Stratified Meta-analysis Research Articles

The efficacy of vaccination against respiratory syncytial virus across priority population subgroups

Abstract Background Respiratory syncytial virus (RSV) has recently become a vaccine-preventable disease as two vaccines have been approved for use and a third one is likely to become available by the end of the year. National Immunization Technical Advisory Groups as well as scientific societies across the world have issued recommendations on RSV vaccination that differ in respect to the identification of the target group. The latter has been identified in respect to age or underlying medical conditions mostly according to epidemiological data. In order to strengthen the evidence basis for future decisions, we performed a stratified meta-analysis of efficacy data considering all the three RSV vaccines currently or soon available. Methods We searched Randomized Controlled Trials (RCTs) assessing the efficacy of RSV vaccines in terms of reduction of RSV-related Lower Respiratory Tract Infection (LRTI). The research was conducted on PubMed and clinicaltrial.gov. The extraction of relevant data was stratified by pre-defined age groups (60-69, 70-79, 80+) and presence of underlying conditions increasing the risk for RSV. Results Three RCTs, one for each of the three vaccines, were considered for the quantitative analysis. Considering the overall 60+ population, the efficacy of RSV vaccines was 78% (95%CI 76-86%) in preventing LRTI. Considering the different age groups (60-69, 70-79, 80+), efficacy was respectively 72% (95%CI 53-84%), 90% (95%CI 66-97%) and 57% (95%CI 0-93%). The efficacy in healthy people and those with at least one underlying condition was similar, namely 77% (95%CI 60-87%) and 78% (95%CI 50-90%). Conclusions The available evidence shows the efficacy of RSV vaccines in reducing LRTI with no differences across different priority groups. Further studies may contribute to better understanding if the efficacy may change according to individual characteristics, that could be highly relevant in the decision-making process. Key messages • The available evidence from RCTs shows the efficacy of RSV vaccines in reducing LRTI with no differences across different priority groups. • National recommendations on RSV vaccination can be further informed for future studies investigating RSV vaccines efficacy across different subgroups.

Extended Postoperative Antibiotic Prophylaxis Is Associated with No Clinical Value and Higher Projected Cost Following Adult Spinal Surgery: A Stratified Meta-Analysis and Probability-Based Cost Projections.

» We aimed to determine the cost-effectiveness of different protocols of extended postoperative antibiotic prophylaxis (E-PAP) following adult spinal surgery.» Both stratified (randomized controlled trials only) and nonstratified (all studies) analyses demonstrated that E-PAP has no significant value in reducing the rate of surgical site infection (SSI), deep SSI, or superficial SSI.» Notably, the E-PAP protocols were associated with a significant increase in the length of hospital stay, resulting in an additional expenditure of $244.4 per episode for the E-PAP 72 hours protocol compared with PAP 24 hours and $309.8 per episode for the E-PAP >48 hours protocol compared with PAP <48 hours.» E-PAP does not demonstrate any significant reduction in the rate of SSIs following spine surgery. However, these extended protocols were significantly associated with an increase in the length of hospital stay and higher overall projected costs. Level of Evidence: Level I. See Instructions for Authors for a complete description of levels of evidence.

Suicide rates among physicians compared with the general population in studies from 20 countries: gender stratified systematic review and meta-analysis

ObjectivesTo estimate age standardised suicide rate ratios in male and female physicians compared with the general population, and to examine heterogeneity across study results.DesignSystematic review and meta-analysis.Data sourcesStudies published between...

Using a Leroux-prior-based conditional autoregression-based strategy to map the short-term association between temperature and bacillary dysentery and its attributable burden in China.

In China, bacillary dysentery (BD) is the third most frequently reported infectious disease, with the greatest annual incidence rate of 38.03 cases per 10,000 person-years. It is well acknowledged that temperature is associated with BD and the previous studies of temperature-BD association in different provinces of China present a considerable heterogeneity, which may lead to an inaccurate estimation for a region-specific association and incorrect attributable burdens. Meanwhile, the common methods for multi-city studies, such as stratified strategy and meta-analysis, have their own limitations in handling the heterogeneity. Therefore, it is necessary to adopt an appropriate method considering the spatial autocorrelation to accurately characterize the spatial distribution of temperature-BD association and obtain its attributable burden in 31 provinces of China. A novel three-stage strategy was adopted. In the first stage, we used the generalized additive model (GAM) model to independently estimate the province-specific association between monthly average temperature (MAT) and BD. In the second stage, the Leroux-prior-based conditional autoregression (LCAR) was used to spatially smooth the association and characterize its spatial distribution. In the third stage, we calculate the attribute BD cases based on a more accurate estimation of association. The smoothed association curves generally show a higher relative risk with a higher MAT, but some of them have an inverted "V" shape. Meanwhile, the spatial distribution of association indicates that western provinces have a higher relative risk of MAT than eastern provinces with 0.695 and 0.645 on average, respectively. The maximum and minimum total attributable number of cases are 224,257 in Beijing and 88,906 in Hainan, respectively. The average values of each province in the eastern, western, and central areas are approximately 40,991, 42,025, and 26,947, respectively. Based on the LCAR-based three-stage strategy, we can obtain a more accurate spatial distribution of temperature-BD association and attributable BD cases. Furthermore, the results can help relevant institutions to prevent and control the epidemic of BD efficiently.

Triangulation of epidemiological evidence and risk of bias evaluation: A proposed framework and applied example using formaldehyde exposure and risk of myeloid leukemias

Evidence triangulation may help identify the impact of study design elements on study findings and to tease out biased results when evaluating potential causal relationships; however, methods for triangulating epidemiologic evidence are evolving and have not been standardized. Building upon key principles of epidemiologic evidence triangulation and risk of bias assessment, and responding to the National Academies of Sciences, Engineering, and Medicine (NASEM) call for applied triangulation examples, the objective of this manuscript is to propose a triangulation framework and to apply it as an illustrative example to epidemiologic studies examining the possible relationship between occupational formaldehyde exposure and risk of myeloid leukemias (ML) including acute (AML) and chronic (CML) types.A nine-component triangulation framework for epidemiological evidence was developed incorporating study quality and ROB guidance from various federal health agencies (i.e., US EPA TSCA and NTP OHAT). Several components of the triangulation framework also drew from widely used epidemiological analytic tools such as stratified meta-analysis and sensitivity analysis. Regarding the applied example, fourteen studies were identified and assessed using the following primary study quality domains to explore potential key sources of bias: 1) study design and analysis; 2) study participation; 3) exposure assessment; 4) outcome assessment; and 5) potential confounding. Across studies, methodological limitations possibly contributing to biased results were observed within most domains. Interestingly, results from one study – often providing the largest and least-precise relative risk estimates, likely reflecting study biases, deviated from most primary study findings indicating no such associations. Triangulation of epidemiological evidence appears to be helpful in exploring inconsistent results for the identification of study results possibly reflecting various biases. Nonetheless, triangulation methodologies require additional development and application to real-world examples to enhance objectivity and reproducibility.

Does intra-oral scan improve the impression accuracy of full-arch implant-supported prostheses: A systematic review and meta-analysis.

The present study aimed to systematically review the studies comparing the accuracy of intraoral scan (IOS) and conventional implant impressions (CI) in completely edentulous patients. Electronic searches were performed in PubMed, Embase and Cochrane CENTRAL up to December 1, 2023. Clinical studies and in vitro studies reporting the accuracy of digital full arch impressions were included. The primary outcome is the 3-dimensional deviations between the study reference models. A risk of bias assessment was performed for clinical studies. A stratified meta-analysis and a single-armed meta-analysis were conducted. A total of 49 studies were included, with 8 clinical studies and 41 in vitro studies. For comparison between IOS and conventional impressions, studies were categorized into two groups based on the different measurement methods employed: RMS and CMM. In studies using RMS, the result favored the IOS in the unparalleled situation with the mean difference of -99.29 μm (95% CI: [-141.38, -57.19], I2 = 81%), while the result was opposite with the mean difference of 13.62 μm (95% CI: [10.97, 16.28], I2 = 26%) when implants were paralleled. For different brands of IOS, the accuracy ranged from 76.11 μm (95% CI: [42.36, 109.86]) to 158.63 μm (95% CI: [-14.68, 331.93]). Accuracy of intraoral scan is clinically acceptable in edentulous arches, especially for unparalleled implants. More clinical studies are needed to verify the present finding.

Global epidemiology of type 2 diabetes in patients with NAFLD or MAFLD: a systematic review and meta-analysis

BackgroundNon-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) shares common pathophysiological mechanisms with type 2 diabetes, making them significant risk factors for type 2 diabetes. The present study aimed to assess the epidemiological feature of type 2 diabetes in patients with NAFLD or MAFLD at global levels.MethodsPublished studies were searched for terms that included type 2 diabetes, and NAFLD or MAFLD using PubMed, EMBASE, MEDLINE, and Web of Science databases from their inception to December 2022. The pooled global and regional prevalence and incidence density of type 2 diabetes in patients with NAFLD or MAFLD were evaluated using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression.ResultsA total of 395 studies (6,878,568 participants with NAFLD; 1,172,637 participants with MAFLD) from 40 countries or areas were included in the meta-analysis. The pooled prevalence of type 2 diabetes among NAFLD or MAFLD patients was 28.3% (95% confidence interval 25.2–31.6%) and 26.2% (23.9–28.6%) globally. The incidence density of type 2 diabetes in NAFLD or MAFLD patients was 24.6 per 1000-person year (20.7 to 29.2) and 26.9 per 1000-person year (7.3 to 44.4), respectively.ConclusionsThe present study describes the global prevalence and incidence of type 2 diabetes in patients with NAFLD or MAFLD. The study findings serve as a valuable resource to assess the global clinical and economic impact of type 2 diabetes in patients with NAFLD or MAFLD.

Body mass index stratified meta-analysis of genome-wide association studies of polycystic ovary syndrome in women of European ancestry

BackgroundPolycystic ovary syndrome (PCOS) is a complex multifactorial disorder with a substantial genetic component. However, the clinical manifestations of PCOS are heterogeneous with notable differences between lean and obese women, implying a different pathophysiology manifesting in differential body mass index (BMI). We performed a meta-analysis of genome-wide association study (GWAS) data from six well-characterised cohorts, using a case–control study design stratified by BMI, aiming to identify genetic variants associated with lean and overweight/obese PCOS subtypes.ResultsThe study comprised 254,588 women (5,937 cases and 248,651 controls) from individual studies performed in Australia, Estonia, Finland, the Netherlands and United States of America, and separated according to three BMI stratifications (lean, overweight and obese). Genome-wide association analyses were performed for each stratification within each cohort, with the data for each BMI group meta-analysed using METAL software. Almost half of the total study population (47%, n = 119,584) were of lean BMI (≤ 25 kg/m2). Two genome-wide significant loci were identified for lean PCOS, led by rs12000707 within DENND1A (P = 1.55 × 10–12) and rs2228260 within XBP1 (P = 3.68 × 10–8). One additional locus, LINC02905, was highlighted as significantly associated with lean PCOS through gene-based analyses (P = 1.76 × 10–6). There were no significant loci observed for the overweight or obese sub-strata when analysed separately, however, when these strata were combined, an association signal led by rs569675099 within DENND1A reached genome-wide significance (P = 3.22 × 10–9) and a gene-based association was identified with ERBB4 (P = 1.59 × 10–6). Nineteen of 28 signals identified in previous GWAS, were replicated with consistent allelic effect in the lean stratum. There were less replicated signals in the overweight and obese groups, and only 4 SNPs were replicated in each of the three BMI strata.ConclusionsGenetic variation at the XBP1, LINC02905 and ERBB4 loci were associated with PCOS within unique BMI strata, while DENND1A demonstrated associations across multiple strata, providing evidence of both distinct and shared genetic features between lean and overweight/obese PCOS-affected women. This study demonstrated that PCOS-affected women with contrasting body weight are not only phenotypically distinct but also show variation in genetic architecture; lean PCOS women typically display elevated gonadotrophin ratios, lower insulin resistance, higher androgen levels, including adrenal androgens, and more favourable lipid profiles. Overall, these findings add to the growing body of evidence supporting a genetic basis for PCOS as well as differences in genetic patterns relevant to PCOS BMI-subtype.

Efficacy of different courses of acupuncture for diarrhea irritable bowel syndrome: A protocol for systematic review and meta-analysis

Irritable Bowel Syndrome (IBS) is the most common functional gastrointestinal disorder. As one of the most common subtypes of IBS, IBS-D can impair the patients’ quality of life (QOL) and decreased work productivity. Acupuncture may be a potential treatment for patients with IBS-D. However, the treatment course of acupuncture was diverse. It is unclear what is the optimal acupuncture treatment courses for acupuncture. The efficacy and safety of different courses of acupuncture for IBS-D have not been systematically evaluated yet. The purpose of this study is to evaluate effectiveness of Acupuncture of different courses in the treatment of IBS-D and provide sufficient evidence for clinical recommendations for IBS-D. We will follow the Preferred reporting items for systematic reviews and meta-analysis protocols (PRISMA-P) guidelines to design the protocol of a systematic review and meta-analysis. This systematic review is registered in PROSPERO (CRD42023418846). We will include randomized controlled trials (RCTs) in which the efficacy of Acupuncture is compared with a placebo, sham acupuncture or Pinaverium bromide in the treatment of IBS-D with no language restrictions. The outcomes of interest will be efficiency rate and the Symptoms Severity Score. RCTs will be searched in the electronic database and Clinical Trials Registry Platform from inception to April 2023. Two independent reviewers will independently select studies, extract data from the included studies, and assess the risk of bias using the Cochrane tool. We will choose a random or fixed-effects model based on the heterogeneity index. We will use the relative risk and mean difference to estimate data with 95% CI. A stratified meta-analysis was conducted to evaluate the effect of different treatment courses of Acupuncture: 2weeks, 4weeks(or 1 months), 6 weeks, and 8 weeks. If there is significant clinical and methodological heterogeneity, we will look for the reason for heterogeneity and perform a subgroup analysis. According to the Grading of Recommendations Assessment, Development and Evaluation (GRADE), we will evaluate the evidence quality and provide the recommendation’s strength.

Neuraxial versus general anesthesia in elderly patients undergoing hip fracture surgery and the incidence of postoperative delirium: a systematic review and stratified meta-analysis

BackgroundEvidence-based effect of anesthetic regimens on postoperative delirium (POD) incidence after hip fracture surgery is still debated. Randomized trials have reported inconsistent contradictory results largely attributed to small sample size, use of outdated drugs and techniques, and inconsistent definitions of adverse outcomes. The primary objective of this meta-analysis was to investigate the impact of different anesthesia regimens on POD, cognitive impairment, and associated complications including mortality, duration of hospital stay, and rehabilitation capacity.MethodsWe identified randomized controlled trials (RCTs) published from 2000 to December 2021, in English and non-English language, comparing the effect of neuraxial anesthesia (NA) versus general anesthesia (GA) in elderly patients undergoing hip fracture surgery, from PubMed, EMBASE, Google Scholar, Web of Science and the Cochrane Library database. They were included if POD incidence, cognitive impairment, mortality, duration of hospital stay, or rehabilitation capacity were reported as at least one of the outcomes. Study protocols, case reports, audits, editorials, commentaries, conference reports, and abstracts were excluded. Two investigators (KYC and TXY) independently screened studies for inclusion and performed data extraction. The risk of bias was assessed using the Cochrane Collaboration risk-of-bias tool. The quality of the evidence for each outcome according to the GRADE working group criteria. The odds ratio (OR) and 95% confidence intervals (CI) were calculated to assess the pooled data.ResultsA total of 10 RCTs with 3968 patients were included in the present analysis. No significant differences were found in the incidence of POD comparing NA vs GA [OR 1.10, 95% CI (0.89 to 1.37)], with or without including patients with a pre-existing condition of dementia or delirium, POD incidence from postoperative day 2–7 [OR 0.31, 95% CI (0.06 to -1.63)], in mini-mental state examination (MMSE) score [OR 0.07, 95% CI (-0.22 to 0.36)], or other neuropsychological test results. NA appeared to have a shorter duration of hospital stay, especially in patients without pre-existing dementia or delirium, however the observed effect did not reach statistical significance [OR -0.23, 95% CI (-0.46 to 0.01)]. There was no difference in other outcomes, including postoperative pain control, discharge to same preadmission residence [OR 1.05, 95% CI (0.85 to 1.31)], in-hospital mortality [OR 1.98, 95% CI (0.20 to 19.25)], 30-day [OR 1.03, 95% CI (0.47 to 2.25)] or 90-day mortality [OR 1.08, 95% CI (0.53–2.24)].ConclusionsNo significant differences were detected in incidence of POD, nor in other delirium-related outcomes between NA and GA groups and in subgroup analyses. NA appeared to be associated with a shorter hospital stay, especially in patients without pre-existing dementia, but the observed effect did not reach statistical significance. Further larger prospective randomized trials investigating POD incidence and its duration and addressing long-term clinical outcomes are indicated to rule out important differences between different methods of anesthesia for hip surgery.Trial registration10.17605/OSF.IO/3DJ6C.

Effect of Early Erythropoietin on Retinopathy of Prematurity: A Stratified Meta-Analysis

Background: Recombinant human erythropoietin (rhEPO) lost its role in minimizing red blood cell transfusion in very preterm infants after it had been associated with severe retinopathy of prematurity (ROP). Previous systematic reviews did not stratify ROP by gestation and birth weight (BW). Objectives: The aim of this study was to investigate the effect of early prophylactic rhEPO on ROP in a stratified meta-analysis of randomized controlled trials (RCTs). Methods: The databases EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched in January 2022 and complemented by citation searching. RCTs comparing early rhEPO treatment with no treatment or placebo were selected if they were published in a peer-reviewed journal and reported ROP outcomes. Previously unpublished data were requested from the study authors to allow stratified analyses by gestational age (GA) and BW. Data were extracted and analyzed using the standard methods of the Cochrane Neonatal Review Group. Pre-specified outcomes were “ROP stage ≥3” (primary outcome) and “any ROP.” Results: Fourteen RCTs, comprising 2,040 infants of <29 weeks of GA, were included for meta-analysis. Data syntheses showed no effects of rhEPO on ROP stage ≥3 or on any ROP, neither in infants of <29 weeks GA, nor in infants of <1,000 g BW, nor in any GA strata. The risk ratio (95% confidence interval) for ROP stage ≥3 in infants of <29 weeks of GA was 1.13 (0.84, 1.53), p = 0.41 (quality of evidence: moderate). Conclusions: The present meta-analysis detected no effects of early rhEPO on ROP in any comparison, but most stratified analyses were limited by low statistical power.

Prevalence of vitamin D deficiency in South America: a systematic review and meta-analysis.

Vitamin D deficiency is considered a global public health issue, even in low-latitude countries where there is abundant sunlight radiation. Nevertheless, the prevalence of vitamin D insufficiency and deficiency in the South American continent has not been well characterized. The aim of this review was to estimate the prevalence of vitamin D deficiency (25-hydroxy-calciferol < 20 ng/mL) in South American populations. Seven electronic databases (MEDLINE, Web of Science, Embase, Biblioteca Virtual de Saúde, SciELO, Scopus, and Google Scholar) were searched systematically for observational studies published before July 1, 2021, and reporting vitamin D status of healthy adults in South America. Data were extracted using a standardized form. Risk of bias was assessed by the Joanna Briggs Institute Critical Appraisal Instrument for Studies Reporting Prevalence. All steps were conducted independently by two authors. Data were pooled using a random-effects model. Stratified meta-analysis and meta-regression were conducted (R software). Of 9460 articles identified, 96 studies with a total of 227 758 participants were included. The overall prevalence of vitamin D deficiency was 34.76% (79 studies; 95%CI, 29.68-40.21; I2 = 99%). There were significant differences in prevalence rates related to age, sex, country, latitude, season, and year of publication. The prevalence of vitamin D deficiency is unexpectedly elevated in South American populations. Public health strategies should include efforts to prevent, detect, and treat vitamin D deficiency. PROSPERO registration number CRD42020169439.

Exercise Training in Pulmonary Hypertension: AN UPDATED SYSTEMATIC REVIEW WITH META-ANALYSIS.

Given that previous reviews on exercise training in pulmonary hypertension (PH) were largely based on a small number of randomized controlled trials (RCT), their conclusions are subject to bias. This review sought to identify the impact of exercise training on functional capacity and health-related quality of life (HRQoL) in PH using advanced statistical approaches such as meta-analysis by stratification according to study design. Five databases were searched from January 2015 to April 2020 to update a previous review. Included articles had data extracted, risk of bias (ROB) assessed, and quality rating performed. Data were analyzed using meta-analysis with a random-effects model for 6-min walk test (6MWT) distance and HRQoL. Heterogeneity was explored using stratified meta-analysis, within patient correlation and meta-regression. A total of 28 studies (11 RCT, 12 pre-/post-studies, 2 two-group non-RCT, and three case series) consisting of 1264 patients were included. Meta-analysis of six RCT demonstrated an improved 6MWT distance by 49.5 m (95% CI, 27.2-71.8: I2 = 73%; 254 participants; low-moderate ROB) with a low correlation coefficient of 0.34, while the 12 pre-/post-non-RCT showed an improvement of 68.69 m (95% CI, 50.50-86.69: I2 = 36%; 784 participants; high ROB) along with improvements in V˙ o2peak (weighted mean difference [WMD] = 3.03 mL/kg/min, 95% CI, 2.17-3.90: I2 = 0%, P = .82), and HRQoL (WMD = 2.74: 95% CI, -0.82 to 6.30). Metaregression showed that the benefit of exercise on 6MWT distance did not significantly vary across the trial study characteristics. This updated review identified an additional body of evidence supporting the efficacy of exercise training on 6MWT distance and HRQoL in stable PH patients. These benefits appeared to be consistent across models of delivery.

Three-Dimensional Accuracy and Stability of Personalized Implants in Orthognathic Surgery: A Systematic Review and a Meta-Analysis.

This systematic review aimed to determine the accuracy/stability of patient-specific osteosynthesis (PSI) in orthognathic surgery according to three-dimensional (3D) outcome analysis and in comparison to conventional osteosynthesis and computer-aided designed and manufactured (CAD/CAM) splints or wafers. The PRISMA guidelines were followed and six academic databases and Google Scholar were searched. Records reporting 3D accuracy/stability measurements of bony segments fixated with PSI were included. Of 485 initial records, 21 met the eligibility (566 subjects), nine of which also qualified for a meta-analysis (164 subjects). Six studies had a high risk of bias (29%), and the rest were of low or moderate risk. Procedures comprised either single-piece or segmental Le Fort I and/or mandibular osteotomy and/or genioplasty. A stratified meta-analysis including 115 subjects with single-piece Le Fort I PSI showed that the largest absolute mean deviations were 0.5 mm antero-posteriorly and 0.65° in pitch. PSIs were up to 0.85 mm and 2.35° more accurate than conventional osteosynthesis with CAD/CAM splint or wafer (p &lt; 0.0001). However, the clinical relevance of the improved accuracy has not been shown. The literature on PSI for multi-piece Le Fort I, mandibular osteotomies and genioplasty procedure is characterized by high methodological heterogeneity and a lack of randomized controlled trials. The literature is lacking on the 3D stability of bony segments fixated with PSI.

Monitoring anti-Xa Levels to Optimize Low-Molecular-Weight-Heparin Thromboprophylaxis in High-Risk Hospitalized Patients: A Stratified Meta-Analysis.

It is uncertain whether monitoring or targeting anti-Xa levels is necessary when using low-molecular-weight-heparin (LMWH) to prevent venous thromboembolism (VTE). This stratified meta-analysis assessed whether monitoring trough or peak anti-Xa levels with LMWH dosing would reduce risk of VTE. Twelve non-randomized studies involving 3604 hospitalized patients met the inclusion criteria and were subject to meta-analysis. Eight studies assessed the association between VTE and peak anti-Xa levels (between .2 and .5 IU/ml) and four studies assessed the benefits of targeting the trough anti-Xa levels (>.1 IU/ml). Achieving an adequate peak or trough anti-Xa level was associated with a reduced risk of VTE (random-effects model odds ratio [OR] .52, 95% confidence interval [CI] .34-.77; P = .001, I2 = 30% and P-value for heterogeneity = .171) compared with using a fixed standard dose of LMWH. Targeting the trough level (OR .40, 95%CI 0.22-.75, P = .004) appeared to be more effective than targeting the peak level (OR .62, 95%CI 0.37-1.03, P = .066), although a formal interaction analysis did not confirm they were statistically different (ratio of ORs = 1.52, 95%CI 0.68-3.40; z score = 1.03, P = .306). Targeting a higher anti-Xa level did not appear to increase the risk of bleeding or transfusion (OR 1.20, 95%CI 0.46-3.17, P = .707).

Letter to the editor regarding the article by Elhage et al.: "Closed-incision negative pressure therapy at -125 mmHg significantly reduces surgical site complications following total hip and knee arthroplasties: A stratified meta-analysis of randomized controlled trials".

Letter to the editor regarding the article by Elhage et al.: "Closed-incision negative pressure therapy at -125 mmHg significantly reduces surgical site complications following total hip and knee arthroplasties: A stratified meta-analysis of randomized controlled trials".

Association between Retinol-Binding Protein 4 Levels and Preeclampsia: A Systematic Review and Meta-Analysis.

Retinol-binding protein 4 (RBP4) is claimed to be associated with the development of preeclampsia, yet the reports are inconclusive. This systematic review and meta-analysis aimed to assess the association between RBP4 levels and preeclampsia. The PubMed, Google Scholar and ScienceDirect databases were searched for studies that investigated RBP4 levels in preeclampsia patients and compared them with normal controls. The meta-analysis was conducted by calculating the standardized mean difference (SMD) of RBP4 between cases and controls. The meta package with the R software was used to perform all statistical analysis. A total of 13 studies, comprising 569 cases and 1411 controls, met the inclusion criteria and were thus included in the meta-analysis. According to the random effect model, the SMD of RBP4 was significantly higher in women with preeclampsia compared with normal controls [SMD of RBP4: 0.55 ng/mL; 95% CI (0.06; 1.05); p = 0.028; I2 = 89%]. Likewise, the stratified meta-analysis showed the same pattern in the studies which measured RBP4 levels in the third trimester, as well as in the studies that investigated severe preeclampsia. Meta-regression did not identify any factor that significantly affected the overall estimate. There was no evidence of reporting bias (Egger's test; t = 0.43; p = 0.587). This meta-analysis with high heterogeneity showed that higher levels of RBP4 were associated with preeclampsia risk. More longitudinal studies spanning the three trimester periods are needed to clarify the association of RBP4 and its dynamics in preeclampsia cases throughout pregnancy.

Second primary malignancies in patients with haematological cancers treated with lenalidomide: a systematic review and meta-analysis

Lenalidomide has been standard therapy for multiple myeloma and other haematological malignancies for more than a decade. Previous meta-analyses identified an association between lenalidomide and second primary malignancies (SPM) in patients with multiple myeloma. However, newer randomised controlled trials using lenalidomide for other indications have not reported an increased incidence of SPM. The aim of this study was to investigate the risk of developing SPM with lenalidomide use in all disease settings. We did a systematic review of randomised controlled trials that reported SPM in patients treated with lenalidomide. PubMed, Embase, CENTRAL, Europe PubMed Central, and ClinicalTrials.gov were searched from Jan 1, 2004, to March 18, 2022. Randomised controlled trials with at least one lenalidomide group and one non-lenalidomide group were selected, regardless of the disease setting. Studies with a median follow-up of less than 12 months were excluded. Summary data were extracted by two reviewers (KS and KL) independently and verified by a third reviewer (JF). We then conducted a meta-analysis to assess the risk ratio (RR) of SPM with lenalidomide use across various disease subtypes using a random-effects model. We chose random effects for the primary analysis because of anticipated heterogeneity between different diseases, but we used fixed effects for stratified meta-analysis of multiple myeloma studies. Risk of bias was assessed with the PROTECT tool. The study was registered with PROSPERO, CRD42021257508. Our search yielded 9078 studies, and 38 trials that included 14 058 patients were eligible for meta-analysis after screening, 18 of which were in multiple myeloma. The RR across all malignancies was 1·16 (95% CI 0·96-1·39). However, there was heterogeneity across indications (p=0·020). The RR when lenalidomide was used for multiple myeloma was 1·42 (1·09-1·84). There was no increase in SPM in lymphoma or chronic lymphocytic leukaemia (0·90 [0·76-1·08]) and myelodysplastic syndrome (0·96 [0·23-3·97]) trials. In the setting of multiple myeloma, lenalidomide increased both solid and haematological SPM, both in the no-transplantation and post-transplantation settings. From the 38 trials, 21 (55%) had low risk of bias, 12 (32%) had unclear risk of bias, and five (13%) had high risk of bias. Based on the current data, lenalidomide-induced SPM seem to occur exclusively in patients with multiple myeloma. Thus, lenalidomide can be used for other indications without the major concern of a therapy-related neoplasm. In the multiple myeloma setting, lenalidomide is an effective drug, but patients should be monitored both for haematological and solid tumour SPM. This monitoring includes patients that have not received autologous haematopoietic stem-cell transplantation. Further investigations are needed to improve understanding on why lenalidomide only promotes SPM in patients with multiple myeloma. None.

Association of Selenium Levels with Gestational Diabetes Mellitus: An Updated Systematic Review and Meta-Analysis.

Several studies have investigated the association between selenium levels and gestational diabetes mellitus (GDM); however, their results are not conclusive. This systematic review and meta-analysis aimed to update and draw conclusions regarding the evidence from published studies that investigated selenium levels in relation to GDM. PubMed, Google Scholar, Cochrane Library and ScienceDirect were searched for studies related to selenium and GDM, published from the inception of each database through to July 2022. The meta-analysis was conducted by measuring the standardized mean difference (SMD) between the selenium levels of women with GDM and those pregnant without GDM (control group). Stratified meta-analysis, meta-regression analysis and reporting bias were applied. The “meta” package in the open-access software R was used to analyze all of the data. A total of 12 studies, including 940 pregnant women with GDM and 1749 controls met this study’s inclusion criteria. The selenium levels were significantly lower in women with GDM compared with the control group (SMD = −0.66; 95% confidence interval (CI): (−1.04, −0.28); p ≤ 0.001). Due to significant heterogeneity (I2 = 94%, Cochrane Q = 186.7; p ≤ 0.0001), the random-effects model was followed. The stratified meta-analysis showed that the selenium levels were lower in the cases compared with the normal controls in the third trimester (SMD = −1.85 (−3.03, −0.66); p ≤ 0.01). The same trend was observed in the studies published before the year 2014 (SMD = −0.99 (−1.70, −0.28); p ≤0.01) and those published in or after 2014 (SMD = −0.45 (−0.90, 0.00); p = 0.05). None of the investigated covariates in the meta-regression analysis (each study’s geographic location, trimester of selenium quantification, World Bank economic classification, method of selenium determination, study design, study quality score, publication year and study’s sample size) were significantly associated with the selenium SMD. The current evidence indicates that selenium levels are lower among women with GDM in comparison to those without GDM; however, after the correction of the reporting bias, the result was no longer significant. Further studies with more prospective designs are needed to confirm this evidence and explain the function of selenium in GDM throughout pregnancy.

Is non-high-density lipoprotein associated with metabolic syndrome? A systematic review and meta-analysis.

IntroductionNovel atherogenic lipid indices, including non-high-density lipoprotein cholesterol (non-HDL-C) which is calculated by subtracting the HDL-C value from the total cholesterol level, atherogenic index (ratio between triglycerides (TG) and HDL-C concentrations (TG/HDL-C)), and Diff-C (calculated by subtracting low-density lipoprotein (LDL-C) from non-HDL-C), have been known as valuable predictors of dyslipidemia and subsequent cardiovascular diseases. Previous studies have reported the potential association of novel atherogenic lipid indices with metabolic syndrome (MetS). This meta-analysis aimed to assess the pooled association of novel atherogenic lipid indices with MetS or its components.MethodsA systematic search was conducted through PubMed, Scopus, and Web of Science (WoS) databases from January 2000 until March 2021 to evaluate the association of novel atherogenic lipid indices, including non-HDL-C, atherogenic index, and the difference between non-HDL-C and LDL-C (Diff-C) with MetS. Observational studies were included without any language restriction. As exclusive studies evaluating the association of non-HDL-C with metabolic syndrome (MetS) were eligible to be included in quantitative analyses, a random-effect meta-analysis was performed to pool the odds ratios (ORs). A stratified meta-analysis was performed based on the definition of MetS [Adult Treatment Panel (ATP) and International Diabetes Federation (IDF)] and the studied population.ResultsOverall, 318 studies were retrieved from an initial systematic search. After screening, 18 and five studies were included in the qualitative and quantitative syntheses, respectively. Qualitative synthesis revealed an association between non-HDL-C, Diff-C, and atherogenic index with MetS and its components. Stratified meta-analysis showed that an increased non-HDL-C level was associated with an increased odds of MetS based on ATP criteria (OR: 3.77, 95% CI: 2.14-5.39) and IDF criteria (OR: 2.71, 95% CI: 1.98-3.44) in adults (OR: 3.53, 95% CI: 2.29-4.78) and in children (OR: 2.27, 95% CI: 1.65-2.90).ConclusionNovel atherogenic lipid indices, including atherogenic index, Diff-c, and non-HDL-C, are strongly associated with increased odds of MetS and its components. The indices could be considered as potential predictors of MetS and its components in clinical practice.