Antithrombotic regimens in patients with percutaneous coronary intervention whom an anticoagulant is indicated: A systematic review and network meta -analysis

Background: Patients undergoing percutaneous coronary intervention (PCI) who require anticoagulant therapy are at increased risk of bleeding. The optimal regimen for these patients is uncertain. This study aimed to compare safety and efficacy of antithrombotic regimens used in patients undergoing PCI with concomitant anticoagulant therapy. Methods: A systematic review and network meta-analysis was performed among studies comparing antithrombotic regimens for anticoagulated patients undergoing PCI. The primary outcome of interest was major bleeding. The secondary outcomes were coronary events. The reference intervention was classic triple therapy (aspirin plus clopidogrel plus VKA). Cluster rank incorporating risk (major bleeding) and benefit (all-cause death) was performed to identify the most appropriate regimen(s). Results: There were 3 RCTs (6 interventions) and 29 non-RCTs (8 interventions) that met the inclusion criteria with 22,179 patients. Network meta-analysis of RCTs indicated that dual therapy (DT), either with vitamin K antagonist (VKA) or direct anticoagulant (DOAC) plus an antiplatelet, significantly reduced the risk of major bleeding compared to triple therapy (TT) [pooled RR of 0.51 (0.30-0.87) and 0.68 (0.49-0.94), respectively]. In addition, VKA-DT significantly reduced the risk of all-cause death compared to TT [pooled RR of 0.40 (0.17-0.93)]. Results from network meta-analysis of non-RCT paralleled that of RCTs. No significant differences of coronary events were found. Conclusions: In conclusion, for anticoagulated patients undergoing PCI, dual therapy, either with warfarin or DOAC plus an antiplatelet, should be considered due to its optimal balance on efficacy and safety

Effects of Non-statin Lipid-Modifying Agents on Cardiovascular Morbidity and Mortality Among Statin-Treated Patients: A Systematic Review and Network Meta-Analysis

Background: Currently, there is a lack of information on the comparative efficacy and safety of non-statin lipid-lowering agents (NST) in cardiovascular (CV) disease risk reduction when added to background statin therapy (ST). This study determine the relative treatment effects of NST on fatal and non-fatal CV events among statin-treated patients.Methods: A network meta-analysis based on a systematic review of randomized controlled trials (RCTs) comparing non-statin lipid-modifying agents among statin-treated patients was performed. PubMed, EMBASE, CENTRAL, and Clinicaltrial.gov were searched up to April 10, 2018. The primary outcomes were CV and all-cause mortalities. Secondary CV outcomes were coronary heart disease (CHD) death, non-fatal myocardial infarction (MI), any stroke, and coronary revascularization. Risks of discontinuations were secondary safety outcomes.Results: Sixty-seven RCTs including 259,429 participants with eight interventions were analyzed. No intervention had significant effects on the primary outcomes (CV mortality and all-cause mortality). For secondary endpoints, proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK) plus statin (PCSK/ST) significantly reduced the risk of non-fatal MI (RR 0.82, 95% CI 0.72–0.93, p = 0.003), stroke (RR 0.74, 95% CI 0.65–0.85, p < 0.001), coronary revascularization (RR 0.84, 95% CI 0.75–0.94, p = 0.003) compared to ST. Combinations of ST and all NST except PCSK and ezetimibe showed higher rate of discontinuation due to adverse events compared to ST.Conclusions: None of NST significantly reduced CV or all-cause death when added to ST. PCSKs and to a lesser extent, ezetimibe may help reduce cardiovascular events with acceptable tolerability profile among broad range of patients

Efficacy and safety of Derris scandens (Roxb.) Benth. for musculoskeletal pain treatment: a systematic review and meta-analysis of randomized controlled trials

Derris scandens (Roxb.) Benth. has been used as active ingredient in Thai traditional medicine recipes for pain treatment. Dry stem powder and ethanolic extract also recommended in Thailand National List of Essential Medicines (NLEMs) for musculoskeletal pain treatment as herbal medicine. However, no summarization of clinical effect and safety has been evaluated.Our study aimed to determine the clinical effects and safety of D. scandens for musculoskeletal pain treatment compared with standard regimen, nonsteroidal anti-inflammatory drugs (NSAIDs).International and Thai databases were searched from inception through August 2015. Comparative randomized controlled trials investigating oral D. scandens for musculoskeletal pain were included. Outcomes of interest included level of pain and adverse event. Mean changes of the outcomes from baseline were compared between D. scandens and NSAIDs by calculating mean difference.From 42 articles identified, 4 studies involving a total of 414 patients were included for efficacy analysis. The effects of oral D. scandens on reducing pain score were no different from those of non-steroidal anti-inflammatory drugs at any time points (3, 7, 14 days and overall). The overall pain reduction in the D. scandens group was not inferior to treatment with NSAIDs (weighted mean difference 0.06; 95% CI: -0.20, 0.31) without evident of heterogeneity (I=0.00%, p=0.768). When compared, the adverse events (AEs) of D. scandens showed no different relative risk with NSAIDs. The major adverse events were gastrointestinal symptoms.D. scandens may be considered as an alternative for musculoskeletal pain reduction

Characterization of hypersensitivity reactions reported among Andrographis paniculata users in Thailand using Health Product Vigilance Center (HPVC) database

Background: Andrographis paniculata (andrographis) is one of the herbal products that are widely used for various indications. Hypersensitivity reactions have been reported among subjects receiving Andrographis paniculata in Thailand. Understanding of characteristics of patients, adverse events, and clinical outcomes is essential for ensuring population safety. This study aimed to describe the characteristics of hypersensitivity reactions reported in patients receiving andrographis containing products in Thailand using national pharmacovigilance database. Methods: Thai Vigibase data from February 2001 to December 2012 involving andrographis products were used. This database includes the reports submitted through the spontaneous reporting system and intensive monitoring programmes. The database contained patient characteristic, adverse events associated with andrographis products, and details on seriousness, causality, and clinical outcomes. Case reports were included for final analysis if they met the inclusion criteria; 1) reports with andrographis being the only suspected cause, 2) reports with terms consistent with the constellation of hypersensitivity reactions, and 3) reports with terms considered critical terms according to WHO criteria. Descriptive statistics were used. Results: A total of 248 case reports of andrographis-associated adverse events were identified. Only 106 case reports specified andrographis herbal product as the only suspected drug and reported at least one term consistent with constellation of hypersensitivity reactions. Most case reports (89%) came from spontaneous reporting system with no previously documented history of drug allergy (88%). Of these, 18 case reports were classified as serious with 16 cases requiring hospitalization. For final assessment, the case reports with terms consistent with constellation of hypersensitivity reactions and critical terms were included. Thirteen case reports met such criteria including anaphylactic shock (n = 5), anaphylactic reaction (n = 4) and angioedema (n = 4). Time to development of symptoms ranged from 5 minutes to 1 day. The doses of andrographis used varied from 352 mg to 1,750 mg. Causality assessment of 13 case reports were certain (n = 3), probable (n = 8) and possible (n = 2). Conclusions: Our findings suggested that hypersensitivity reactions have been reported among patients receiving Andrographis paniculata. Healthcare professionals should be aware of this potential risk. Further investigation of the causal relationship is needed; meanwhile including hypersensitivity reactions for andrographis product labeling should be considered

The effect of door-to-balloon delay in primary percutaneous coronary intervention on clinical outcomes of STEMI: a systematic review and meta-analysis protocol

BACKGROUND: Acute myocardial infarction (AMI) is a medical emergency in which sudden occlusion of coronary artery(ies) results in ischemia and necrosis of the cardiac tissues. Reperfusion therapies that aim at reopening the occluded artery remain the mainstay of treatment for AMI. Primary percutaneous coronary intervention (PCI), which enables the restoration of blood flow by reopening the occluded artery(ies) via a catheter with an inflatable balloon, is currently the preferred treatment for AMI with ST segment elevation (STEMI). The door-to-balloon (D2B) delay refers to the time interval counting from the arrival of a patient with STEMI at a hospital to the time of the balloon inflation (or stent deployment) that reopens the occluded artery(ies). Reducing this delay in primary PCI is thought to be an important strategy toward achieving better patient outcomes. Unfortunately, significant reduction of D2B delay in the USA over the last decade has not been shown to be associated with improved STEMI mortality. It has been suggested that the lack of impact could be due to the expanding use of primary PCI in STEMI as well as the survival cohort effect, leading to a shift toward a higher risk population receiving the procedure. Others have suggested that reduction in D2B delay may not be as impactful as expected, given that it only represents a small fraction of the total ischemic time. Although most existing evidence have pointed to the presence of a beneficial effect of shorter D2B delay, some inconsistencies however exist. This study aims to synthesize available evidence in order to answer the following questions: (1) what is the overall effect of D2B delay on clinical outcomes in patients with STEMI treated with primary PCI? (2) What factors explain the differences of the effect estimates among the studies? (3) What are the important strength and limitation of the existing body of evidence? METHOD: We will search PubMed/MEDLINE, EMBASE, ClinicalTrials.gov, WHO International Clinical Trials Registry, CINAHL Database, and the Cochrane Library using a predefined search strategy. Other sources of literature will include proceedings from the European Society of Cardiology, the American College of Cardiology, the American Heart Association, the EUROPCR, and the ProQuest Dissertations and Theses Database. We will include data from observational studies (case-control and cohort study design) and randomized control trials (that have investigated the relationship of D2B time and clinical outcome(s) in an adult (older than 18) STEMI population). Mortality (cardiac related and all-cause) and incidence heart failure (HF) have been prioritized as the primary outcomes. All eligible studies will be assessed for risk of bias using the Risk Of Bias in Non-randomized Studies - of Interventions tool. The Grading of Recommendations, Assessment, and Evaluation (GRADE) framework will be used to report the quality of evidence and strength of recommendations. We will proceed to analyze the data quantitatively if the pre-specified conditions are satisfied. DISCUSSION: Recent discussion on the negative findings of improved D2B delay over time being unrelated to better STEMI outcomes at the population level has reminded us of an important knowledge gap we have on this domain. This systematic review will serve to address some of these key questions not previously examined. Answers to these questions could clarify the controversies and offer empirical support for or against the suggested hypotheses. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015026069 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13643-016-0304-7) contains supplementary material, which is available to authorized users

To Switch or Not to Switch Payment Scheme? Determinants and Effects in a Bargaining Game

The incentive scheme selected in a laboratory experiment might trigger different type of behavior in participants. This paper is an attempt to screen the strategies adopted by agents in a bargaining game when buyer and seller have partly conflicting interests and are asymmetrically informed. We allow participants to choose the incentive scheme through which they will be paid at the end of the experiment controlling for past experience and individual characteristics. It is well known that payment method is highly correlated to the risk preferences shown by individuals, but little research is devoted to the analysis of the behavior induced by Random Lottery Incentive scheme (RLI for short) and Cumulative Scheme payment (CS for short) both on individual and social results. This paper aims to fill the gap

Relationship between the HLA-B*1502 allele and carbamazepine-induced Stevens-Johnson Syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis

IMPORTANCE: The US Food and Drug Administration recommends screening for the HLA-B*1502 allele before initiation of carbamazepine therapy in patients of Asian ancestry, but there remains unclear evidence of a relationship between HLA-B*1502 and Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) among carbamazepine users, especially in some racial/ethnic populations. OBJECTIVE: To determine the relationship between the HLA-B*1502 allele and carbamazepine-induced SJS and TEN. DATA SOURCES: A comprehensive search of the following data sources was performed without language restriction from the inception of the database until January 8, 2013: EMBASE, PubMed, clinicaltrials.gov, Cochrane Library, IPA (International Pharmaceutical Abstracts), HuGENet (Human Genome Epidemiology Network), and CINAHL (Cumulative Index to Nursing and Allied Health Literature), and the reference lists of identified studies. STUDY SELECTION: Inclusion criteria were studies that investigated the relationship between HLA-B*1502 and carbamazepine-induced SJS and TEN and that reported sufficient data for calculating the frequency of HLA-B*1502 carriers among cases and controls. The search yielded 525 articles, of which 16 met the inclusion criteria. The studies included 227 SJS or TEN cases, 602 matched control subjects, and 2949 population control subjects. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted the following data: study design, eligibility criteria, diagnostic criteria, patient demographics, genotype distribution, HLA-B genotyping technique, selection of cases and controls, dosage of carbamazepine and duration of use, and results of Hardy-Weinberg equilibrium in the control group. The Newcastle-Ottawa Scale was used to assess the quality of studies. The overall odds ratios (ORs) with corresponding 95% CIs were calculated using a random-effects model. The primary analysis was based on matched control studies. Subgroup analyses by race/ethnicity were also performed. MAIN OUTCOME AND MEASURE: The primary outcomewas carbamazepine-induced SJS and TEN. The outcome measure is given as an overall OR. RESULTS: The summary OR for the relationship between HLA-B*1502 and carbamazepine-induced SJS and TEN was 79.84 (95% CI, 28.45-224.06). Racial/ethnic subgroup analyses yielded similar findings for Han-Chinese (115.32; 18.17-732.13), Thais (54.43; 16.28-181.96), and Malaysians (221.00; 3.85-12 694.65). Among individuals of white or Japanese race/ethnicity, no patients with SJS or TEN were carriers of the HLA-B*1502 allele. CONCLUSIONS AND RELEVANCE: We found a strong relationship between the HLA-B*1502 allele and carbamazepine-induced SJS and TEN in Han-Chinese, Thai, and Malaysian populations. HLA-B*1502 screening in patients requiring carbamazepine therapy is warranted

Efficacy of Tongkat Ali (Eurycoma longifolia) on erectile function improvement: Systematic review and meta-analysis of randomized controlled trials

Objective: To determine the efficacy of Tongkat Ali (Eurycoma longifolia) herbal extract on erectile function improvement. Methods: Comprehensive electronic databases were searched from inception through October 2014. Randomized controlled trials investigating Tongkat Ali compared to placebo were included. Outcome of interest was the improvement of erectile dysfunction. The difference of changes from baseline of the outcome between Tongkat Ali and placebo was pooled using weighted mean difference (WMD). Methodological quality of included studies was assessed using Jadad's quality scale and Cochrane's risk of bias. Results: Of the 342 articles identified, 2 studies involving a total of 139 participants were analyzed. No significance between group difference was found in the mean WMD of the change in the 5- item version of the international index of erectile function (IIEF-5) at week-12 (0.91; 95% CI: -1.50 to 3.33 with I2=89.5%, P-value=0.002) with statistical heterogeneity. Based on the subgroup analysis, significant improved IIEF-5 score of 2.15 (95% CI 1.03-3.27) was found in subjects with lower baseline IIEF-5 score, but this was not seen among those with higher baseline IIEF-5 score. Conclusion: Based on current evidence, the herbal extract of Tongkat Ali may have clinical effect on erectile function. However, more efficacy trials are warranted to further support current evidence

The effect of door-to-balloon delay in primary percutaneous coronary intervention on clinical outcomes of STEMI: a systematic review and meta-analysis protocol

Daniel Reidpath - ORCID: 0000-0002-8796-0420 https://orcid.org/0000-0002-8796-0420Background Acute myocardial infarction (AMI) is a medical emergency in which sudden occlusion of coronary artery(ies) results in ischemia and necrosis of the cardiac tissues. Reperfusion therapies that aim at reopening the occluded artery remain the mainstay of treatment for AMI. Primary percutaneous coronary intervention (PCI), which enables the restoration of blood flow by reopening the occluded artery(ies) via a catheter with an inflatable balloon, is currently the preferred treatment for AMI with ST segment elevation (STEMI). The door-to-balloon (D2B) delay refers to the time interval counting from the arrival of a patient with STEMI at a hospital to the time of the balloon inflation (or stent deployment) that reopens the occluded artery(ies). Reducing this delay in primary PCI is thought to be an important strategy toward achieving better patient outcomes. Unfortunately, significant reduction of D2B delay in the USA over the last decade has not been shown to be associated with improved STEMI mortality. It has been suggested that the lack of impact could be due to the expanding use of primary PCI in STEMI as well as the survival cohort effect, leading to a shift toward a higher risk population receiving the procedure. Others have suggested that reduction in D2B delay may not be as impactful as expected, given that it only represents a small fraction of the total ischemic time. Although most existing evidence have pointed to the presence of a beneficial effect of shorter D2B delay, some inconsistencies however exist. This study aims to synthesize available evidence in order to answer the following questions: (1) what is the overall effect of D2B delay on clinical outcomes in patients with STEMI treated with primary PCI? (2) What factors explain the differences of the effect estimates among the studies? (3) What are the important strength and limitation of the existing body of evidence? Method We will search PubMed/MEDLINE, EMBASE, ClinicalTrials.gov, WHO International Clinical Trials Registry, CINAHL Database, and the Cochrane Library using a predefined search strategy. Other sources of literature will include proceedings from the European Society of Cardiology, the American College of Cardiology, the American Heart Association, the EUROPCR, and the ProQuest Dissertations and Theses Database. We will include data from observational studies (case-control and cohort study design) and randomized control trials (that have investigated the relationship of D2B time and clinical outcome(s) in an adult (older than 18) STEMI population). Mortality (cardiac related and all-cause) and incidence heart failure (HF) have been prioritized as the primary outcomes. All eligible studies will be assessed for risk of bias using the Risk Of Bias in Non-randomized Studies - of Interventions tool. The Grading of Recommendations, Assessment, and Evaluation (GRADE) framework will be used to report the quality of evidence and strength of recommendations. We will proceed to analyze the data quantitatively if the pre-specified conditions are satisfied. Discussion Recent discussion on the negative findings of improved D2B delay over time being unrelated to better STEMI outcomes at the population level has reminded us of an important knowledge gap we have on this domain. This systematic review will serve to address some of these key questions not previously examined. Answers to these questions could clarify the controversies and offer empirical support for or against the suggested hypotheses.https://doi.org/10.1186/s13643-016-0304-75pubpub1

Comparative effectiveness of telemedicine strategies on type 2 diabetes management: A systematic review and network meta-analysis

The effects of telemedicine strategies on the management of diabetes is not clear. This study aimed to investigate the impact of different telemedicine strategies on glycaemic control management of type 2 diabetes patients. A search was performed in 6 databases from inception until September 2016 for randomized controlled studies that examined the use of telemedicine in adults with type 2 diabetes. Studies were independently extracted and classified according to the following telemedicine strategies: teleeducation, telemonitoring, telecase-management, telementoring and teleconsultation. Traditional and network meta-analysis were performed to estimate the relative treatment effects. A total of 107 studies involving 20,501 participants were included. Over a median of 6 months follow-up, telemedicine reduced haemoglobin A1c (HbA1c) by a mean of 0.43% (95% CI: −0.64% to −0.21%). Network meta-analysis showed that all telemedicine strategies were effective in reducing HbA1c significantly compared to usual care except for telecase-management and telementoring, with mean difference ranging from 0.37% and 0.71%. Ranking indicated that teleconsultation was the most effective telemedicine strategy, followed by telecase-management plus telemonitoring, and finally teleeducation plus telecase-management. The review indicates that most telemedicine strategies can be useful, either as an adjunct or to replace usual care, leading to clinically meaningful reduction in HbA1c