A pilot study evaluating high dose esomeprazole, bismuth subcitrate and amoxicillin for eradicating Helicobacter pylori infection in Iran.

BACKGROUND: Helicobacter pylori (H. pylori) is strongly associated with peptic ulcer disease and gastric cancer. We evaluated two triple therapy regimens comprising esomeprazole, high dose bismuth, and different doses of amoxicillin for first-line H. pylori eradication. MATERIALS AND METHODS: Two hundred patients with dyspepsia and naive H. pylori infection were randomly assigned into two groups (n = 100). Both groups were treated for 14 days similarly with esomeprazole (40 mg, twice daily) and bismuth subcitrate (240 mg, three times daily), but the dose of amoxicillin was varied between Groups A (750 mg) and B (1000 mg) three times daily. Treatment compliance and side effect were evaluated following the therapies and after 8 weeks, a negative test of stool H. pylori antigen confirmed eradication. RESULTS: The two groups were comparable with respect to sex and age. According to intention to treat analysis, eradication rates were 80% (95% CI: 77.2%-82.8%) and 90% (95% CI: 84.1%-95.9%) in A and B groups, respectively (p = 0.22). Per-protocol eradication rates were 87% (95% CI: 80.4%-93.6%) and 92.8% (95% CI: 87.7%-97.9%), respectively (p = 0.23). Severe adverse effects were 3% and 2%, respectively (p = 0.34). CONCLUSION: High dose esomeprazole, amoxicillin and bismuth achieved 92.8% cure rates per protocol in a country with a high background rate of resistance. Additional studies are needed to ascertain whether this therapy can be further improved. Until then, it can be recommended as a first-line H. pylori eradication in north of Iran.

Eradication rate and adherence with high-dose amoxicillin and proton pump inhibitor as first-line treatment for Helicobacter pylori infection: Experience from University Hospital in Chile.

INTRODUCTION: In Chile, more than 70% of adults are infected by Helicobacter pylori. Clarithromycin should not be used in any regimen if there is >15% resistance to this antibiotic, being greater than 26% in our population. In this scenario, the effectiveness of triple therapy (proton pump inhibitor [PPI], clarithromycin, amoxicillin) was only 63.8%. AIM: To evaluate the eradication rate and safety of dual therapy (esomeprazole and amoxicillin) in high doses, through a prospective, observational, and descriptive study. METHODS: Patients with a positive urease test obtained in an upper digestive endoscopy were included. Any other previous H. pylori eradication regimen were excluded. All patients were treated with esomeprazole 40 mg three times a day and amoxicillin 750 mg four times a day for 14 days. The eradication rate of the dual therapy was evaluated with the H. pylori stool antigen test (the Pylori-Strip® test used) 6 weeks after completing the eradication treatment and with at least 14 days without PPI, being a negative result, confirmation of the effectiveness of this regimen. RESULTS: Of 122 patients, 106 had a negative H. pylori antigen in stool; The intention-to-treat and per protocol analysis, the eradication rates were 91.8% [95% CI: 87%-97%] and 94% [95% CI: 90%-98%], respectively. Four patients discontinued treatment due to adverse effects. Smoking and adherence to treatment were associated with eradication rate. CONCLUSIONS: In this cohort of patients with H. pylori infection, high-dose dual therapy has a high eradication rate and good adherence, raising the possibility that it could be used as first-line therapy in our country. Studies with a larger number of patients should confirm these results.

Co-administration of AYUSH 64 as an adjunct to standard of care in mild and moderate COVID-19: A randomized, controlled, multicentric clinical trial.

OBJECTIVE: Evaluate the efficacy of AYUSH 64, a standard polyherbal Ayurvedic drug in COVID-19. METHODS: During the first pandemic wave, 140 consenting and eligible hospitalized adult participants with mild-moderate symptomatic disease (specific standard RT-PCR assay positive) were selected as per a convenience sample, and randomized (1:1 ratio) to an open-label (assessor blind) two-arm multicentric drug trial; standard of care (SOC as per Indian guidelines) versus AYUSH 64 combined with SOC (AYUSH plus). Participants were assessed daily and discharged once clinical recovery (CR, primary efficacy) was achieved which was based on a predetermined set of criteria (resolution of symptoms, normal peripheral oximetry, and negative specific RT-PCR assay). Each participant was followed using an indigenous software program(mobile phone) and completed a 12-week study period. The dose of AYUSH 64 was 2 tablets oral, 500 mg each, bid for 12 weeks (AYUSH plus only). Significant P was <0.05 (two-sided). On randomization, the groups were found well matched. RESULTS: The mean interval time from randomization to CR was significantly superior in the AYUSH plus group [mean 6.45 days versus 8.26 days, 95% Confidence Interval of the difference -3.02 to -0.59 (P = 0.003, Student's 't test] as per-protocol analysis (134 participants); significant (P = 0.002) on an intention to treat analysis. 70% of the participants in AYUSH plus recovered during the first week (P = 0.046, Chi-square) and showed a significantly better change in physical health, fatigue, and quality of life measures. 48 adverse events, mostly mild and gut related, were reported by each group. There were 20 patient withdrawals (8 in AYUSH plus) but none due to an AE. There were no deaths. Daily assessment (hospitalization) and supervised drug intake ensured robust efficacy data. The open-label design was a concern (study outcome). CONCLUSIONS: AYUSH 64 in combination with SOC hastened recovery, reduced hospitalization, and improved health in COVID-19. It was considered safe and well-tolerated. Further clinical validation (Phase III) is required. TRIAL REGISTRATION: CTRI/2020/06/025557.

Oral traditional Chinese patent medicines combined with non-steroidal anti-inflammatory drugs for primary dysmenorrhea: A protocol for Bayesian network meta-analysis and systematic review.

INTRODUCTION: Primary dysmenorrhea (PD) was the most common gynecological disorder, with an increasingly high prevalence worldwide. PD often accompanied other dysmenorrhea-associated symptoms to trigger exacerbations, and even cause depression and anxiety for patients. As the effective first-line medication, non-steroidal anti-inflammatory drugs (NSAIDs) have become widespread across China and combined with oral traditional Chinese patent medicines (TCPMs) for PD in clinical practice. We hope to provide better efficacy and safety evidence about oral TCPMs combined with NSAIDs (oral TCPMs+NSAIDs) for patients with PD by this network meta-analysis. METHODS AND ANALYSIS: We will perform a Bayesian network meta-analysis of all oral TCPMs+NSAIDs for clinical diagnosis as PD. PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, VIP information resource integration service platform databases, and clinical registers will be searched from the database inception to June 30, 2022 to find randomized controlled trials. Two reviewers will independently screen and check titles and abstracts and read the full text. Data extraction with the same criteria will be conducted by two researchers, including study characteristics, participant characteristics, interventions and comparators, and outcomes. We will perform the network meta-analysis by the Bayesian random method to analyze the direct and indirect comparisons. Meta-regression with multiple covariates will be conducted to find the potential heterogeneity. We will perform the sensitivity analysis to identify the potential effect on the robustness of our results. Evidence certainty of all interventions in outcomes will be identified and assessed by Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessment. Funnel plots with Egger test and Begg's test to detect the potential publication bias. TRIAL REGISTRATION: PROSPERO registration number: CRD42021265675.

Efficacy and safety of modified Bushen Yiqi formulas (MBYF) as an add-on to formoterol and budesonide in the management of COPD: study protocol for a multicentre, double-blind, placebo-controlled, parallel-group, randomized clinical trial: FB-MBYF Trial.

BACKGROUND: Inhaled glucocorticoid corticosteroid (ICS), long-acting ß2-adrenoceptor agonist (LABA), and other drugs have limited therapeutic effects on COPD with significant individual differences. Traditional Chinese medicine (TCM)-modified Bushen Yiqi formula (MBYF) demonstrates advantages in COPD management in China. This study aims to evaluate the efficacy and safety of MBYF as an add-on to budesonide/formoterol in COPD patients and confirm the related genes affecting the therapeutic effect in the treatment of COPD. METHODS: In this multicentre, randomised, double-blind, placebo-controlled, parallel-group study, eligible patients with COPD will randomly receive a 360-day placebo or MBYF as an adjuvant to budesonide/formoterol in a 1:1 ratio and be followed up with every 2 months. The primary outcomes will be the frequency, times, and severity of acute exacerbation of COPD (AECOPD), COPD assessment test (CAT) score, and pulmonary function tests (PFTs). The secondary outcomes will include the modified Medical Research Council (mMRC) dyspnoea scale, 6-min walking test (6MWT), BODE index, quantitative scores of syndromes classified in TCM, inflammation indices, and hypothalamic-pituitary-adrenaline (HPA) axis function. We will also test the genotype to determine the relationship between drugs and efficacy. All the data will be recorded in case report forms (CRFs) and analysed by SPSS V.20.0. DISCUSSION: A randomized clinical trial design to evaluate the efficacy and safety of MBYF in COPD is described. The results will provide evidence for the combination therapy of modern medicine and TCM medicine, and individual therapy for COPD. TRIAL REGISTRATION: ID:  ChiCTR1900026124 , Prospective registration.

Efficacy and safety of Tengfu Jiangya tablet combined with valsartan/amlodipine in the treatment of stage 2 hypertension: study protocol for a randomized controlled trial.

BACKGROUND: The prevalence rate of hypertension in the Chinese population is on the rise, and the control rate of hypertension is low. International guidelines, including the 2018 Chinese Guidelines for the Management of Hypertension, recommend optimized drug selection and combination therapy for patients with stage 2 hypertension and blood pressure ≥ 160/100 mmHg, including valsartan/amlodipine (Val/Aml). The traditional Chinese medicine (TCM) compound Tengfu Jiangya tablet (TJT; No. Z20110021, Shandong Provincial Food and Drug Administration) is prepared in the medical institution of Affiliated Hospital of Shandong University of Traditional Chinese Medicine. It is an effective compound preparation of TCM for the treatment of hypertension in the national clinical research base of TCM. The aim of this study was to evaluate the efficacy and safety of TJT combined with Val/Aml in the treatment of stage 2 hypertension with hyperactivity of liver yang. METHODS: This randomized double-blind, placebo-controlled, multicenter trial will be conducted with a total of 288 participants with stage 2 hypertension at seven clinical trial centers. The stratified random method will be used, and the subcenter will be taken as the stratification factor. Eligible patients will be randomly assigned (1:1) into groups receiving either TJT or placebo three times daily for 28 days, both combined with Val/Aml 80/5 mg. The primary efficacy endpoint is the reduction in the mean sitting systolic blood pressure (msSBP) and the mean sitting diastolic blood pressure (msDBP) from baseline to week 4. Adverse events and laboratory test results will be monitored throughout the trial. DISCUSSION: This is the first placebo-controlled randomized trial conducted to evaluate the efficacy and safety of a Chinese herbal extract combined with Val/Aml in patients with stage 2 hypertension. Our study may help to provide evidence-based recommendations of a complementary preventive measure for stage 2 hypertension. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000030611 . Registered on 8 March 2020.

The effect of Taohong Siwu decoction combined with antihypertensive medicine in the treatment of hypertension: Meta-analysis.

BACKGROUND: Taohong Siwu Decoction (THSWD) is a classic prescription of traditional Chinese medicine. Recent research has shown that the practical components of THSWD have specific curative effects on various cardiovascular diseases, including hypertension, suggesting THSWD could effectively lower blood pressure (BP) with fewer side effects. However, little information is available regarding the effectiveness of THSWD combined with antihypertensive medicine on hypertension. OBJECTIVE: This meta-analysis aimed to study the efficacy and safety of THSWD in treating hypertension. METHODS: According to the search strategy, 8 databases were searched, including China Knowledge Network (CNKI), Wanfang Database, VIP Database, Pubmed, China Biomedical Literature Database (CBM), web of science, EMBASE and Cochrane Library, for the randomized controlled trial of THSWD on hypertension. 9 RCTs were included and 827 patients were involved. This meta-analysis used RevMan 5.4 to evaluate the articles. RESULTS: This review included 9 RCTs. All studies were THSWD with the antihypertensive drug compared with single antihypertensive western medicine. The total effective rate of THSWD combined with corresponding western medicine was significantly improved (Relative risk = 1.26; 95% CI: 1.16-1.37, P < .00001), which could effectively reduce the systolic BP (MD = -15.28 mm Hg; 95% CI: -20.17 to -10.40, P < .00001=, diastolic BP (MD = -9.70 mm Hg; 95% CI: -12.66 to -6.73, P < .00001), Triglycerides (MD = -1.48, 95%CI: -2.09 to -0.87, P < .00001), total cholesterol (MD = -1.43, 95% CI: -1.63 to -1.24, P < .00001) and low density lipoprotein cholesterol (MD = -0.93, 95% CI: -1.07 to -0.80, P < .00001). Compared with the single routine western medicine group, THSWD combined with the corresponding western medicine increased serum high-density lipoprotein (MD = 0.41, 95% CI: 0.35 to 0.46, P < .00001). CONCLUSION: THSWD combined with antihypertensive drugs in treating hypertension was curative in lowering BP, improving blood lipid levels and reducing the incidence of adverse reactions compared to antihypertensive medications treatment. However, more high-quality studies are needed due to the biased results and the small number of studies for further verification of the effectiveness of THSWD, and providing a new treatment for clinical reference.

Comparative efficacy and safety of biologic therapies for moderate-to-severe Crohn's disease: a systematic review and network meta-analysis.

BACKGROUND: Data are needed to inform the positioning of biologic therapy in the treatment of moderate-to-severe Crohn's disease, both first line and after previous biologic exposure. We aimed to assess the comparative efficacy and safety of biologics in patients with Crohn's disease. METHODS: We did a systematic review and network meta-analysis of phase 2 and phase 3 randomised controlled trials done in adults (≥18 years) with moderate-to-severe Crohn's disease (Crohn's Disease Activity Index [CDAI] 220-450) treated with tumour necrosis factor (TNF) antagonists, anti-integrin, anti-interleukin (IL)-12 and IL-23p40, or anti-IL23p19 agents, either alone or in combination with immunosuppressants, as their first-line biologic or after previous biologic exposure, compared with placebo or an active comparator. The minimum duration of therapy was 14 days for trials reporting induction of remission in active disease and 22 weeks in trials reporting maintenance of remission. We searched Medline, EMBASE, the Cochrane CENTRAL Register of Controlled Trials, conference proceedings, trial registries, and unpublished data from inception to June 3, 2021, without any language restrictions. Summary estimates of the primary and secondary outcomes were extracted from the published reports; individual patient-level data were not sought. The primary endpoint was induction of clinical remission in patients with active disease (CDAI <150) and maintenance of remission in patients with response to induction therapy, with data extracted from published reports. A network meta-analysis with multivariate consistency model random-effects meta-regression was done, with rankings based on surface under the cumulative ranking curve (SUCRA) values. FINDINGS: The search strategy yielded 18 382 citations, of which 31 trials were eligible for inclusion. On the basis of 15 randomised controlled trials including 2931 biologic-naive patients, infliximab monotherapy (odds ratio [OR] 4·53 [95% CI 1·49-13·79]), infliximab combined with azathioprine (7·49 [2·04-27·49]), adalimumab (3·01 [1·25-7·27]), and ustekinumab (2·63 [1·10-6·28]) were associated with significantly higher odds of inducing remission compared to certolizumab pegol (all moderate confidence); infliximab and azathioprine combination therapy was also associated with significantly higher odds of inducing remission than vedolizumab (3·76 [1·01-14·03]; low confidence). On the basis of ten randomised controlled trials including 2479 patients with previous biologic exposure, adalimumab after loss of response to infliximab (OR 2·82 [95% CI 1·20-6·62]; low confidence), and risankizumab (2·10 [1·12-3·92]; moderate confidence), were associated with higher odds of inducing remission than vedolizumab. No differences between active interventions were observed in maintenance trials. Most trials were at low or uncertain risk of bias. INTERPRETATION: Although biologic treatment choices in patients with moderate-to-severe Crohn's disease must be individualised for each patient, this analysis suggests that either infliximab with azathioprine or adalimumab might be preferred as a first-line therapy, and adalimumab (after infliximab loss of response) or risankizumab might be preferred as a second-line therapy, for induction of clinical remission. FUNDING: None.

Cardiovascular and kidney outcomes of spironolactone or eplerenone in combination with ACEI/ARBs in patients with diabetic kidney disease.

BACKGROUND: Mineralocorticoid receptor antagonist (MRA) when combined with either angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may provide additional benefits of cardiovascular and kidney disease risk reduction in patients with diabetic kidney disease (DKD) and hypertension. We evaluated the effectiveness of combination therapy (MRAs, either spironolactone or eplerenone, plus ACEI/ARB) compared with monotherapy (ACEI/ARB only) in patients with DKD and hypertension. METHODS: Retrospective cohort study was performed in patients (age ≥ 18 years) with hypertension, diabetes, and albuminuria between 2008 and 2018 within an integrated health system. MRA with ACEI/ARB compared to ACEI/ARB alone was evaluated on composite of cardiovascular events, progression to end-stage kidney disease, or all-cause mortality. Hyperkalemia was compared as a safety outcome. RESULTS: We identified 1282 patients who received MRAs with ACEI/ARBs and 5484 patients who received ACEI/ARBs alone. Median exposure time for combination therapy was 126 days. The rates per 100 person-years of cardiovascular, kidney, or all-cause mortality outcomes were 12.2 and 9.2 for combination therapy and monotherapy, respectively (hazard ratios = 1.24, 95% Confidence Interval (CI):0.94, 1.63). Patients receiving combination therapy had greater reduction in urine albumin-to-creatinine ratio compared with monotherapy (Mean reduction: 823 and 585 mg/g; p < 0.001, respectively). Hyperkalemia was more frequent in combination therapy versus monotherapy (22.3 vs. 10.9 per 100 person-years for combination and monotherapy, respectively; hazard ratios = 1.78, 95%CI: 1.42, 2.24). CONCLUSIONS: Among patients with DKD and hypertension, the short-term use of MRAs, either spironolactone or eplerenone, in combination with ACEI/ARBs, was not associated with lower risk of cardiovascular or kidney outcomes compared with ACEI/ARB monotherapy. The risk of hyperkalemia and the short duration of combination therapy may suggest a real-world clinical challenge for MRA with ACEI/ARB combination therapy.

Effectiveness and safety of Chinese herbal formula combined with western medicine for ankylosing spondylitis: A protocol for systematic review and meta-analysis.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic progressive inflammatory disease of the spine, which mainly invades the sacroiliac joint, spine, and large joints near the trunk, leading to fibrous and skeletal ankylosis and deformity, and can cause damage to the eyes, lung, cardiovascular, kidney and other organs. Chinese herbal formulas (CHF) is an important interventions of Traditional Chinese Medicine (TCM), and CHFs combined with western medicine are widely used in clinical practice to treat AS. METHODS: Eight databases will be systematically retrieved from their inceptions to March 2021. Only randomized controlled trials (RCTs) of CHFs combined with western medicine for AS treatment will meet the inclusion criteria. The primary outcomes we focus on include clinical effectiveness rate, TCM syndrome score, TCM symptom score, Bath ankylosing spondylitis disease activity index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), chest expansion, nocturnal spinal pain, adverse reactions, erythrocyte sedimentation rate (ESR), and C protein response (CRP). The research screening, data extraction, and risk of bias assessment will be performed independently by 2 researchers, and divergence will be solved by a third researcher. Revman 5.3 software will be used for meta-analysis. The confidence of evidence will be graded using grading of recommendations assessment, development, and evaluation (GRADE) algorithm and methodological quality will be assessed adopting risk of bias in systematic reviews (ROBIS). RESULTS: This systematic review (SR) will provide evidence-based medical evidence for AS therapy by CHF combined with western medicine and we will submit the findings of this SR for peer-review publication. CONCLUSIONS: This SR will provide latest and updated summary proof for assessing the effectiveness and safety of CHF combined with western medicine for AS. REGISTRATION NUMBER: INPLASY 202150089.

The safety and effectiveness of salvianolate in preventing perioperative venous thromboembolism in China: A PRISMA-compliant meta-analysis based on RCTs.

BACKGROUND: Salvianolate, a common drug for stabilizing heart disease and Angina Pectoris, is considered to be off-label for preventing venous thromboembolism (VTE) or anticoagulation at present. However, many clinical studies have showed that salvianolate can effectively inhibit the deep-vein thrombosis (DVT) incidence, and prevent VTE of perioperative patients in the real world in China. OBJECTIVE: This analysis aimed to evaluate the effectiveness and safety of salvianolate in preventing VTE in perioperative patients. METHODS: Databases of PubMed, Cochrane Library, Embase, CNKI, Wanfang and VIP were searched until July 2019. Literature retrieval, data extraction and quality assessment were independently completed by two researchers and checked with each other. Review Manager 5.2 software was applied for meta-analysis. RESULTS: A total of 429 studies were retrieved, including 11 randomized controlled trials (RCTs) with a total of 1149 subjects. Compared with low molecular weight heparin (LMWH) group alone, salvianolate combined LMWH group had lower DVT incidence in preventing perioperative thrombosis (2.75% and 14.23%, OR: 0.21, 95% CI:[0.08,0.53]; P = .0009). The incidence of adverse reactions of experimental group was similar to that of control group (1.79% and 2.31%, OR: 0.65, 95% CI:[0.18,2.35]. P = .51). Compared with the control group, D-dimer level (D-D), platelet count (PLT), fibrinogen (FIB), whole blood high shear viscosity (WBHSV), and whole blood low shear viscosity (WBLSV) were all significantly decreased (P < .01), and prothrombin time (PT) was significantly increased (P < .05). CONCLUSION: Salvianolate combined LMWH has better effectiveness and the same safety in preventing venous thromboembolism in perioperative patients. However, due to the small number of included literatures, large sample studies are still needed to further verify this conclusion.

Triple vs Dual Inhaler Therapy and Asthma Outcomes in Moderate to Severe Asthma: A Systematic Review and Meta-analysis.

IMPORTANCE: The benefits and harms of adding long-acting muscarinic antagonists (LAMAs) to inhaled corticosteroids (ICS) and long-acting ß2-agonists (LABAs) for moderate to severe asthma remain unclear. OBJECTIVE: To systematically synthesize the outcomes and adverse events associated with triple therapy (ICS, LABA, and LAMA) vs dual therapy (ICS plus LABA) in children and adults with persistent uncontrolled asthma. DATA SOURCES: MEDLINE, Embase, CENTRAL, ICTRP, FDA, and EMA databases from November 2017, to December 8, 2020, without language restriction. STUDY SELECTION: Two investigators independently selected randomized clinical trials (RCTs) comparing triple vs dual therapy in patients with moderate to severe asthma. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses, including individual patient-level exacerbation data, were used. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to assess certainty (quality) of the evidence. MAIN OUTCOMES AND MEASURES: Severe exacerbations, asthma control (measured using the Asthma Control Questionnaire [ACQ-7], a 7-item list with each item ranging from 0 [totally controlled] to 6 [severely uncontrolled]; minimal important difference, 0.5), quality of life (measured using the Asthma-related Quality of Life [AQLQ] tool; score range, 1 [severely impaired] to 7 [no impairment]; minimal important difference, 0.5), mortality, and adverse events. RESULTS: Twenty RCTs using 3 LAMA types that enrolled 11 894 children and adults (mean age, 52 years [range, 9-71 years]; 57.7% female) were included. High-certainty evidence showed that triple therapy vs dual therapy was significantly associated with a reduction in severe exacerbation risk (9 trials [9932 patients]; 22.7% vs 27.4%; risk ratio, 0.83 [95% CI, 0.77 to 0.90]) and an improvement in asthma control (14 trials [11 230 patients]; standardized mean difference [SMD], -0.06 [95% CI, -0.10 to -0.02]; mean difference in ACQ-7 scale, -0.04 [95% CI, -0.07 to -0.01]). There were no significant differences in asthma-related quality of life (7 trials [5247 patients]; SMD, 0.05 [95% CI, -0.03 to 0.13]; mean difference in AQLQ score, 0.05 [95% CI, -0.03 to 0.13]; moderate-certainty evidence) or mortality (17 trials [11 595 patients]; 0.12% vs 0.12%; risk ratio, 0.96 [95% CI, 0.33 to 2.75]; high-certainty evidence) between dual and triple therapy. Triple therapy was significantly associated with increased dry mouth and dysphonia (10 trials [7395 patients]; 3.0% vs 1.8%; risk ratio, 1.65 [95% CI, 1.14 to 2.38]; high-certainty evidence), but treatment-related and serious adverse events were not significantly different between groups (moderate-certainty evidence). CONCLUSIONS AND RELEVANCE: Among children (aged 6 to 18 years) and adults with moderate to severe asthma, triple therapy, compared with dual therapy, was significantly associated with fewer severe asthma exacerbations and modest improvements in asthma control without significant differences in quality of life or mortality.

Efficacy of Bi Qi Capsules in combination with methotrexate in the treatment of rheumatoid arthritis: A protocol of double-blind randomized controlled trial.

BACKGROUND: It is known that Bi Qi Capsules (BQC) have synergistic effects when combined with Methotrexate, but there is a lack of clinical studies on the long-term efficacy and safety of the combination of the 2 in the treatment of rheumatoid arthritis (RA). Therefore, the purpose of this randomized controlled trial was to evaluate the long-term efficacy and safety of this treatment. METHODS: This was a prospective, double-blind, single-simulation, randomized controlled trial investigating the efficacy and safety of BQC in combination with Methotrexate in the treatment of RA, and was approved by the Clinical Research Ethics Committee of the hospital. Patients were randomized in a 1:1 ratio to either the observation or control group and were respectively followed up for 6 months after receiving 12 weeks of treatment. The observation indexes included: total effective rate, DAS-28 score, inflammatory indexes, and adverse reactions. Finally, the collected data was statistically analyzed by SPSS version 18.0. DISCUSSION: This study evaluated the long-term efficacy of BQC in combination with Methotrexate in the treatment of RA. The trial results of this study will provide new ideas for choosing a combination of Chinese and Western medicine protocols for the treatment of RA. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/U85GX.

A Randomized Trial of Tenapanor and Phosphate Binders as a Dual-Mechanism Treatment for Hyperphosphatemia in Patients on Maintenance Dialysis (AMPLIFY).

BACKGROUND: Hyperphosphatemia is associated with cardiovascular morbidity and mortality in patients receiving maintenance dialysis. It is unknown whether combining two therapies with different mechanisms of action-tenapanor, an inhibitor of paracellular phosphate absorption, and phosphate binders-is safe and effective for the management of hyperphosphatemia in patients receiving maintenance dialysis. METHODS: This double-blind phase 3 trial enrolled 236 patients undergoing maintenance dialysis with hyperphosphatemia (defined in this trial as serum phosphorus 5.5-10 mg/dl inclusive) despite receiving phosphate binder therapy (sevelamer, nonsevelamer, sevelamer plus nonsevelamer, or multiple nonsevelamer binders). These participants were randomly assigned to receive oral tenapanor 30 mg twice daily or placebo for 4 weeks. The primary efficacy end point was the change in serum phosphorus concentration from baseline to week 4. RESULTS: Of the 236 randomized patients, 235 (99.6%) were included in the full analysis set; this included 116 in the tenapanor plus binder group and 119 in the placebo plus binder group. A total of 228 patients (96.6%) completed the 4-week treatment period. In the full analysis set (mean age 54.5 years, 40.9% women), patients treated with tenapanor plus binder achieved a larger mean change in serum phosphorus concentration from baseline to week 4 compared with placebo plus binder (-0.84 versus -0.19 mg/dl, P<0.001). Diarrhea was the most commonly reported adverse event, resulting in study drug discontinuation in four of 119 (3.4%) and two of 116 (1.7%) patients receiving tenapanor plus binder or placebo plus binder, respectively. CONCLUSIONS: A dual-mechanism treatment using both tenapanor and phosphate binders improved control of hyperphosphatemia in patients undergoing maintenance dialysis compared with phosphate binders alone. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: AMPLIFY, NCT03824587.

Successful Combination of Systemic Agents for the Treatment of Atopic Dermatitis Resistant to Dupilumab Therapy.

BACKGROUND: Dupilumab, a monoclonal antibody inhibiting the signaling pathway of IL-4/IL-13, was shown to be safe and effective in the treatment of moderate/severe atopic dermatitis (AD) in several clinical trials and real-life experiences, with only a small percentage of patients showing to be resistant or to lose disease control. OBJECTIVES: In this study, we investigated the effectiveness and safety in combining dupilumab with systemic agents or phototherapy in patients experiencing an inadequate response to dupilumab. METHODS: This retrospective, monocentric, observational study consecutively included patients aged >18 years, with moderate-severe AD, under treatment with dupilumab. In this cohort of patients, we analyzed data of subjects who experienced an inadequate response to dupilumab, even when combined with topical corticosteroids, and for whom an additional systemic treatment or phototherapy was combined to dupilumab. RESULTS: In this study, we included a total population of 69 patients treated with dupilumab. In 12/69 patients (17.4%) showing an inadequate response to dupilumab, a combined treatment consisting of dupilumab plus methylprednisolone (n = 5), cyclosporine (n = 4), methotrexate (n = 2), or narrow band-UVB (n = 1) was administered. Overall, after 8 weeks of combined therapy, the majority of patients (11 of 12) obtained an improvement of signs and symptoms of AD. Patients treated with combined therapy did not experience any adverse events, neither did they withdraw treatment because of the occurrence of adverse events. CONCLUSIONS: This study suggests that the combination of dupilumab with a conventional drug or phototherapy may represent a valid therapeutic choice, maintaining a good safety profile in AD patients recalcitrant to dupilumab monotherapy.

Lipid peroxidation aggravates anti-tuberculosis drug-induced liver injury: Evidence of ferroptosis induction.

Anti-tuberculosis drug-induced liver injury (ATB-DILI) is a common adverse reaction of anti-tuberculosis drug treatment. Studies have shown that isoniazid (INH) and rifampicin (RFP) are mainly metabolized in the liver and a large amount of intracellular glutathione is used up during the metabolism of these drugs, resulting in lipid peroxidation and hepatocyte death. Ferroptosis is a novel form of programmed cell death caused by iron-ion-dependent lipid peroxidation. In this study, we explored lipid peroxidation and ferroptosis during ATB-DILI. Morphology of ferroptosis was discovered in ATB-DILI mouse livers by transmission electron microscopy. Flow cytometry was used to assess the molecular markers of lipid peroxidation and ferroptosis including reactive oxygen species, lipid peroxidation, and cellular iron content. Glutathione peroxidase 4 (GPX4) was depleted, while acyl-CoA synthetase long chain family member 4 (ACSL4) was overexpressed in the ATB-DILI tissues. And glutathione supplementation significantly reduced the level of lipid peroxidation and the risk of liver damage. Retrospective study of tuberculosis patients who underwent INH and RFP treatment also revealed an association between the intake of glutathione and a negative ATB-DILI rate. In addition, iron supplementation enhanced the degree of lipid peroxidation and liver injury induced by INH and RFP in vivo and clinical retrospective study. Taken together, these results indicate that lipid peroxidation and evidence suggestive of ferroptosis occurs during ATB-DILI, and glutathione replenishment prevents this process while iron supplementation augmenting this effect.

The efficacy and safety of acupoint application combined with western medicine for allergic rhinitis: A protocol for systematic review and meta-analysis.

BACKGROUND: Acupoint application combined with western medicine has been used for treating allergic rhinitis widely. However, the efficacy and safety of acupoint application combined with western medicine for allergic rhinitis are unclear. This study aims to evaluate the efficacy and safety of acupoint application combined with western medicine for allergic rhinitis. METHODS: Randomized controlled trials of acupoint application combined with western medicine for allergic rhinitis will be searched in PubMed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database, and China biomedical literature database from inception to July, 2020. And Baidu Scholar, Google Scholar, International Clinical Trials Registry Platform, and Chinese Clinical Trials Registry will be searched to obtain more relevant studies comprehensively. Two researchers will perform data extraction and risk of bias assessment independently. Statistical analysis will be conducted in RevMan 5.3. RESULTS: This study will summarize the present evidence by exploring the efficacy and safety of acupoint application combined with western medicine for the treatment of allergic rhinitis. CONCLUSIONS: The findings of the study will provide helpful evidence for the efficacy and safety of acupoint application combined with western medicine in the treatment of allergic rhinitis, facilitating clinical practice and further scientific studies. ETHICS AND DISSEMINATION: The private information from individuals will not publish. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/NSGJH.

Combined Intravenous Sildenafil and L-Arginine Administration in a Porcine Animal Model: Hemodynamic Safety Profile and Effects on Coronary Blood Flow.

BACKGROUND: Endothelial dysfunction in the nitric oxide-cyclic guanosine monophosphate pathway is a potential contributor to perioperative myocardial ischemia. The nitric oxide precursor, L-arginine, and the cyclic guanosine monophosphate degradation blocker, sildenafil, have vasodilatory effects under high dosage. OBJECTIVE: This study examined the hemodynamic safety and effect profiles of the combined administration of L-arginine and sildenafil using an in-vivo pig model. METHODS: Hemodynamic safety including mean arterial pressure, central venous pressure, heart rate, coronary vascular resistance, and systemic vascular resistance, as well as effect profiles including cardiac output and left anterior descending blood flow were measured in ten female swine after administrations of L-arginine, sildenafil, as well as combined L-arginine and sildenafil. Measurements were compared using repeated-measures analysis of variance and linear mixed models. RESULTS: The combination of L-arginine and sildenafil produced a significant dose-dependent increase in left anterior descending flow and cardiac output. In contrast, mean arterial pressure, heart rate, central venous pressure, coronary vascular resistance, and systemic vascular resistance did not show any significant changes. No significant change in serum osmolality was observed after administrations of L-arginine. CONCLUSIONS: The combined intravenous administration of sildenafil and L-arginine in a porcine animal model was safe, well tolerated, and had at least additive effects on left anterior descending artery blood flow. Simultaneous application of both drugs might have dose-sparing effects leading to desired coronary effects at lower and safer sildenafil and L-arginine plasma concentrations. Hyperosmolality was only a minor factor in L-arginine hemodynamic effects.

Add-On Therapies in Cardiovascular Disease: Reviewing ICER's Report and the Potential Effect on Payers.

DISCLOSURES: No outside funding supported this commentary. The authors have nothing to disclose.

The Effectiveness and Value of Rivaroxaban and Icosapent Ethyl as Additive Therapies for Cardiovascular Disease.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, Commonwealth Fund, California Health Care Foundation, National Institute for Health Care Management (NIHCM), New England States Consortium Systems Organization, Blue Cross Blue Shield of Massachusetts, Harvard Pilgrim Health Care, Kaiser Foundation Health Plan, and Partners HealthCare to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, Allergan, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Cambia Health Services, CVS, Editas, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Pearson is employed by ICER; Synnott was employed by ICER at the time of this report. Ollendorf, Campbell, and McQueen received grants from ICER for work on this review. Ollendorf also reports advisory board, consulting, and other fees from Sarepta Therapeutics, DBV Technologies, EMD Serono, Gerson Lehman Group, The CEA Registry Sponsors, Autolus, Analysis Group, Amgen, AbbVie, Cytokinetics, Aspen Institute/University of Southern California, and University of Colorado, unrelated to this review.