scholarly journals The effect of dexmedetomidine and clonidine on the inflammatory response in critical illness: a systematic review of animal and human studies

Critical Care ◽  
2019 ◽  
Vol 23 (1) ◽  
Author(s):  
Charles A. Flanders ◽  
Alistair S. Rocke ◽  
Stuart A. Edwardson ◽  
J. Kenneth Baillie ◽  
Timothy S. Walsh

Abstract Background The α2 agonists, dexmedetomidine and clonidine, are used as sedative drugs during critical illness. These drugs may have anti-inflammatory effects, which might be relevant to critical illness, but a systematic review of published literature has not been published. We reviewed animal and human studies relevant to critical illness to summarise the evidence for an anti-inflammatory effect from α2 agonists. Methods We searched PubMed, the Cochrane library, and Medline. Animal and human studies published in English were included. Broad search terms were used: dexmedetomidine or clonidine, sepsis, and inflammation. Reference lists were screened for additional publications. Titles and abstracts were screened independently by two reviewers and full-text articles obtained for potentially eligible studies. Data extraction used a bespoke template given study diversity, and quality assessment was qualitative. Results Study diversity meant meta-analysis was not feasible so descriptive synthesis was undertaken. We identified 30 animal studies (caecal ligation/puncture (9), lipopolysaccharide (14), acute lung injury (5), and ischaemia-reperfusion syndrome (5)), and 9 human studies. Most animal (26 dexmedetomidine, 4 clonidine) and all human studies used dexmedetomidine. In animal studies, α2 agonists reduced serum and/or tissue TNFα (20 studies), IL-6 (17 studies), IL-1β (7 studies), NFκB (6 studies), TLR4 (6 studies), and a range of other mediators. Timing and doses varied widely, but in many cases were not directly relevant to human sedation use. In human studies, dexmedetomidine reduced CRP (4 studies), TNFα (5 studies), IL-6 (6 studies), IL-1β (3 studies), and altered several other mediators. Most studies were small and low quality. No studies related effects to clinical outcomes. Conclusion Evidence supports potential anti-inflammatory effects from α2 agonists, but the relevance to clinically important outcomes is uncertain. Further work should explore whether dose relationships with inflammation and clinical outcomes are present which might be separate from sedation-mediated effects.

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Kei Hayashida ◽  
Ryosuke Takegawa ◽  
Muhammad Shoaib ◽  
Tomoaki Aoki ◽  
Rishabh C. Choudhary ◽  
...  

Abstract Background Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their multifactorial roles, mitochondria are also critical in the progression of critical illnesses. Transplantation of mitochondria has been reported as a potential promising approach to treat critical illnesses, particularly ischemia reperfusion injury (IRI). However, a systematic review of the relevant literature has not been conducted to date. Here, we systematically reviewed the animal and human studies relevant to IRI to summarize the evidence for mitochondrial transplantation. Methods We searched MEDLINE, the Cochrane library, and Embase and performed a systematic review of mitochondrial transplantation for IRI in both preclinical and clinical studies. We developed a search strategy using a combination of keywords and Medical Subject Heading/Emtree terms. Studies including cell-mediated transfer of mitochondria as a transfer method were excluded. Data were extracted to a tailored template, and data synthesis was descriptive because the data were not suitable for meta-analysis. Results Overall, we identified 20 animal studies and two human studies. Among animal studies, 14 (70%) studies focused on either brain or heart IRI. Both autograft and allograft mitochondrial transplantation were used in 17 (85%) animal studies. The designs of the animal studies were heterogeneous in terms of the route of administration, timing of transplantation, and dosage used. Twelve (60%) studies were performed in a blinded manner. All animal studies reported that mitochondrial transplantation markedly mitigated IRI in the target tissues, but there was variation in biological biomarkers and pathological changes. The human studies were conducted with a single-arm, unblinded design, in which autologous mitochondrial transplantation was applied to pediatric patients who required extracorporeal membrane oxygenation (ECMO) for IRI–associated myocardial dysfunction after cardiac surgery. Conclusion The evidence gathered from our systematic review supports the potential beneficial effects of mitochondrial transplantation after IRI, but its clinical translation remains limited. Further investigations are thus required to explore the mechanisms of action and patient outcomes in critical settings after mitochondrial transplantation. Systematic review registration The study was registered at UMIN under the registration number UMIN000043347.


BMJ Open ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. e039813
Author(s):  
Xinxing Lai ◽  
Jian Liu ◽  
Tianyi Zhang ◽  
Luda Feng ◽  
Ping Jiang ◽  
...  

IntroductionWith the threat of a worldwide pandemic of COVID-19, it is important to identify the prognostic factors for critical conditions among patients with non-critical COVID-19. Prognostic factors and models may assist front-line clinicians in rapid identification of high-risk patients, early management of modifiable factors, appropriate triaging and optimising the use of limited healthcare resources. We aim to systematically assess the clinical, laboratory and imaging predictors as well as prediction models for severe or critical illness and mortality in patients with COVID-19.Methods and analysisAll peer-reviewed and preprint primary articles with a longitudinal design that focused on prognostic factors or models for critical illness and mortality related to COVID-19 will be eligible for inclusion. A systematic search of 11 databases including PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, VIP, Wanfang Data, SinoMed, bioRxiv, Arxiv and MedRxiv will be conducted. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data extraction will be performed using the modified version of the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies checklist and quality will be evaluated using the Newcastle-Ottawa Scale and the Quality In Prognosis Studies tool. The association between prognostic factors and outcomes of interest will be synthesised and a meta-analysis will be conducted with three or more studies reporting a particular factor in a consistent manner.Ethics and disseminationEthical approval was not required for this systematic review. We will disseminate our findings through publication in a peer-reviewed journal.PROSPERO registration numberCRD 42020178798.


2019 ◽  
Vol 34 (10) ◽  
pp. 1948-1964 ◽  
Author(s):  
Mathilde Bourdon ◽  
Khaled Pocate-Cheriet ◽  
Astri Finet de Bantel ◽  
Veronika Grzegorczyk-Martin ◽  
Aureli Amar Hoffet ◽  
...  

Abstract STUDY QUESTION Is there a difference in clinical pregnancy and live birth rates (LBRs) between blastocysts developing on Day 5 (D5) and blastocysts developing on Day 6 (D6) following fresh and frozen transfers? SUMMARY ANSWER D5 blastocyst transfers (BTs) present higher clinical pregnancy and LBRs than D6 in both fresh and frozen transfers. WHAT IS KNOWN ALREADY BT is increasingly popular in assisted reproductive technology (ART) centers today. To our knowledge, no meta-analysis has focused on clinical outcomes in both fresh and frozen BT. Concerning frozen blastocysts, one meta-analysis in 2010 found no significant difference in pregnancy outcomes between D5 and D6 BT. Since then, ART practices have evolved particularly with the wide use of vitrification, and more articles comparing D5 and D6 BT cycles have been published and described conflicting results. STUDY DESIGN, SIZE, DURATION Systematic review and meta-analysis of published controlled studies. Searches were conducted from 2005 to February 2018 on MEDLINE and Cochrane Library and from 2005 to May 2017 on EMBASE, Eudract and clinicaltrials.gov, using the following search terms: blastocyst, Day 5, Day 6, pregnancy, implantation, live birth and embryo transfer (ET). PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 47 full-text articles were preselected from 808 references, based on title and abstract and assessed utilizing the Newcastle–Ottowa Quality Assessment Scales. Study selection and data extraction were carried out by two independent reviewers according to Cochrane methods. Random-effect meta-analysis was performed on all data (overall analysis) followed by subgroup analysis (fresh, vitrified/warmed, slow frozen/thawed). MAIN RESULTS AND THE ROLE OF CHANCE Data from 29 relevant articles were extracted and integrated in the meta-analysis. Meta-analysis of the 23 studies that reported clinical pregnancy rate (CPR) as an outcome, including overall fresh and/or frozen ET cycles, showed a significantly higher CPR following D5 ET compared with D6 ET (risk ratio (RR) = 1.27, 95% CI: 1.15–1.39, P < 0.001). For CPR, calculated subgroup RRs were 2.38 (95% CI: 1.74–3.24, P < 0.001) for fresh BT; 1.27 (95% CI: 1.16–1.39, P < 0.001) for vitrified/warmed BT; and 1.15 (95% CI: 0.93–1.41, P = 0.20) for slow frozen/thawed BT. LBR was also significantly higher after D5 BT (overall RR = 1.50 (95% CI: 1.32–1.69), P < 0.001). The LBR calculated RRs for subgroups were 1.74 (95% CI: 1.37–2.20, P < 0.001) for fresh BT; 1.38 (95% CI: 1.23–1.56, P < 0.001) for vitrified/warmed BT; and 1.44 (95% CI: 0.70–2.96, P = 0.32) for slow frozen/thawed BT. Sensitivity analysis led to similar results and conclusions: CPR and LBR were significantly higher following D5 compared to D6 BT. LIMITATIONS, REASONS FOR CAUTION The validity of meta-analysis results depends mainly on the quality and the number of the published studies available. Indeed, this meta-analysis included no randomized controlled trial (RCT). Slow frozen/thawed subgroups showed substantial heterogeneity. WIDER IMPLICATIONS OF THE FINDINGS In regards to the results of this original meta-analysis, ART practitioners should preferably transfer D5 rather than D6 blastocysts in both fresh and frozen cycles. Further RCTs are needed to address the question of whether D6 embryos should be transferred in a fresh or a frozen cycle. STUDY FUNDING/COMPETING INTEREST(S) This work was sponsored by an unrestricted grant from GEDEON RICHTER France. The authors have no competing interests to declare. REGISTRATION NUMBER CRD42018080151.


BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e040997
Author(s):  
Varo Kirthi ◽  
Paul Nderitu ◽  
Uazman Alam ◽  
Jennifer Evans ◽  
Sarah Nevitt ◽  
...  

IntroductionThere is growing evidence of a higher than expected prevalence of retinopathy in prediabetes. This paper presents the protocol of a systematic review and meta-analysis of retinopathy in prediabetes. The aim of the review is to estimate the prevalence of retinopathy in prediabetes and to summarise the current data.Methods and analysisThis protocol is developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines. A comprehensive electronic bibliographic search will be conducted in MEDLINE, EMBASE, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Google Scholar and the Cochrane Library. Eligible studies will report prevalence data for retinopathy on fundus photography in adults with prediabetes. No time restrictions will be placed on the date of publication. Screening for eligible studies and data extraction will be conducted by two reviewers independently, using predefined inclusion criteria and prepiloted data extraction forms. Disagreements between the reviewers will be resolved by discussion, and if required, a third (senior) reviewer will arbitrate.The primary outcome is the prevalence of any standard features of diabetic retinopathy (DR) on fundus photography, as per International Clinical Diabetic Retinopathy Severity Scale (ICDRSS) classification. Secondary outcomes are the prevalence of (1) any retinal microvascular abnormalities on fundus photography that are not standard features of DR as per ICDRSS classification and (2) any macular microvascular abnormalities on fundus photography, including but not limited to the presence of macular exudates, microaneurysms and haemorrhages. Risk of bias for included studies will be assessed using a validated risk of bias tool for prevalence studies. Pooled estimates for the prespecified outcomes of interest will be calculated using random effects meta-analytic techniques. Heterogeneity will be assessed using the I2 statistic.Ethics and disseminationEthical approval is not required as this is a protocol for a systematic review and no primary data are to be collected. Findings will be disseminated through peer-reviewed publications and presentations at national and international meetings including Diabetes UK, European Association for the Study of Diabetes, American Diabetes Association and International Diabetes Federation conferences.PROSPERO registration numberCRD42020184820.


Author(s):  
Antonio Jose Martin-Perez ◽  
María Fernández-González ◽  
Paula Postigo-Martin ◽  
Marc Sampedro Pilegaard ◽  
Carolina Fernández-Lao ◽  
...  

There is no systematic review that has identified existing studies evaluating the pharmacological and non-pharmacological intervention for pain management in patients with bone metastasis. To fill this gap in the literature, this systematic review with meta-analysis aims to evaluate the effectiveness of different antalgic therapies (pharmacological and non-pharmacological) in the improvement of pain of these patients. To this end, this protocol has been written according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) and registered in PROSPERO (CRD42020135762). A systematic search will be carried out in four international databases: Medline (Via PubMed), Web of Science, Cochrane Library and SCOPUS, to select the randomized controlled clinical trials. The Risk of Bias Tool developed by Cochrane will be used to assess the risk of bias and the quality of the identified studies. A narrative synthesis will be used to describe and compare the studies, and after the data extraction, random effects model and a subgroup analyses will be performed according to the type of intervention, if possible. This protocol aims to generate a systematic review that compiles and synthesizes the best and most recent evidence on the treatment of pain derived from vertebral metastasis.


2021 ◽  
pp. 1-9
Author(s):  
William M. Jackson ◽  
Nicholas Davis ◽  
Johanna Calderon ◽  
Jennifer J. Lee ◽  
Nicole Feirsen ◽  
...  

Abstract Context: People with CHD are at increased risk for executive functioning deficits. Meta-analyses of these measures in CHD patients compared to healthy controls have not been reported. Objective: To examine differences in executive functions in individuals with CHD compared to healthy controls. Data sources: We performed a systematic review of publications from 1 January, 1986 to 15 June, 2020 indexed in PubMed, CINAHL, EMBASE, PsycInfo, Web of Science, and the Cochrane Library. Study selection: Inclusion criteria were (1) studies containing at least one executive function measure; (2) participants were over the age of three. Data extraction: Data extraction and quality assessment were performed independently by two authors. We used a shifting unit-of-analysis approach and pooled data using a random effects model. Results: The search yielded 61,217 results. Twenty-eight studies met criteria. A total of 7789 people with CHD were compared with 8187 healthy controls. We found the following standardised mean differences: −0.628 (−0.726, −0.531) for cognitive flexibility and set shifting, −0.469 (−0.606, −0.333) for inhibition, −0.369 (−0.466, −0.273) for working memory, −0.334 (−0.546, −0.121) for planning/problem solving, −0.361 (−0.576, −0.147) for summary measures, and −0.444 (−0.614, −0.274) for reporter-based measures (p < 0.001). Limitations: Our analysis consisted of cross-sectional and observational studies. We could not quantify the effect of collinearity. Conclusions: Individuals with CHD appear to have at least moderate deficits in executive functions. Given the growing population of people with CHD, more attention should be devoted to identifying executive dysfunction in this vulnerable group.


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Lijun Zhang ◽  
Yangyang Wang ◽  
Lianlian Xiong ◽  
Yanfang Luo ◽  
Zhijun Huang ◽  
...  

Abstract Background Patients with chronic kidney disease (CKD) have a high prevalence of cardiovascular diseases, which often lead to physical inactivity that correlates with CKD exacerbation. The benefits of regular exercise to cardiovascular health have been well established in healthy population and highly suggestive in patients with CKD. To further strengthen the evidence base for the management of CKD, this meta-analysis was performed to systematically evaluate the effects of exercise therapy on renal function, blood pressure, blood lipid and body mass index (BMI) in non-dialysis CKD patients. Methods This meta-analysis was conducted following a previous protocol. Randomized controlled trials (RCTs) examining the effects of exercise therapy in non-dialysis CKD patients were searched in Pubmed, Embase, Cochrane Library, and three major Chinese biomedical databases (CNKI, WANGFANG and VIP) from their start date to October 30th, 2018. The Cochrane systematic review methods were applied for quality assessment and data extraction, and Revman version 5.3 was used for systematic review and meta-analysis. Results 13 RCTs, representing 421 patients with non-dialysis CKD, were included in this meta-analysis. Compared to the controls, exercise therapy brought an increase in eGFR (MD = 2.62, 95% CI:0.42 to 4.82, P = 0.02, I2 = 22%), and decreases in systolic blood pressure (SBP) (MD = -5.61, 95% CI:-8.99 to − 2.23, P = 0.001, I2 = 44%), diastolic blood pressure (DBP) (MD = -2.87, 95% CI:-3.65 to − 2.08, P < 0.00001, I2 = 16%) and BMI (MD = -1.32, 95% CI:-2.39 to − 0.25, P = 0.02, I2 = 0%) in non-dialysis CKD patients. Exercise therapy of short-term (< 3 months) decreased triglyceride (TG) level (P = 0.0006). However, exercise therapy did not significantly affect serum creatinine (SCr), total cholesterol (TC), high density lipoprotein (HDL) or low density lipoprotein (LDL) in non-dialysis CKD patients. Conclusion Exercise therapy could benefit non-dialysis CKD patients by increasing eGFR while reducing SBP, DBP and BMI. Additionally, short-term intervention of exercise could decrease TG.


Author(s):  
Annie S Jasper ◽  
Jackson S Musuuza ◽  
Jessica S Tischendorf ◽  
Vanessa W Stevens ◽  
Shantini D Gamage ◽  
...  

Abstract Background The Infectious Diseases Society of America recommends either a fluoroquinolone or a macrolide as a first-line antibiotic treatment for Legionella pneumonia, but it is unclear which antibiotic leads to optimal clinical outcomes. We compared the effectiveness of fluoroquinolone versus macrolide monotherapy in Legionella pneumonia using a systematic review and meta-analysis. Methods We conducted a systematic search of literature in PubMed, Cochrane, Scopus, and Web of Science from inception to 1 June 2019. Randomized controlled trials and observational studies comparing macrolide with fluoroquinolone monotherapy using clinical outcomes in patients with Legionella pneumonia were included. Twenty-one publications out of an initial 2073 unique records met the selection criteria. Following PRISMA guidelines, 2 reviewers participated in data extraction. The primary outcome was mortality. Secondary outcomes included clinical cure, time to apyrexia, length of hospital stay (LOS), and the occurrence of complications. The review and meta-analysis was registered with PROSPERO (CRD42019132901). Results Twenty-one publications with 3525 patients met inclusion criteria. The mean age of the population was 60.9 years and 67.2% were men. The mortality rate for patients treated with fluoroquinolones was 6.9% (104/1512) compared with 7.4% (133/1790) among those treated with macrolides. The pooled odds ratio assessing risk of mortality for patients treated with fluoroquinolones versus macrolides was 0.94 (95% confidence interval, .71–1.25, I2 = 0%, P = .661). Clinical cure, time to apyrexia, LOS, and the occurrence of complications did not differ for patients treated with fluoroquinolones versus macrolides. Conclusions We found no difference in the effectiveness of fluoroquinolones versus macrolides in reducing mortality among patients with Legionella pneumonia.


BMJ Open ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. e028238 ◽  
Author(s):  
Shimels Hussien Mohammed ◽  
Tesfa Dejenie Habtewold ◽  
Mulugeta Molla Birhanu ◽  
Tesfamichael Awoke Sissay ◽  
Balewgizie Sileshi Tegegne ◽  
...  

ObjectiveLow neighbourhood socioeconomic status (NSES) has been linked to a higher risk of overweight/obesity, irrespective of the individual’s own socioeconomic status. No meta-analysis study has been done on the association. Thus, this study was done to synthesise the existing evidence on the association of NSES with overweight, obesity and body mass index (BMI).DesignSystematic review and meta-analysis.Data sourcesPubMed, Embase, Scopus, Cochrane Library, Web of Sciences and Google Scholar databases were searched for articles published until 25 September 2019.Eligibility criteriaEpidemiological studies, both longitudinal and cross-sectional ones, which examined the link of NSES to overweight, obesity or BMI, were included.Data extraction and synthesisData extraction was done by two reviewers, working independently. The methodological quality of included studies was assessed using the Newcastle-Ottawa Scale for the observational studies. The summary estimates of the relationships of NSES with overweight, obesity and BMI statuses were calculated with random-effects meta-analysis models. Heterogeneity was assessed by Cochran’s Q and I2 statistics. Subgroup analyses were done by age categories, continents, study designs and NSES measures. Publication bias was assessed by visual inspection of funnel plots and Egger’s regression test.ResultA total of 21 observational studies, covering 1 244 438 individuals, were included in this meta-analysis. Low NSES, compared with high NSES, was found to be associated with a 31% higher odds of overweight (pooled OR 1.31, 95% CI 1.16 to 1.47, p<0.001), a 45% higher odds of obesity (pooled OR 1.45, 95% CI 1.21 to 1.74, p<0.001) and a 1.09 kg/m2 increase in mean BMI (pooled beta=1.09, 95% CI 0.67 to 1.50, p<0.001).ConclusionNSES disparity might be contributing to the burden of overweight/obesity. Further studies are warranted, including whether addressing NSES disparity could reduce the risk of overweight/obesity.PROSPERO registration numberCRD42017063889


BMJ Open ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. e025440 ◽  
Author(s):  
Xiaofen Wang ◽  
Kun Tang ◽  
Ling Chen ◽  
Sixiang Cheng ◽  
Huilan Xu

ObjectiveTo explore the association between sepsis and retinopathy of prematurity (ROP) in premature infants.DesignA systematic review and meta-analysis.Data sourcesWe performed a systematic search of PubMed, the Cochrane Library and Embase from 1 January, 2000, to 1 January, 2018, with no language restrictions and reported the relationship between sepsis and ROP.Eligibility criteriaOriginal observational studies, including cohort studies and case-control studies.Data extraction and synthesisTwo reviewers independently completed the study selection and data extraction. The OR and corresponding 95% CI were used to measure the risk of sepsis in patients with ROP. The heterogeneity between studies was evaluated using Cochran’s Q test and the I2statistic. The Newcastle-Ottawa Scale was adopted to evaluate the quality of each of the included studies, and the Grading of Recommendations Assessment, Development and Evaluation approach was used to assess the quality of the evidence.ResultsSixteen studies with a total sample size of 12 466 premature infants and 2494 cases of ROP were included in this meta-analysis. Adjusted analysis showed that sepsis was closely related to any stage of ROP (OR = 1.57, 95% CI 1.31 to 1.89) and severe stage of ROP (OR = 2.33, 95% CI 1.21 to 4.51) in premature infants, with 56.3% and 81.8% heterogeneity, respectively. Subgroup analyses showed that heterogeneity was obvious in prospective cohort studies (I2= 62.1%, p<0.001). In a sensitivity analysis, we found that removing any single study did not significantly change the overall effect value. The quality of the evidence was rated as low for both any stage of ROP and severe stage of ROP.ConclusionsSepsis increases the risk of ROP in preterm infants. However, considering that all included studies are observational and causality can rarely be established, additional evidence is needed to substantiate this finding and provide advice for practice.


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