Meta-regression of treatments for metastatic colorectal cancer:Quantifying incremental benefit from 2000 to 2012

To evaluate the overall effectiveness of treatments for metastatic colorectal cancer, a meta-regression was undertaken in which randomized studies from 2000 to 2012 were evaluated and the temporal trend for both overall survival(OS) and progression-free survival(PFS) was determined. Our literature search was essentially based on Pub Med but information sources were scanned. Trials were included if a fluoropyrimidine regimen was given to at least one arm and information on PFS and OS was available. Medians for OS and PFS were our end-points. Covariates included temporal trend, arm allocation and Kirsten rat sarcoma status. In analyzing 130 treatment arms identified through our literature search, meta-regression showed an improvement with time for both OS(P < 0.001) and PFS(P < 0.001). The increase in median OS was from 14.9 mo in 2000 to 18.8 mo in 2012. Likewise, the improvement in PFS was from 5.7 to 8.1 mo. Multivariate analysis confirmed these findings. A post-hoc multivariate analysis was focused on patient arms treated with bevacizumab(n = 17) or without bevacizumab(n = 113); the multivariate-adjusted improvement attributable to bevacizumab was 1.66 mo for OS(P = 0.071) and 1.59 mo for PFS(P = 0.002). Overall, our results indicatethat OS and PFS have improved from 2000 to 2012 but the extent of this improvement is small and seems to have quite a questionable clinical relevance.

The Effectiveness of Non-Surgical Weight Management Interventions for Obesity in the UK: A Review and Meta-Regression Analysis

Background: Obesity is regarded as one of the most serious challenges public health faces in the 21st century for adults and children alike. Accordingly weight management interventions remain a public health priority aiming to reduce the burden of obesity and co-morbidities. Therefore this review aims to assess the effectiveness of non-surgical weight management interventions for obesity in the UK. Method: Thirty one databases were searched that identified 20 articles for inclusion. Articles were screened and quality scored using the “Effective Public Health Practice Project Quality Assessment Tool”. Meta-regression analysis (MRA) was undertaken on seven studies that allowed for effect size calculations. Results: In adult populations, lifestyle interventions that targeted both diet and physical activity, delivered in the private sector were most effective in reducing weight and/or BMI, and were more cost-effective. In children the most successful interventions mirrored adult interventions, but were family-orientated. MRA supported these findings. Most frequent intervention duration was 12 weeks. Discussion: The results provide evidence to support policy makers for the effective delivery of weight management interventions. Findings suggest that weight management interventions in the UK are effective in reducing weight and/or BMI for both children and adults. Interventions delivered in the private sector (e.g. Weight Watchers), targeting diet and physical activity levels, demonstrated the highest levels of effectiveness. However, compared to these models, NHS programmes are less well defined in the research literature and may not have been optimised. For children, effectiveness is improved by family-level programmes incorporating children and their parents.

Hepatitis C virus among blood donors and general population in Middle East and North Africa:Meta-analyses and meta-regressions

BACKGROUND Despite the Middle East and North Africa(MENA)Region reported to have the highest prevalence of hepatitis C virus(HCV)globally,HCV infection levels in the majority of MENA countries remain inadequately characterized.Blood donor data have been previously used as a proxy to assess levels and trends of HCV in the general population,however,it is unclear how comparable these populations are in MENA and whether blood donors provide an appropriate proxy.AIM To delineate HCV epidemiology among blood donors and the general population in the MENA.METHODS The data source was the systematically gathered MENA HCV Epidemiology Synthesis Project Database.Random-effects meta-analyses and meta-regressions were conducted.For comparison,analyses were conducted for Europe,utilizing the Hepatitis C Prevalence Database of the European Centre for Disease Prevention and Control.RESULTS One thousand two hundred and thirteen HCV antibody prevalence measures and 84 viremic rate measures were analyzed for MENA.Three hundred and seventyseven antibody prevalence measures were analyzed for Europe.In MENA,pooled mean prevalence was 1.58%[95%confidence interval(CI):1.48%–1.69%]among blood donors and 4.49%(95%CI:4.10%–4.90%)in the general population.In Europe,pooled prevalence was 0.11%(95%CI:0.10%–0.13%)among blood donors and 1.59%(95%CI:1.25%–1.97%)in the general population.Prevalence in the general population was 1.72-fold(95%CI:1.50–1.97)higher than that in blood donors in MENA,but it was 15.10-fold(95%CI:11.48–19.86)higher in Europe.Prevalence was declining at a rate of 4%per year in both MENA and Europe[adjusted risk ratio:0.96(95%CI:0.95–0.97)in MENA and 0.96(95%CI:0.92–0.99)in Europe].Pooled mean viremic rate in MENA was 76.29%(95%CI:67.64%–84.02%)among blood donors and 65.73%(95%CI:61.03%–70.29%)in the general population.CONCLUSION Blood donor data provide a useful proxy for HCV infection in the wider population in MENA,but not Europe,and could improve HCV burden estimations and assess progress toward HCV elimination by 2030.

Factors and Their Impact on Treatment Effect of Acupuncture in Different Outcomes:A Meta-Regression of Acupuncture Randomized Controlled Trials

Background:The effects of acupuncture have varied in different randomized controlled trials(RCTs),and there are many factors that influence treatment effect of acupuncture in different outcomes,with conflicting results.Objective:To identify factors and their impact on the treatment effect of acupuncture in different outcomes.Methods:Acupuncture RCTs were searched from 7 databases including Medline(Pub Med),Embase,Cochrane Central Register of Controlled Trials,China National Knowledge Infrastructure,Wanfang Database,VIP Database,and China Biology Medicine disc between January 1st,2015 and December 31st,2019.Eligible studies must compare acupuncture to no acupuncture,sham acupuncture,or waiting lists,and report at least 1patient-important outcome.A multi-level meta-regression was conducted using a 3-level robust mixed model and univariate analyses were performed for all independent variables,even those excluded from the multivariable model due to collinearities.We used thresholds of 0.2 and 0.4 for the difference of standardized mean differences(SMDs),categorising them as small(<0.2),moderate(0.2–0.4),or large(>0.4) effects.Results:The pain construct analysis involved 211 effect estimates from 153 studies and 14 independent variables.High-frequency acupuncture treatment sessions produced larger effects compared to low-frequency sessions [large magnitude,the difference of adjusted SMDs 0.46,95% confidence interval(CI) 0.07 to 0.84;P=0.02].The non-pain symptoms construct analysis comprised 323 effect estimates from 231 studies and 15 independent variables.Penetrating acupuncture showed moderately larger effects when compared to non-penetrating acupuncture(0.30,95% CI 0.06 to 0.53;P=0.01).The function construct analysis included 495 effect estimates from 274 studies and 14 independent variables.Penetrating acupuncture and the flexible acupuncture regimen showed moderately larger effects,compared to non-penetrating acupuncture and fixed regimen,respectively(0.40,95% CI 0 to 0.80;P=0.05;0.29,95% CI 0.06 to 0.53;P=0.01).Conclusions:High-frequency acupuncture sessions appear to be a more effective approach to managing painful symptoms.Penetrating acupuncture demonstrated greater effect in relieving nonpainful symptoms.Both penetrating acupuncture type and flexible acupuncture regimen were linked to significant treatment effects in function outcomes.Future studies should consider the factors that are significantly associated with the effects of acupuncture in patient-important outcomes.

Calcium requirements for Chinese adults by cross-sectional statistical analyses of calcium balance studies： an individual participant data and aggregate data meta-regression

Background Chinese dietary reference intakes for calcium are largely based on foreign studies. We undertook meta- regression to estimate calcium requirements for Chinese adults derived from calcium balance data in Chinese adults. Methods We searched PubMed, Cochrane CENTRAL, and SinoMed from inception to March 5, 2014, by using a structured search strategy. The bibliographies of any relevant papers and journals were also screened for potentially eligible studies. We extracted a standardized data set from studies in Chinese adults that reported calcium balance data. The relationship between calcium intake and output was examined by an individual participant data （IPD） and aggregate data （AD） meta-regression. Results We identified 11 metabolic studies in Chinese adults within 18-60 years of age. One hundred and forty-one IPD （n=35） expressed as mg/d, 127 IPD （n=32） expressed as mg.kg body wt-l-d-1, and 44 AD （n=132） expressed as mg/d were collected. The models predicted a neutral calcium balance （defined as calcium output （Y） equal to calcium intake （C）） at intakes of 460 mg/d （Y=0.60C＋183.98） and 8.27 mg.kg body wt-l.d-1 （Y=0.60C＋3.33） for IPD, or 409 mg/d （Y=0.66C＋139.00） for AD. Calcium requirements at upper intakes were higher than that at lower intakes in all these models. Conclusion Calcium requirement for Chinese adults 18-60 years of age approximately ranges between 400 mg/d and 500 mg/d when consuming traditional plant-based Chinese diets.

A meta-regression evaluating the effectiveness and prognostic factors of oral phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction

The effectiveness of phosphodiesterase type 5 inhibitors （PDE5-1s） for erectile dysfunction （ED） varies considerably among trials, but available studies investigating the factors that affect the effectiveness are few and findings are not consistent. A systematic search was performed in PubMed, Cochrane Library, and EMBASE to identify randomized controlled trials comparing PDE5-1s with placebo for the treatment of ED. The methodological quality of included studies was assessed by the Cochrane Collaboration＇s tool for assessing risk of bias. The associations between prespecified study-level factors and effectiveness were tested by a random effects meta-regression model. This study included 93 trials with 26 139 patients. When all PDE5-1s were grouped together, Caucasian ethnicity was associated with 15.636% （95% confidence interval [CI]： 0.858% to 32.579%） increase in risk ratio （RR） for Global Assessment Questionnaire question-1 （GAQ-1）, and 1.473 （95% CI： 0.406 to 2.338） score increase in mean difference （MD） for posttreatment International Index of Erectile Function-Erectile Function domain score （IIEF-EF）, compared to Asian ethnicity. A one-score increase in baseline IIEF-EF was associated with -5.635% （95% CI： -9.120% to -2.017%） reduction in RR for GAQ-1, and -0.229 （95% CI： -0.425 to -0.042） score decrease in MD for posttreatment IIEF-EF. In conclusion, PDE5-1s are more effective in Caucasians than Asians, and in patients with more severe ED.

应用集萃法分析海河流域滨海湿地退化成因

近年来,海河流域滨海湿地退化现象严重,为科学合理地对其实施恢复和保护,须探究湿地退化的影响因素,辨识主要退化成因。广泛收集关于海河流域滨海湿地退化评价的实证研究案例,采用集萃法中的Meta-regression模型,对湿地退化因素及其影响程度进行了综合性的对比与分析。结合57个研究案例,提取525个观察值,筛选出自然和人为两类共9种退化影响因素,通过模型拟合得到各因素对湿地退化的影响程度。模型结果显示:海河流域滨海湿地的退化受到人为与自然因素的双重影响。人为因素中,水资源开采(1.512)、水质污染(0.813)、水产养殖(0.593)、围垦与建设占用(0.436)对湿地退化均为正效应,政策法规(-1.202)呈负效应;自然因素中,降水量(-0.788)与河流径流量(-1.176)对湿地退化呈显著负效应,气温(0.037)与生物多样性损失(0.072)呈较弱的正效应。海河流域滨海湿地的退化影响因素按照影响程度大小排序为:水资源开采>政策法规>河流径流量>水质污染>降水量>水产养殖>围垦与建设占用>生物多样性损失>气温,湿地退化的核心成因在于湿地水资源的补给与存蓄受到了威胁。据此建议,海河流域滨海湿地的恢复与保护应优先解决水源问题,同时应加强相关政策、规划和法律的制定与执行。

Hydrocephalus after subarachnoid hemorrhage:A metaanalytic comparison of aneurysm treatments

AIM: To compare two treatments for ruptured cerebral aneurysm with reference to the relative risk of developing hydrocephalus.METHODS: We reviewed the English language literature on the risk of developing hydrocephalus after aneurysm treatment.Data were divided by type of study(randomized controlled trial,cohort trial,nonrandomized comparison,prospectively- and retrospectively-collected observational study).They were also divided by type of aneurysm treatment(microvascular- clipping,or endovascular- coiling).Additional predictive variables collected for each publication were average age,gender distribution,measures of hemorrhage volume and subarachnoid hemorrhage severity,aneurysm locations,time to treatment,duration of follow-up and date of publication.We employed meta-analysis to calculate pooled risk ratios of developing hydrocephalus in cases receiving aneurysm clipping vs those receiving coiling.Meta-regression was used to correct pooled results for covariates.RESULTS: Because indications for the two treatments are different,there is little clinical equipoise for treating most cases.The single randomized,controlled trial dealt with a small subset of ruptured aneurysms.Neither this nor pooled values from other studies which compared the two treatments had the power to demonstrate significant differences between the two treatments.Nor was there an apparent difference when observational data were meta-analytically pooled.However,when meta-regression was used to correct for predictive variables known to differ between the two treatment groups,a highly-significant difference appeared.Coiling is used more commonly in older,sicker patients with aneurysms in certain locations.These cases are more likely to develop hydrocephalus.When corrected for these covariates,the risk of hydrocephalus was found to be significantly lower in coiled vs clipped cases(P = 0.014).CONCLUSION: Pooled observational data were necessary to demonstrate that coiling ruptured cerebral aneurysms is associated with a lower risk of developing hydrocephalus than is clipping.

Effectiveness of digital psychotherapeutic intervention among perinatal women:A systematic review and meta-analysis of randomized controlled trials

BACKGROUND The perinatal period is a challenging time of substantial emotional,physiological,social,and relational changes.Depression,anxiety,and stress symptoms are common,and co-exist in the perinatal period.Digital technology continues to grow at an unprecedented pace with wide application,including psychotherapeutic intervention.A growing number of meta-analyses supported the application of digital psychotherapeutic intervention across different populations,but relatively few meta-and meta-regression analyses have concentrated on perinatal women.AIM To evaluate the effectiveness of digital psychotherapeutic intervention on improving psychological outcomes among perinatal women and identify its essential features.METHODS Randomized controlled trials(RCTs)were obtained from eight databases,including Cumulative Index to Nursing and Allied Health Literature,Cochrane Library,Embase,Scopus,PsycINFO,PubMed,Web of Science,and ProQuest Dissertation and Theses from inception up until November 24,2020.Comprehensive Meta-analysis 3.0 software was used to conduct meta-and metaregression analyses.The Cochrane risk-of-bias tool and the Grading of the Recommendation,Assessment,Development,and Evaluation system were adopted to assess the individual and overall qualities of the evidence,respectively.RESULTS A total of 25 RCTs that included 3239 women were identified.Meta-analyses revealed that intervention significantly improved depression(Hedges’s g=0.49),anxiety(g=0.25),and stress(g=0.47)symptoms compared to the control.Subgroup analyses demonstrated that a website platform with≥eight therapistguided sessions using the theoretical principle of cognitive behavioral therapy was more effective than other treatments in improving depression symptoms in postnatal women.Meta-regression analyses observed that the age of perinatal women and the type of psychotherapy also had statistically significant effects on depression symptoms.Egger’s regression asymmetry tests suggested that no publication biases occurred,but the overall quality of the evidence was very low.CONCLUSION This review suggests that digital psychotherapeutic intervention may be a potential solution to reduce psychological problems in perinatal women.Further high-quality RCTs with large sample sizes are needed.

What is the purpose of launching World Journal of Meta-Analysis?

The exponential growth of scientific evidence(i.e., primary research) and the ongoing development of methods to summarize such evidence, such as meta-analyses and mixed treatment comparisons(i.e., secondary research), make the worldwide dissemination of highquality meta-analyses and pertinent articles a key scientific priority. The World Journal of Meta-Analysis will apply an electronic open access publishing approach combined with a timely and thorough peer-review of submitted manuscripts, weighing more on quality than priority, in order to improve the dissemination of systematic reviews and meta-analyses, as well as novelties and advancements in methods related to them, focusing on clinical medicine, but spanning all biomedical, epidemiological, and psychological research fields.

Expertise and Ideology in Statistical Evaluation of Circumcision for Protection against HIV Infection

Aim: To critically evaluate data and arguments by Van Howe defending his stance opposing male circumcision (MC), in particular his meta-regression analyses evaluating the ability of MC to reduce HIV infection risk in heterosexual populations within and outside Africa. Methods: We performed metaregression analysis of log odds of HIV infection between uncircumcised and circumcised men using a single covariate (MC prevalence) in the meta-regression model involving the metareg package in STATA 13 for 103 populations worldwide and for populations within Africa. The meta-regression of log odds and MC prevalence was fitted to a line, as were empirical Bayes estimates resulting from post-estimation. Results: Our critical evaluation of Van Howe’s arguments attempting to undermine the scientific evidence in support of the benefits of MC in protection of men against HIV during heterosexual intercourse, as well as other infections and conditions, together with his use of statistics to support his beliefs, revealed serious flaws, obfuscation and missing data. We therefore performed our own meta-regression analysis using a trivariate model. Doing so revealed that for MC prevalences of 50%, 75% and 100% for general populations within Africa, odds ratios for HIV risk in uncircumcised vs. circumcised men were 1.35, 1.58 and 1.85, respectively. Our meta-regression analysis of data for all countries yielded similar findings. For a general population outside Africa with 100% MC prevalence, OR was 1.5. Van Howe failed to acknowledge that since MC prevalence in US whites (91%) and blacks (76%) exceeds 75% his results support MC having a protective effect in those population groups. Conclusions: The protective effect of MC against HIV infection during heterosexual intercourse applies to populations both within and outside Africa. The debate engineered by MC opponents, and led by Van Howe, now appears to have run its course. The scientific evidence has prevailed.

Assessment of Lactational Performance in Dairy Cows Receiving a Rumen Protected B Vitamin Blend during Lactation: Part 2: A Regression Analysis of 50 Studies

A previous series of meta-analyses demonstrated that a protected blend of B vitamins (RPBV: folic acid, B12, pyridoxine, pantothenic acid, and biotin;Jefo, St. Hyacinthe, QC, Canada) improved milk fat and protein yield, with variation in the extent of the response. These results represent additional analyses of the same dataset to determine if the degree of response to RPVB on milk, fat and protein yield might be related to the level of production, lactation number, or days in milk (DIM). Results from 50 on-farm switchback trials conducted in 7 countries between 2005 and 2015 were included in the analysis. All herds participated in monthly milk recording services, and all were Holstein herds. A total of 6483 cows, averaging 163 DIM on the first test date, participated in the studies. Data were analyzed using regression models that accounted for the effects of trial, period, days in milk (DIM) and lactation number on milk and component yield. Milk yield and fat yield increased with B vitamin inclusion, and the extent of change was determined to increase with lactation number (P < 0.05). Protein yield increased with the RPBV and was unaffected by lactation number (P < 0.05) Responses to the RPBV occurred throughout lactation but were found to decline with DIM for milk, fat and protein yield. The global equation revealed that milk yield with the rumen-protected B vitamin blend = 4.05 + [0.917 × control milk] - [0.0063 × DIM] + [0.246 × Lactation number] (R2 = 0.798) The use of regression models allows changes in milk, fat and protein yields with the rumen-protected B vitamin blend to be more accurately predicted.