Triple Regimen Research Articles

Efficacy and safety of encorafenib-based regimens in colorectal cancer: A systematic review of clinical trials.

e15600 Background: BRAF gene mutation is present in 10% of the world’s 3rd common cancer, i.e., colorectal cancer (CRC). Constitutive activation of the mitogen-activated protein kinase pathway (MAPKP) results from this mutation, abnormal activation of MAPKP, inhibiting apoptosis and enhancing proliferative activity. In this systematic review, we will assess the efficacy of encorafenib (a BRAF inhibitor) based regimens in CRC. Methods: We followed PRISMA guidelines to conduct this systematic review. A literature search was performed on PubMed, Embase, and Clinicaltrials.gov with mesh terms, ‘’Colorectal Neoplasms’’ and “Proto-Oncogene Proteins B-raf” from the inception of data till 01/05/2023. We screened 4572 articles and included 1 randomized clinical trial (RCT, N = 665), and 4 non-randomized trials (nRCTs, N = 175), measuring the efficacy of encorafenib (E) based regimens in BRAF V600-mutated CRC. Results: In 4 clinical trials (N = 840), 246 patients treated with a double regimen and 373 treated with a triple regimen of E. In 2 clinical trials (N = 319), triple therapy of E + C + Binimetinib showed an overall response rate (ORR) of 47.8% and 26% in the untreated metastatic CRC (mCRC) and phase III randomized trial triple regimen arm, respectively. A recent trial on triple therapy of E + C + nivolumab (N) showed an ORR of 45% with overall survival (OS) and progression-free survival (PFS) of 11.4 and 7.3 months, respectively. In 1 randomized trial (N = 665), ORR improved from 2% in the control arm to 26% and 20% in triple and double regimens, respectively, which was mainly partial response (PR) with complete response (CR) of 4-5% in both groups. The OS was 9 and 8.4 months with a hazard ratio (HR) for death vs. control of 0.52; (95% confidence interval [CI], 0.39 to 0.70; P < 0.001) and 0.60; (95% CI, 0.45 to 0.79; P < 0.001) in the triple and dual regimen, respectively. In 1 trial of dose escalation study, alpelisib (A) was added to E + C and the addition of this third drug showed minimal changes in the ORR from 18 to 19%, and PFS improved from 3.7 to 4.2 months. (Table 1). Conclusions: A combination of BRAF inhibitors with anti-EGFR monoclonal antibodies showed a clinically significant increase in antitumor activity in BRAF-mutated mCRC compared to standard therapy. The addition of MEK/PI3K inhibitor as a third drug to E + C also showed some improvement in ORR and PFS. Triple therapy with E + C + N was also effective and tolerated well by the microsatellite stable (MSS) BRAF mutated mCRC population. Randomized trials are needed. [Table: see text]

EE202 Cost-Effectiveness of Dolutegravir Versus Efavirenz-Based Combined Antiretroviral Regimens in HIV Infected Treatment-Naïve Patients at Nigeria’s University College Hospital.

DTG-based and EFV-based triple combination ARV regimen are the recognized first line therapy for the management of HIV in Nigeria. The cost effectiveness of DTG-based regimen against EFV-based regimen are yet to be known in Nigerian tertiary hospitals.

A study of cadonilimab combined with regorafenib as second-line or later therapy in patients with advanced hepatocellular carcinoma (aHCC).

e16154 Background: Current second-line treatment options for aHCC patients (pts), including single TKI or anti-PD-1+anti-CTLA4, result in limited survival benefits, objective responses or increasing concerns regarding adverse effects. An exploration of safer and more effective second-line or later therapies for aHCC is paramount. Cadonilimab is a first-in-class bispecific, humanized IgG1 antibody targeting PD-1 and CTLA-4, which has the potential to boost immune surveillance in HCC. Previous data indicated that cadonilimab possesses an improved safety profile and an encouraging anti-tumour activity compared to combined administration of anti-PD-1 plus anti-CTLA-4 antibodies. Regorafenib was the first TKI that approved globally as a second-line treatment of aHCC. Here, we evaluated the safety of cadonilimab plus regorafenib as second-line or later therapy in pts with aHCC. Methods: The study population derived from prospectively collected retrospectively analyzed data (10/2022-02/2023) of pts treated with cadonilimab plus regorafenib as second-line or later therapy for aHCC at Tianjin Cancer Hospital Airport Hospital. The primary endpoint was safety. Results: We identified 29 pts with aHCC who received cadonilimab plus regorafenib. The median age was 59 years; 86.2% were male; 72% were ECOG PS 0; 72% had a Child-Pugh score of A at diagnosis. High risk factors for HCC included MVI (3pts), ≥3 tumour lesions (10pts), tumour diameter ≥5cm (5pts), AFP≥400ng/mL (5pts). Six pts (21%) received cadonilimab plus regorafenib in the second-line while the rest of pts (79%) received it as third-line or later. All pts previously received at least one line of immunotherapy combined with anti-angiogenic target agents. Seven pts received triple combination regimens (ICIs+TKIs/Bev+HAIC) before. At time of data extraction, no pts were assessed for efficacy due to the COVID-19 pandemic (especially the outbreak in early December 2022) and short follow-up time, we focused on the safety and tolerability in this report. Any grade treatment related adverse events (TRAEs) occurred in 24pts (83%). The most common TRAEs of any grade were hypoalbuminemia (24%), lymphocyte count decreased (21%), rash (14%), nausea (14%) and infusion reaction (14%). Only four (14%) patients experienced grade 3 TRAEs including infusion reaction (2pts), lymphocyte count decreased (1pt) and gastrointestinal hemorrhage (1pt, regorafenib related). No grade 4-5 TRAEs were observed. Conclusions: The combination of cadonilimab plus regorafenib was generally well tolerated. The prospective trail of cadonilimab combined with regorafenib as second-line or later therapy for aHCC is ongoing (NCT05644379). Although it needs to be reconfirmed, the treatment responses of some patients are encouraging (including sharp decrease in AFP level and/or reduced tumor size). Related data will be reported in the future.

Susceptibility patterns and virulence genotypes of Helicobacter pylori affecting eradication therapy outcomes among Egyptian patients with gastroduodenal diseases.

Helicobacter pylori (H. pylori) is a significant human pathogen that is responsible for a variety of illnesses, including mucosa-associated lymphoid tissue lymphoma, gastric cancer, peptic ulcers, and gastritis. To investigate the frequency of H. pylori infection and its resistance patterns among Egyptian patients and to determine the influence of H. pylori virulence genetic determinants on the eradication success of 14-d triple therapy regimen. H. pylori infections were investigated in 72 patients with gastroduodenal complications suggestive of H. pylori infection. The cagA and vacA genotypes of cultured strains were studied using polymerase chain reaction. The patients underwent 14 d of triple-therapy treatment. The treatment response was examined using histology and a rapid urease test 6 wk after therapy discontinuation. The intention-to-treat eradication rate was 59.2% (95%CI: 48.2%-70.3%). Rates of H. pylori resistance to clarithromycin, amoxicillin, and metronidazole were 52.8%, 81.9%, and 100%, respectively. Successful eradication of H. pylori was more significantly associated with vacA s1-positive strains [adjusted odds ratio (aOR) = 0.507, 95%CI: 0.175-0.822]. A significant association was found between failed eradication rate and H. pylori strains resistant to clarithromycin (aOR = 0.204, 95%CI: -0.005 to 0.412) and amoxicillin (aOR = 0.223, 95%CI: 0.026-0.537). This study's low H. pylori eradication rate following 14-d triple therapy is concerning and worrying. H. pylori pan-resistance to metronidazole followed by the high resistance to ciprofloxacin, amoxicillin, and clarithromycin in this research is challenging and of great concern.

Bleeding risk in patients prescribed dual antiplatelet therapy and triple therapy after coronary interventions: the ADAPTT retrospective population-based cohort studies.

Bleeding among populations undergoing percutaneous coronary intervention or coronary artery bypass grafting and among conservatively managed patients with acute coronary syndrome exposed to different dual antiplatelet therapy and triple therapy (i.e. dual antiplatelet therapy plus an anticoagulant) has not been previously quantified. The objectives were to estimate hazard ratios for bleeding for different antiplatelet and triple therapy regimens, estimate resources and the associated costs of treating bleeding events, and to extend existing economic models of the cost-effectiveness of dual antiplatelet therapy. The study was designed as three retrospective population-based cohort studies emulating target randomised controlled trials. The study was set in primary and secondary care in England from 2010 to 2017. Participants were patients aged ≥ 18 years undergoing coronary artery bypass grafting or emergency percutaneous coronary intervention (for acute coronary syndrome), or conservatively managed patients with acute coronary syndrome. Data were sourced from linked Clinical Practice Research Datalink and Hospital Episode Statistics. Coronary artery bypass grafting and conservatively managed acute coronary syndrome: aspirin (reference) compared with aspirin and clopidogrel. Percutaneous coronary intervention: aspirin and clopidogrel (reference) compared with aspirin and prasugrel (ST elevation myocardial infarction only) or aspirin and ticagrelor. Primary outcome: any bleeding events up to 12 months after the index event. Secondary outcomes: major or minor bleeding, all-cause and cardiovascular mortality, mortality from bleeding, myocardial infarction, stroke, additional coronary intervention and major adverse cardiovascular events. The incidence of any bleeding was 5% among coronary artery bypass graft patients, 10% among conservatively managed acute coronary syndrome patients and 9% among emergency percutaneous coronary intervention patients, compared with 18% among patients prescribed triple therapy. Among coronary artery bypass grafting and conservatively managed acute coronary syndrome patients, dual antiplatelet therapy, compared with aspirin, increased the hazards of any bleeding (coronary artery bypass grafting: hazard ratio 1.43, 95% confidence interval 1.21 to 1.69; conservatively-managed acute coronary syndrome: hazard ratio 1.72, 95% confidence interval 1.15 to 2.57) and major adverse cardiovascular events (coronary artery bypass grafting: hazard ratio 2.06, 95% confidence interval 1.23 to 3.46; conservatively-managed acute coronary syndrome: hazard ratio 1.57, 95% confidence interval 1.38 to 1.78). Among emergency percutaneous coronary intervention patients, dual antiplatelet therapy with ticagrelor, compared with dual antiplatelet therapy with clopidogrel, increased the hazard of any bleeding (hazard ratio 1.47, 95% confidence interval 1.19 to 1.82), but did not reduce the incidence of major adverse cardiovascular events (hazard ratio 1.06, 95% confidence interval 0.89 to 1.27). Among ST elevation myocardial infarction percutaneous coronary intervention patients, dual antiplatelet therapy with prasugrel, compared with dual antiplatelet therapy with clopidogrel, increased the hazard of any bleeding (hazard ratio 1.48, 95% confidence interval 1.02 to 2.12), but did not reduce the incidence of major adverse cardiovascular events (hazard ratio 1.10, 95% confidence interval 0.80 to 1.51). Health-care costs in the first year did not differ between dual antiplatelet therapy with clopidogrel and aspirin monotherapy among either coronary artery bypass grafting patients (mean difference £94, 95% confidence interval -£155 to £763) or conservatively managed acute coronary syndrome patients (mean difference £610, 95% confidence interval -£626 to £1516), but among emergency percutaneous coronary intervention patients were higher for those receiving dual antiplatelet therapy with ticagrelor than for those receiving dual antiplatelet therapy with clopidogrel, although for only patients on concurrent proton pump inhibitors (mean difference £1145, 95% confidence interval £269 to £2195). This study suggests that more potent dual antiplatelet therapy may increase the risk of bleeding without reducing the incidence of major adverse cardiovascular events. These results should be carefully considered by clinicians and decision-makers alongside randomised controlled trial evidence when making recommendations about dual antiplatelet therapy. The estimates for bleeding and major adverse cardiovascular events may be biased from unmeasured confounding and the exclusion of an eligible subgroup of patients who could not be assigned an intervention. Because of these limitations, a formal cost-effectiveness analysis could not be conducted. Future work should explore the feasibility of using other UK data sets of routinely collected data, less susceptible to bias, to estimate the benefit and harm of antiplatelet interventions. This trial is registered as ISRCTN76607611. This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 8. See the NIHR Journals Library website for further project information.

Intercontinental Deceased-donor Kidney Transplantation in Dutch Antilleans: Favorable Outcomes Despite Prolonged Ischemia.

Intercontinental Deceased-donor Kidney Transplantation in Dutch Antilleans: Favorable Outcomes Despite Prolonged Ischemia.

The benefit of the bismuth add-on to the 2-week clarithromycin-based triple regimen for Helicobacter pylori eradication: a propensity score-matched retrospective study

BackgroundBismuth salt is bacteriostatic and bactericidal against Helicobacter pylori (H. pylori). Little is known about the benefit of bismuth itself. Recently in Korea, government regulation changed to allow bismuth add-on to conventional triple eradication regimens. Study aimed the additional benefit of the bismuth add-on to the 2-week clarithromycin-based triple regimen for H. pylori eradication.MethodsA single-centered retrospective review of electronic medical records was conducted in Seoul, Korea. Treatment-naïve H. pylori infected subjects treated with the clarithromycin-based triple regimen were consecutively enrolled. After propensity score matching, 118 subjects who were treated with rabeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg twice daily for 14 days (PAC) and matched 118 subjects with PAC plus bismuth subcitrate potassium 300 mg twice daily for 14 days (PACB) were included in the final analysis. The primary endpoint was the eradication success rates in each group.Article title: Kindly check and confirm the edit made in the article title.Yes, I agree with the article title. ResultsThe eradication success rates were 91.5% (86.4–96.6%) for PACB regimen and 81.4% (74.2–88.5%) for PAC in the intention-to-treat analysis, and 97.3% (94.2–100%) for PACB and 88.1% (81.9–94.3%) for PAC in the per-protocol analysis. The relative risk of eradication failure for PACB over PAC was calculated as 0.184 (0.0492–0688, p value = 0.005) in multiple regression logistic analysis. Compliance and adverse event incidence were not different between the two groups.Author names: Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [Da Wit], Last name: [Shin]. Author 2 Given name: [Dae Young], Last name: [Cheung]. Author 3 Given name: [Ji Hee], Last name: [Song]. Author 4 Given name: [Fan Hee], Last name: [Lee]. Author 5 Given name: [Jin Il], Last name: [Kim]. Yes. I found the names presented are accurate and in the correct sequence. Author 1 Given name: [Da Wit], Last name: [Shin].Author 2 Given name: [Dae Young], Last name: [Cheung].Author 3 Given name: [Ji Hee], Last name: [Song].Author 6 Given name: [Han Hee], Last name: [Lee].Author 7 Given name: [Jin Il], Last name: [Kim].ConclusionThe bismuth add-on to the 2-week clarithromycin-based triple regimen increased the eradication success rate.

From Antibiotic Resistance to Antibiotic Renaissance: A New Era in Helicobacter pylori Treatment.

Helicobacter pylori (H. pylori) is a common bacterial infection that can cause gastric diseases, including gastric cancer. The standard treatment for H. pylori infection is a combination of antibiotics and acid suppressants, but antibiotic resistance has become a significant problem that can reduce treatment efficacy. The development of novel treatment strategies for H. pylori is necessary to reduce the burden of this infection on public health.This review article examines H. pyloriantibiotic resistance and future treatment possibilities. We discuss transitioning from trial and error to antimicrobial stewardship and using multi-strain probiotics as an adjunct therapy for H. pylori eradication. This review article provides an extensive overview of H. pylori antibiotic resistance and future treatment possibilities. It begins with an introduction and background of the topic, followed by a literature review. The review of the literature covers the transition from trial and error to antimicrobial stewardship, the diagnosis and treatment of H. pylori, the comparative effectiveness of multiple first-line treatment regimens, the ideal H. pylori treatment for the present and future, the use of probiotics to reduce adverse events and improve eradication rates, and the use of novel and effective therapeutic regimens in an era of increasing antibiotic resistance. The conclusion summarizes the review's findings and provides recommendations for future research. The terms Helicobacter pylori, infection, antibiotic resistance, clarithromycin, macrolide resistance, proton pump inhibitors, vonoprazan, triple regimen, susceptibility, and stewardship were used in a PubMed literature search. Finally, the article highlights the urgent need for a global collaborative approach toward tackling antibiotic resistance in H. pylori infections.

Dual antiplatelet therapy with concomitant anticoagulation: current perspectives on triple therapy.

Anticoagulation and antiplatelet therapy are individually mainstays of treatment for multiple cardiovascular conditions. Antiplatelet therapy, most commonly with dual agents, is vital in the setting of coronary artery disease with acute coronary syndrome requiring percutaneous coronary intervention to prevent in-stent complications. A multitude of cardiovascular conditions with increased thromboembolic risk also require anticoagulation, including atrial fibrillation, venous or arterial thrombosis, and prosthetic heart valves to name a few. There is often an overlap in comorbidities as our patient population ages and becomes more complex, frequently necessitating a combination of both anticoagulation and antiplatelet agents, known as "triple therapy". To reduce or treat thromboembolic disease states as well as reduce platelet aggregation for coronary stent protection, many patients are placed at an increased bleeding risk without compelling evidence of reduction in major adverse cardiac events. With this comprehensive review of the existing literature, we aim to analyse different strategies and durations of triple therapy medication regimens.

Probiotic Supplementation for Treatment of Helicobacter pylori Infection: A Double-Blind Randomized Clinical Trial

Background/Aims: The effects of probiotic supplementation on <i>Helicobacter pylori (H. pylori)</i> eradication therapy are not completely understood. In this study, we investigated the effects of continuous probiotic administration on eradication rates, recrudescence, and symptom response following completion of a course of <i>H. pylori</i> therapy.Methods: This prospective, randomized, double-blind placebo-controlled trial was performed between June 2018 and 2020. Twohundred seventy patients who received a standard triple regimen for <i>H. pylori</i> eradication, were included in the study. Participants were randomized to receive a probiotic as adjunctive therapy (<i>Enterococcus faecium</i> 4.5×10<sup>8</sup> and Bacillus subtilis 5.0×10<sup>7</sup>; Medilac-S®, Hanmi Pharmaceuticals, Seoul, Korea) or a placebo (one tablet thrice daily) for 28 days, following <i>H. pylori</i> eradication. Participants who showed successful eradication underwent a repeat <sup>13</sup>C-urea breath test after 6 months.Results: Eradication rates in the probiotic and placebo groups were 77.1% and 72.4%, respectively (<i>P</i>=0.48) using per-protocol analysis. Using intention-to-treat analysis, eradication rates were 67.4% and 65.9%, respectively (<i>P</i>=0.43). Of 149 patients who were followed-up after 6 months, four patients had recrudescence (2.7%). Recrudescence rates did not differ between the probiotic and placebo groups. Of the 76 patients who had non-ulcer dyspepsia, 60 (78.9%) showed symptom resolution after 6 months. This beneficial effect was most pronounced in patients with postprandial distress syndrome (<i>P</i>=0.02).Conclusions: Consecutive probiotic supplementation following <i>H. pylori</i> eradication therapy did not increase eradication rates or decrease recrudescence rates.

Brucellosis of the spine – A global public health problem - An analysis of 37 patients from a ‘high risk’ region

BackgroundBrucellosis is a global public health issue. Brucellosis of the spine presents as a wide spectrum. The aim was to present the outcome analysis of patients treated for Spinal Brucellosis in the endemic region. Secondly to assess the accuracy of IgG and IgM Elisa in the diagnosis. ResultsA retrospective study of all patients who were treated for Brucellosis of the spine from 2010 to 2020 was conducted. Confirmed cases of Brucellosis of spine and who had adequate follow up after completion of treatment were included. The outcome analysis was based on clinical, laboratory and radiological parameters. There were 37 patients enrolled with a mean age of 45 and an average follow up of 24 months. All of them presented with pain and 30% had neurological deficits. Surgical intervention was done in 24%(9/37patients). All the patients were treated with triple drug regimen for an average duration of 6 months. Those patients with relapse had a 14month period of triple drug regimen. The sensitivity and specificity of IgM was 50% and 85.71%. The sensitivity and specificity of IgG was 81.82% and 7.69%.76% of them had good functional outcome and 82% of them had near normal neurological recovery and 97.3%(36 patients) were healed of the disease with relapse in one patient(2.7%). ConclusionsMajority (76%) of the patients with Brucellosis of the spine were treated conservatively. Average duration of treatment of triple drug regimen was 6 months. The sensitivity of IgM & IgG was 50% and 81.82% The specificity of IgM and IgG was 85.71% and 7.69% respectively.

Clinical efficacy and long-term immunogenicity of an early triple dose regimen of SARS-CoV-2 mRNA vaccination in cancer patients

Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity. Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases. A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P<0.05) and chemotherapy (92.8%±18.1, P<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients, of which 18 were severe. No patient receiving a third dose within 90 days of the second dose experienced severe infection. This study demonstrates the benefit of early administration of the third dose among cancer patients.

Intravenous metronidazole-, levofloxacin-containing triple therapy for treating patients with Helicobacter pylori-related active peptic ulcer complications: A pilot study.

The aim of this pilot study was to evaluate the efficacy and safety of intravenous use esomeprazole, metronidazole, and/or levofloxacin in the treatment of Helicobacter pylori (H.pylori)-associated peptic ulcer complications. Inpatients with peptic ulcer complications who were not able to take oral medicine were randomly assigned to three groups: triple therapy (esomeprazole, levofloxacin, metronidazole) and dual therapy (esomeprazole, levofloxacin/metronidazole) for 7 days. After intravenous treatment, all patients received open-label oral esomeprazole 20 mg bid for another 1 month. All subjects were followed up for gastroscopy at the seventh day of intravenous treatment to confirm the ulcer healing and 13 C-urea breath test to confirm successful H.pylori eradication 4-6 weeks after completion of oral esomeprazole therapy. The H.pylori eradication rate of both LEV-dual therapy (33.3%, 95% CI: 9.7%-70.0%) and MTZ-dual therapy (50%, 95% CI: 21.5%-78.5%) was significantly lower than that of triple therapy (95%, 95% CI: 71.1%-97.4%) (p=.003, .016). There were no significant differences in the adverse effects among all treatment groups, and the adverse effects were rare. The intravenous triple regimen, consisting of proton-pump inhibitor, metronidazole, and levofloxacin, could be considered in patients of H.pylori-associated peptic ulcer complications if oral medicine cannot be provided.

COMPARING THE EFFICACY OF CONCOMITANT THERAPY WITH THE STANDARD TRIPLE REGIMEN AS FIRST LINE THERAPY OF HELICOBACTOR PYLORI ERADICATION

Objective: To compare the effectiveness of Concomitant therapy with standard triple regimen in H.pylori Eradication.&#x0D; Methods: It was a randomised control trial at OPD of Department of Gastroenterology, Jinnah Hospital Lahore and involved 170 patients, who fullfilled the selection criteria of study were enrolled in the study from OPD of Department of Gastroenterology, Jinnah Hospital Lahore. 85 cases were given Concomitant therapy (Group-A) and 85 cases were given Standard triple regimen (Group-B). Informed consent was obtained. Demographic information (name, age, and sex) were taken. The mean age was 40.43 ± 17.01 years in the Concomitant therapy group and 42.99 ± 12.98 years in the Standard triple regimen group. In group A, 62% cases had ages less than 45 years, and 37.6% of cases had age 45 years or above. In group B, 68.2% cases had an age less than 45 years and 31.8% of cases had an age of 45 years and above. In group A, 50.6% cases were male and 49.4% cases were female. In group B, 72.9% cases were male and 27.1% cases were female. In group A, 58.8%, 22.4%, and 18.8% of cases had low, middle, and high socioeconomic status respectively. In group B, 57.6%, 29.4 and 13% of cases had low, middle, and high socioeconomic status respectively.&#x0D; In the Concomiant therapy group, eradication was achieved in 93.8%. In conventional triple regimen, eradication was achieved in 61.4% cases (p-value&lt;0.001).&#x0D; Conclusions: Eradication achievement was significantly more common with Concomitant therapy as compared to the conventional triple regimen. Concomitant therapy was much effective than the Standard triple regimen in all age groups, both genders, and all socioeconomic groups.

Effectiveness of pangenotypic retreatment of chronic hepatitis C after prior failure of pangenotypic therapies.

Despite the overall excellent efficacy of pangenotypic direct‑acting antiviral (DAA) options, there is still a small percentage of patients with hepatitis C virus (HCV) infection who do not respond to the therapy. This analysis was designed to evaluate the effectiveness of pangenotypic retreatment in the cases of pangenotypic therapy failure. The study included patients treated with the pangenotypic regimen, selected from the EpiTer‑2 database, a real‑world project evaluating DAA‑based treatment in Poland. Of a total 15 123 patients, 4345 received 1 course of the pangenotypic treatment (PAN group) and 48 patients were retreated with pangenotypic regimens after a failure of the pangenotypic therapy (PAP group). The patients from the PAP group were more often men (79% vs 53%; P <0.001), had higher median (interquartile range [IQR]) body mass index (27.5 [25.7-30.1] vs 25.7 [22.9-28.7] kg/m2; P <0.001), were more often infected with genotype 3 (58% vs 27%; P <0.001), and more frequently had liver cirrhosis (46% vs 21%; P <0.001) than the patients in the PAN group. Importantly, no significant difference in the treatment effectiveness was found between the PAP and PAN groups with sustained virologic response (SVR) rate of 89.6% vs 93.7% (P = 0.39) in intention‑to‑treat, and 91.5% vs 97.6% (P = 0.17) in the per-protocol analysis. The selection of a specific retherapy regimen did not affect SVR. Our study demonstrated the excellent effectiveness of pangenotypic regimens and confirmed that most DAA nonresponders could be successfully retreated with another pangenotypic regimen. The best retreatment strategy is a triple pangenotypic regimen, especially in patients with unfavorable response factors, such as genotype 3 infection, cirrhosis, and male sex.

Long-term impact of add-on sequential triple combination therapy in pulmonary arterial hypertension: real world experience.

Sequential triple combination therapy is recommended for pulmonary arterial hypertension (PAH) patients who are not at therapeutic goal on dual therapy, but long-term data on efficacy and safety is scarce. To assess the long-term impact of sequential triple combination therapy in patients with PAH who are not at goal on dual combination therapy. We performed a retrospective observational study in a racially/ethnically diverse cohort of consecutive PAH patients on a stable dual therapy regimen who remained in intermediate- or high-risk category and were subsequently initiated on sequential triple combination therapy. We studied interval change in functional, echocardiographic, and hemodynamic parameters, REVEAL 2.0 risk category and ERS/ESC 2022 simplified four-strata risk category. Multivariate logistic regression analysis was performed to identify independent predictors of successful risk reduction (achievement or maintenance of REVEAL 2.0 low-risk category). Kaplan-Meier survival curves were created to assess the effect of risk reduction on survival. Out of 414 PAH patients seen in our program, 55 patients received add-on sequential triple combination regimen and had follow-up hemodynamic data. The mean age was 57 years, with 85% women. The most common etiology of PAH was idiopathic/heritable (41.8%). Most patients were WHO functional class III (76.4%), and 34.5% of patients were in high-risk category (REVEAL 2.0). On a median follow-up of 68 weeks, there was a significant improvement in WHO Functional Class (p < 0.001), six-minute walk distance (35 m) with 61.8% of patients achieving low-risk status by REVEAL 2.0, and a 28% of patients' improvement in pulmonary vascular resistance. Female gender was identified as a strong predictor of successful risk reduction, whereas Hispanic ethnicity estimated right atrial pressure on echocardiogram and pericardial effusion predicted lower probability of risk reduction. Patients who achieved or maintained low-risk status had significantly improved survival. Add-on sequential triple combination therapy significantly increased functional, echocardiographic, and hemodynamic parameters with improvement in risk category and survival.

Antidiabetic drug utilization in type 2 diabetes mellitus patients at a tertiary care hospital in South India

Background: Diabetes mellitus in India is estimated to be 77 million individuals affected by this disease, which is likely to go up to 134 million by 2045. Globally, it is projected at 9.3% in 2019 (463 million persons). It is projected to increase to 10.2% by 2030 (578 million) and 2045. Aims and Objectives: The study aimed to analyze antidiabetic drug utilization in type 2 diabetes mellitus patients in south India tertiary care hospital. Materials and Methods: This cross-sectional and observational study was conducted at the endocrinology Department of a Tertiary Care Medical College and Hospital in south India over 12 months. After obtaining informed consent, diagnosed adult type 2 diabetes patients receiving any antidiabetic drugs were included in the study. Demographic, and clinical proportions of each class of antidiabetic drug were analyzed. Results: Out of 364 patients, age distribution (years): 30–39 (11%), 40–49 (25%), 50–59 (34%), 60–69 (22%), and &gt;70 (8%); Gender: male (37%) and female (63%); duration of diabetes (years): newly diagnosed (7%), &lt;5 years (21%), 5–10 years (24%), and &gt;10 years (43%); body mass index (kg/m2): range 21–29.6, hemoglobin A1C (%): Range 6.1–9.4. Associated comorbidities: hypertension (38%), dyslipidemia (21%), diabetic nephropathy (7%), diabetic retinopathy (2%), diabetic foot ulcer (4%), and diabetic retinopathy (2%). Metformin is the most common drug used in all regimens, with over 90% of participants using it in monotherapy and over 80% of participants using it in combination with other drugs. Conclusion: In almost all the patients, the treatment initiation was done by metformin; in two-thirds of patients’ treatment, intensification was done with glimepiride, insulin, Dipeptidyl peptidase-4is, or pioglitazone as dual, triple, or quadruple drug combination regimen where metformin was also an integral part of the combination regimen.

A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial of olanzapine plus triple antiemetic regimen for the prevention of multiday highly emetogenic chemotherapy-induced nausea and vomiting (OFFER study).

Evidence supports prophylactic use of olanzapine for the treatment of chemotherapy-induced nausea and vomiting (CINV). However, most studies to date have focused on patients with single-day highly emetogenic chemotherapy (HEC). Currently, administration of antiemetic therapies for nausea and vomiting induced by multiday chemotherapy regimens remains a challenge. In this study, we evaluated the efficacy of olanzapine combined with triple antiemetic therapy for the prevention of CINV in patients receiving multiday chemotherapy. We performed a randomized, double-blind, placebo-controlled phase 3 trial in 22 hospitals. Eligible patients were between 18 and 75 years old, were diagnosed with malignant solid tumors, and they had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. All the study participants were scheduled to be treated with chemotherapy regimens containing 3-day cisplatin (3-day total dose ≥75mg/m2). Randomization was computer generated and stratified by gender and chemotherapy treatment history. Allocation was done via an interactive web response system. Enrolled patients were randomly assigned 1:1 to receive either 5mg olanzapine or placebo orally before bedtime for 5 days combined with intravenous fosaprepitant (150mg) 1h before the administration of cisplatin on day 1, ondansetron hydrochloride intravenously, and dexamethasone orally 30min before cisplatin from days 1 to 3. Dexamethasone was also administered at the same time on days 4 and 5. The primary endpoint was the proportion of subjects with complete response (no vomiting and no rescue therapy) within the overall phase (days 1-8) after starting chemotherapy. Baseline plasma concentrations of P-substance and 5-HT were measured for exploratory analysis. This study was registered at ClinicalTrials.gov, number NCT04536558. Between December 2020 and September 2021, 349 patients with malignant solid tumors were enrolled in the study, with 175 participants randomly assigned to receive olanzapine and 174 participants assigned to receive placebo. The proportion of patients who achieved a complete response in the overall phase was significantly higher in the olanzapine group than in the placebo group (69% vs. 58%, P=0.031). A complete response benefit was observed in the olanzapine group versus the placebo group in almost all the subgroups. Four factors were considered significantly associated with complete response in multivariable analysis: treatment group, gender, baseline plasma concentration of 5-HT, and prior radiotherapy. All the reported adverse events associated with olanzapine administration were grades 1 and2. Olanzapine (5mg) combined with fosaprepitant, ondansetron, and dexamethasone was better than triple antiemetic therapy alone for patients receiving multiday chemotherapy regimens. Based on these results, the four-drug combination should be recommended as the best antiemetic regimen given to patients receiving multiday cisplatin-based chemotherapy and baseline plasma concentration of 5-HT may be used to identify individuals who are prone to CINV. However, all these findings need to be further validated in future studies. Jiangsu Hansoh Pharmaceutical Group Co., Ltd. provided research grant and study drugs for this investigator-initiated study.

Brief communication: global temporal trends in the efficacy of clarithromycin-based regimens for the treatment of Helicobacter pylori infection.

Helicobacter pylori eradication rates achieved with clarithromycin-based triple therapies are declining due to antibiotic resistance, but data regarding temporal changes in efficacy with these eradication therapies are scarce. To evaluate the efficacy of clarithromycin-based triple eradication regimens over time. A comprehensive literature review and time-trend analysis. Bibliographies of recently published systematic literature reviews were searched and supplemented with a targeted literature review conducted using Medline and Embase databases and ProQuest from conception to May 2021. Studies reporting H. pylori eradication rates of clarithromycin-based triple therapies were included and temporal trends were estimated using a random-effects model. Eradication rates for triple therapies containing proton pump inhibitors (PPIs), clarithromycin, and amoxicillin showed a significant decline over the past 23 years (p = 0.0315). However, this decline was not significant when eradication rates achieved with vonoprazan-based triple therapy were included (p = 0.3910). Vonoprazan-based triple therapy partially mitigated the decline in eradication rates seen with PPI-based triple therapy, likely due to more powerful acid suppression of vonoprazan.

Real-world outcomes associated with vonoprazan-based versus proton pump inhibitor-based therapy for Helicobacter pylori infection in Japan.

Japanese guidelines recommend triple therapy with vonoprazan or a proton pump inhibitor (PPI) in combination with antibiotics to treat Helicobacter pylori (H. pylori) infection. While studies have shown improved eradication rates and reduced costs with vonoprazan versus PPIs, there is little data describing healthcare resource use (HCRU) and treatment patterns. To compare patients treated with a vonoprazan-based or PPI-based regimen for H. pylori infection in Japan in terms of their characteristics, HCRU, healthcare costs, clinical outcomes, and treatment patterns. Retrospective matched cohort. We used data from the Japan Medical Data Center claims database (July 2014-January 2020) to identify adult patients with H. pylori infection and a first observed use of vonoprazan or a PPI in 2015 or later (index date). Patients prescribed a vonoprazan-based or a PPI-based regimen were matched 1:1 using propensity score matching. HCRU, healthcare costs, diagnostic tests, a proxy for H. pylori eradication (i.e. no triple therapy with amoxicillin in combination with metronidazole or clarithromycin >30 days after the index date), and second-line treatment were described during the 12-month follow-up period. Among 25,389 matched pairs, vonoprazan-treated patients had fewer all-cause and H. pylori-related inpatient stays and outpatient visits than PPI-treated patients, resulting in lower all-cause healthcare costs [185,378 Japanese yen (JPY) versus 230,876 JPY, p < 0.001]. Over 80% of patients received a post-treatment test for H. pylori. Fewer vonoprazan-treated than PPI-treated patients subsequently received an additional triple regimen for H. pylori infection (7.1% versus 20.0%, p < 0.001) or a prescription for vonoprazan or a PPI as monotherapy (12.4% versus 26.4%, p < 0.001) between 31 days and 12 months after the index date. Patients with H. pylori infection who were treated with vonoprazan-based therapy had lower rates of subsequent H. pylori treatment, lower overall and H. pylori-related HCRU, and lower healthcare costs than patients treated with PPI-based therapy.