Factors Associated with Antiretroviral Therapy Defaulting among Adult Patients Receiving Care at Chikankata Mission Hospital, Chikankata District, Zambia

Background: Defaulting on antiretroviral therapy has been identified as the most important factor contributing to the antiretroviral therapy failure rate. This study aimed to investigate factors associated with defaulting on antiretroviral therapy among adult patients receiving care at Chikankata Mission Hospital antiretroviral therapy clinic. Method: Cross-sectional analytical study on 385 participants selected by a computer generated random numbers technique of simple random sampling from among the patients receiving antiretroviral therapy at Chikankata Mission Hospital. Data collected were processed and analysed using Statistical Package for Social Science version 27. Univariate and backward multivariable logistic regression analysis was performed to identify factors associated with antiretroviral therapy defaulting. The level of significance was set at 5% with a confidence level of 95%. Results: Over half (58.4%) of the study participants defaulted on antiretroviral therapy. About 65.8% of study participants indicated improved health as the reason they defaulted on antiretroviral therapy. Most participants indicated that it was important to always go for antiretroviral therapy services (Adjusted Odds Ratio 1.95;95% Confidence Interval: [1.14 - 3.33], p = 0.015). Very few participants indicated poor family support for antiretroviral therapy services (Adjusted Odds Ratio 4.08;95% Confidence Interval: [2.02 - 8.23], p Conclusion: Defaulting on antiretroviral therapy continues to be a significant problem and needs to be addressed as a matter of priority. More counselling and awareness-raising programmes are required to improve knowledge and understanding on the importance of attending scheduled antiretroviral therapy clinics and services as well as the consequences of defaulting on antiretroviral therapy.

Cognitive Behavioral Therapy for Tinnitus in Adults: A Review of Efficacy in Quality-of-Life Enhancement

Background: Tinnitus, characterized by the perception of sounds without an external source, significantly affects quality of life. Cognitive Behavioral Therapy (CBT) has emerged as a promising approach for managing tinnitus-related distress and enhancing psychological well-being. Objectives: This review aims to analyze the effectiveness of CBT in tinnitus management, focusing on alleviating distress, enhancing coping mechanisms, and improving overall well-being. Methods: PubMed and World of Science databases were systematically searched using keywords related to tinnitus, CBT, and quality of life. English, peer-reviewed studies focusing on adult populations were included. Studies involving pediatric populations or not meeting inclusion criteria were excluded. Data extraction was performed using PRISMA guidelines, with a narrative synthesis approach for analysis. Methodological quality and risk of bias were assessed using appropriate tools. The search engine initially identified 155 studies that met the inclusion criteria for the systematic review. However, upon further evaluation, 140 of these studies were excluded due to their non-randomized design. Of the remaining 15 studies, 11 were found to be partially accessible but ultimately excluded from the review as they did not meet the full accessibility criteria. Therefore, only four studies remained in the review, deemed suitable for inclusion based on their randomized design and full accessibility. Results: Studies by Beukes et al. [1]-[3] and Simoes et al. [4] evaluated CBT’s effectiveness. With internet-based CBT, Beukes et al. demonstrated reductions in tinnitus distress, negative cognitions, and comorbidities. Simoes et al. proposed combination treatments for tinnitus management. The review outcome suggests that CBT is an effective treatment for tinnitus, as it can help reduce tinnitus distress and improve quality of life. However, limitations in sample sizes and follow-up durations highlight the need for further research to establish CBT’s long-term efficacy and optimal parameters. Integrating internet-based CBT into comprehensive care strategies can enhance the well-being of individuals affected by tinnitus.

2024 Adult Compendium of Physical Activities:A third update of the energy costs of human activities

Background:The Compendium of Physical Activities was published in 1993 to improve the comparability of energy expenditure values assigned to self-reported physical activity(PA)across studies.The original version was updated in 2000,and again in 2011,and has been widely used to support PA research,practice,and public health guidelines.Methods:This 2024 update was tailored for adults 19-59 years of age by removing data from those≥60 years.Using a systematic review and supplementary searches,we identified new activities and their associated measured metabolic equivalent(MET)values(using indirect calorimetry)published since 2011.We replaced estimated METs with measured values when possible.Results:We screened 32,173 abstracts and 1507 full-text papers and extracted 2356 PA energy expenditure values from 701 papers.We added303 new PAs and adjusted 176 existing MET values and descriptions to reflect the addition of new data and removal of METs for older adults.We added a Major Heading(Video Games).The 2024 Adult Compendium includes 1114 PAs(912 with measured and 202 with estimated values)across 22 Major Headings.Conclusion:This comprehensive update and refinement led to the creation of The 2024 Adult Compendium,which has utility across research,public health,education,and healthcare domains,as well as in the development of consumer health technologies.The new website with the complete lists of PAs and supporting resources is available at https://pacompendium.com.

Older Adult Compendium of Physical Activities:Energy costs of human activities in adults aged 60 and older

Purpose:To describe the development of a Compendium for estimating the energy costs of activities in adults>60 years(OA Compendium).Methods:Physical activities(PAs)and their metabolic equivalent of task(MET)values were obtained from a systematic search of studies published in 4 sport and exercise databases(PubMed,Embase,SPORTDiscus(EBSCOhost),and Scopus)and a review of articles included in the 2011 Adult Compendium that measured PA in older adults.MET values were computed as the oxygen cost(VO_(2),mL/kg/min)during PA divided by 2.7 m L/kg/min(MET_(60+))to account for the lower resting metabolic rate in older adults.Results:We identified 68 articles and extracted energy expenditure data on 427 PAs.From these,we derived 99 unique Specific Activity codes with corresponding MET_(60+)values for older adults.We developed a website to present the OA Compendium MET_(60+)values:https://pacompendium.com.Conclusion:The OA Compendium uses data collected from adults>60 years for more accurate estimation of the energy cost of PAs in older adults.It is an accessible resource that will allow researchers,educators,and practitioners to find MET_(60+)values for older adults for use in PA research and practice.

Revolutionizing gastric cancer treatment:The potential of immunotherapy

Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.

Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy:A case report and review of literature

BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced HCC.CASE SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal pain.Enhanced computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL.Therefore,he was judged to have advanced HCC.During treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of lenvatinib.In the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be halved.Postoperative pathological diagnosis indicated a complete response.The patient recovered well after the operation,and no tumor recurrence was found.CONCLUSION Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect.Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.

Immunotherapy for esophageal cancer:Where are we now and where can we go

Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.

Activation of endogenous neurogenesis and angiogenesis by basic fibroblast growth factor-chitosan gel in an adult rat model of ischemic stroke

Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Mental emotional disorder is a predictor of stroke incidence in adults:Ten year results of the Bogor Cohort Study on Non-Communicable Disease Risk Factors in Indonesia

Objective:To determine the stroke predictors for the 10-year of follow-up in Bogor City,Indonesia.Methods:The prospective study analyzed the data of 4445 stroke-free subjects aged 25 years and above that was part of"the Bogor Cohort Study on Non-Communicable Disease Risk Factors".Data were collected by interview method with structured questionnaires,physical measurements three times a year,and laboratory examination every two years during a 10-year follow-up(2011-2021,without examination in 2020).The incidence of stroke is based on anamnesis results and examination by a neurologist.Other stroke predictor variables include characteristics,biological conditions,and risk behavior.We analysed 4445 stroke-free samples with Cox proportional hazard regression test.Results:During the 10-year observation,stroke incidence was 440 person-years per 100000 population(95%CI 370-530).During the follow-up of ten years,the main predictor of stroke was mental-emotional disorders with HR 4.2(95%CI 2.8-6.3)after adjustment by age,hypertension,obesity,abdominal obesity,and high LDL-cholesterol levels.Conclusions:Mental-emotional disorders are the strongest predictor of stroke incidence.Hence,psychological factors must be controlled in a stroke prevention program.

Association of daily sitting time and leisure-time physical activity with body fat among U.S.adults

Background:Prolonged sitting and reduced physical activity lead to low energy expenditures.However,little is known about the joint impact of daily sitting time and physical activity on body fat distribution.We investigated the independent and joint associations of daily sitting time and physical activity with body fat among adults.Methods:This was a cross-sectional analysis of U.S.nationally representative data from the National Health and Nutrition Examination Survey2011-2018 among adults aged 20 years or older.Daily sitting time and leisure-time physical activity(LTPA)were self-reported using the Global Physical Activity Questionnaire.Body fat(total and trunk fat percentage)was determined via dual X-ray absorptiometry.Results:Among 10,808 adults,about 54.6%spent 6 h/day or more sitting;more than one-half reported no LTPA(inactive)or less than 150 min/week LTPA(insufficiently active)with only 43.3%reported 150 min/week or more LTPA(active)in the past week.After fully adjusting for sociodemographic data,lifestyle behaviors,and chronic conditions,prolonged sitting time and low levels of LTPA were associated with higher total and trunk fat percentages in both sexes.When stratifying by LTPA,the association between daily sitting time and body fat appeared to be stronger in those who were inactive/insuufficiently active.In the joint analyses,inactive/insuufficiently active adults who reported sitting more than 8 h/day had the highest total(female:3.99%(95%confidence interval(95%CI):3.09%-4.88%);male:3.79%(95%CI:2.75%-4.82%))and trunk body fat percentages(female:4.21%(95%CI:3.09%-5.32%);male:4.07%(95%CI:2.95%-5.19%))when compared with those who were active and sitting less than 4 h/day.Conclusion:Prolonged daily sitting time was associated with increased body fat among U.S.adults.The higher body fat associated with 6 h/day sitting may not be offset by achieving recommended levels of physical activity.

Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

Versatile strategies for adult neurogenesis:avenues to repair the injured brain

Brain injuries due to trauma or stroke are major causes of adult death and disability.Unfortunately,few interventions are effective for post-injury repair of brain tissue.After a long debate on whether endogenous neurogenesis actually happens in the adult human brain,there is now substantial evidence to support its occurrence.Although neurogenesis is usually significantly stimulated by injury,the reparative potential of endogenous differentiation from neural stem/progenitor cells is usually insufficient.Alternatively,exogenous stem cell transplantation has shown promising results in animal models,but limitations such as poor long-term survival and inefficient neuronal differentiation make it still challenging for clinical use.Recently,a high focus was placed on glia-to-neuron conversion under single-factor regulation.Despite some inspiring results,the validity of this strategy is still controversial.In this review,we summarize historical findings and recent advances on neurogenesis strategies for neurorepair after brain injury.We also discuss their advantages and drawbacks,as to provide a comprehensive account of their potentials for further studies.

Back to the drawing board:Overview of the next generation of combination therapy for inflammatory bowel disease

Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.

Adjuvant therapy for hepatocellular carcinoma:Dilemmas at the start of a new era

Approximately 50%-70%of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or ablation.As a result,many patients receive adjuvant therapy after curative resection or ablation in order to prolong recurrence-free survival.The therapy recommended by national guidelines can differ,and guidelines do not specify when to initiate adjuvant therapy or how long to continue it.These and other unanswered questions around adjuvant therapies make it difficult to optimize them and determine which may be more appropriate for a given type of patient.These questions need to be addressed by clinicians and researchers.

Adult neurogenesis:a real hope or a delusion?

Adult neurogenesis,the process of creating new neurons,involves the coordinated division,migration,and differentiation of neural stem cells.This process is restricted to neurogenic niches located in two distinct areas of the brain:the subgranular zone of the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricle,where new neurons are generated and then migrate to the olfactory bulb.Neurogenesis has been thought to occur only during the embryonic and early postnatal stages and to decline with age due to a continuous depletion of neural stem cells.Interestingly,recent years have seen tremendous progress in our understanding of adult brain neurogenesis,bridging the knowledge gap between embryonic and adult neurogenesis.Here,we discuss the current status of adult brain neurogenesis in light of what we know about neural stem cells.In this notion,we talk about the importance of intra cellular signaling molecules in mobilizing endogenous neural stem cell prolife ration.Based on the current understanding,we can declare that these molecules play a role in targeting neurogenesis in the mature brain.However,to achieve this goal,we need to avoid the undesired proliferation of neural stem cells by controlling the necessary checkpoints,which can lead to tumorigenesis and prove to be a curse instead of a blessing or hope.

Experience of primary intestinal lymphangiectasia in adults: Twelve case series from a tertiary referral hospital

BACKGROUND While primary intestinal lymphangiectasia(PIL)is considered a rare condition,there have been several reported cases in adults.Nevertheless,the absence of clear guidance from diagnosis to treatment and prognosis poses challenges for both physicians and patients.AIM To enhance understanding by investigating clinical presentation,diagnosis,treatment,complications,and prognoses in adult PIL cases.METHODS We enrolled adult patients diagnosed with PIL between March 2016 and September 2021.The primary outcome involved examining the diagnosis and treatment process of these patients.The secondary outcomes included identifying complications(infections,thromboembolism)and assessing prognoses(frequency of hospitalization and mortality)during the follow-up period.RESULTS Among the 12 included patients,peripheral edema(100%)and diarrhea(75%)were the main presenting complaints.Laboratory tests showed that all the pati-ents exhibited symptoms of hypoalbuminemia and hypogammaglobulinemia.Radiologically,the predominant findings were edema of the small intestine(67%)and ascites(58%).The typical endoscopic finding with a snowflake appearance was observed in 75%of patients.Among the 12 patients,two responded positive-ly to octreotide and sirolimus,and eight who could undergo maintenance therapy discontinued subsequently.Complications due to PIL led to infection in half of the patients,thromboembolism in three patients,and one death.CONCLUSION PIL can be diagnosed in adults across various age groups,with different severity and treatment responses among patients,leading to diverse complications and prognoses.Consequently,tailored treatments will be necessary.We anticipate that our findings will contribute to the management of PIL,an etiology of protein-losing enteropathy.

Virologic Response among Children and Adults in an Antiretroviral Therapy Programme in Northern Nigeria: A Cross-Sectional Descriptive Study

Introduction: Viral load suppression is a key determinant of successful anti-retroviral therapy. The study aimed to determine virologic response to Antiretroviral therapy in the large cohort of children and adults living with Human Immune deficiency Virus. Materials and Methods: Viral Load results from the HIV Ribonucleic Acid Polymerase Chain Reaction register of 10,887 children and adults on cART in 4 states in Northern Nigeria between 2017 and 2019 were retrieved and analyzed in the PCR Molecular Laboratory of the Federal Teaching Hospital, Gombe. Results: 10,887 children and adults were analyzed. Males were 28.4% (3094) and 71.6% (7793) females. 2.9% (311);3.5% (386);7.3% (797);65.2% (7098);14.5% (1583);5.2% (562) and 1.3% (150) were aged 0 - 9 years, 11 - 18 years;19 - 25 years, 26 - 45 years;46 - 55 years;56 - 65 years and 10 years. The most recent CD4count before viral load request was ≥1000/μL in 7.4% (810/10887);500 -999/μL in 39.0% (4240);350 - 499 μL in 22.7% (2466) and 1000 c/mL in 26.5% (821/3094) males and 24.1% (1876/7793) females. Viral load was significantly lower among females (p-value 0.007). 50.5% (157/311);52.1% (201/386);28.5% (227/797);23.5% (1670/7098);19.9% (315/1583);17.8% (100/562) and 18.0% (27/150) aged 0 - 9 years, 11 - 18 years;19 - 25 years, 26 - 45 years;46 - 55 years;56 - 65 years and 1000 c/mL respectively. Viral load was >1000 c/mL in 28.2% (229/811) for those on HAART for 6 months - 1 year and 23.6% (1243/5275) after receiving Highly Active Antiretroviral Therapy (HAART) for 1 - 5 years. 26.3% (1072/4075) and 21.1% (153/726) had viral load > 1000 c/mL after receiving HAART for 6 - 10 and >10 years respectively (p-value 0.001). Conclusion: HIV viral suppression was below the WHO recommended threshold.

A Stable Open-Shell Conjugated Diradical Polymer with Ultra-High Photothermal Conversion Efficiency for NIR-Ⅱ Photo-Immunotherapy of Metastatic Tumor

Massive efforts have been concentrated on the advance of eminent near-infrared(NIR) photothermal materials(PTMs) in the NIR-Ⅱ window(1000–1700 nm), especially organic PTMs because of their intrinsic biological safety compared with inorganic PTMs. However, so far, only a few NIR-Ⅱresponsive organic PTMs was explored, and their photothermal conversion efficiencies(PCEs) still remain relatively low. Herein, donor–acceptor conjugated diradical polymers with open-shell characteristics are explored for synergistically photothermal immunotherapy of metastatic tumors in the NIR-Ⅱ window. By employing side-chain regulation, the conjugated diradical polymer TTB-2 with obvious NIR-Ⅱ absorption was developed, and its nanoparticles realize a record-breaking PCE of 87.7% upon NIR-Ⅱ light illustration. In vitro and in vivo experiments demonstrate that TTB-2 nanoparticles show good tumor photoablation with navigation of photoacoustic imaging in the NIR-Ⅱ window, without any side-effect. Moreover, by combining with PD-1 antibody,the pulmonary metastasis of breast cancer is high-effectively prevented by the efficient photo-immunity effect. Thus, this study explores superior PTMs for cancer metastasis theranostics in the NIR-Ⅱ window, offering a new horizon in developing radical-characteristic NIR-Ⅱ photothermal materials.

Optimized sequential therapy vs 10- and 14-d concomitant therapy for eradicating Helicobacter pylori: A randomized clinical trial

BACKGROUND A cure for Helicobacter pylori(H.pylori)remains a problem of global concern.The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide.Optimizing sequential therapy seems to be one of the most attractive strategies in terms of efficacy,tolerability and cost.The most common sequential therapy consists of a dual therapy[proton-pump inhibitors(PPIs)and amoxicillin]for the first period(5 to 7 d),followed by a triple therapy for the second period(PPI,clarithromycin and metronidazole).PPIs play a key role in maintaining a gastric pH at a level that allows an optimal efficacy of antibiotics,hence the idea of using new generation molecules.This open-label prospective study randomized 328 patients with confirmed H.pylori infection into three groups(1:1:1):The first group received quadruple therapy consisting of twice-daily(bid)omeprazole 20 mg,amoxicillin 1 g,clarith-romycin 500 mg and metronidazole 500 mg for 10 d(QT-10),the second group received a 14 d quadruple therapy following the same regimen(QT-14),and the third group received an optimized sequential therapy consisting of bid rabe-prazole 20 mg plus amoxicillin 1 g for 7 d,followed by bid rabeprazole 20 mg,clarithromycin 500 mg and metronidazole 500 mg for the next 7 d(OST-14).AEs were recorded throughout the study,and the H.pylori eradication rate was determined 4 to 6 wk after the end of treatment,using the 13C urea breath test.RESULTS In the intention-to-treat and per-protocol analysis,the eradication rate was higher in the OST-14 group compared to the QT-10 group:(93.5%,85.5%P=0.04)and(96.2%,89.5%P=0.03)respectively.However,there was no statist-ically significant difference in eradication rates between the OST-14 and QT-14 groups:(93.5%,91.8%P=0.34)and(96.2%,94.4%P=0.35),respectively.The overall incidence of AEs was significantly lower in the OST-14 group(P=0.01).Furthermore,OST-14 was the most cost-effective among the three groups.CONCLUSION The optimized 14-d sequential therapy is a safe and effective alternative.Its eradication rate is comparable to that of the 14-d concomitant therapy while causing fewer AEs and allowing a gain in terms of cost.