scholarly journals Impact of PCSK9 monoclonal antibodies on circulating hs-CRP levels: a systematic review and meta-analysis of randomised controlled trials

BMJ Open ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. e022348 ◽  
Author(s):  
Ye-Xuan Cao ◽  
Sha Li ◽  
Hui-Hui Liu ◽  
Jian-Jun Li

ObjectiveTo evaluate the potential effects of proprotein convertase subtilisin/kexin type 9 monoclonal antibody (PCSK9-mAb) on high-sensitivity C reactive protein (hs-CRP) concentrations.DesignA systematic review and meta-analysis of randomised controlled trials.Data sourcesPubMed, MEDLINE, the Cochrane Library databases, ClinicalTrials.gov and recent conferences were searched from inception to May 2018.Eligibility criteria for selecting studiesAll randomised controlled trials that reported changes of hs-CRP were included.ResultsTen studies involving 4198 participants were identified. PCSK9-mAbs showed a slight efficacy in reducing hs-CRP (−0.04 mg/L, 95% CI: −0.17 to 0.01) which was not statistically different. The results did not altered when subgroup analyses were performed including PCSK9-mAb types (alirocumab: 0.12 mg/L, 95% CI: −0.18 to 0.43; evolocumab: 0.00 mg/L, 95% CI: −0.07 to 0.07; LY3015014: −0.48 mg/L, 95% CI: −1.28 to 0.32; RG7652: 0.35 mg/L, 95% CI: −0.26 to 0.96), treatment duration (≤12w: 0.00 mg/L, 95% CI: −0.07 to 0.07; >12w: −0.11 mg/L, 95% CI: −0.45 to −0.23), participant characteristics (familial hypercholesterolaemia: 0.00 mg/L, 95% CI: −0.07 to 0.07; non-familial hypercholesterolaemia: 0.07 mg/L, 95% CI: −0.12 to 0.26; mix: −0.48 mg/L, 95% CI: −1.28 to 0.32) and treatment methods (monotherapy: 0.00 mg/L, −0.08 to 0.07; combination therapy: −0.08 mg/L, −0.37 to 0.21). Meta-regression analyses suggested no significant linear correlation between baseline age (p=0.673), sex (p=0.645) and low-density lipoprotein cholesterol reduction (p=0.339).ConclusionsOur updated meta-analysis suggested that PCSK9-mAbs had no significant impact on circulating hs-CRP levels irrespective of PCSK9-mAb types, participant characteristics and treatment duration or methods.

BMJ Open ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. e047344
Author(s):  
Qingwu Wu ◽  
Lianxiong Yuan ◽  
Huijun Qiu ◽  
Xinyue Wang ◽  
Xuekun Huang ◽  
...  

ObjectivesTo assess the efficacy and safety of omalizumab for chronic rhinosinusitis with nasal polyps (CRSwNP) and to identify evidence gaps that will guide future research on omalizumab for CRSwNP.DesignSystematic review and meta-analysis.Data sourcesA comprehensive search was performed in PubMed, Embase, Web of Science and the Cochrane Library on 13 October 2020.Eligibility criteriaRandomised controlled trials (RCTs) comparing omalizumab with placebo, given for at least 16 weeks in adult patients with CRSwNP.Data extraction and synthesisTwo independent authors screened search results, extracted data and assessed studies using the Cochrane risk of bias tool. Data were pooled using the inverse-variance method and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed by the χ2 test and the I2 statistic.ResultsA total of four RCTs involving 303 participants were identified. When comparing omalizumab to placebo, there was a significant difference in Nasal Polyps Score (MD=−1.20; 95% CI −1.48 to −0.92), Nasal Congestion Score (MD=−0.67; 95% CI −0.86 to −0.48), Sino-Nasal Outcome Test-22 (MD=−15.62; 95% CI −19.79 to −11.45), Total Nasal Symptom Score (MD=−1.84; 95% CI −2.43 to −1.25) and reduced need for surgery (risk ratio (RR)=5.61; 95% CI 1.99 to 15.81). Furthermore, there was no difference in the risk of serious adverse events ((RR=1.40; 95% CI 0.29 to 6.80), adverse events (RR=0.83; 95% CI 0.60 to 1.15) and rescue systemic corticosteroid (RR=0.52; 95% CI 0.17 to 1.61).ConclusionsThis was the first meta-analysis that identified omalizumab significantly improved endoscopic, clinical and patient-reported outcomes in adults with moderate to severe CRSwNP and it was safe and well tolerated.PROSPERO registration numberCRD42020207639.


2019 ◽  
Vol 96 (1134) ◽  
pp. 197-205 ◽  
Author(s):  
Mehdi Koushki ◽  
Mostafa Lakzaei ◽  
Hadi Khodabandehloo ◽  
Hossein Hosseini ◽  
Reza Meshkani ◽  
...  

BackgroundResveratrol is a naturally occurring polyphenol compound mainly found in grapes and red wine. The evidence has suggested that resveratrol has an antioxidant effect. However, the results are inconsistent and inconclusive. Thus, we conducted a systematic review and meta-analysis to evaluate the effect of resveratrol supplementation on markers of oxidative stress.MethodsWe searched PubMed, ISI Web of Science, EMBASE, Scopus and the Cochrane library up to December 2018 to identify randomised controlled trials (RCTs) assessing resveratrol supplementation effects on oxidative markers. Heterogeneity, publication bias, risk of bias and subgroup analysis were analysed. This meta-analysis was conducted in accordance with the guidelines of the Preferred ReportingItems for Systematic Reviews and Meta-Analysis (PRISMA).ResultsMeta-analysis of data from 12 RCTs did not support significant effect of resveratrol supplementation on circulating levels of superoxide dismutase (SOD) (standardized mean difference (SMD) (1.12), (95% CI −0.91 to 3.1), p=0.28), catalase (CAT) (SMD (−0.07), (95% CI −1.4 to 1.3), p=0.92) and glutathione peroxidase (GPx) (SMD (−0.76), (95% CI −2.56 to 1.04), p=0.40). Although, resveratrol supplementation increased significantly circulating total antioxidant capacity (TAC) concentrations (SMD (0.52), (95% CI −0.02 to 1.07), p=0.05). Severe heterogeneity was observed between studies, and no obvious publication bias was observed in included RCTs.ConclusionCollectively, our findings of available RCTs did no show any benefit of resveratrol supplementation on SOD, CAT and GPx except for TAC. Well-designed RCTs are necessary to confirm these results.


2019 ◽  
Vol 122 (9) ◽  
pp. 1021-1032
Author(s):  
Amir Hadi ◽  
Arman Arab ◽  
Sajjad Moradi ◽  
Ana Pantovic ◽  
Cain C. T. Clark ◽  
...  

AbstractA number of clinical trials have examined the effect of l-arginine on lipid profile in recent years; however, the results remain equivocal. Therefore, the present study aims to summarise and quantitatively examine the available evidence on the effectiveness l-arginine supplementation on lipid parameters using a systematic review and meta-analytic approach. Online databases including PubMed, Scopus, ISI Web of Science, Cochrane Library and Google Scholar were searched up to April 2019 for randomised controlled trials that examined the effect of l-arginine supplementation on lipid profile in adults. Treatment effects were expressed as weighted mean difference (WMD) and the corresponding standard error in concentrations of serum lipids. To estimate the overall effect of l-arginine supplementation, we used the random-effects model. In total, twelve studies were included in the systematic review. The meta-analysis revealed that l-arginine supplementation did not significantly change the concentrations of total cholesterol (WMD: –5·03 mg/dl; 95 % CI –10·78, 0·73; P = 0·08; inconsistency index (I2) = 39·0 %), LDL (WMD: –0·47 mg/dl; 95 % CI –3·61, 2·66; P = 0·76; I2 = 0·0 %), or HDL (WMD: 0·57 mg/dl; 95 % CI –1·28, 2·43; P = 0·54; I2 = 68·4 %). A significant reduction was observed only in serum TAG levels (WMD: –7·04 mg/dl; 95 % CI –11·42, –2·67; P < 0·001; I2 = 0·0 %). This meta-analysis concludes that l-arginine supplementation can significantly reduce blood TAG levels; however, there is insufficient evidence to support its hypocholesterolaemic effects. To draw straightforward conclusions regarding generalised recommendations for l-arginine supplementation for improving lipid profile, there is a need for more well-controlled trials targeting exclusively patients with dyslipidaemia.


BMJ Open ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. e034812 ◽  
Author(s):  
Tolesa Bekele ◽  
Patrick Rawstorne ◽  
Bayzidur Rahman

ObjectiveThis study aimed to provide clarification on the benefits of water, sanitation and hygiene (WASH) alone separately and combined with nutrition in improving child growth outcomes.DesignSystematic review and meta-analysis.MethodsWe conducted a systematic review using the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. PubMed, MEDLINE, EMBASE, Scopus, Cochrane Library, Web of Science and Science Direct were searched in May 2018 and last updated in April 2019. We included studies that reported WASH interventions alone separately or combined with nutrition. Fixed and random-effects models were used to estimate pooled effect in mean difference (MD). Heterogeneity and publication bias statistics were performed.ResultsA total of 18 studies were included: 13 cluster randomised controlled trials (RCTs) and 5 non-randomised controlled trials (non-RCTs). Non-RCTs showed effect of WASH interventions alone on height-for-age z-score (HAZ) (MD=0.14; 95% CI 0.08 to 0.21) but RCTs did not. WASH alone of non-RCTs and RCTs that were delivered over 18–60 months indicated an effect on HAZ (MD=0.04; 95% CI 0.01 to 0.08). RCTs showed an effect for children <2 years (MD=0.07; 95% CI 0.01 to 0.13). Non-RCTs of WASH alone and those that included at least two components, improved HAZ (MD=0.15; 95% CI 0.07 to 0.23) but RCTs did not. WASH alone of non-RCTs and RCTs separately or together showed no effect on weight-for-age z-score (WAZ) and weight-for-height z-score (WHZ). Combined WASH with nutrition showed an effect on HAZ (MD=0.13; 95% CI 0.08 to 0.17) and on WAZ (MD=0.09; 95% CI 0.05 to 0.13) and was borderline on WHZ.ConclusionsWASH interventions alone improved HAZ when delivered over 18–60 months and for children <2 years. Combined WASH with nutrition showed a strong effect on HAZ and WAZ and a borderline effect on WHZ. Integrated WASH with nutrition interventions may be effective inimproving child growth outcomes.


BMJ Open ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. e019438 ◽  
Author(s):  
Laura Chiavaroli ◽  
Cyril W C Kendall ◽  
Catherine R Braunstein ◽  
Sonia Blanco Mejia ◽  
Lawrence A Leiter ◽  
...  

ObjectiveCarbohydrate staples such as pasta have been implicated in the obesity epidemic. It is unclear whether pasta contributes to weight gain or like other low-glycaemic index (GI) foods contributes to weight loss. We synthesised the evidence of the effect of pasta on measures of adiposity.DesignSystematic review and meta-analysis using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.Data sourcesMEDLINE, Embase, CINAHL and the Cochrane Library were searched through 7 February 2017.Eligibility criteria for selecting studiesWe included randomised controlled trials ≥3 weeks assessing the effect of pasta alone or in the context of low-GI dietary patterns on measures of global (body weight, body mass index (BMI), body fat) and regional (waist circumference (WC), waist-to-hip ratio (WHR), sagittal abdominal diameter (SAD)) adiposity in adults.Data extraction and synthesisTwo independent reviewers extracted data and assessed risk of bias. Data were pooled using the generic inverse-variance method and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed (Cochran Q statistic) and quantified (I2statistic). GRADE assessed the certainty of the evidence.ResultsWe identified no trial comparisons of the effect of pasta alone and 32 trial comparisons (n=2448 participants) of the effect of pasta in the context of low-GI dietary patterns. Pasta in the context of low-GI dietary patterns significantly reduced body weight (MD=−0.63 kg; 95% CI −0.84 to –0.42 kg) and BMI (MD=−0.26 kg/m2; 95% CI −0.36 to –0.16 kg/m2) compared with higher-GI dietary patterns. There was no effect on other measures of adiposity. The certainty of the evidence was graded as moderate for body weight, BMI, WHR and SAD and low for WC and body fat.ConclusionsPasta in the context of low-GI dietary patterns does not adversely affect adiposity and even reduces body weight and BMI compared with higher-GI dietary patterns. Future trials should assess the effect of pasta in the context of other ‘healthy’ dietary patterns.Trial registration numberNCT02961088; Results.


2018 ◽  
Vol 25 (7) ◽  
pp. 389-401 ◽  
Author(s):  
Jen-Wu Huang ◽  
Yi-Ying Lin ◽  
Nai-Yuan Wu

Object The purpose of this study was to evaluate the clinical effectiveness of telemedicine on changes in body mass index for overweight and obese people as well as for diabetes and hypertension patients. Methods A systematic review of articles published before 31 August 2014, was conducted using searches of Medline, Cochrane Library, EMBASE, and CINAHL Plus. The inclusion criteria were randomised controlled trials that compared telemedicine interventions with usual care or standard treatment in adults and reported a change in body mass index. A meta-analysis was conducted for eligible studies, and the primary outcome was a change in body mass index. Subgroup analysis was performed for the type of telemedicine, main purpose of intervention, and length of intervention. Results Twenty-five randomised controlled trials comprising 6253 people were included in the qualitative and quantitative analyses. The length of intervention ranged from nine weeks to two years. The meta-analysis revealed significant differences in body mass index changes (pooled difference in means = –0.49, 95% confidence interval –0.63 to –0.34, p < 0.001) between the telemedicine and control groups. The subgroup analyses found that either Internet-based or telephone-based intervention was associated with greater changes in body mass index than in controls. Telemedicine intervention was effective in improving body mass index whether it was used for diabetes control, hypertension control, weight loss, or increasing physical activity and was also effective for people with and without diabetes or hypertension. However, only interventions with a duration ≥ 6 months significantly decreased body mass index compared to controls. Conclusion Both patients with chronic disease and overweight/obese people could benefit from telemedicine interventions. We suggest that an effective telemedicine approach should be longer than six months and emphasise the importance of post-interventional follow-ups.


BJPsych Open ◽  
2021 ◽  
Vol 7 (6) ◽  
Author(s):  
Shoumitro Deb ◽  
Meera Roy ◽  
Rachel Lee ◽  
Madiha Majid ◽  
Bharati Limbu ◽  
...  

Background Although widely used, the current evidence for the efficacy of antidepressant and anti-anxiety medications for people with autism spectrum disorder (ASD) is limited and conflicting. Aims We carried out a systematic review and meta-analysis of randomised controlled trials that assessed the effectiveness of these medications in people with ASD. Method We searched the following databases: Cochrane Library, Medline, EMBASE, CINAHL, PsycINFO, ERIC, DARE and ClinicalTrials.gov. Additionally, we hand-searched 11 relevant journals. We used the Cochrane risk-of-bias tool and Jadad score to assess the quality of each included study. We carried out a meta-analysis using a random effects model. Results We included 15 randomised controlled trials (13 on antidepressants and two on anti-anxiety medications) for a total of 958 people with ASD. Data showed contradictory findings among the studies, with larger studies mostly showing a non-significant difference in outcomes between the treatment and the placebo groups. Meta-analysis of pooled Yale-Brown Obsessive Compulsive Scale and Clinical Global Impression Scale data from nine studies (60%) did not show any statistically significant inter-group difference on either of the outcome measures. The adverse effects reported were mild and, in most studies, their rates did not show any significant inter-group difference. Conclusions Given the methodological flaws in the most included studies and contradictory findings, it is difficult to draw any definitive conclusion about the effectiveness of either antidepressant or anti-anxiety medications to treat either ASD core symptoms or associated behaviours. Robust, large-scale, randomised controlled trials are needed to address this issue.


BMJ Open ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. e039159
Author(s):  
Desye Gebrie ◽  
Desalegn Getnet ◽  
Tsegahun Manyazewal

BackgroundDespite global containment measures to fight the coronavirus disease 2019 (COVID-19), the pandemic continued to rise, rapidly spread across the world, and resulting in 2.6 million confirmed cases and 185 061 deaths worldwide as of 23 April 2020. Yet, there are no approved vaccines or drugs to make the disease less deadly, while efforts are underway. Remdesivir, a nucleotide-analogue antiviral drug developed for Ebola, is determined to prevent and stop infections with COVID-19, while results are yet controversial. Here, we aim to conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) to evaluate the efficacy of remdesivir in patients with COVID-19.Method and analysisWe will search MEDLINE-PubMed, Embase, Cochrane Library, ClinicalTrials.gov and Google scholar databases for articles published as of 30 June 2020 and we will complete the study on 30 August 2020. We will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 guidelines for the design and reporting of the results. We will include RCTs that assessed the efficacy of remdesivir versus placebo or standard of care. The primary endpoint will be time to clinical recovery. The secondary endpoints will be proportion of participants relieved from clinical symptoms defined at the time (in hours) from initiation of the study treatment, all-cause mortality, discharged date, frequency of respiratory progression and treatment-emergent adverse events. RevMan V.5.3 software will be used for statistical analysis. Random effects model will be carried out to calculate mean differences for continuous outcome data and risk ratio for dichotomous outcome data between remdesivir and placebo or standard of care.Ethics and disseminationThere are no ethical considerations associated with this study as we will use publicly available data from previously published studies. We plan to publish results in open-access peer-reviewed journals and present at international and national conferences.PROSPERO registration numberCRD42020177953.


BMJ Open ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. e051136
Author(s):  
Jialu Qian ◽  
Shiwen Sun ◽  
Lu Liu ◽  
Xiaoyan Yu

IntroductionPostpartum fatigue is a common symptom among new mothers after their pregnancy. It has a considerable negative impact on women’s functional and mental status as well as the development of babies. Identifying effective interventions to prevent or reduce postpartum fatigue is meaningful to improve the quality of life and avoid adverse outcomes of this vulnerable population. This systematic review aims to synthesise non-pharmacological evidence and evaluate the effectiveness of interventions for reducing postpartum fatigue among puerperas.Methods and analysisThis review will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. We will systematically search the Cochrane Library, PubMed, Embase, Web of Science, PsycINFO, CINAHL and ProQuest databases to identify clinical trials implementing non-pharmacological interventions conducted during 0–78 weeks postpartum for fatigue reduction. An additional search of OpenGrey will be conducted to identify grey literature. The search will be performed on 30 March 2021 without restrictions on time and language. Two independent reviewers will be responsible for study selection, data extraction and study quality assessment. The Cochrane risk-of-bias tool will be adopted to evaluate the risk biases of the included randomised controlled trials, and the Risk of Bias in Non-randomised Studies of Interventions will be applied to evaluate non-randomised controlled trials. Any disagreements will be referred to a third reviewer to reach a consensus. Findings will be qualitatively synthesised, and a meta-analysis will be conducted for the statistical combination if outcome data are sufficient and available.Ethics and disseminationThis systematic review will not involve the collection of primary data and will be based on published data. Therefore, ethics approval is not required. The final findings will be disseminated through peer-reviewed journals and academic conferences.PROSPERO registration numberCRD42021234869


2020 ◽  
Vol 97 (1143) ◽  
pp. 40-47
Author(s):  
LiPei Shu ◽  
Jiao Huang ◽  
Jing Chen Liu

Ultrasound guidance has been reported to facilitate the performance of lumbar punctures (LPs). However, the use of ultrasound guidance has not yet received consistent conclusions. We performed a systematic review and meta-analysis to determine the efficacy of ultrasound-guided LPs. PubMed, Embase and the Cochrane Library were searched for randomised controlled trials comparing ultrasound guidance with traditional palpation for LPs in adults. The primary outcome was risk of failed procedures. A random-effects Mantel-Haenzsel model or random-effects inverse variance model was used to calculate relative risks (RRs) or standardised mean differences (SMDs) with 95% CIs. Twenty-eight trials (N=2813) met the inclusion criteria. Ultrasound-guided LPs were associated with a reduced risk of failed procedures (RR=0.58, 95% CI 0.39 to 0.85, p=0.005). No significant heterogeneity was detected (I2=27%) among these trials. It further decreased first attempt to failure (RR=0.43, 95% CI 0.30 to 0.62, p<0.00001), mean attempts to success (SMD=−0.61, 95% CI −0.80 to −0.43, p=0.00001) and incidences of complications of headache and backache (RR=0.63, 95% CI 0.46 to 0.85, p=0.003). Ultrasound guidance is an effective technique for LPs in adults.


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