Pooled Effect Estimates Research Articles

SCAI Technical Review on Management of Patent Foramen Ovale.

Patent foramen ovale (PFO) is a common anatomic variant associated with intermittent right-to-left shunting. Transcatheter PFO closure has been proposed to address multiple clinical conditions including stroke, transient ischemic attack, migraine, and decompression illness. A systematic review was conducted using the GRADE approach to address 5 questions formulated by the Society for Cardiovascular Angiography and Interventions (SCAI) Guideline Panel in patient, intervention, comparator, outcome (PICO) format. Medical literature from January 2015 through May 2021 was searched. Extracted data underwent review and risk-of-bias assessment by 2 independent researchers. Pooled effect estimates were calculated. Certainty of evidence was determined for each query. Our search identified 2701 titles and abstracts, of which 30 met eligibility criteria and informed the technical review. Data were abstracted to address outcomes of PFO closure for patients with and without prior stroke, in comparison to antiplatelet therapy, in comparison to anticoagulation, and with various post-procedure antithrombotic regimens. In appropriately selected patients with prior stroke, transcatheter PFO closure reduces the risk of recurrent stroke more than antiplatelet therapy alone. Evidence to support PFO closure is weaker regarding older patients, anticoagulation, thrombophilia, transient ischemic attack, migraine, and decompression illness. Data from this technical review will inform the SCAI Guideline for Transcatheter Patent Foramen Ovale Closure.

P-734 How common is spontaneous pregnancy after In vitro Fertilisation (IVF) Livebirth? Systematic review and meta-analysis

Abstract Study question How common is spontaneous pregnancy after IVF resulting in livebirth? How can this evidence inform future pregnancy planning by women who have successful IVF? Summary answer Current evidence suggests that spontaneous pregnancy occurs in at least one in five women in the first three years after having a baby via IVF. What is known already It is known that some women having IVF go on to conceive naturally. This reproductive history is of media interest often described as “miracle” pregnancies (1). Women with this experience also identify themselves as a rarity, and their subsequent pregnancies include rapid-repeat, unplanned and unwelcomed pregnancies (2). Study design, size, duration An initial scoping review revealed few, heterogeneous studies reporting rates of spontaneous pregnancy or livebirth after successful IVF. These studies suggested that this event is not rare, prompting this first systematic review and meta-analysis. This aims to identify, appraise and synthesise the current evidence on the rate of spontaneous pregnancy after successful IVF. Participants/materials, setting, methods Ovid Medline, Embase and PsycINFO were searched on 24/09/2021 using a strategy containing thesaurus and free text terms for the concepts of spontaneous pregnancy, assisted reproduction and livebirth. The search was limited to English language, human studies and publications from 1980. Results were de-duplicated and managed in EndNote, screened by title/abstract and then full text. Random-effects meta-analyses were used to produce a pooled effect estimate of the incidence of spontaneous pregnancy after IVF livebirth. Main results and the role of chance 1108 distinct references were identified, reducing to 54 when screened by title and abstract. On evaluation of full text, 11 studies were included in this review. Rates of spontaneous pregnancy after IVF livebirth ranged from 10-33% of women. However, studies varied widely according to methodology, population, cause of subfertility, type and outcome of fertility treatment and length of follow-up. Different covariates were investigated and inconsistently found to be associated with spontaneous conception after IVF including younger age, shorter duration of subfertility, fewer number of treatment cycles prior to first delivery and specific causes of subfertility (unexplained, no male factor). The pooled estimate for the rate of spontaneous pregnancy after IVF livebirth was 19% (95% CI, 16%-22%). The pooled estimate was robust when stratifying by IVF/intracytoplasmic sperm injection (ICSI), outcome measure and follow up period. It is a likely underestimate as some studies reported on livebirths (i.e. excluding adverse pregnancy outcomes) and did not include spontaneous births that occurred outside of the study region. Moreover, no studies gave due consideration to contraception, plannedness of pregnancies, change in partner, nor serial spontaneous pregnancies in the same woman. Limitations, reasons for caution The current evidence is relatively scarce and diverse. Sample sizes are typically small with only two studies of over a thousand women. Better evidence, in the form of national, data-linked studies, is needed to provide more accurate estimates of this rate, analysis of associated factors and trends over time. Wider implications of the findings These findings refute a widely held misconception that spontaneous pregnancy after IVF livebirth is a rare phenomenon. They should be used to counsel women having babies via IVF and inform their decision-making regarding the timing and mode of conception of future pregnancies and contraception use. Trial registration number N/A

Maternal bisphenol A and triclosan exposure and allergic diseases in childhood: a meta-analysis of cohort studies.

Bisphenol A (BPA) and triclosan (TCS) are both endocrine-disrupting chemicals (EDCs), and pregnant women are usually exposed to them through daily consumption. This study aimed to explore the relationship between prenatal BPA and TCS exposure and allergic diseases in childhood by systematic review and meta-analysis. We searched the topic of prenatal BPA and TCS exposure and allergic diseases in childhood published before March 22, 2021, in four databases, including PubMed, Web of Science, Embase, and Cochrane. Statistical analysis was completed using Stata software (version 16.0). Seven papers on BPA and four papers on TCS were included in this meta-analysis. The association between prenatal exposure to BPA and total allergic diseases in childhood showed a pooled effect estimate of 1.13 (95% CI, 1.04, 1.23), with I2 = 0.0% (P = 0.615). The effect estimates between BPA exposure and each allergic disease were 1.18 (95% CI, 1.02, 1.36) for wheezing, 1.23 (95% CI, 1.01, 1.50) for asthma, 1.03 (95% CI, 0.89, 1.18) for eczema/rashes or hives, and 1.19 (95% CI, 0.91, 1.56) for aeroallergies. Prenatal exposure to TCS had no association with the four types of allergic disease in childhood. BPA exposure during the prenatal period was positively associated with allergic disease in childhood. Strengthening prenatal EDC exposure control is necessary for child health.

Adverse Pregnancy Outcomes and International Immigration Status: A Systematic Review and Meta-analysis.

Background:Disparities in health outcomes between immigrant and native-origin populations, particularly pregnant women, pose significant challenges to healthcare systems. The aim of this systematic-review and meta-analysis was to investigate the risk of adverse pregnancy outcomes among immigrant-women compared to native-origin women in the host country.Methods:PubMed (including MEDLINE), Scopus, and Web of Science were searched to retrieve studies published in English language up to September 2020. All observational studies examining the prevalence of at least one of the short-term single pregnancy outcomes for immigrants who crossed international borders compared to native-origin pregnant population were included. The meta-prop method was used for the pooled-estimation of adverse pregnancy-outcomes’ prevalence. For pool-effect estimates, the association between the immigration-status and outcomes of interest, the random-effects model was applied using the model described by DerSimonian and Laird. I2 statistic was used to assess heterogeneity. The publication bias was assessed using the Harbord-test. Meta-regression was performed to explore the effect of geographical region as the heterogeneity source.Findings:This review involved 11 320 674 pregnant women with an immigration-background and 56 102 698 pregnant women as the native-origin population. The risk of emergency cesarean section (Pooled-OR = 1.1, 95%CI = 1.0–1.2), shoulder dystocia (Pooled-OR = 1.1, 95%CI = 1.0–1.3), gestational diabetes mellites (Pooled-OR = 1.4, 95%CI = 1.2–1.6), small for gestational age (Pooled-OR=1.3, 95%CI = 1.1–0.4), 5-min Apgar less than 7 (Pooled-OR = 1.2, 95%CI = 1.0–1.3) and oligohydramnios (Pooled-OR = 1.8, 95%CI = 1.0–3.3) in the immigrant women were significantly higher than those with the native origin background. The immigrant women had a lower risk of labor induction (Pooled-OR = 0.8, 95%CI = 0.7–0.8), pregnancy induced hypertension (Pooled-OR = 0.6, 95%CI = 0.5–0.7) preeclampsia (Pooled-OR = 0.7, 95%CI = 0.6–0.8), macrosomia (Pooled-OR = 0.8, 95%CI = 0.7–0.9) and large for gestational age (Pooled-OR = 0.8, 95%CI = 0.7–0.8). Also, the risk of total and primary cesarean section, instrumental-delivery, preterm-birth, and birth-trauma were similar in both groups. According to meta-regression analyses, the reported ORs were not influenced by the country of origin.Conclusion:The relationship between the immigration status and adverse perinatal outcomes indicated a heterogenous pattern, but the immigrant women were at an increased risk of some important adverse pregnancy outcomes. Population-based studies with a focus on the various aspects of this phenomena are required to explain the source of these heterogenicities.

Interventions to improve water, sanitation, and hygiene for preventing soil-transmitted helminth infection.

BackgroundIt is estimated that 1.5 billion people are infected with soil‐transmitted helminths (STHs) worldwide. Re‐infection occurs rapidly following deworming, and interruption of transmission is unlikely without complementary control efforts such as improvements in water, sanitation, and hygiene (WASH) access and behaviours.ObjectivesTo assess the effectiveness of WASH interventions to prevent STH infection.Search methodsWe used standard, extensive Cochrane search methods. The latest search date was 19 October 2021.Selection criteriaWe included interventions to improve WASH access or practices in communities where STHs are endemic. We included randomized controlled trials (RCTs), as well as trials with an external control group where participants (or clusters) were allocated to different interventions using a non‐random method (non‐RCTs). We did not include observational study designs. Our primary outcome was prevalence of any STH infection. Prevalence of individual worms was a secondary outcome, including for Ascaris lumbricoides, Trichuris trichiura, hookworm (Ancylostoma duodenale or Necator americanus), or Strongyloides stercoralis. Intensity of infection, measured as a count of eggs per gram of faeces for each species, was another secondary outcome.Data collection and analysisTwo review authors independently reviewed titles and abstracts and full‐text records for eligibility, performed data extraction, and assessed risk of bias using the Cochrane risk of bias assessment tool for RCTs and the EPOC tool for non‐RCTs. We used a random‐effects meta‐analysis to pool study estimates. We used Moran’s I² statistic to assess heterogeneity and conducted subgroup analyses to explore sources of heterogeneity. We assessed the certainty of the evidence using the GRADE approach.Main resultsWe included 32 studies (16 RCTs and 16 non‐RCTs) involving a total of 52,944 participants in the review. Twenty‐two studies (14 RCTs (16 estimates) and eight non‐RCTs (11 estimates)) reported on our primary outcome, prevalence of infection with at least one STH species. Twenty‐one studies reported on the prevalence of A lumbricoides (12 RCTs and 9 non‐RCTs); 17 on the prevalence of T trichiura (9 RCTs and 8 non‐RCTs); 18 on the prevalence of hookworm (10 RCTs and 8 non‐RCTs); and one on the prevalence of S stercoralis (1 non‐RCT). Sixteen studies measured the intensity of infection for an individual STH type. Ten RCTs and five non‐RCTs reported on the intensity of infection of A lumbricoides; eight RCTs and five non‐RCTs measured the intensity of infection of T trichiura; and eight RCTs and five non‐RCTs measured the intensity of hookworm infection. No studies reported on the intensity of infection of S stercoralis.The overall pooled effect estimates showed that the WASH interventions under study may result in a slight reduction of any STH infection, with an odds ratio (OR) of 0.86 amongst RCTs (95% confidence interval (CI) 0.74 to 1.01; moderate‐certainty evidence) and an OR of 0.71 amongst non‐RCTs (95% CI 0.54 to 0.94; low‐certainty evidence). All six of the meta‐analyses assessing individual worm infection amongst both RCTs and non‐RCTs had pooled estimates in the preventive direction, although all CIs encapsulated the null, leaving the possibility of the null or even harmful effects; the certainty of the evidence ranged from very low to moderate. Individual studies assessing intensity of infection showed mixed evidence supporting WASH. Subgroup analyses focusing on narrow specific subsets of water, sanitation, and hygiene interventions did very little to elucidate which interventions might be better than others. Data on intensity of infection (e.g. faecal egg count) were reported in a variety of ways across studies, precluding the pooling of results for this outcome.We did not find any studies reporting adverse events resulting from the WASH interventions under study or from mass drug administration (MDA).Authors' conclusionsWhilst the available evidence suggests that the WASH interventions under study may slightly protect against STH infection, WASH also serves as a broad preventive measure for many other diseases that have a faecal oral transmission route of transmission. As many of the studies were done in addition to MDA/deworming (i.e. MDA was ongoing in both the intervention and control arm), our data support WHO recommendations for implementation of improvements to basic sanitation and adequate access to safe water alongside MDA. The biological plausibility for improved access to WASH to interrupt transmission of STHs is clear, but WASH interventions as currently delivered have shown impacts that were lower than expected. There is a need for more rigorous and targeted implementation research and process evaluations in order that future WASH interventions can better provide benefit to users. Inconsistent reporting of the intensity of infection underscores the need to define the minimal, standard data that should be collected globally on STHs to enable pooled analyses and comparisons.

Hydrophobic versus hydrophilic acrylic intraocular lens on posterior capsule opacification: a Meta-analysis.

To conduct a Meta-analysis pooling randomized controlled trials (RCTs) to compare hydrophobic with hydrophilic acrylic intraocular lenses in terms of posterior capsule opacification (PCO) development. Electronic databases including PubMed, Embase, and the Cochrane Library were queried from their starting till January 2020. RCTs investigating the impact of hydrophobic versus hydrophilic acrylic intraocular lenses on PCO were considered eligible in this study. The pooled effect estimates were calculated using the random-effects model. Thirteen RCTs comprising of 939 patients (1263 eyes) were covered in this study. Patients with hydrophobic acrylic intraocular lenses had a lower PCO score than those with a hydrophilic acrylic intraocular lenses [standard mean difference: -1.80; 95% confidence interval (CI): -2.62 to -0.98; P<0.001]. Moreover, the frequency of neodymium-doped yttrium aluminum garnet (Nd:YAG) capsulotomy in patients with hydrophobic acrylic intraocular lenses was significantly lower than patients with hydrophilic acrylic intraocular lenses (relative risk: 0.38; 95%CI: 0.20-0.71; P=0.003). These findings suggest that hydrophobic acrylic intraocular lenses are superior to hydrophilic acrylic intraocular lenses in patients after cataract surgery due to lower PCO score and reduced Nd:YAG capsulotomy. While similar studies are conducted by other researchers, the present study conducted subgroup analyses that show superior results with hydrophobic lenses in trials conducted in western countries.

The impact of COVID-19 lockdown on abortion care: a time series analysis of data from Marie Stopes Nepal

The COVID-19 pandemic significantly impacted sexual and reproductive health and rights. Nepal implemented a nationwide lockdown in March 2020, limiting population movement and service access. The 36 clinics run by Marie Stopes Nepal (MSN) closed for varying periods at the beginning of lockdown. This study assesses the impact of lockdown and associated clinic closures on abortion services within MSN’s network. An interrupted time-series analysis of clinic-level MSN data compared abortion service use in the pre-closure and post-reopening periods, focusing on the following outcomes: number of abortion care visits, proportion of abortion-related visits, gestational age at time of abortion care and demographics of patients accessing abortion care. Subsequent meta-analyses combined clinic-level results to generate outcome-specific pooled effect estimates. As MSN clinics reopened, during ongoing wider lockdown, weekly visits for abortion care decreased by 37% on average, but abortion increased as a proportion of services post-reopening (OR: 1.53) compared with pre-closure, with no evidence of a change in the proportion of higher gestation abortions. The demographic profile of abortion care clients was altered, with post-reopening clients more likely to have completed primary education (OR: 1.54) and be aged 25 years or older (OR: 1.31) compared with pre-closure clients. COVID-19 lockdown and associated clinic closures reduced the absolute number of abortion services provided within MSN’s network, impacting the composition of service provision. Reductions in safe abortion and wider SRH access will have wide-ranging consequences, curtailing crucial reproductive rights. Policy-makers must ensure ongoing abortion access to protect rights and ensure access.

Meta-analysis. What have we learned?

Meta-analyses constitute fundamental tools of the Evidence-Based Medicine (EBM) aiming at synthesizing outcome data from individual trials in order to produce pooled effect estimates for various outcomes of interest. Combining summary data from several studies increases the sample size, improves the statistical power of the findings as well as the precision of the obtained effect estimates. For all these reasons, meta-analyses are thought of providing the best evidence to support clinical practice guidelines. However, the strength of the provided evidence is closely dependent on the quality of included studies as well as the rigour of the meta-analytic process. In addition, over the course of the evolution of the current meta-analytic methodology, some concerns have been expressed on the ultimate usefulness of such a complex and time consuming procedure on establishing timely, valid evidence on various specified topics in the field of Orthopaedics and Trauma Surgery. This article provides an overview of the appropriate methodology, benefits and potential drawbacks of the meta-analytic procedure.

Effects of Protein Supplementation Associated with Resistance Training on Body Composition and Muscle Strength in Older Adults: A Systematic Review of Systematic Reviews with Meta-analyses

There are some controversial findings regarding the benefits of combining protein supplementation with resistance training in order to optimize adaptations to training in older adults. The aim of this review was to summarize the evidence from meta-analyses assessing the effects of protein supplementation combined with resistance training on body composition and muscle strength in the older population. We included systematic reviews with meta-analyses of randomized clinical trials that examined the effects of protein and/or amino acid supplementation associated with resistance training compared with resistance training alone on lean body mass, muscle mass, and muscle strength in older people. The search was performed using the MEDLINE (PubMed), Embase, Cochrane Database of Systematic Reviews, Google Scholar, and OpenGrey databases. Methodological quality was assessed using the Assessing the Methodological Quality of Systematic Reviews 2 checklist, and the quality of evidence was determined using the Grading of Recommendations Assessment, Development and Evaluation system. The pooled effect estimates were computed from the standardized mean difference and the 95% confidence interval achieved by each meta-analysis, using random effects models. Five reviews were included, all of moderate methodological quality. In the analyses, protein supplementation combined with resistance training was associated with greater increases in lean body mass and muscle mass when compared with resistance training alone. However, no differences were observed between the interventions on muscle strength increases. The quality of evidence ranged from moderate to very low. Protein supplementation associated with resistance training induces greater increases in lean body mass compared with resistance training alone. In addition, it is suggested that the use of protein supplementation enhances gains in muscle mass but does not promote greater increases in muscle strength.

Therapeutic Effect and Optimal Electrode Placement of Transcutaneous Neuromuscular Electrical Stimulation in Patients with Post-Stroke Dysphagia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: To date, there is no conclusive evidence that transcutaneous neuromuscular electrical stimulation (TNMES) benefits patients with post-stroke dysphagia (PSD). In addition, the optimal TNMES electrode placement has not been well-established. This systematic review and meta-analysis were conducted to investigate these two research gaps. Methods: Five major databases were systematically searched for randomized controlled trials (RCTs) through January 2022. Effect sizes were computed using Hedges’ g statistic, which were then entered into the random-effects model to obtain pooled effect estimates. Results: Twenty-four RCTs met the eligibility criteria. On the improvement of swallowing function, TNMES alone was not superior to conventional swallowing therapies (CSTs); combined therapy of TNMES and CSTs significantly surpassed CSTs alone (standardized mean difference (SMD) = 0.91, 95% confidence interval (95% CI): 0.68 to 1.14, p < 0.0001; I2 = 63%). Moreover, significant pooled effect sizes were observed in subgroups with horizontal electrode placement above the hyoid bone (SMD = 0.94, 95% CI: 0.72 to 1.16; I2 = 0%) and horizontal electrode placement just above and below the hyoid bone (SMD = 0.87, 95% CI: 0.59 to 1.14; I2 = 0%). The largest pooled effect size was observed in the subgroup that individualized electrode placement according to dysphagia evaluation (SMD = 1.65, 95% CI: 0.38 to 2.91; I2 = 90%). Conclusion: TNMES should be used in combination with CSTs for PSD. Horizontal electrode placement should target suprahyoid muscles or both suprahyoid and thyrohyoid muscles.

Polycystic ovary syndrome and the risk of endometrial, ovarian and breast cancer: An updated meta-analysis.

This updated meta-analysis aimed to further quantify the risk of endometrial, ovarian, and breast cancer in patients with polycystic ovary syndrome (PCOS), thus providing updated and more reliable estimates. We identified relevant articles by searching electronic databases of PubMed, Embase, Web of Science, and Chinese Biological Medical Literature (CBM) published up to March 20, 2021. The pooled effect estimates and their 95% confidence intervals (CIs) were calculated using the random-effect model or the fixed-effect model. A total of 26 eligible studies were included. We found that PCOS was significantly associated with endometrial cancer (odds ratios [OR]: 3.66, 95%CI: 2.05-6.54, P < 0.001), but not with ovarian or breast cancer (OR: 1.23, 95%CI: 0.99-1.53, P = 0.059; OR: 0.94, 95%CI: 0.78-1.14, P = 0.551, respectively). However, in subgroups of high-quality studies, cohort studies, younger women (54 years or less or premenopausal), and studies with unadjusted body mass index (BMI), PCOS patients had a significantly higher risk of ovarian cancer. These results indicated that PCOS is a significant risk factor for endometrial cancer independent of BMI, but not for breast cancer. PCOS may increase the risk of ovarian cancer in younger women.

Drug-Drug Interactions Between Mycophenolic Acid and Proton Pump Inhibitors: A Systematic Review and Meta-Analysis.

The objective of the present study was to determine the impact of proton pump inhibitors (PPIs) on the pharmacokinetics and pharmacodynamics of mycophenolic acid (MPA). PubMed, Embase, Web of Sciences, and Scopus were systematically searched to identify relevant studies reporting pharmacokinetic parameters [including trough concentration (C0), maximum concentration (Cmax), time to maximum concentration (Tmax), the dose-adjusted area under the concentration-time curve from time 0-12 hours (AUC0-12 h/D), and half-life (t1/2)], and pharmacodynamic outcomes of MPA (eg, acute graft rejection and adverse drug reactions), with and without PPI administration. Pooled effect estimates were calculated using a random-effects model. Twelve studies involving 473 participants were eligible for inclusion, 11 of which were included in the meta-analysis. PPI exposure was significantly associated with lower C0 [mean difference (MD) = -0.62 mg/L; P = 0.003] lower Cmax (MD = -4.71 mg/L; P = 0.01), and longer Tmax (MD = 0.30 hours; P = 0.0001) of MPA. However, no significant association was observed between PPI exposure and AUC0-12 h/D, t1/2, or any pharmacodynamic outcomes. Based on subgroup analysis, it can be suggested that a significant association between PPI exposure and altered MPA pharmacokinetics was mainly associated with mycophenolate mofetil but not enteric-coated mycophenolate sodium. Coadministration of PPIs and mycophenolate mofetil significantly altered the pharmacokinetics of MPA, particularly by decreasing MPA absorption. However, PPI-MPA interactions did not impact pharmacodynamic outcomes of MPA.

MAJOR ADVERSE EVENTS WITH THE USE OF FINERENONE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: A META-ANALYSIS OF CARDIOVASCULAR OUTCOME TRIALS

Objective: Type 2 diabetes mellitus (T2DM) is recognized as the main cause of chronic kidney disease (CKD) and end-stage renal disease worldwide, carrying enormous human and financial costs. Mineralocorticoid receptor antagonists (MRAs) have been shown to decrease proteinuria and albuminuria, posing a favorable effect against the progression of CKD. Recently, we welcomed the publication of two large randomized controlled trials (RCTs), namely FIGARO-DKD and FIDELIO-DKD, addressing the cardio-renal efficacy of finerenone, a newer MRA, in patients with T2DM. Herein we sought to assess major adverse events with the use of finerenone in patients with T2DM. Design and method: We pooled data from the two relevant, published RCTs with finerenone in patients with T2DM, to provide pooled effect estimates for its cardio-renal efficacy and safety. We utilized data from published reports, also searching relevant supplementary appendices for any missing data. We assessed the following safety outcomes: acute kidney injury (AKI), hospitalization due to AKI, hyperkalemia, hospitalization due to hyperkalemia, all-cause death, hospitalization for any cause Results: We demonstrated that finerenone increased the risk for hyperkalemia by two times compared to placebo (RR = 2.03, 95% CI; 1.82–2.26, I2 = 0%, p &lt; 0.00001), while it also significantly increased the risk for hospitalization due to hyperkalemia (RR = 5.86, 95% CI; 2.99 – 11.47, I2 = 0%, p &lt; 0.00001). We have also documented that finerenone did not significantly affect the risk for development of AKI (p = 0.94) or hospitalization in the context of AKI (p = 0.92). In addition, finerenone resulted in a marginally non-significant reduction in the risk for all-cause death, equal to 10% (p = 0.05). Conclusions: Finerenone appears to provide significant cardiovascular and renal benefits for patients with T2DM. However, extra caution is required, since hyperkalemia appears to be the most important side effect with the use of finerenone, representing also the main cause of hospitalization due to a drug side effect. Large-scale use of potassium-binding drugs, such as patiromer or zirconium, as adjunct to finerenone might be a reasonable treatment combination in high-risk patients for hyperkalemia.

Anti-CD19 chimeric antigenic receptor T cell as a second-line therapy for patients with relapsed/refractory diffuse large B-cell lymphoma.

e19502 Background: Inconsistent results observed in recent trials (ZUMA-7, TRANSFORM, BELINDA) assessing chimeric antigenic receptor T (CAR-T) cell therapy in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) prompted a meta-analysis to assess the available evidence and to compare the effectiveness of different CAR-T products. Methods: MEDLINE and EMBASE were searched to identify full-text or abstract publications of phase 3 randomized controlled trials (RCTs) assessing CAR-T in patients with R/R DLBCL compared to standard of care (SOC). Efficacy outcomes included event-free survival (EFS), progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and complete response (CR). CR rates were also compared between CAR-T and patients in SOC arm who received autologous stem-cell transplantation (ASCT). Safety outcomes included grade &gt; 3 any adverse events (AE), cytokine release syndrome (CRS) and neurological toxicity (NT). A DerSimonian-Laird random-effects meta-analysis was conducted to pool effect estimates. Freeman-Tukey transformation method was used to estimate pooled proportion (PP) of safety events specific to CAR-T. Mixed treatment comparisons were computed using a frequentist network meta-analysis approach. Results: Of 1803 studies identified, three RCTs with 865 patients were included. Meta-analysis showed significant improvement in EFS (HR: 0.51; 95% CI: 0.27-0.97; I2: 92%), PFS (HR: 0.47; 95% CI: 0.37-0.60; I2: 0%) with CAR-T compared to SOC. OS was not significantly different between the two groups (HR 0.76; 95% CI: 0.56 to 1.03; I2: 29%). Higher objective response (RR: 1.49; 95% CI: 1.13-1.97; I2: 81%), and CR rates (RR: 1.55; 95% CI: 1.07-2.24; I2: 79%) were observed with CAR-T compared to SOC. However, CAR-T was associated with lower CR when compared to patients who underwent ASCT (RR: 0.65; 95% CI: 0.46-0.90; I2: 89%). The safety profile was not different between CAR-T and SOC. The incidences of grade ≥3 CRS (PP: 4.19; 95% CI: 1.60-7.80; I2: 57%) and grade ≥3 NT (PP: 7.57; 95% CI: 0.20-22.6; I2: 95%) were low. Mixed treatment comparisons showed significant EFS benefit with liso-cel (rank 1: HR: 0.37; 95% CI: 0.22-0.61) and axi-cel (rank 2: HR: 0.42; 95% CI: 0.29-0.61) compared to tisa-cel (rank 3). No significant differences were observed among different CAR-T products for PFS or OS improvement. The safety profile of CAR-T products was comparable with tisa-cel (rank 1) being the safest. Conclusions: CAR-T therapy, as a second line treatment, appears to be effective in achieving higher response rates and delaying the disease progression compared to SOC in R/R DLBCL. However, given lack of OS benefit coupled with lower response rates when compared to patients who received ASCT, we should exercise caution in adopting CAR-T as second line therapy for all patients with R/R DLBCL.

Comparative Evaluation of Retention and Cariostatic Effect of Hydrophilic and Hydrophobic Resin-Based Sealants

Evidence-based information should be provided to clinicians to explain the effectiveness of hydrophilic and hydrophobic forms of resin based sealants (RBSs). To assess and evaluate the retention and cariostatic effect of hydrophilic and hydrophobic RBSs in primary and/ or permanent teeth with at least a follow-up period of 3 months. Five databases were searched up to September 2021 for randomized and non-randomized clinical trials (RCTs and non-RCTs) that evaluated the retention and cariostatic effect of hydrophilic and hydrophobic RBSs. Two authors nominated the papers, extracted data, and assessed the risk of bias. By comparing the retention rate and caries incidence between groups, pooled-effect estimates of included articles were generated. After removing duplicates from the 2,810 titles found, only 1938 remained. Twelve of these were thoroughly examined. A total of 12 papers met the inclusion criteria in qualitative analysis: seven RCTs and five non-RCTs. Only ten studies were included in the meta-analysis: five RCTs and five non-RCTs. After 12 months of follow-up, no significant difference was found in the retention of hydrophilic and hydrophobic RBSs with and without a bonding agent. After 12 months of follow-up, no significant difference was found in the cariostatic effect of hydrophilic and hydrophobic RBSs. There was no statistically significant difference in retention and the cariostatic impact was found between hydrophilic and hydrophobic RBSs.

A Hybrid Covariate Microaggregation Approach for Privacy-Preserving Logistic Regression

Abstract Distributed data networks (DDNs) with horizontally partitioned datasets are viable resources for multicenter research studies and pharmacosurveillance. Within DDNs, maintaining confidentiality and limiting the disclosure of sensitive information is critical. Consequently, data sharing between partners within the same network is either restricted or completely prohibited during statistical modeling. Current privacy-preserving methods for logistic regression span two extreme paradigms: meta-analysis (MA), which combines estimates based on partner-specific estimates, is convenient for the analytical center (AC) but requires separate implementations of the analysis by each data node; while distributed regression (DR), which provides overall estimates based on partner-specific data summaries, produces rigorous solutions but is an iterative process that is both time and resource consuming. A practical middle ground that combines the convenience of MA and the rigor of DR is lacking. We propose a likelihood-based approach for logistic regression modeling that combines the rigor of DR and the convenience of MA. The two-stage approach has an equivalent estimation performance as DR but foregoes its multiple iterative steps through an MA update step, and is therefore more user-friendly. The approach uses only aggregate-level covariates to estimate a starting pooled effect estimate and within-node data summaries for a single-shot update of the pooled estimate without requiring individual covariate values at the AC. We call the approach hybrid Pooled Logistic Regression (hPoLoR) and show that it conveniently provides accurate and efficient estimates of the standard individual-level log odds ratios and standard errors without revealing personal data. Hence hPoLoR provides a rigorous yet convenient and application-friendly alternative to MA and DR. The method is demonstrated through extensive simulations and application to the JCUSH data.

The role of serum testosterone and dehydroepiandrosterone sulfate in kidney function and clinical outcomes in chronic kidney disease: a systematic review and meta-analysis.

Objective/designTestosterone might mediate sex differences in kidney function and chronic kidney disease (CKD). However, few studies analyzing the association between testosterone and kidney function showed conflicting results. Therefore, we performed a systematic review and meta-analysis.MethodsSix electronic databases were searched from inception to March 4, 2020, for studies that investigated the association of (i) testosterone status with kidney function in the general population or (ii) testosterone status with clinical outcomes (kidney function decline, kidney failure, cardiovascular (CV) events, and cardiovascular and all-cause mortality) in CKD patients. We used random and fixed-effect models to obtain pooled effect estimates with 95% confidence intervals (CIs).ResultsNo randomized–controlled trials that met the inclusion criteria were identified. One study was conducted in the general population and reported an increased risk of incident CKD with low vs normal testosterone (hazard ratio (HR): 1.38, 95% CI: 1.05;1.80). Seven studies were conducted in men with CKD and included testosterone as determinant, of which six could be meta-analyzed. Low testosterone was associated with an increased risk of all-cause mortality and CV events (pooled HR: 1.98, 95% CI: 1.36;2.89; pooled HR of 2.40, 95% CI: 1.22;4.71, respectively). Two studies showed an increased risk of all-cause mortality with decreased dehydroepiandrosterone sulfate (DHEAS) in men with CKD; results regarding CV events were conflicting.ConclusionsAlthough literature is scarce, evidence suggests that lower testosterone may increase CKD risk in the general population and risk of all-cause mortality and CV events in men with CKD. Whether testosterone supplementation could prevent these potential detrimental outcomes should be determined in future intervention studies.

Evaluating agreement between bodies of evidence from randomized controlled trials and cohort studies in medical research: a meta-epidemiological study

BackgroundRandomized controlled trials (RCTs) and cohort studies are the most common study design types used to assess the treatment effects of medical interventions. To evaluate the agreement of effect estimates between bodies of evidence (BoE) from randomized controlled trials (RCTs) and cohort studies and to identify factors associated with disagreement.MethodsSystematic reviews were published in the 13 medical journals with the highest impact factor identified through a MEDLINE search. BoE-pairs from RCTs and cohort studies with the same medical research question were included. We rated the similarity of PI/ECO (Population, Intervention/Exposure, Comparison, Outcome) between BoE from RCTs and cohort studies. The agreement of effect estimates across BoE was analyzed by pooling ratio of ratios (RoR) for binary outcomes and difference of mean differences for continuous outcomes. We performed subgroup analyses to explore factors associated with disagreements.ResultsOne hundred twenty-nine BoE pairs from 64 systematic reviews were included. PI/ECO-similarity degree was moderate: two BoE pairs were rated as “more or less identical”; 90 were rated as “similar but not identical” and 37 as only “broadly similar”. For binary outcomes, the pooled RoR was 1.04 (95% CI 0.97–1.11) with considerable statistical heterogeneity. For continuous outcomes, differences were small. In subgroup analyses, degree of PI/ECO-similarity, type of intervention, and type of outcome, the pooled RoR indicated that on average, differences between both BoE were small. Subgroup analysis by degree of PI/ECO-similarity revealed high statistical heterogeneity and wide prediction intervals across PI/ECO-dissimilar BoE pairs.ConclusionsOn average, the pooled effect estimates between RCTs and cohort studies did not differ. Statistical heterogeneity and wide prediction intervals were mainly driven by PI/ECO-dissimilarities (i.e., clinical heterogeneity) and cohort studies. The potential influence of risk of bias and certainty of the evidence on differences of effect estimates between RCTs and cohort studies needs to be explored in upcoming meta-epidemiological studies.

Fine particulate matter and cardiorespiratory health in China: A systematic review and meta-analysis of epidemiological studies

This review aimed to systematically summarize the epidemiological literature on the cardiorespiratory effects of PM2.5 published during the 13th Five-Year Plan period (2016–2020) in China. Original articles published between January 1, 2016 and June 30, 2021 were searched in PubMed, Web of Science, the China National Knowledge Internet Database and Wanfang Database. Random- or fixed-effects models were used to pool effect estimates where appropriate. Of 8558 records identified, 145 met the full eligibility criteria. A 10 µg/m³ increase in short-term PM2.5 exposure was significantly associated with increases of 0.70%, 0.86%, 0.38% and 0.96% in cardiovascular mortality, respiratory mortality, cardiovascular morbidity, and respiratory morbidity, respectively. The specific diseases with significant associations included stroke, ischemic heart disease, heart failure, arrhythmia, chronic obstructive pulmonary disease, pneumonia and allergic rhinitis. The pooled estimates per 10 µg/m³ increase in long-term PM2.5 exposure were 15.1%, 11.9% and 21.0% increases in cardiovascular, stroke and lung cancer mortality, and 17.4%, 11.0% and 4.88% increases in cardiovascular, hypertension and lung cancer incidence respectively. Adverse changes in blood pressure, heart rate variability, systemic inflammation, blood lipids, lung function and airway inflammation were observed for either short-term or long-term PM2.5 exposure, or both. Collectively, we summarized representative exposure-response relationships between short- and long-term PM2.5 exposure and a wide range of cardiorespiratory outcomes applicable to China. The magnitudes of estimates were generally smaller in short-term associations and comparable in long-term associations compared with those in developed countries. Our findings are helpful for future standard revisions and policy formulation. There are still some notable gaps that merit further investigation in China.

Rationale and Approach to Evaluating Interventions to Promote Child Health in LMICs.

Rationale and Approach to Evaluating Interventions to Promote Child Health in LMICs.