Effect of traditional Chinese medicine on gut microbiota in adults with type 2 diabetes: A systematic review and meta-analysis

BackgroundDespite advances in research on type 2 diabetes mellitus (T2DM) with the development of science and technology, the pathogenesis and treatment response of T2DM remain unclear. Recent studies have revealed a significant role of the microbiomein the development of T2DM, and studies have found that the gut microbiota may explain the therapeutic effect of traditional Chinese medicine (TCM), a primary branch of alternative and complementary medicine, in the treatment of T2DM. The aim of this study was to systematically review all randomized controlled trials (RCTs) on TCM for gut microbiota to assess the effectiveness and safety of TCM in T2DM patients.MethodsAll RCTs investigating the effects of TCM interventions on modulating gut microbiota and improving glucose metabolism in the treatment of T2DM adults were included. Meta-analyses were conducted when sufficient data were available, other results were reported narratively. The study protocol was pre-specified, documented, and published in PROSPERO (registration no. CRD42020188043).ResultsFive studies met the eligibility criteria ofthe systematic review. All five studies reported the effects of TCM interventions on the gut microbiota modulation and blood glucose control. There were statistically significant improvements in HbA1c (mean difference [MD]: -0.69%; [95% CI −0.24, −0.14]; p = 0.01, I² = 86%), fasting blood glucose (MD: −0.87 mmol/l; [95% CI -1.26, -0.49]; p < 0.00001, I² = 75%) and 2-h postprandial blood glucose(MD: -0.83mmol/l; [95% CI: -1.01, -0.65]; p < 0.00001, I² = 0%). In addition, there were also statistically significant improvements in homeostasis model assessment of insulin resistance (HOMA-IR) (standardized mean difference [SMD]: −0.99, [95% CI −1.25 to -0.73]; p < 0.00001, I² = 0%) and homeostasis model assessment of β-cell function (HOMA-β) (SMD: 0.54, [95% CI 0.21 to 0.87]; p = 0.001, I² = 0%).There was a significant change in the relative abundance of bacteria in the genera Bacteroides (standardized mean difference [SMD] 0.87%; [95% CI 0.58, 1.16], however, the change in Enterococcus abundance was not statistically significant (SMD: -1.71%; [95% CI: -3.64, 0.23]; p = 0.08) when comparing TCM supplementaltreatment with comparator groups. Other changes in the gut microbiota, including changes in the relative abundances of some probiotics and opportunistic pathogens at various taxon levels, and changes in diversity matrices (α and β), were significant by narrative analysis. However, insufficient evidences were found to support that TCM intervention had an effect on inflammation.ConclusionTCM had the effect of modulating gut microbiota and improving glucose metabolisms in T2DM patients. Although the results of the included studies are encouraging, further well-conducted studies on TCM interventions targeting the gut microbiota are needed.     

Sumac fruit supplementation improve glycemic parameters in patients with metabolic syndrome and related disorders: A systematic review and meta-analysis

BackgroundMetabolic syndrome (MetS) is the one of the main causes of mortality worldwide. Several randomized controlled trials (RCTs) have revealed the beneficial effects of sumac (Rhus coriaria) on cardiometabolic risk factors. However, the entirety of the evidence has yet to be summarized in a systematic review.ObjectiveThe aim of this systematic review and meta-analysis was to evaluate the effects of sumac on several cardiometabolic risk factors in patients with MetS and related disorders.MethodsWe reviewed Medline, Scopus, Web of Science and Cochrane CENTRAL for RCTs published from inception to December 2020 evaluating the impact of sumac in adults with MetS or related disorders. Outcome measures included anthropometric measures, glycemic indices, blood lipids, blood pressure and liver enzymes. Pooled effect sizes were reported as standard mean differences (SMDs) and 95% confidence intervals (CIs). Trials were pooled using a random effects model.ResultsNine studies enrolling 526 participants met the inclusion criteria for this meta-analysis. Our results indicate that sumac intake significantly decrease fasting blood sugar (FBS) (SMD: −0.28; 95% CI: −0.54, -0.02; I² = 00.0%), insulin (SMD: −0.67; 95% CI: −0.99, -0.36; I² = 03.7%), and insulin resistance (measured through the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)) (SMD: −0.79; 95% CI: −1.24, -0.34; I² = 50.1%). Sumac intake did not have a significant impact on weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), waist to hip ratio (WHR), HbA1c, total cholesterol (TC), triglycerides (TG), high density lipoproteins (HDL), low density lipoprotein (LDL), systolic blood pressure (SBP), diastolic blood pressure (DBP), aspartate transaminase (AST) and alanine transaminase (ALT).ConclusionSumac, as an adjuvant therapy, may decrease serum levels of FBS, insulin and HOMA-IR. However, due to high heterogeneity in the included studies, these findings must be interpreted with great caution. Larger, well-designed placebo-controlled clinical trials are still needed to further evaluate the capacity of sumac as a complementary treatment to control MetS risk factors.     

Ferrous Sulfate Supplementation Causes Significant Gastrointestinal Side-Effects in Adults: A Systematic Review and Meta-Analysis

BackgroundThe tolerability of oral iron supplementation for the treatment of iron deficiency anemia is disputed.ObjectiveOur aim was to quantify the odds of GI side-effects in adults related to current gold standard oral iron therapy, namely ferrous sulfate.MethodsSystematic review and meta-analysis of randomized controlled trials (RCTs) evaluating GI side-effects that included ferrous sulfate and a comparator that was either placebo or intravenous (IV) iron. Random effects meta-analysis modelling was undertaken and study heterogeneity was summarised using I² statistics.ResultsForty three trials comprising 6831 adult participants were included. Twenty trials (n = 3168) had a placebo arm and twenty three trials (n = 3663) had an active comparator arm of IV iron. Ferrous sulfate supplementation significantly increased risk of GI side-effects versus placebo with an odds ratio (OR) of 2.32 [95% CI 1.74–3.08, p<0.0001, I² = 53.6%] and versus IV iron with an OR of 3.05 [95% CI 2.07-4.48, p<0.0001, I² = 41.6%]. Subgroup analysis in IBD patients showed a similar effect versus IV iron (OR = 3.14, 95% CI 1.34-7.36, p = 0.008, I² = 0%). Likewise, subgroup analysis of pooled data from 7 RCTs in pregnant women (n = 1028) showed a statistically significant increased risk of GI side-effects for ferrous sulfate although there was marked heterogeneity in the data (OR = 3.33, 95% CI 1.19-9.28, p = 0.02, I² = 66.1%). Meta-regression did not provide significant evidence of an association between the study OR and the iron dose.ConclusionsOur meta-analysis confirms that ferrous sulfate is associated with a significant increase in gastrointestinal-specific side-effects but does not find a relationship with dose.     

MALDI-TOF mass spectrometry rapid pathogen identification and outcomes of patients with bloodstream infection: A systematic review and meta-analysis

There was inconsistent evidence regarding the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for microorganism identification with/without antibiotic stewardship team (AST) and the clinical outcome of patients with bloodstream infections (BSI). In a systematic review and meta-analysis, we evaluated the effectiveness of rapid microbial identification by MALDI-TOF MS with and without AST on clinical outcomes. We searched PubMed and EMBASE databases from inception to 1 February 2022 to identify pre–post and parallel comparative studies that evaluated the use of MALDI-TOF MS for microorganism identification. Pooled effect estimates were derived using the random-effects model. Twenty-one studies with 14,515 patients were meta-analysed. Compared with conventional phenotypic methods, MALDI-TOF MS was associated with a 23% reduction in mortality (RR = 0.77; 95% CI: 0.66; 0.90; I² = 35.9%; 13 studies); 5.07-h reduction in time to effective antibiotic therapy (95% CI: −5.83; −4.31; I² = 95.7%); 22.86-h reduction in time to identify microorganisms (95% CI: −23.99; −21.74; I² = 91.6%); 0.73-day reduction in hospital stay (95% CI: −1.30; −0.16; I² = 53.1%); and US$4140 saving in direct hospitalization cost (95% CI: $-8166.75; $-113.60; I² = 66.1%). No significant heterogeneity sources were found, and no statistical evidence for publication bias was found. Rapid pathogen identification by MALDI-TOF MS with or without AST was associated with reduced mortality and improved outcomes of BSI, and may be cost-effective among patients with BSI.     

Association of the variants in the PPARG gene and serum lipid levels: a meta‐analysis of 74 studies

Considerable studies have been carried out to investigate the relationship between the polymorphisms of PPARG (Pro12Ala, C161T and C1431T) and serum lipid levels, but the results were inconclusive. Hence, we conducted a meta-analysis to clarify the association. MEDLINE, EMBASE and the Cochrane Library databases were searched systematically. The subgroup analysis was performed based on ethnicity. Seventy-four studies with 54,953 subjects were included in this meta-analysis. In Pro12Ala, the group with the ‘PP’ (C/C genotype) genotype group had lower levels of total cholesterol (TC) (mean difference, MD: −0.02, P < 0.00001; I² = 28%), low-density lipoprotein cholesterol (LDL-C) (MD: −0.02, P < 0.00001; I² = 30%) and higher levels of triglyceride (TG) (MD: 0.06, P < 0.00001; I² = 30%) than the combined ‘PA+AA’ (PA = C/G genotype, AA = G/G genotype) genotype group in Asian population, and the group with the ‘PP’ genotype had higher levels of TG (MD: 0.07, P < 0.02; I² = 67%) than the combined ‘PA+AA’ genotype group in non-Asian population. No statistically significant differences in the levels of TC, TG, high-density lipoprotein cholesterol, LDL-C were detected between different genotypes in C161T(Asian or non-Asian) and C1431T(Asian) polymorphisms. This meta-analysis was a renewed and confirmed study to assess the association between PPARG polymorphisms and serum lipid levels in Asian and non-Asian populations. There is a prominent association between Pro12Ala polymorphism and the levels of TC, LDL-C and TG in Asian population. No statistically significant differences in serum lipid levels were detected between different genotypes in C161T and C1431T polymorphisms.     

Induction of labour at 41 weeks or expectant management until 42 weeks: A systematic review and an individual participant data meta-analysis of randomised trials

BackgroundThe risk of perinatal death and severe neonatal morbidity increases gradually after 41 weeks of pregnancy. Several randomised controlled trials (RCTs) have assessed if induction of labour (IOL) in uncomplicated pregnancies at 41 weeks will improve perinatal outcomes. We performed an individual participant data meta-analysis (IPD-MA) on this subject.Methods and findingsWe searched PubMed, Excerpta Medica dataBASE (Embase), The Cochrane Library, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and PsycINFO on February 21, 2020 for RCTs comparing IOL at 41 weeks with expectant management until 42 weeks in women with uncomplicated pregnancies. Individual participant data (IPD) were sought from eligible RCTs. Primary outcome was a composite of severe adverse perinatal outcomes: mortality and severe neonatal morbidity. Additional outcomes included neonatal admission, mode of delivery, perineal lacerations, and postpartum haemorrhage. Prespecified subgroup analyses were conducted for parity (nulliparous/multiparous), maternal age (<35/≥35 years), and body mass index (BMI) (<30/≥30). Aggregate data meta-analysis (MA) was performed to include data from RCTs for which IPD was not available.From 89 full-text articles, we identified three eligible RCTs (n = 5,161), and two contributed with IPD (n = 4,561). Baseline characteristics were similar between the groups regarding age, parity, BMI, and higher level of education. IOL resulted overall in a decrease of severe adverse perinatal outcome (0.4% [10/2,281] versus 1.0% [23/2,280]; relative risk [RR] 0.43 [95% confidence interval [CI] 0.21 to 0.91], p-value 0.027, risk difference [RD] −57/10,000 [95% CI −106/10,000 to −8/10,000], I² 0%). The number needed to treat (NNT) was 175 (95% CI 94 to 1,267).Perinatal deaths occurred in one (<0.1%) versus eight (0.4%) pregnancies (Peto odds ratio [OR] 0.21 [95% CI 0.06 to 0.78], p-value 0.019, RD −31/10,000, [95% CI −56/10,000 to −5/10,000], I² 0%, NNT 326, [95% CI 177 to 2,014]) and admission to a neonatal care unit ≥4 days occurred in 1.1% (24/2,280) versus 1.9% (46/2,273), (RR 0.52 [95% CI 0.32 to 0.85], p-value 0.009, RD −97/10,000 [95% CI −169/10,000 to −26/10,000], I² 0%, NNT 103 [95% CI 59 to 385]). There was no difference in the rate of cesarean delivery (10.5% versus 10.7%; RR 0.98, [95% CI 0.83 to 1.16], p-value 0.81) nor in other important perinatal, delivery, and maternal outcomes. MA on aggregate data showed similar results.Prespecified subgroup analyses for the primary outcome showed a significant difference in the treatment effect (p = 0.01 for interaction) for parity, but not for maternal age or BMI. The risk of severe adverse perinatal outcome was decreased for nulliparous women in the IOL group (0.3% [4/1,219] versus 1.6% [20/1,264]; RR 0.20 [95% CI 0.07 to 0.60], p-value 0.004, RD −127/10,000, [95% CI −204/10,000 to −50/10,000], I² 0%, NNT 79 [95% CI 49 to 201]) but not for multiparous women (0.6% [6/1,219] versus 0.3% [3/1,264]; RR 1.59 [95% CI 0.15 to 17.30], p-value 0.35, RD 27/10,000, [95% CI −29/10,000 to 84/10,000], I² 55%).A limitation of this IPD-MA was the risk of overestimation of the effect on perinatal mortality due to early stopping of the largest included trial for safety reasons after the advice of the Data and Safety Monitoring Board. Furthermore, only two RCTs were eligible for the IPD-MA; thus, the possibility to assess severe adverse neonatal outcomes with few events was limited.ConclusionsIn this study, we found that, overall, IOL at 41 weeks improved perinatal outcome compared with expectant management until 42 weeks without increasing the cesarean delivery rate. This benefit is shown only in nulliparous women, whereas for multiparous women, the incidence of mortality and morbidity was too low to demonstrate any effect. The magnitude of risk reduction of perinatal mortality remains uncertain. Women with pregnancies approaching 41 weeks should be informed on the risk differences according to parity so that they are able to make an informed choice for IOL at 41 weeks or expectant management until 42 weeks.Study Registration: PROSPERO CRD42020163174

Mårten Alkmark and co-workers report on a meta-analysis of randomized trials of labour induction at 41 weeks'' gestation as compared with expectant management until 42 weeks.     

The Efficacy and Safety of Selective H1-Antihistamine versus Leukotriene Receptor Antagonist for Seasonal Allergic Rhinitis: A Meta-Analysis

Background

Both selective H₁-antihistamine (SAH) and leukotriene receptor antagonist (LTRA) have been shown to be effective in treating patients with seasonal allergic rhinitis (SAR), but it is still uncertain which treatment option is optimal. This meta-analysis was aimed to compare the efficacy and safety of SAH and LTRA for SAR.

Materials and Methods

PubMed, EMBASE and the Cochrane Library were searched for all eligible studies that compared the efficacy and safety of SAH and LTRA for SAR up to September 7, 2014. The pooled mean difference (MD), odd ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using a fixed- or random-effects model.

Results

Nine studies with 5781 SAR patients were included. The results showed that SAH is superior to LTRA in terms of the daytime eye symptoms score (DESS) and composite symptoms score (CSS) for SAR (MD = 0.06, 95% CI, 0.03 to 0.10, P = 0.000, I ² = 99%; MD = 0.03, 95% CI, 0.01 to 0.05, P = 0.010, I ² = 98%), whereas LTRA overmatched SAH with respect to the night-time symptoms score (NSS) (MD = −0.04, 95% CI, −0.05 to −0.02, P = 0.000, I ² = 97%). Additionally, the results of subgroup analysis indicated that the dose, duration and gender of the patients might impact the comparisons of the effects of SAH and LTRA on their efficacy for SAR.

Conclusion

This meta-analysis suggested that SAH and LTRA have similar effects and safety for SAR, but SAH is more appropriate for daytime nasal symptoms (congestion, rhinorrhea, pruritus and sneezing), while LTRA is better suited for nighttime symptoms (difficulty going to sleep, nighttime awakenings, and nasal congestion on awakening), respectively. Meanwhile, the dose, duration and gender of patients may influence the anti-SAR effects of SAH and LTRA.     

Effectiveness of Pulsed Electromagnetic Fields on Bone Healing: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

The effect of pulsed electromagnetic field (PEMF) on bone healing is still uncertain and it has not been established as a standardized treatment. The aim of this systematic review and meta-analysis is to evaluate the effect of PEMF on bone healing in patients with fracture. We searched CNKI, Wan Fang, VIP, EMbase, PubMed, CENTRAL, Web of Science, Physiotherapy Evidence Database, and Open Grey websites for randomized controlled trials (published before July 2019 in English or Chinese) comparing any form of PEMF to sham. Reference lists were also searched. Related data were extracted by two investigators independently. The bias risk of the articles and the evidence strength of the outcomes were evaluated. Twenty-two studies were eligible and included in our analysis (n = 1,468 participants). The pooled results of 14 studies (n = 1,131 participants) demonstrated that healing rate in PEMF group was 79.7% (443/556), and that in the control group was 64.3% (370/575). PEMF increased healing rate (RR = 1.22; 95% confidence interval [CI] = 1.10–1.35; I² = 48%) by the Mantel–Haenszel analysis, relieved pain (standardized mean difference (SMD) = −0.49; 95% CI = −0.88 to −0.10; I² = 60%) by the inverse variance analysis, and accelerated healing time (SMD = −1.01; 95% CI = −2.01 to −0.00; I² = 90%) by the inverse variance analysis. Moderate quality evidence suggested that PEMF increased healing rate and relieved pain of fracture, and very low-quality evidence showed that PEMF accelerated healing time. Larger and higher quality randomized controlled trials and pre-clinical studies of optimal frequency, amplitude, and duration parameters are needed. © 2020 Bioelectromagnetics Society.     

Comparison of Clinical Efficacy and Safety between Indacaterol and Tiotropium in COPD: Meta-Analysis of Randomized Controlled Trials

Two once-daily inhaled bronchodilators, indacaterol and tiotropium, are widely used as first-line therapy in stable COPD patients. This study was performed to compare the clinical efficacy and safety between indacaterol and tiotropium in patients with moderate-to-severe COPD. MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched to identify all published randomized controlled trials (RCTs). The primary outcome was trough forced expiratory volume in 1 second (FEV₁) at week 12. Four RCTs were eligible for inclusion (three RCTs with moderate-to-severe COPD patients and one RCT with only severe COPD patients). Trough FEV₁ at weeks 12 and 26 were not significantly different between indacaterol and tiotropium by the standardized mean difference with 0.014 (95% CI, -0.036, 0.063, I²= 23.5%) and with 0.037 (95% CI, -0.059 to 0.133, I²= 0%) along with differences in means of 0.003L and 0.014L, respectively. Indacaterol and tiotropium also showed similar St. George`s Respiratory Questionnaire (SGRQ) total scores and percentages of patients with SGRQ improvement (≥ 4 units) at week 26. The incidences of nasopharyngitis, serious cardiovascular events, and serious adverse events were not different between indacaterol and tiotropium, while those of cough (OR = 1.68, P < 0.001, and RR = 1.63) and COPD worsening (OR = 1.18, P = 0.003, and RR = 1.12) were higher for indacaterol than tiotropium. However, when one study with only severe COPD patients was removed from the meta-analysis, the difference in the incidence of COPD worsening between indacaterol and tiotropium became non-significant (OR = 1.13, P = 0.204, and RR = 1.09). The clinical efficacy and serious adverse events between indacaterol and tiotropium were equivocal in patients with moderate-to-severe COPD. Cough is a common complaint associated with indacaterol, and COPD worsening needs to be carefully monitored in severe COPD patients when treated with indacaterol.     

Remote Ischemic Preconditioning Reduces Perioperative Cardiac and Renal Events in Patients Undergoing Elective Coronary Intervention: A Meta-Analysis of 11 Randomized Trials

Background

Results from randomized controlled trials (RCT) concerning cardiac and renal effect of remote ischemic preconditioning(RIPC) in patients with stable coronary artery disease(CAD) are inconsistent. The aim of this study was to explore whether RIPC reduce cardiac and renal events after elective percutaneous coronary intervention (PCI).

Methods and Results

RCTs with data on cardiac or renal effect of RIPC in PCI were searched from Pubmed, EMBase, and Cochrane library (up to July 2014). Meta-regression and subgroup analysis were performed to identify the potential sources of significant heterogeneity(I ²≥40%). Eleven RCTs enrolling a total of 1713 study subjects with stable CAD were selected. Compared with controls, RIPC significantly reduced perioperative incidence of myocardial infarction (MI) [odds ratio(OR)  = 0.68; 95% CI, 0.51 to 0.91; P = 0.01; I² = 41.0%] and contrast-induced acute kidney injury(AKI) (OR = 0.61; 95% CI, 0.38 to 0.98; P = 0.04; I² = 39.0%). Meta-regression and subgroup analyses confirmed that the major source of heterogeneity for the incidence of MI was male proportion (coefficient  = −0.049; P = 0.047; adjusted R² = 0.988; P = 0.02 for subgroup difference).

Conclusions

The present meta-analysis of RCTs suggests that RIPC may offer cardiorenal protection by reducing the incidence of MI and AKI in patients undergoing elective PCI. Moreover, this effect on MI is more pronounced in male subjects. Future high-quality, large-scale clinical trials should focus on the long-term clinical effect of RIPC.     

Age at Menarche,Level of Education,Parity and the Risk of Hysterectomy: A Systematic Review and Meta-Analyses of Population-Based Observational Studies

Background

Although rates have declined, hysterectomy is still a frequent gynaecological procedure. To date, there has been no systematic quantification of the relationships between early/mid-life exposures and hysterectomy. We performed a systematic review and meta-analyses to quantify the associations between age at menarche, education level, parity and hysterectomy.

Methods

Eligible studies were identified by searches in PubMed and Embase through March 2015. Study-specific estimates were summarised using random effects meta-analysis. Heterogeneity was explored using sub-group analysis and meta-regression.

Results

Thirty-two study populations were identified for inclusion in at least one meta-analysis. Each year older at menarche was associated with lower risk of hysterectomy—summary hazard ratio 0.86 (95% confidence interval: 0.78, 0.95; I² = 0%); summary odds ratio 0.88 (95% confidence interval: 0.82, 0.94; I² = 61%). Low education levels conferred a higher risk of hysterectomy in the lowest versus highest level meta-analysis (summary hazard ratio 1.87 (95% confidence interval: 1.25, 2.80; I² = 86%), summary odds ratio 1.51 (95% confidence interval: 1.35, 1.69; I² = 90%)) and dose-response meta-analysis (summary odds ratio 1.17 (95% confidence interval: 1.12, 1.23; I² = 85%) per each level lower of education). Sub-group analysis showed that the birth cohort category of study participants, the reference category used for level of education, the year the included article was published, quality of the study (as assessed by the authors) and control for the key variables accounted for the high heterogeneity between studies in the education level meta-analyses. In the meta-analyses of studies of parity and hysterectomy the results were not statistically significant.

Conclusions

The present meta-analyses suggest that the early life factors of age at menarche and lower education level are associated with hysterectomy, although this evidence should be interpreted with some caution due to variance across the included studies.     

Effect of Exercise Interventions on Kainate Induced Status Epilepticus and Associated Co-morbidities; A Systematic Review and Meta-Analysis

Purpose

To conduct a systematic review and meta-analysis of studies testing the effect of exercise in Kainic-acid (KA) induced status-epilepticus (SE) and to quantify the efficacy of exercise strategies in the prognosis of SE and co-morbidities.

Methods

Two authors searched online databases (Pubmed and Web of Science) independently for studies testing the efficacy of exercise programs in KA-induced SE models. Reviewers autonomously extracted data on models used, exercise interventions and prognosis in all reported outcomes (behavioral, histological, biochemical and cognitive outcomes). All studies were summarized and relevant outcomes’ data were pooled by means of a meta-analysis.

Results

Among 14 selected studies; Quantitative analysis of studies with pre-SE exercise interventions showed significant reduction in mortality rate among 76 animals of four studies (RR?=?0.57, [95% CI 0.34, 0.95], p?=?0.03, I²?=?57%) and seizure rating score among three studies (n?=?56) with MD?=???1.04, [95% CI ??2.07, ??0.00], p?=?0.05, I²?=?71%. Three studies (n?=?62) presented with improved anti-oxidant enzymes’ profile (SMD?=?0.75, [95% CI 0.55, 2.31], p?=?0.0008, I²?=?44%) as a result of exercise intervention. Same intervention failed to show any significant measure for BDNF level and neuroprotection assessed through neuronal number in different brain areas with MD?=???1.22, [95% CI ??136.66, 134.22], p?=?0.99, I²?=?0% and SMD?=???0.05, [95% CI ??0.62, 0.52], p?=?0.86, I²?=?61% respectively. Qualitative review concluded in the reduction of median seizure score, depression and anxiety-like behaviors with improved cognitive performances in pre-SE exercised animals while improved memory and learning capabilities with increased neurogenesis were observed in post-SE exercised models.

Conclusions

Exercise before SE reduces behavioral seizures and oxidative stress with improvements in cognitive abilities. Post-SE exercise enhances learning and memory with neurogenesis in KA models. More extensive research on morphological and biochemical profiles is needed to explore underlying mechanisms.

     

Early versus Delayed Antiretroviral Therapy for HIV and Tuberculosis Co-Infected Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

ObjectiveTo compare important clinical outcomes between early and delayed initiation of antiretroviral therapy (ART) in adults who had a co-infection of human immunodeficiency virus (HIV) and tuberculosis (TB).MethodsWe performed a systematic search for relevant publications on PubMed, EMBASE, and the International Clinical Trials Registry Platform. We included randomized controlled trials (RCTs) that compared early ART initiation (within four weeks after anti-TB treatment starting) and delayed ART initiation (after eight weeks but less than twelve weeks of anti-TB treatment starting) in the course of TB treatment. Pooled estimates with corresponding 95% confidence interval (95%CI) were calculated with random-effects model. Sensitivity analysis was performed to investigate the stability of pooled estimates.ResultsA meta-analysis was evaluated from six RCTs with 2272 participants. Compared to delayed ART initiation, early ART initiation significantly reduces all-cause mortality in HIV-positive patients with TB [incidence rate ratio (IRR) 0.75, 95%CI 0.59 to 0.95; I² = 0.00%; p = 0.67], even though there is an increased risk for IRD [IRR 2.29, 95%CI 1.81 to 2.91; I²2 = 0.00%; p = 0.56]. Additionally, early ART initiation was not associated with an increased risk for grade 3-4 drug-related adverse events [IRR 0.99, 95%CI 0.83 to 1.18; I² = 0.00%; p = 0.56].ConclusionsAlthough limited evidence, our results provide support for early ART initiation in the course of anti-TB treatment. However, more well-designed cohort or intervention studies are required to further confirm our findings.     

Exploring the influence of rural residence on uptake of organized cancer screening – A systematic review of international literature

Lower screening uptake could impact cancer survival in rural areas. This systematic review sought studies comparing rural/urban uptake of colorectal, cervical and breast cancer screening in high income countries. Relevant studies (n = 50) were identified systematically by searching Medline, EMBASE and CINAHL. Narrative synthesis found that screening uptake for all three cancers was generally lower in rural areas. In meta-analysis, colorectal cancer screening uptake (OR 0.66, 95 % CI = 0.50−0.87, I² = 85 %) was significantly lower for rural dwellers than their urban counterparts. The meta-analysis found no relationship between uptake of breast cancer screening and rural versus urban residency (OR 0.93, 95 % CI = 0.80–1.09, I² = 86 %). However, it is important to note the limitation of the significant statistical heterogeneity found which demonstrates the lack of consistency between the few studies eligible for inclusion in the meta-analyses. Cancer screening uptake is apparently lower for rural dwellers which may contribute to poorer survival. National screening programmes should consider geography in planning.     

Association between Cryptosporidium infection and cancer: A systematic review and meta-analysis

The link between cryptosporidiosis and cancer has been suggested by some epidemiological studies. This systematic review and meta-analysis was conducted to further understand this relationship. In the current study, six electronic databases were reviewed for Cryptosporidium infection in cancer patients. We used random effects model and 95% confidence intervals (CI) to determine the overall odds ratio (OR). Heterogeneity was calculated with Cochran's Q test and I²statistic. In total, 19 studies involving 3562 individuals with case-control (nine) and cross-sectional (ten) designs were included in our project. The pooled overall random effect favored a statistically significant increased risk of Cryptosporidium infection in cancer patients compared with non-cancer individuals [OR = 3.3; 95% CI: 2.18–4.98]. The overall heterogeneity was medium (χ² = 25.77; I² = 30.2%, P = .11). The pooled ORs in case-control and cross-sectional studies were [OR = 5.60; 95% CI: 3.43–9.13; χ² = 5.51; I² = 0.00%, P = .70] and [OR = 2.08; 95% CI: 1.18–3.67; χ² = 13.69; I² = 34.3, P = .13], respectively. T-value and P-value were 0.54 and 0.57 based on the results of Harbord's modified's regression test. In summary, this meta-analysis demonstrates that Cryptosporidium infection is associated with cancer. Also, it found that study design and year of publication are the specific sources of heterogeneity. Further studies should be carried out to investigate the impact of Cryptosporidium infection in the onset or development of cancer in the future.     

Evolution of heterogeneity (i(2)) estimates and their 95% confidence intervals in large meta-analyses

Background

Assessment of heterogeneity is essential in systematic reviews and meta-analyses of clinical trials. The most commonly used heterogeneity measure, I², provides an estimate of the proportion of variability in a meta-analysis that is explained by differences between the included trials rather than by sampling error. Recent studies have raised concerns about the reliability of I² estimates, due to their dependence on the precision of included trials and time-dependent biases. Authors have also advocated use of 95% confidence intervals (CIs) to express the uncertainty associated with I² estimates. However, no previous studies have explored how many trials and events are required to ensure stable and reliable I² estimates, or how 95% CIs perform as evidence accumulates.

Methodology/Principal Findings

To assess the stability and reliability of I² estimates and their 95% CIs, in relation to the cumulative number of trials and events in meta-analysis, we looked at 16 large Cochrane meta-analyses - each including a sufficient number of trials and events to reliably estimate I² - and monitored the I² estimates and their 95% CIs for each year of publication. In 10 of the 16 meta-analyses, the I² estimates fluctuated more than 40% over time. The median number of events and trials required before the cumulative I² estimates stayed within +/−20% of the final I² estimate was 467 and 11. No major fluctuations were observed after 500 events and 14 trials. The 95% confidence intervals provided good coverage over time.

Conclusions/Significance

I² estimates need to be interpreted with caution when the meta-analysis only includes a limited number of events or trials. Confidence intervals for I² estimates provide good coverage as evidence accumulates, and are thus valuable for reflecting the uncertainty associated with estimating I².     

The Effectiveness of Thyroid Hormone Replacement Therapy on Heart Failure and Low-Triiodothyronine Syndrome: An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials

ObjectiveThe purpose of this study was to conduct a systematic review and meta-analysis evaluating the role of thyroid hormone therapy in patients with heart failure and low-triiodothyronine syndrome.MethodsThe electronic databases PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and China Biology Medicine disc were systematically searched to identify eligible studies published before November 27, 2021. The mean difference was pooled for randomized controlled trials using a random-effects model.ResultsThe meta-analysis showed that thyroid hormone treatment improved the left ventricular ejection fraction (weighted mean difference [WMD] 5.61, 95% confidence interval [CI]: 4.38 to 6.85, I² = 63.12%, P < 0.01). The cardiac output improved with thyroid hormone therapy (WMD 0.65, 95% CI: 0.42 to 0.89, I² = 84.28%, P < 0.01). The early-to-late diastolic transmitral flow velocity in the thyroid hormone group was also improved compared to the control group (WMD 0.29, 95% CI: 0.15 to 0.42, I² = 95.08%, P < 0.01). The left ventricular diastolic dysfunction was decreased with thyroid hormone treatment (WMD ?5.17, 95% CI: ?7.47 to ?2.88, I² = 90.18%, P < 0.01). The brain natriuretic peptide decreased with thyroid hormone treatment (standardized mean difference ?1.49, 95% CI: ?2.15 to ?0.84, I² = 90.18%, P < 0.01). Noradrenaline decreased with thyroid hormone therapy (WMD ?349.86, 95% CI: ?401.05 to ?298.67, I² = 0%, P < 0.01). Free triiodothyronine increased with thyroid hormone treatment (standardized mean difference 2.18, 95% CI: 0.75 to 2.60, I² = 98.20%, P < 0.01).ConclusionThis meta-analysis showed that thyroid hormone replacement therapy was effective in patients with heart failure and low-triiodothyronine syndrome.     

Serum Anticholinergic Activity and Cognitive and Functional Adverse Outcomes in Older People: A Systematic Review and Meta-Analysis of the Literature

Introduction

Studies have reported associations between serum anticholinergic activity (SAA) and decline in cognitive performance, delirium, and functional impairment. The aim of this meta-analysis was to explore and quantify associations between SAA and adverse cognitive and functional outcomes in older people.

Materials and Methods

A literature search in Ovid MEDLINE, EMBASE, PsycINFO and IPA from 1946–2014 was completed. The primary outcomes of interest were cognitive and functional adverse outcomes associated with SAA in older people aged 55 years and above. The Cochrane Risk-Bias assessment tool was used to assess bias in randomised controlled trials (RCTs). The Newcastle-Ottawa Scale was used to assess the quality of non-RCTs. Meta-analyses were conducted for RCTs and cohort studies separately. Heterogeneity was assessed using I² tests.

Results

The primary electronic literature search identified a total of 1559 records in the 4 different databases. On the basis of full-text analysis, 33 studies that met the inclusion criteria. The review included 4 RCTs, 5 prospective cohort studies, 3 longitudinal cohort studies, 17 cross-sectional studies, and 4 case-control studies. Twenty-four of the retrieved studies examined an association between SAA and cognitive outcomes, 2 studies examined an association with SAA and functional outcomes and 8 studies examined associations between SAA and both cognitive, and functional outcomes. The meta-analysis on 4 RCTs showed no association with higher SAA and cognitive performance (I² = 89.38%, H² = 25.53 and p-value = <0.05) however, the pooled data from 4 observational studies showed elevated SAA was associated with reduced cognitive performance (I² = 0.00%, H² = 3.37 and p-value = 0.34).

Conclusion

This systematic review summarises the limitations of the SAA on predicting cognitive and functional outcomes in older people. SAA measured by receptor bioassay is flawed and its use in older people with multimorbidity and polypharmacy is questionable.     

Prediction of the energy value of rabbit feeds varying widely in fibre content

Digestibility trials of 23 pelleted diets, with one or two ingredients and having 8.7–53.5% acid detergent fibre (ADF) on a dry matter (DM) basis, were carried out in adult rabbits fed ad libitum. Using a step-wise linear regression approach, the relationship between the digestible energy content (DE) or the coefficient of digestibility of gross energy (dGE) and the chemical composition of diets was established. Excluding beet pulp, with a very high crude fibre digestibility (54.8%), the prediction equations obtained were: DE (MJ kg⁻¹ DM) = 14.2 − 0.205 ADF + 0.218 EE + 0.057 CP (R² = 0.965, RSD = 0.494) and dGE (%) = 83.2 − 1.07 ADF (R² = 0.951, RSD = 3.15) where ADF, ether extract (EE) and crude protein (CP) are expressed as a percentage on a DM basis. When diets with level of EE or CP higher than 6% or 18% respectively (grape marc, olive oil cake, brewer's grains, sunflower meal) were also removed, the prediction equations became: DE = 15.9 − 0.219 ADF (R² = 0.974, RSD = 0.391) and dGE = 85.6 − 1.20 ADF (R² = 0.977, RSD = 2.02). The contents in DE, digestible crude protein and undigestible crude fibre of 21 ingredients are presented and discussed in comparison with other studies.     

Effects of chromium supplementation on lipid profile in patients with type 2 diabetes: A systematic review and dose-response meta-analysis of randomized controlled trials

BackgroundThe purpose of this study was to determine the influence of chromium supplementation on lipid profile in patients with type 2 diabetes mellitus (T2DM).MethodsA systematic search was performed in Scopus, Embase, Web of Science, the Cochrane library and PubMed databases to find randomized controlled trials (RCTs) related to the effect of chromium supplementation on lipid profile in patients with T2DM, up to June 2020. Meta-analyses were performed using the random-effects model, and I² index was used to evaluate heterogeneity.ResultsThe primary search yielded 725 publications. 24 RCTs (with 28 effect size) were eligible. Our meta-analysis indicated that chromium supplementation resulted in a significant decrease in serum levels of triglyceride (TG) (MD: -6.54 mg/dl, 95 % CI: -13.08 to -0.00, P = 0.050) and total cholesterol (TC) (WMD: -7.77 mg/dl, 95 % CI: -11.35 to -4.18, P < 0.001). Furthermore, chromium significantly increases high-density lipoprotein (HDL) (WMD: 2.23 mg/dl, 95 % CI: 0.07–4.40, P = 0.043) level. However, chromium supplementation did not have significant effects on low-density lipoprotein (LDL) (WMD: -8.54 mg/dl, 95 % CI: -19.58 to 2.49, P = 0.129) level.ConclusionChromium supplementation may significantly improve lipid profile in patients with T2DM by decreasing TG and TC and increasing HDL. However, based on our analysis, chromium failed to affect LDL. It should be noted that the lipid-lowering properties of chromium supplementation were small and may not reach clinical importance.