Relevant Randomised Clinical Trials Research Articles

Design of knowledge-based mechanistic model of atherosclerotic cardiovascular disease for in silico trials

Abstract In silico trials applying a computational model (CM) of atherosclerotic cardiovascular disease (ASCVD) to virtual patients receiving alternative treatments provide an attractive option to complement randomised clinical trials (RCTs) by adding comparative effectiveness data and facilitating the demonstration of drug benefit. In silico modelling allows comparison between treatments with each virtual patient being his own control, and is not limited by the number of patients, comparative arms or trial duration. This study aims at building a knowledge-based mechanistic model of ASCVD. Once validated, the model will be used to run in silico clinical trials to compare the benefit of inclisiran, an siRNA targeting PCSK9 mRNA, vs other lipid-lowering therapies (LLT) on cardiovascular (CV) events in patients with ASCVD. An extensive literature review was performed to identify pathophysiological mechanisms involved in ASCVD and therapeutic mechanisms of action (MOAs). Every piece of knowledge extracted from the literature is awarded a strength of evidence grading to allow tracking of uncertainty in the model. A panel of multidisciplinary experts reviewed knowledge models and subsequent modelling hypotheses to validate their relevance. Knowledge was translated into mathematical equations. Each functional relationship between entities is represented by a biochemical/biophysical reaction with its reaction rate. A system of ordinary differential equations provides dynamics of modelled biological entities. A strategy of model calibration/validation was defined with the expert panel, by selecting relevant RCT and registry data, that the model should be able to reproduce. A virtual population was generated to account for inter-patient variability. A mechanistic CM of ASCVD (including 72 biological entities, 750 parameters) was built from knowledge, describing lipoproteins metabolism and cholesterol homeostasis, dynamics of atherosclerotic plaque growth with lipoproteins infiltration in the intima and evolution of lipidic, necrotic and fibrotic tissues as well as plaque rupture leading to myocardial infarction, ischemic stroke, lower extremity arterial disease or CV death. It also includes the impact of several risk factors (age, sex medical history, diabetes, hypertension, smoking, systemic inflammation, chronic kidney disease) and available LLT (atorvastatin, rosuvastatin, ezetimibe, evolocumab and inclisiran). After calibration, the model and virtual population reproduce pharmacokinetics of LLT, lipoproteins decrease under combinations of LLT and associated reduction in clinical events. ASCVD is ideally suited for in silico modelling: extensive literature is available regarding the pathophysiology, therapeutic MOAs are known and easily integrated in the model, clinically relevant outcomes are adequate model outputs, RCT and registry data exist to calibrate/validate the model. The next step is validation of the model before using it to run in silico trials.Plaque growth and rupture modelMulti-scale in silico model

Effect of yoga on anthropometry, quality of life, and lipid profile in patients with obesity and central obesity: A systematic review and meta-analysis

ObjectiveThis systematic review and meta-analysis aimed to determine the effectiveness of yoga on anthropometry, quality of life, and lipid profiles in patients with obesity and central obesity. MethodologyThe Cochrane Central Register of Controlled Trials (CENTRAL) and PubMed (1985-January 2022) and trial registries for relevant randomised clinical trials were used. Relevant and published randomised clinical trials were reviewed and evaluated. The primary outcomes were anthropometry measurements, which were weight, waist circumference, body mass index (BMI), and body fat percentages. The secondary outcomes were changes in quality of life, psychological impact, lipid profile measurement, presence of adverse events, and changes in blood pressure and blood glucose. We assessed the data for risk of bias, heterogeneity, sensitivity, reporting bias, and quality of evidence. Results15 studies are included, involving 1161 participants. The analysis performed is based on three comparisons. For the first comparison between yoga and control, yoga reduces the waist circumference (MD −0.84, 95% CI [−5.12 to 3.44]), while there is no difference in body weight, BMI, or body fat percentages. In the second comparison between yoga and calorie restriction, yoga reduces body weight (MD −3.47, 95% CI [−6.20 to −0.74]), while there is no difference in waist circumference, BMI, or body fat percentage. In the third comparison between yoga and exercise, yoga reduces the body weight (MD −7.58, 95% CI [−11.51 to −3.65]), while there is no difference in waist circumference or BMI. For the secondary outcomes, yoga intervention reduces total cholesterol (MD −17.12, 95% CI [−32.24 to −2.00]) and triglycerides (MD −21.75, 95% CI [−38.77 to −4.73]) compared to the control group, but there is no difference compared to the calorie restriction and exercise group. There is no difference in the rest of the outcomes, which are LDL, HDL, quality of life, psychological impact, adverse events, blood pressure, and blood glucose. However, findings are not robust due to a high risk of bias and low-quality evidence. ConclusionFrom our review, there were methodological drawbacks and very low to moderate quality of evidence across all comparisons, and hence, it is inconclusive to say that yoga can significantly improve anthropometric parameters. More well-designed trials are needed to confirm and support the beneficial effects of yoga.

Optimal first-line treatment for metastatic ALK+ non-small cell lung cancer-a narrative review.

First-line treatment options for patients with advanced non-small cell lung cancer (aNSCLC) whose tumors harbour anaplastic lymphoma kinase (ALK) gene rearrangements have rapidly evolved from chemotherapy, to the first in class ALK-targeted tyrosine kinase inhibitor (TKI) crizotinib in 2011, and now include no fewer than five Food and Drug Administration (FDA)-approved ALK inhibitors. However, while superiority to crizotinib has been established, head-to-head clinical trials comparing newer generation ALK inhibitors are lacking, and decisions on optimal first-line treatment must be based on analysis of the relevant trials, with attention to systemic and intracranial efficacy, toxicity profile as well as consideration of patient factors and preferences. Here we aim to synthesise findings from review of these trials and to describe options for optimal first-line treatment for ALK+ NSCLC. A literature review of relevant randomised clinical trials was undertaken using Embase database. There were no limitations to time frame or language applied. Crizotinib was established as the standard of care first-line treatment for patients with ALK+ aNSCLC in 2011. Since this time, alectinib, brigatinib, ensartinib and lorlatinib have all demonstrated superiority as first-line treatments compared to crizotinib, based on progression free survival, intra-cranial efficacy, and side-effect profiles. Options for optimal first-line treatment for ALK+ aNSCLC include alectinib, brigatinib and lorlatinib. This review serves as a resource summarizing data from key clinical trials with ALK inhibitors to aid in decision making when tailoring treatment for patients. Future research in the field includes real world analysis of efficacy and toxicity of next-generation ALK-inhibitors, identification of mechanisms of tumor persistence and acquired resistance, development of novel ALK inhibitors, and use of ALK-TKIs in earlier stage disease.

Plum supplementation and lipid profile: a systematic review and meta-analysis of randomised controlled trials.

Plums are abundant in bioactive compounds which have been associated with numerous health benefits. In the present study, we aimed at examining the impact of plum supplementation on lipid profile of individuals. Electronic bibliographical databases were searched for relevant randomised clinical trials. Articles meeting our eligibility criteria were included for data extraction and final analysis. Weighted mean difference (WMD) was estimated using a random-effect model. Of the total articles retrieved in the initial search, nine articles were found to be eligible to be included in the analysis. Our results show that plum supplementation significantly improves total cholesterols levels in the unhealthy individuals. Moreover, plum supplementation reduces the LDL-c levels in the pooled sample (WMD = -11⋅52 mg/dl; 95% CI -21⋅93, -1⋅11, P = 0⋅03, I 2 = 98⋅7%) and also in some of the subgroups of individuals (dried plum, unhealthy subjects, duration more than 8 weeks). Moreover, it had a significant reducing effect on TC levels just in unhealthy subjects. Although plum supplementation did not have any significant impact on serum levels of TG nor HDL-c. Our results show that supplementation with plums is potentially effective in reducing serum total cholesterol and LDL-c.

Pressure redistributing static chairs for preventing pressure ulcers.

Sitting can be viewed as a therapeutic intervention and an important part of a person's recovery process; but the risk of ulceration must be mitigated. Interventions for ulcer prevention in those at risk from prolonged sitting include the use of specialist cushions and surfaces, especially for wheelchair users. Whilst there is interest in the effects of different pressure redistributing cushions for wheelchairs, the benefits of pressure redistributing static chairs, compared with standard chairs, for pressure ulcer development in at-risk people are not clear. To assess the effects of pressure redistributing static chairs on the prevention of pressure ulcers in health, rehabilitation and social care settings, and places of residence in which people may spend their day. In June 2021 we searched the following electronic databases to identify reports of relevant randomised clinical trials: the Cochrane Wounds Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid Embase and EBSCO CINAHL Plus (Cumulative Index to Nursing and Allied Health Literature). We also searched clinical trials registers for ongoing and unpublished studies, and reference lists of relevant systematic reviews, meta-analyses and health technology reports. There were no restrictions by language, date of publication or study setting. We sought to include published or unpublished randomised controlled trials that assessed pressure redistributing static chairs in the prevention or management of pressure ulcers. Two review authors independently performed study selection. We planned that two review authors would also assess the risk of bias, extract study data and assess the certainty of evidence according to GRADE methodology. We did not identify any studies that met the review eligibility criteria, nor any registered studies investigating the role of pressure redistributing static chairs in the prevention or management of pressure ulcers. Currently, there is no randomised evidence that supports or refutes the role of pressure redistributing static chairs in the prevention or management of pressure ulcers. This is a priority area and there is a need to explore this intervention with rigorous and robust research.

The combination of transcatheter arterial chemoembolisation (TACE) and thermal ablation versus TACE alone for hepatocellular carcinoma.

Hepatocellular carcinoma is the sixth most common cancer worldwide. Hepatic resection is regarded as the curative therapy for hepatocellular carcinoma. However, only about 20% of people with hepatocellular carcinoma are candidates for resection, which highlights the importance of effective nonsurgical therapies. Until now, transcatheter arterial chemoembolisation (TACE) is the most common palliative therapy for hepatocellular carcinoma, but its clinical benefits remain unsatisfactory. During recent years, some studies have reported that the combination of TACE plus thermal ablation can confer a more favourable prognosis than TACE alone. However, clear and compelling evidence to prove the beneficial or harmful effects of the combination of TACE and thermal ablation therapy is lacking. To assess the beneficial and harmful effects of the combination of thermal ablation with TACE versus TACE alone in people with hepatocellular carcinoma. We performed searches in the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials in the Cochrane Library, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science. We endeavoured to identify relevant randomised clinical trials also in the China National Knowledge Infrastructure (CNKI) and Wanfang databases. We searched trial registration websites for ongoing studies. We also handsearched grey literature sources. The date of last search was 22 December 2020. We planned to include all randomised clinical trials comparing the combination of TACE plus thermal ablation versus TACE alone for hepatocellular carcinoma, no matter the language, year of publication, publication status, and reported outcomes. We planned to use standard methodological procedures expected by Cochrane. We planned to calculate risk ratios (RRs) with the corresponding 95% confidence intervals (CIs). For time-to-event variables, we planned to use the methods of survival analysis and express the intervention effect as a hazard ratio (HR) with 95% Cl. If the log HR and the variance were not directly reported in reports, we planned to calculate them indirectly, following methods for incorporating summary time-to-event data into meta-analysis. We planned to assess the risk of bias of the included studies using the RoB 2 tool. We planned to assess the certainty of evidence with GRADE and present the evidence in a summary of findings table. Out of 2224 records retrieved with the searches, we considered 135 records eligible for full-text screening. We excluded 21 of these records because the interventions used were outside the scope of our review or the studies were not randomised clinical trials. We listed the remaining 114 records, reporting on 114 studies, under studies awaiting classification because we could not be sure that these were randomised clinical trials from the information in the study paper. We could not obtain information on the registration of the study protocol for any of the 114 studies. We could not obtain information on study approval by regional research ethics committees, either from the study authors or through our own searches of trial registries. Corresponding authors did not respond to our enquiries about the design and conduct of the studies, except for one from whom we did not receive a satisfactory response. We also raised awareness of our concerns to editors of the journals that published the 114 studies, and we did not hear back with useful information. Moreover, there seemed to be inappropriate inclusion of trial participants, based on cancer stage and severity of liver disease, who should have obtained other interventions according to guidelines from learned societies. Accordingly, we found no confirmed randomised clinical trials evaluating the combination of TACE plus thermal ablation versus TACE alone for people with hepatocellular carcinoma for inclusion in our review. We identified five ongoing trials, by handsearching in clinical trial websites. We could not find for inclusion any confirmed randomised clinical trials assessing the beneficial or harmful effects of the combination of TACE plus thermal ablation versus TACE alone in people with hepatocellular carcinoma. Therefore, our results did not show or reject the efficiency of the combination of TACE plus thermal ablation versus TACE alone for people with hepatocellular carcinoma. We need trials that compare the beneficial and harmful effects of the combination of TACE plus thermal ablation versus TACE alone in people with hepatocellular carcinoma, not eligible for treatments with curative intent (liver transplantation, ablation surgical resection) and who have sufficient liver reserve, as assessed by the Child Pugh score, and who do not have extrahepatic metastases. Therefore, future trial participants must be classified at Barcelona Clinic Liver Cancer Stage B (intermediate stage) (BCLC-B) or an equivalent, with other staging systems.

Interventions for altering blood pressure in people with acute subarachnoid haemorrhage.

Interventions for altering blood pressure in people with acute subarachnoid haemorrhage.

Reading, Conducting, and Developing Systematic Review and Individual Patient Data Meta-Analyses in Psychiatry for Treatment Issues.

Introduction: Individual participant data meta-analyses (IPD-MAs) include the raw data from relevant randomised clinical trials (RCTs) and involve secondary analyses of the data. Performed since the late 1990s, ~50 such meta-analyses have been carried out in psychiatry, mostly in the field of treatment. IPD-MAs are particularly relevant for three objectives: (1) evaluation of the average effect of an intervention by combining effects from all included trials, (2) evaluation of the heterogeneity of an intervention effect and sub-group analyses to approach personalised psychiatry, (3) mediation analysis or surrogacy evaluation to replace a clinical (final) endpoint for the evaluation of new treatments with intermediate or surrogate endpoints. The objective is to describe the interest and the steps of an IPD-MA method applied to the field of psychiatric therapeutic research.Method: The method is described in three steps. First, the identification of the relevant trials with an explicit description of the inclusion/exclusion criteria for the RCT to be incorporated in the IPD-MA and a definition of the intervention, the population, the context and the relevant points (outcomes or moderators). Second, the data management with the standardisation of collected variables and the evaluation and the assessment of the risk-of-bias for each included trial and of the global risk. Third, the statistical analyses and their interpretations, depending on the objective of the meta-analysis. All steps are illustrated with examples in psychiatry for treatment issues, excluding study protocols.Conclusion: The meta-analysis of individual patient data is challenging. Only strong collaborations between all stakeholders can make such a process efficient. An “ecosystem” that includes all stakeholders (questions of interest prioritised by the community, funders, trialists, journal editors, institutions, …) is required. International medical societies can play a central role in favouring the emergence of such communities.

Rapid maxillary expansion for interceptive orthodontic treatment of palatally displaced canine: A systematic review.

The present systematic review aims to summarise the relevant randomised clinical trials and estimate the efficacy of interceptive orthodontic intervention, in particular if an interceptive treatment with rapid maxillary expansion could be successful in managing of palatally displaced canines (PDCs). A search strategy was developed on electronic databases including Medline, Web of Science, Scopus and Cochrane Collaboration Trial from 1925 to 2019. Two reviewers independently reviewed the sources deciding for a full reading according to the inclusion and exclusion criteria. Methodological quality criteria were applied to the selected articles. Three randomised clinical trials (RCTs) and one prospective longitudinal study were included in the systematic review. Generally, the intervention groups showed a higher incidence of successful eruption of PDCs (45.1% - 65.7%) compared with the control groups (13.1% - 13.6%). Based on the literature published, authors reached a reasonable conclusion that rapid maxillary expansion can facilitate the eruption of PDCs. Authors suggest to associate maxillary expansion with deciduous canine extraction or prevention of mesial movement of the upper first molars.

THE EFFECTS OF ADDING EXERCISE TO USUAL CARE ON BLOOD PRESSURE IN PATIENTS WITH HYPERTENSION, TYPE II DIABETES MELLITUS, AND/OR CARDIOVASCULAR DISEASE (PRELIMINARY RESULT)

Objective: Exercise is one of the most commonly recommended interventions for hypertension, type II diabetes, and/or cardiovascular disease. However, previous reviews have shown conflicting evidence on the effects of exercise and especially the effects in low- and middle-income countries (LMICs) is debated. Our objective was to assess the beneficial and harmful effects of adding exercise to usual care for people with hypertension, type II diabetes, and/or cardiovascular disease in high-income countries (HICs) and LMICs. Design and method: We searched CENTRAL, MEDLINE, EMBASE, LILACS from inception to present time, and further searched the bibliography of retrieved articles and reviews. We included relevant randomised clinical trials and cluster randomised trials irrespective of trial duration, publication status, publication year, and language. Two independent investigators assessed each trial for methodological quality. A random-effects model was used to meta-analyse data, we used test of interaction to compare the effects of exercise in HIC and LMIC, and heterogeneity (I2) was assessed by the χ2 test on Cochran's Q statistic. Our protocol was registered with PROSPERO, number CRD42019142313 and published before our literature search was conducted. Results: We included 96 trials randomising 6002 participants with type II diabetes (34 trials), hypertension (26 trials), and rest were trials on CVDs. The mean follow-up for the trials was 5.21 (SD: ± 4.07) months. Meta-analysis including all trials showed that exercise compared with control decreased the systolic blood pressure (SBP) 4.66 mmHg (95% CI: -6.24 -3.07; I2 93.6, p < 0.001). Test of interaction showed that the decrease in SBP was higher in LMICs (-8.69; 95% CI -11.95 -5.43; I2 89.73, p < 0.001) compared to HICs (-3.315; 95% CI -5.002 -1.62; I2 93.05, p = 0.000) and the difference was significant (Q = 8.25 p < 0.001). Likewise, exercise decreased the overall diastolic blood pressure (DBP) 2.98 (95% CI; -4.04 -1.93; I2 = 93.35, p < 0.001) however the difference was not significant between LMICs and HICs (Q = 1.66 p = 0.198). Conclusions: This reiterates the possibility of implementing exercise on population level as a cheap, low risk, non-pharmacological cardiovascular prevention.

Saffron for mild cognitive impairment and dementia: A systematic review and meta‐analysis of randomised clinical trials

AbstractBackgroundSaffron (stigma of Crocus sativus L.) from Iridaceae family is a well‐known traditional herbal medicine that has been used for hundreds of years to treat several diseases such as depressive mood, cancer and cardiovascular disorders. Recently, anti‐dementia property of saffron has been indicated. However, the effects of saffron for the management of dementia remain controversial. The aim of the present study is to explore the effectiveness and safety of saffron in treating mild cognitive impairment and dementia.MethodAn electronic database search of some major English and Chinese databases was conducted until 31th May 2019 to identify relevant randomised clinical trials (RCT). The primary outcome was cognitive function and the secondary outcomes included daily living function, global clinical assessment, quality of life (QoL), psychiatric assessment and safety. Rev‐Man 5.3 software was applied to perform the meta‐analyses.ResultA total of four RCTs were included in this review. The analysis revealed that saffron significantly improves cognitive function measured by the Alzheimer’s Disease Assessment Scale‐cognitive subscale (ADAS‐cog) and Clinical Dementia Rating Scale‐Sums of Boxes (CDR‐SB), compared to placebo groups. In addition, there was no significant difference between saffron and conventional medicine, as measured by cognitive scales including ADAS‐cog, CDR‐SB and SCIRS. Saffron improved daily living function, but the changes were not statistically significant. Adverse events were mild.ConclusionSaffron has the potential to improve cognitive function and activities of daily living in patients with Alzheimer’s disease and mild cognitive impairment (MCI). However due to limited high quality studies there is insufficient evidence to make any recommendations for clinical use. Further clinical trials on larger sample sizes are warranted to shed more light on its efficacy and safety.

Saffron for mild cognitive impairment and dementia: a systematic review and meta-analysis of randomised clinical trials

BackgroundSaffron (stigma of Crocus sativus L.) from Iridaceae family is a well-known traditional herbal medicine that has been used for hundreds of years to treat several diseases such as depressive mood, cancer and cardiovascular disorders. Recently, anti-dementia property of saffron has been indicated. However, the effects of saffron for the management of dementia remain controversial. The aim of the present study is to explore the effectiveness and safety of saffron in treating mild cognitive impairment and dementia.MethodsAn electronic database search of some major English and Chinese databases was conducted until 31st May 2019 to identify relevant randomised clinical trials (RCT). The primary outcome was cognitive function and the secondary outcomes included daily living function, global clinical assessment, quality of life (QoL), psychiatric assessment and safety. Rev-Man 5.3 software was applied to perform the meta-analyses.ResultsA total of four RCTs were included in this review. The analysis revealed that saffron significantly improves cognitive function measured by the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) and Clinical Dementia Rating Scale-Sums of Boxes (CDR-SB), compared to placebo groups. In addition, there was no significant difference between saffron and conventional medicine, as measured by cognitive scales such as ADAS-cog and CDR-SB. Saffron improved daily living function, but the changes were not statistically significant. No serious adverse events were reported in the included studies.ConclusionsSaffron may have the potential to improve cognitive function and activities of daily living in patients with Alzheimer’s disease and mild cognitive impairment (MCI). However, due to limited high-quality studies there is insufficient evidence to make any recommendations for clinical use. Further clinical trials on larger sample sizes are warranted to shed more light on its efficacy and safety.

Ketamine for post-operative pain treatment in spinal surgery. A protocol for a systematic review with meta-analysis and trial sequential analysis.

Post-operative pain treatment with ketamine has been demonstrated to have post-operative opioid-sparing and anti-hyperalgesic effects. However, evidence regarding the beneficial and harmful effects and the optimal dose and timing of perioperative treatment with ketamine for patients undergoing spinal surgery is unclear. The objective of this systematic review is to assess the analgesic, serious and non-serious adverse effects of perioperative pain treatment with ketamine for patients undergoing spinal surgery. This protocol for a systematic review is written according to The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will search Embase, CENTRAL, PubMed, WHO's ICTRP, EU Clinical Trial Register and ClinicalTrials.gov to identify relevant randomised clinical trials. We will include all randomised clinical trials assessing perioperative ketamine treatment versus placebo or no intervention for patients undergoing spinal surgery. Two authors will independently screen trials for inclusion using Covidence, extract data and assess risk of bias using Cochrane's RoB tool. We will analyse data using Review Manager and Trial Sequential Analysis. Meta-analysis will be performed according to the Cochrane guidelines and results will be validated according to the eight-step procedure suggested by Jakobsen et al. We will present our primary findings in a 'summary of findings' table. We will evaluate the overall certainty of evidence using the GRADE approach. This systematic review will assess the beneficial and harmful effects of perioperative pain treatment with ketamine for patients undergoing spinal surgery and have the potential to inform best practice and advance research.

The Effects of Evening-Primrose Oil on Menopausal Symptoms: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Background:Evening primrose oil (EPO) has been a treatment option for reducing menopausal symptoms, but evidence for its use is inadequate.Objective:The study aimed to determine the effectiveness of EPO in treating menopausal symptoms among peri and postmenopausal women.Study design:This is a systematic review with meta-analyses of randomised clinical trials (RCTs).Methods:We searched CENTRAL, Medline, Embase and trial registries for relevant RCTs. The methodology and reporting were carried out grounded on references from the Cochrane collaboration and the preferred reporting items for systematic reviews and meta-analyses statement. Review Manager version 5.3.5 was used to perform all the statistical analyses.Results:Five RCTs, recruiting a total of 402 peri and postmenopausal women were identified. EPO did not reduce the frequency of daily vasomotor symptoms (MD 0.01 episodes, 95% CI -0.54 to 0.57, P=0.960), frequency of daytime hot flash episodes (MD -0.51 episodes, 95% CI -2.05 to 1.03, P=0.510), frequency of night sweat episodes (MD 0.33 episodes, 95% CI -0.48 to 1.13, P=0.430) and severity of vasomotor symptoms (SMD -0.45, 95% CI -1.56 to 0.66, P=0.420) in comparison to control. EPO was associated with a minimal reduction in the severity of overall menopausal symptoms in comparison to control (SMD -1.18; 95% CI-2.18 to -0.18, P=0.02). There were insufficient data to pool results for musculoskeletal symptoms, mood, sexuality, sleeping disorders and quality of life.Conclusion:EPO may reduce the severity of overall menopausal symptoms but is not effective to reduce the frequency and severity of vasomotor symptoms. The evidence quality ranged from very low to moderate. Further research is needed to enhance related evidence.

Safety and efficacy of dual versus triple antithrombotic therapy (DAT vs TAT) in patients with atrial fibrillation following a PCI: a systematic review and network meta-analysis

ObjectiveCreating an appropriate antithrombotic therapy for patients with atrial fibrillation (AF) who have undergone percutaneous coronary intervention (PCI) remains a dilemma. Several clinical trials compared the use of a dual...

Effects of adding adjunctive hyperbaric oxygen therapy to standard wound care for diabetic foot ulcers: a protocol for a systematic review with meta-analysis and trial sequential analysis.

IntroductionDiabetic foot ulcer represents a major health problem globally. Preliminary studies have indicated that systemic treatment of diabetic foot ulcer patients with hyperbaric oxygen therapy have beneficial effects on wound healing, risk of amputation, glycaemic control, atherosclerosis, inflammatory markers and other clinical and laboratory parameters. This protocol for a systematic review aims at identifying the beneficial and harmful effects of adding hyperbaric oxygen therapy to standard wound care for diabetic foot ulcers.Methods and analysisThis protocol was performed following the recommendations of the Cochrane Collaboration and the eight-step assessment procedure suggested by Jakobsen and colleagues. We plan to include all relevant randomised clinical trials assessing the effects of hyperbaric oxygen therapy in the treatment of diabetic foot ulcer versus any control group with any intervention defined as standard wound care or similar, together with sham interventions. Our primary outcome will be: all-cause mortality, serious adverse events and quality of life. Our secondary outcomes will be: healing of index wound, major amputation and wound infection. Any eligible trial will be assessed and classified as either high risk of bias or low risk of bias, and our conclusions will be based on trials with low risk of bias. The analyses of the extracted data will be performed using Review Manager 5 and Trial Sequential Analysis. For both our primary and secondary outcomes, we will create a ‘Summary of Findings’ table and use GRADE (Grading of Recommendations Assessment, Development and Evaluation) assessment to assess the quality of the evidence.Ethics and disseminationWe use publicly accessible documents as evidence, there is no participant involvement at an individual level and an institutional ethics approval is not required. The results of the review will be sought published in a peer-reviewed journals, also in the event of insignificant results or null results, and thereby it will be disseminated to clinicians and public available.PROSPERO registration numberCRD42019139256.

Adding exercise to usual care in patients with hypertension, type 2 diabetes mellitus and/or cardiovascular disease: a protocol for a systematic review with meta-analysis and trial sequential analysis

BackgroundHypertension, type 2 diabetes mellitus and cardiovascular disease are among the leading causes of mortality globally. Exercise is one of the commonly recommended interventions/preventions for hypertension, type 2 diabetes mellitus and cardiovascular disease. However, the previous reviews have shown conflicting evidence on the effects of exercise. Our objective is to assess the beneficial and harmful effects of adding exercise to usual care for people with hypertension, type 2 diabetes mellitus and/or cardiovascular disease.MethodsThis protocol for a systematic review was undertaken using the recommendations of The Cochrane Collaboration, the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) and the eight-step assessment procedure suggested by Jakobsen et al. We plan to include all relevant randomised clinical trials and cluster-randomised trials assessing the effects of adding exercise to usual care for people with hypertension, type 2 diabetes mellitus and/or cardiovascular disease. We will search the Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Latin American and Caribbean Health Sciences Literature (LILACS), Science Citation Index Expanded on Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Science Journal Database (VIP) and BIOSIS. We will systematically assess the risks of random errors using Trial Sequential Analysis as well as risks of bias of all included trials. We will create a ‘Summary of Findings’ table in which we will present our primary and secondary outcomes, and we will assess the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE).DiscussionThe present systematic review will have the potential to aid patients, clinicians and decision-makers recommending exercise and thereby, benefit patients with hypertension, type 2 diabetes mellitus and/or cardiovascular disease.Systematic review registrationPROSPERO CRD42019142313

Fever control interventions versus placebo, sham or no intervention in adults: a protocol for a systematic review with meta-analysis and Trial Sequential Analysis

IntroductionFever is an integral part of the inflammatory response and has therefore likely a physiological role in fighting infections. Nevertheless, whether fever in itself is beneficial or harmful in adults...

The effects of adding angiotensin receptor neprilysin inhibitors to usual care in patients with heart failure: a protocol for a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis

BackgroundHeart failure is a highly prevalent disease with a global prevalence of 37 million, and the prevalence is increasing. Patients with heart failure are at an increased risk of death and morbidity. Traditionally, patients with heart failure have been treated with a beta-blocker in addition to an inhibitor of the renin-angiotensin-aldosterone system. However, new drugs are currently being added to the recommended guideline therapy. The latest drug to be added combines inhibition of the renin-angiotensin-aldosterone system pathway with inhibiting the neprilysin enzyme and is therefore classified as an ARNI. Our objective is to identify the beneficial and harmful effects of ARNIs in the treatment of patient with heart failure.MethodsThis protocol for a systematic review was undertaken using the recommendations of the Cochrane, the Preferred Report Items of Systematic reviews with Meta-Analysis Protocols, and the eight-step assessment procedure suggested by Jakobsen and colleagues. We plan to include all relevant randomised clinical trials assessing the use of ARNIs in the treatment of patients with heart failure. We will search the Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Latin American and Caribbean Health Sciences Literature (LILACS), Science Citation Index Expanded on Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Science Journal Database (VIP), and BIOSIS to identify relevant trials. We will also search for grey literature and unpublished trials. Extracted data will be analysed using Review Manager 5, STATA 5, and Trial Sequential Analysis. Our primary outcomes will be all-cause mortality and serious adverse events. We will create a ‘Summary of Findings’ table in which we will present our primary and secondary outcomes, and we will assess the quality of evidence using the GRADE assessment.DiscussionThe present systematic review will have the potential to aid clinicians in decision-making and thereby, benefit patients with heart failure.Systematic review registrationPROSPERO CRD42019129336

2018 Update of the EULAR recommendations for the management of large vessel vasculitis

BackgroundSince the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have...