Trial Sequential Meta-analysis Research Articles

Critical appraisal and trial sequential meta-analysis for the association of CCND1 G870A gene polymorphism with the risk for colorectal cancer in Asian population

Critical appraisal and trial sequential meta-analysis for the association of CCND1 G870A gene polymorphism with the risk for colorectal cancer in Asian population

Efficacy of permissive underfeeding for critically ill patients: an updated systematic review and trial sequential meta-analysis

BackgroundOur previous study in 2011 concluded that permissive underfeeding may improve outcomes in patients receiving parenteral nutrition therapy. This conclusion was tentative, given the small sample size. We conducted the present systematic review and trial sequential meta-analysis to update the status of permissive underfeeding in patients who were admitted to the intensive care unit (ICU).MethodsSeven databases were searched: PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang, Chinese Biomedical Literature Database, and Cochrane Library. Randomized controlled trials (RCTs) were included. The Revised Cochrane risk-of-bias tool (ROB 2) was used to assess the risk of bias in the enrolled trials. RevMan software was used for data synthesis. Trial sequential analyses (TSA) of overall and ICU mortalities were performed.ResultsTwenty-three RCTs involving 11,444 critically ill patients were included. There were no significant differences in overall mortality, hospital mortality, length of hospital stays, and incidence of overall infection. Compared with the control group, permissive underfeeding significantly reduced ICU mortality (risk ratio [RR] = 0.90; 95% confidence interval [CI], [0.81, 0.99]; P = 0.02; I2 = 0%), and the incidence of gastrointestinal adverse events decreased (RR = 0.79; 95% CI, [0.69, 0.90]; P = 0.0003; I2 = 56%). Furthermore, mechanical ventilation duration was reduced (mean difference (MD) = − 1.85 days; 95% CI, [− 3.44, − 0.27]; P = 0.02; I2 = 0%).ConclusionsPermissive underfeeding may reduce ICU mortality in critically ill patients and help to shorten mechanical ventilation duration, but the overall mortality is not improved. Owing to the sample size and patient heterogeneity, the conclusions still need to be verified by well-designed, large-scale RCTs.Trial Registration The protocol for our meta-analysis and systematic review was registered and recorded in PROSPERO (registration no. CRD42023451308). Registered 14 August 2023

Efficacy and safety of collagen derivatives for osteoarthritis: A trial sequential meta-analysis

To investigate the efficacy and safety of collagen derivatives for osteoarthritis. PubMed, Embase, and Cochrane Library were searched till June 2023 for randomized controlled trials (RCTs) investigating collagen derivatives for treating osteoarthritis. Data were independently extracted by two authors. The risk of bias was assessed using the RoB 2 tool. A random-effects meta-analysis was performed within a frequentist framework. The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations approach. A total of 35 RCTs involving 3165 patients were included. The main analysis of the primary outcome was based on 25 RCTs involving 2856 patients. Collagen derivatives exerted small-to-moderate effects on pain alleviation (standardized mean difference [SMD] -0.35, 95% confidence interval [CI] -0.48 to -0.22, moderate certainty) and function improvement (SMD -0.31, 95%CI -0.41 to -0.22, high certainty) compared with the control. Collagen derivatives were safe; they did not increase the risk of withdrawal or adverse events compared with the control. The trial sequential analyses indicated that this study had sufficient statistical power for deriving definitive conclusions, confirming the robustness of our findings. Strong evidence supports the efficacy and safety of collagen derivatives for osteoarthritis treatment.

The efficacy of Omega-3 polyunsaturated fatty acids for severe burn patients: A systematic review and trial sequential meta-analysis of randomized controlled trials

Severe burns lead to metabolic changes, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. Omege-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties. In the absence of substantial evidence for use on major burns, we systematically reviewed the efficacy of omega-3 PUFAs for patients with severe burns. We comprehensively searched MEDLINE, Web of Science, Embase, Cochrane Library, China National Knowledge Internet, Wang Fang Data, Chinese Biomedicine Database, and Science Direct databases to collect randomised controlled trials of omega-3 PUFAs administered to patients with burns from January 2000 to June 2023. Two researchers independently screened the literatures, extracted the data, and assessed the risk of bias in the included studies. The outcomes were mortality, the risk of severe sepsis, septic shock, and multiple organ dysfunction syndrome. Data synthesis was conducted using Review Manager. Trial sequential analyses (TSA) for outcomes were performed. Three randomised controlled trials involving 140 patients were included. Of these, 71 patients received omega-3 PUFAs. The results showed that omega-3 PUFAs significantly reduced the incidence of severe sepsis, septic shock, multiple organ dysfunction syndrome (RR=0.38, 95% CI [0.19, 0.75], P=0.005), C-reactive protein levels (MD=-39.70[-81.63, 2.23], P=0.06), and improved respiratory outcomes. However, there was no difference in 14-day mortality (RR=1.10, 95%CI [0.59, 2.05], P=0.75). TSA showed that the results for the incidence of severe sepsis, septic shock, multiple organ dysfunction syndrome are insufficient and inconclusive. Omega-3 PUFAs may reduce inflammatory response and risk of sepsis, septic shock, and multiple organ dysfunction syndrome in severe burns patients and may shorten hospital stay but cannot reduce risk of death. Due to the limitation of the quantity and quality of the included studies, the evidence level is low, and the conclusions need to be verified by larger scale and higher quality randomised controlled trials.

Epicardial adipose tissue in patients with chronic obstructive pulmonary disease: systematic review with meta‑analysis and trial sequential analysis

BackgroundLimited data suggest that chronic obstructive pulmonary disease (COPD) patients have pathologic elevated epicardial adipose tissue (EAT), which is splanchnic fat tissue with anti-inflammatory properties and regulating free fatty acids functions. Therefore, there is a need for meta-analysis to explore the relationship between EAT and COPD.MethodsOnline databases were systematically searched for studies about EAT in COPD patients published up to October 5th, 2022. The EAT data of the COPD patient group and the control group were included. Trial sequential analysis (TSA) and meta-analysis were applied to assess the difference in EAT between patients with and without COPD. TSA software and Stata 12.0 were used in all statistical analyses.ResultsThe final analysis included 5 studies (n = 596 patients). COPD patients had significantly more EAT than control subjects (SMD: 0.0.802; 95% CI: 0.231, 1.372; P = 0.006; TSA-adjusted 95% CI 1.20, 1.80; P < 0.0001). And higher CRP levels in COPD patients than non-COPD patients, whereas triglycerides and LDL were not significantly different between patients with and without COPD.ConclusionEAT is abnormally elevated in COPD patients, which may be related to systemic inflammatory responses in COPD.PROSPERO numberCRD42021228273.

Value of immunonutrition in patients undergoing pancreatic resection: a trial sequential meta-analysis

BackgroundThe benefits of immunonutrition (IM) in patients who underwent pancreatic surgery are unclear. MethodsA meta-analysis of randomized clinical trials (RCTs) comparing IM with standard nutrition (SN) in pancreatic surgery was carried out. A random-effects trial sequential meta-analysis was made, reporting Risk Ratio (RR), mean difference (MD), and required information size (RIS). If RIS was reached, false negative (type II error) and positive results (type I error) could be excluded. The endpoints were morbidity, mortality, infectious complication, postoperative pancreatic fistula (POPF) rates, and length of stay (LOS). ResultsThe meta-analysis includes 6 RCTs and 477 patients. Morbidity (RR 0.77; 0.26 to 2.25), mortality (RR 0.90; 0.76 to 1.07), and POPF rates were similar. The RISs were 17,316, 7,417, and 464,006, suggesting a type II error. Infectious complications were lower in the IM group, with a RR of 0.54 (0.36–0.79; 95 CI). The LOS was shorter in IM (MD -0.3 days; −0.6 to −0.1). For both, the RISs were reached, excluding type I error. ConclusionThe IM can reduce infectious complications and LOS The small differences in mortality, morbidity, and POPF make it impossible to exclude type II error due to large RISs.

Trial Sequential Analysis and Updated Meta-Analysis of Fluvoxamine on Clinical Deterioration in Adult Patients with Symptomatic COVID-19 Infection

Preliminary meta-analyses suggested that fluvoxamine was effective in treating COVID-19 infection. However, the reliability of this evidence has not yet been examined. MEDLINE, CENTRAL, EMBASE, PsycINFO, and ClinicalTrials.gov were searched to identify any randomized controlled trials (RCTs) from the inception of the databases to 5 February 2023. We used trial sequential analysis (TSA) to examine the reliability of the current existing evidence on the benefits of fluvoxamine on COVID-19 infection. The primary outcome was clinical deterioration, as defined in the original study (reported as odds ratio (OR), with 95% confidence intervals), and the secondary outcome was hospitalization. In the TSA, we used the relative risk reduction thresholds of 10, 20, and 30%. The updated meta-analysis of the five RCTs showed that fluvoxamine was not associated with lower odds of clinical deterioration when compared with a placebo (OR: 0.81; 0.59-1.11). The effect of fluvoxamine lay within the futility boundary (i.e., lack of effect) when using a 30% relative risk reduction threshold. The effect estimates lay between the superiority and futility boundary using the 10% and 20% threshold, and the required size of information was not reached for these two thresholds. The effect of fluvoxamine on the odds of hospitalization was not statistically significant (0.76; 0.56-1.03). In conclusion, there is no reliable evidence that fluvoxamine, when compared to a placebo, reduces the relative risk of clinical deterioration among adult patients with COVID-19 infection by 30%, and a relative risk reduction of 20% or 10% is still uncertain. The role of fluvoxamine as a COVID-19 treatment cannot be justified.

Feedback for Promoting Motor Skill Learning in Physical Education: A Trial Sequential Meta-Analysis.

Feedback can be used as an effective teaching method in physical education (PE) to promote students' learning of motor skills. However, there is no objective synthetic evidence to support the role of feedback in PE. Additionally, the effect of each feedback subtype on students' motor skill learning is still unclear. This study aimed to conduct a meta-analysis and trial sequential analysis (TSA) to evaluate the effects of feedback and feedback subtypes on students' motor skill learning. Nine databases were searched through September 2022 to identify appropriate literature. Meta-analysis was conducted using Review Manager 5.4 software and TSA was performed using TSA version 0.9.5.10 beta software. Fifteen studies were included. Feedback significantly improved students' motor skill learning in PE (SMD 0.47; 95% CI 0.01, 0.93; Z = 2.02; p = 0.04). The TSA confirmed the result of the meta-analysis. Sensitivity analyses showed that the subtypes of feedback, including visual feedback, visual combined verbal feedback, visual self-model, visual expert model, corrective feedback, and teacher-regulated feedback, significantly improved students' learning of motor skills. In contrast, verbal, evaluative, and informational feedback did not produce changes in motor skill learning. Both complex and simple motor skills were improved by feedback. The use of feedback in PE benefits motor skill learning, regardless of whether the motor skills are complex or simple.

Comparative effectiveness and safety of open triple-branched stent graft technique with stented elephant trunk implantation in treating Stanford type A aortic dissection: A trial sequential meta-analysis.

The optimal surgical intervention for Stanford type A aortic dissection is controversial. The aim of this trial sequential meta-analysis was to investigate the comparative effectiveness and safety of open triple-branched stent graft and stent elephant trunk implantation for total aortic arch reconstruction in Sandford type A aortic dissection. PubMed, Embase, Cochrane library, Chinese Biomedical Literature database (CBM), and China National Knowledge Infrastructure (CNKI) were searched for retrieving relevant studies from inception to February 28, 2022. We evaluated 30-day mortality, procedure-related time including cardiopulmonary bypass (CPB), aortic cross-clamp (ACC), and selective cerebral perfusion (SCP),the incidence of postoperative complications including paralysis, cerebral embolism, and acute renal failure, intensive care unit (ICU) time, and medical expenditure. Statistical analysis was performed by RevMan 5.4 and trial sequential analysis (TSA) software. Six studies involving 260 dissection cases were included eventually. Total aortic arch reconstruction with open triple-branched stent graft was comparable to the stented elephant trunk implantation in 30-day mortality, incidence of postoperative complications, ICU time, and medical expenditure, but open triple-branched stent graft was related to shorter procedure-related time including CPB (mean difference [MD] = -46.11, 95% confidence interval [CI] = -67.24 to -24.98, p < .001), ACC (MD = -42.82, 95%CI = -66.74 to -18.90, p < .001), and SCP (MD = -17.88, 95%CI = -33.36 to -2.39, p = .02). TSA confirmed robustness of findings. Our analysis suggested that total aortic arch reconstruction with open triple-branched stent graft may be an effective and simplified procedure than the stented elephant trunk implantation.

An Updated Trial Sequential Meta-analysis of Vitamin D Receptor Gene Polymorphism (Fok1, Bsm1, Taq1 and Apa1) and Risk to Tuberculosis.

The online version contains supplementary material available at 10.1007/s12291-022-01091-3.

Trial sequential meta-analysis of laparoscopic versus open pancreaticoduodenectomy: is it the time to stop the randomization?

BackgroundThe advantages of LPD compared with OPD remain debatable. The study aimed to compare the laparoscopic (LPD) versus open (OPD) for pancreaticoduodenectomy.MethodsA meta-analysis of randomized studies (RCTs) comparing LPD and OPD was made. The results were reported as relative risk (RRs) or mean differences (MDs). The trial sequential analysis was used to test the type I and type II errors defining the required information size (RIS). The primary outcome was mortality, major morbidity, and postoperative pancreatic fistula (POPF). R1 resection, post-pancreatectomy hemorrhage, delayed gastric emptying, biliary fistula, reoperation, readmission, operative time (OT), lymph nodes harvested, and length of stay (LOS) were also studied.ResultsFour RCTs, counting 818 patients, were found. The RRs for mortality, major morbidity, and POPF were 1.16, 1.04, and 0.86, without significant differences. The RISs were 35,672, 16,548, and 8206. To confirm this equivalence, at least 34,854, 15,730, and 7338 should be randomized. OT was significantly longer in LPD than OPD, with an MD of 63.22. The LOS was significantly shorter in LPD than in OPD, with − 1.76 days. The RISs were 1297 and 1273, excluding a false-positive result. No significant differences were observed for the remaining endpoints, and RISs suggested that more than 3000 patients should be randomized to confirm the equivalence.ConclusionThe equivalence of LPD and OPD for mortality, major morbidity, and POPF is affected by type II error. The RISs to demonstrate a superiority of one of the two techniques seem unrealistic to obtain.

Efficacy of Moxibustion for Primary Osteoporosis: A Trial Sequential Meta-Analysis of Randomized Controlled Trials.

Background Primary osteoporosis (PO) is a systemic metabolic skeletal disease. Previous studies have shown that moxibustion can reduce pain intensity and enhance response rate, bone mineral density (BMD), and living function of the patients with PO. However, consensus on its efficacy does not exist, and evidence of moxibustion for PO is also insufficient. Methods We searched five English and four Chinese databases with various additional sources and published reviews through December 1, 2021, to evaluate potentially concerned randomized controlled trials (RCTs). Two independent researchers addressed selection screening, data extraction, and risk of bias assessment. The data of this meta-analysis were analyzed using the RevMan v.5.4 software. Additionally, the trial sequential analysis v.0.9.5.10 β was used to estimate the sample size. In contrast, the quality of evidence from the RCTs was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation tool. Results The current meta-analysis included 14 RCTs containing 898 participants. The methodological quality of the RCTs was moderate. The review demonstrated that a combination of moxibustion and conventional medicine (CM) significantly reduced pain intensity and improved the BMD compared with CM. Furthermore, it was found that moxibustion plus CM/moxibustion could improve response rates compared with CM. However, it was found that the reduction of pain intensity and improvement of BMD by moxibustion showed no significant difference compared with CM. It was also evident that the sample size of most outcomes was inadequate. Moreover, all evidence obtained in this study was ranked as low to critically low. Conclusions In conclusion, it was demonstrated that moxibustion is a potentially effective agent for treating PO. However, high-quality studies should be implemented in the future because this study only obtained low-quality evidence. This study was registered in the PROSPERO platform (CRD42021291310).

Screening for atrial fibrillation to prevent stroke: a meta-analysis.

AimsWe aimed to summarize existing evidence from published randomized trials that assessed atrial fibrillation (AF) screening for stroke prevention.Methods and resultsWe searched MEDLINE for randomized trials that enrolled patients without known AF, screened for AF using electrocardiogram-based methods, and reported stroke outcomes. For this analysis, we excluded studies that focused on post-stroke populations. We combined data using a random-effects model and performed trial sequential meta-analysis using an O’Brien-Fleming alpha-spending function.We identified four randomized clinical trials with a total of 35 836 participants. The populations, screening intervention, and definition of stroke varied markedly. As compared with no screening, AF screening was associated with a reduction in stroke (relative risk 0.91; 95% confidence interval: 0.84–0.99]. Trial sequential meta-analysis found that the cumulative z-score did not cross the stopping boundary.After polling members of the AF-SCREEN and AFFECT-EU consortia, we identified a further 12 trials that are complete but have not yet reported stroke outcomes or are ongoing and expected to collect stroke outcomes. These consortia are planning an individual participant data meta-analysis which will permit the exploration of methodological heterogeneity.ConclusionsIf and how to screen for AF is an important public health concern. The body of evidence published to date suggests that AF could be effective to prevent strokes in some settings. The AF-SCREEN/AFFECT-EU individual patient data meta-analysis aims to comprehensively assess the benefits and risks of AF screening, and determine how population, screening method, and health-system factors influence stroke prevention.

Extended, standard, or De-escalation antiplatelet therapy for patients with coronary artery disease undergoing percutaneous coronary intervention? A trial-sequential, bivariate, influential, and network meta-analysis.

The relative safety and efficacy of de-escalation, extended duration (ED) (&gt;12-months), and standard dual antiplatelet therapy for 12-months (DAPT-12) in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains controversial. Online databases were queried to identify relevant randomized control trials (RCTs). ED-DAPT, high-potency (HP) DAPT, shorter duration (SD) DAPT, and low-dose (LD) DAPT were compared with DAPT-12. A trial sequential, bivariate, influential, and frequentist network meta-analysis (NMA) was performed to determine the pooled estimates. A total of 30 RCTs comprising 81208 (40839 experimental, 40369 control arm) patients with CAD were included in the quantitative analysis. On NMA, compared with DAPT-12, all types of de-escalation, HP-DAPT-12, and ED-DAPT strategies had a statistically non-significant difference in the incidence of MACE at a median follow-up of 1-year. Similarly, there was no significant difference in the incidence of stroke, stent thrombosis, target lesion revascularization (TLR), target vessel revascularization (TVR), and all-cause mortality between DAPT-12 and all other strategies. The network estimates showed a significantly lower incidence of major bleeding with DAPT for 3-months followed by P2Y12-inhibitor monotherapy (RR 0.62, 95% CI 0.45-0.84), while a higher risk of bleeding with HP-DAPT for 12 months (RR 1.55, 95% CI 1.16-2.06). The net clinical benefit and rankograms also favoured DAPT-3 (P2Y12) and discouraged the use of HP-DAPT-12 and ED-DAPT. A subgroup analysis of 19 RCTs restricted to patients who presented with acute coronary syndrome (ACS) mirrored the findings of pooled analysis. A sensitivity analysis revealed no influence of any individual study or individual strategy on net ischemic estimates. The trial sequential analysis (TSA) illustrated a consistently non-significant difference at the interim analysis of trials, reaching the futility area for MACE, while the cumulative Z-values line surpassed the monitoring boundary as well as the required information size for major bleeding favouring de-escalation strategy. DAPT for three months followed by ticagrelor-only and use of aspirin+clopidogrel after a short period of high potency DAPT appears to be a safe strategy for treating post-PCI patients. However, given the methodological limitations and inclusion of a small number of trials in novel de-escalation strategies, these findings need validation by future large scale RCTs.

Effect of Vitamin D Supplementation on In Vitro Fertilization Outcomes: A Trial Sequential Meta-Analysis of 5 Randomized Controlled Trials.

Despite numerous studies indicating an imperative role of vitamin D for reproduction, the importance of vitamin D supplementation on in vitro fertilization (IVF) outcomes remains controversial. We therefore performed this meta-analysis to investigate the IVF outcomes of vitamin D supplementation in infertile women with vitamin D deficiency. We systematically searched PubMed, Embase and the Cochrane library for identifying all relevant studies published before August 2021. Pregnancy rate was defined as the primary outcome while good quality embryo, fertilization rate, ongoing pregnancy, and miscarriage were secondary outcomes. We used Review Manager 5.3 (RevMan) to conduct meta-analysis and examined the robustness of the primary outcome by trial sequential analysis. Five studies were included in the final analysis and it suggested that vitamin D supplementation was associated with improved chemical pregnancy rate (risk ratio [RR] = 1.53, 95% confidence interval [CI] = 1.06 to 2.20, p = 0.02) but not benefited in improving clinical pregnancy rate (RR = 1.34, 95% CI = 0.81 to 2.24, p = 0.25) and all secondary outcomes. Trial sequential analysis suggested further studies are needed to confirm this conclusion. We concluded that vitamin D supplementation should be prescribed to improve chemical pregnancy in infertile women with vitamin D deficiency and more studies are required to further confirm this finding.

Does delirium prevention reduce risk of in‐patient falls among older adults? A systematic review and trial sequential meta‐analysis

To determine whether delirium prevention interventions reduce the risk of falls among older hospitalised patients. A systematic search of health-care databases was undertaken. Given the frequency of small sample sized trials, a trial sequential meta-analysis was conducted to present estimate summary effects to date. A Bayesian approach was used to estimate the posterior probability of the delirium prevention interventions reducing falls risk by various clinically relevant levels. Five randomised controlled trials were included in our final meta-analysis. There was a 43% reduction in the risk of falls among participants in the delirium prevention intervention arm, compared to the control; however, confidence intervals were wide (RE RR=0.57, 95% CI 0.32; 1.00, p=0.05). This result was found to be statistically significant, according to traditional significance levels (z>1.96) and the more conservative trial sequential analysis monitoring boundaries. The posterior probabilities of the delirium prevention intervention reducing the risk of falls by 10%, 20% and 30% were 0.86, 0.63 and 0.29 respectively. The results of this systematic review and trial sequential meta-analysis suggest that delirium prevention trials may reduce the risk of in-hospital falls among older patients by 43%. However, despite significant risk reduction found upon meta-analysis, the variation among study populations and intervention components raised questions around its application in clinical practice. Further research is required to investigate what the necessary components of a multifactorial intervention are to reduce both delirium and fall incidence among older adult in-patients.

CDK5 Regulatory Subunit-Associated Protein 1-Like 1 Gene Polymorphisms and Gestational Diabetes Mellitus Risk: A Trial Sequential Meta-Analysis of 13,306 Subjects.

ObjectivesThe CDK5 regulatory subunit-associated protein 1-like 1 (CDKAL1) contributes to islet β-cell function and insulin secretion by inhibiting the activation of CDK5. The current studies on the relationship between CDKAL1 polymorphisms rs7756992 A>G and rs7754840 C>G and the risk of gestational diabetes mellitus (GDM) have drawn contradictory conclusions.Materials and MethodsA meta-analysis with a fixed- or random-effects model was conducted to estimate the correlation between studied CDKAL1 polymorphisms and GDM risk with the summary odds ratio (OR) and 95% confidence interval (CI). In addition, trial sequential analysis (TSA) and false-positive report probability (FPRP) analysis were performed to confirm the study findings.ResultsA total of 13,306 subjects were included in the present study. Meta-analysis results showed that the variant heterozygous and homozygous genotypes of the two polymorphisms were associated with increased GDM risk in comparison with the wild-type AA genotype (AG vs. AA: OR = 1.23, 95% CI = 1.08, 1.41, p = 0.002; GG vs. AA: OR = 1.47, 95% CI = 1.05, 2.05, p = 0.024 for rs7756992; and CG vs. GG: OR = 1.36, 95% CI = 1.13, 1.65, p = 0.002; CC vs. GG: OR = 1.76, 95% CI = 1.37, 2.26, p < 0.001 for rs7754840). The TSA confirmed a significant association between rs7754840 and the susceptibility to GDM because the cumulative Z-curve crossed both the conventional cutoff value and the TSA boundaries under the heterozygote and homozygote models.ConclusionsThis study supported the finding that rs7756992 and rs7754840 are associated with susceptibility to GDM. However, further functional studies are warranted to clarify the mechanism.

Living Systematic Reviews.

Systematic reviews are difficult to keep up to date, but failure to do so leads to poor review currency and accuracy. "Living systematic review" (LSR) is an approach that aims to continually update a review, incorporating relevant new evidence as it becomes available. LSRs may be particularly important in fields where research evidence is emerging rapidly, current evidence is uncertain, and new research may change policy or practice decisions.This chapter describes the concept and processes of living systematic reviews. It describes the general principles of LSRs, when they might be of particular value, and how their procedures differ from conventional systematic reviews. The chapter focuses particularly on two methods of sequential meta-analysis that may be particularly useful for LSRs: Trial Sequential Analysis and Sequential Meta-Analysis, which both control for Type I error, Type II error (failing to detect a genuine effect) and take account of heterogeneity.

Ethnicity based comprehensive evaluation of polymorphism in interferon-gamma gene and its association with pulmonary and extra-pulmonary tuberculosis risk: An updated trial sequential meta-analysis.

Host genetic background plays an important role in susceptibility to intracellular infectious pathogens like Mycobacterium tuberculosis (Mtb). Cellular immune response activation is vital for protection to these pathogens. Interferon-gamma (IFN-γ) plays a crucial role in this activation and preventing the intracellular growth of Mtb. A mutation in the IFN-γ gene, therefore, may lead to increased susceptibility to tuberculosis (TB) that may vary in different ethnic groups and its consequence also varies in pulmonary and extra-pulmonary TB (EPTB). Several IFN-γ gene polymorphisms are investigated for susceptibility to TB, but their associations are not always consistent as its impact may vary from one ethnicity to the other as well as with the type of TB. Hence, we performed a meta-analysis to overcome this problem. The present study involves comprehensive meta-analysis of + 874T/A polymorphism in the IFN-γ gene based on type of TB within five different ethnic groups to show its association with increased susceptibility to TB. Using PubMed and Google Scholar databases, a total of 50 case-control studies were retrieved having 8152 cases and 9755 controls in this meta-analysis. Thirty-eight studies of + 874T/A polymorphism of IFN-γ gene were correlated for Pooled odds ratios with 95% confidence intervals. The polymorphism was analyzed for six genetic models for five major ethnic groups accounting for heterogeneity among studies. Moreover, the sub-group analysis was based on the type of TB within each ethnic group. Trial sequential analysis was also performed for all the sub-groups to estimate the statistical consistency. IFN-γ +874 T/A polymorphism analysis clearly confirmed the increased association of + 874AA genotype with increased TB risk. This polymorphism also showed significant association in East Asian, European, American, and African ethnic groups whereas no such association was found in Asians. Patients with pulmonary TB (PTB) confirmed the association in East Asians, Africans, and Americans, whereas patients with EPTB showed association in Asian and East Asian populations only. This study reaffirms the association of IFN-γ+874 T/A polymorphism with TB risk. It specifically confirms that IFN-γ+874 T/A polymorphism increases the susceptibility of pulmonary infection in Africans and Americans, while the East Asian population is more susceptible to both, pulmonary and EPTB.

Efficacy of acupuncture for migraine prophylaxis: a trial sequential meta-analysis.

Acupuncture is commonly used for migraine prophylaxis; however, evidence of its efficacy was equivocal. We aimed to evaluated the efficacy of acupuncture in migraine prophylaxis and calculated the required information size (RIS) to determine whether further clinical studies are required. We searched Cochrane library, EMBASE and PubMed from inception to April 23th, 2020. Randomized trials that compared acupuncture with conventional drug therapy or sham acupuncture were included. The primary outcome was migraine episodes. Secondary outcomes were responder rate and adverse event. Twenty studies (n = 3380) met the inclusion criteria. When it comes to migraine episodes, Acupuncture was superior over sham acupuncture [SMD = - 0.29, 95% CI (- 0.47 to - 0.11), P = 0.002] after treatment, while the difference between acupuncture and prophylactic drugs was not significant [SMD = - 0.21, 95% CI (- 0.42 to 0.00), P = 0.06].Both TSA graphs indicated that more RCTs are needed. As for responder rate, the results after treatment showed that acupuncture was statistically significantly better than sham acupuncture [RR 1.30, 95% CI (1.09-1.55), P = 0.003] as well as conventional drugs [RR 1.24, 95% CI (1.04-1.48), P = 0.01]. Both of their cumulative Z-curves intersected with the trial sequential monitoring boundaries favoring acupuncture. Compared to prophylactic medication, acupuncture can cause less adverse events [RR 0.34, 95% CI (0.14-0.81), P = 0.01]. Acupuncture can reduce migraine episodes compared to sham one and can be an alternative and safe prophylactic treatment for conventional drugs therapy, but it should be further verified through more RCTs. Available studies suggested acupuncture was superior to sham acupuncture and conventional drugs in terms of responder rate as verified by TSA.