficacy of sequential therapy and the applicability of genotypic resistance to guide the selection of antibiotics in the third-line treatment of Helicobacter pylori have not been reported. We aimed to assess the efficacy of genotypic resistance-guided sequential therapy in third-line treatment. Genotypic and phenotypic resistances were determined in patients who failed at least two eradication therapies by PCR with direct sequencing and agar dilution test, respectively. The patients were retreated with sequential therapy containing esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and metronidazole plus clarithromycin, levofloxacin or tetracycline for another 7 days (all twice daily), according to genotypic resistance determined using gastric biopsy specimens. Eradication status was determined by the (13)C-urea breath test. Trial registered at clinicaltrials.gov (identifier: NCT01032655). The overall eradication rate was 80.7% (109/135, 95% CI 73.3%-86.5%) in the intention-to-treat analysis. The presence of amoxicillin resistance (OR 6.83, 95% CI 1.62-28.86, P = 0.009) and prior sequential therapy (OR 4.77, 95% CI 1.315-17.3, P = 0.017), but not tetracycline resistance (tetracycline group), were associated with treatment failure. The eradication rates in patients who received clarithromycin-, levofloxacin- and tetracycline-based sequential therapies were 78.9% (15/19), 92.2% (47/51) and 71.4% (25/35) in strains susceptible to clarithromycin, levofloxacin and tetracycline, respectively. A simple molecular method guiding sequential therapy can achieve a high eradication rate in the third-line treatment of refractory H. pylori infection.