Acupuncture for migraine: A systematic review and meta-regression of randomized controlled trials.

OBJECTIVES: This meta-analysis aimed to explore the relationship between the dose of acupuncture sessions, acupuncture frequency, and acupuncture duration and its effects on migraine. METHODS: Eight databases were searched for randomized controlled trials (RCTs) evaluating the efficacy of penetrating manual acupuncture for migraine published in English and Chinese from inception to June 20, 2024. The robust-error meta-regression (REMR) approach and non-linear meta-regression with restricted cubic spline (RCS) were used to investigate the dose-response association between acupuncture sessions, acupuncture frequency, and acupuncture duration and the frequency of migraine attacks. The potential nonlinear relationships was tested by restricting the regression coefficient to zero and a P value＜0.1. The statistical analysis was conducted using Stata 17.0. The risk of bias was independently assessed by two reviewers using the Cochrane tool. The reporting quality for acupuncture procedures was evaluated by STRICTA criteria. RESULTS: Thirty-two RCTs involving 1562 participants were included, and the results showed a J-shaped dose-response association between acupuncture sessions, acupuncture frequency, and acupuncture duration and migraine attack frequency. After 16 acupuncture sessions, the change in the frequency of migraine attacks was 3.95 (95 %CI: 3.13 to 4.77). Three sessions of acupuncture a week resulted in a significant decrease in the frequency of migraine attacks, reaching 4.04 (95 % CI: 2.49 to 5.58). After two months of acupuncture, the frequency of migraine attacks decreased significantly, showing a difference of 4.05 (95 % CI: 3.61 to 4.49). Subsequently, the improvement trend gradually flattened, yielding diminishing benefits to patients. The risk of bias showed that seven studies were rated as "low risk", two were rated as "high risk", and the others were rated as "unclear risk". The reporting quality of RCTs of acupuncture for migraine remain suboptimal. CONCLUSIONS: A non-linear dose-response relationship was found between acupuncture sessions, acupuncture frequency, and acupuncture duration and migraine attack frequency. The results of our study recommend 16 sessions of acupuncture with a frequency of 3 sessions/week and a treatment duration of 1.5 to 2 months. REGISTRATION NUMBER: This meta-analysis has been registered on PROSPERO (CRD42023400493).

Biologicals for the treatment of lupus nephritis: a Bayesian network meta-regression analysis.

Background: Previous studies comparing the efficacy and safety of different treatment regimens for lupus nephritis are scarce. Moreover, confounding factors such as the duration of follow-up were hardly adjusted in those studies, potentially compromising the results and their extents to clinical settings. Objective: To rigorously investigate the efficacy and safety of biologics in patients with lupus nephritis using Bayesian network meta-regression analyses that adjust for the follow-up period, in order to provide more robust evidence for clinicians. Methods: Databases comprising PubMed, Embase, MedlinePlus, Cochrane Library, Google Scholars, and Scopus were retrieved for eligible articles from inception to February 29, 2024. The primary endpoint was the complete response rate, the secondary endpoint was the partial response rate, the tertiary endpoints were the adverse events, and infection-related adverse events. Napierian Logarithm of hazard ratio (lnHR) and the standard error of lnHR (selnHR) were generated for dichotomous variants by STATA 18.0 MP and then put into Rstudio 4.3.2 to conduct Bayesian network meta-analysis as well as network meta-regression analysis to yield hazard ratio (HR) as pairwise effect size. Results: Ten studies involving 2138 patients and 11 treatment regimens were ultimately included. In the original analysis, for the primary endpoint, compared to the control group, obinutuzumab (22.6 months), abatacept-30mg (20.5 months), abatacept-10mg (17.8 months), and belimumab (23.3 months) demonstrated significant superiority (HR ranged from 1.6 to 2.5), more ever, their significance regarding relative efficacy was correlated with follow up period, namely "time window" (shown in parentheses above). For the secondary endpoint, compared to the control group, obinutuzumab and abatacept-30mg showed conspicuous preponderance (HR ranged from 1.6 to 2.4), "time window" was also detected in abatacept-30mg (20.5 months), whereas obinutuzumab remained consistently obviously effective regardless of the follow-up period (shown in parentheses above). For the tertiary endpoint, there were no differences among active regimens and control. Conclusions: Considering the efficacy and safety and "time window" phenomenon, we recommend obinutuzumab as the preferred treatment for LN. Certainly, more rigorous head-to-head clinical trials are warranted to validate those findings.

Are changes in pain intensity related to changes in balance control in individuals with chronic non-specific low back pain? A systematic review and meta-analysis.

PURPOSE: The aim of this study is to summarize the evidence regarding whether pain reduction in individuals with chronic non-specific low back pain (CNSLBP) following conservative interventions is related to corresponding improvements in balance control. METHODS: Randomized controlled trials were identified from 5 databases (MEDLINE, Cochrane Library, Embase, Web of Science, and PsycINFO). Two reviewers independently screened and identified relevant studies that investigated the effects of nonsurgical or nonpharmacological CNSLBP treatments on both pain intensity and balance control. Meta-regression analyses were performed to establish the associations between post-treatment changes in these 2 variables. RESULTS: 31 studies involving 1280 participants with CNSLBP were included. Moderate-quality evidence suggested that pain reduction was associated with and explained 34-45 % of decreases in body sway, as measured by center-of-pressure (CoP) area and CoP velocity with eyes open. However, no significant association was observed between pain reduction and CoP area or velocity in anteroposterior/mediolateral directions. Similarly, there was no significant association between pain reduction and CoP distance or radius. Low-quality evidence indicated that pain relief explained a 15 % improvement in one-leg stance with eyes open but not in the eyes-closed condition. Additionally, very low-quality evidence suggested that pain relief explained a 44 % decrease in the static anteroposterior stability index with eyes closed but not in the eyes-open, mediolateral, or overall conditions. Furthermore, low-quality evidence indicated that reduced pain was associated with and accounted for 25-43 % of the improved composite and posteromedial scores of the star-excursion balance test, rather than the anterior and posterolateral scores. CONCLUSION: Depending on the type of balance assessment, pain relief following conservative interventions may slightly to moderately enhance balance control in individuals with CNSLBP. Clinicians should pay close attention to the balance control in patients with CNSLBP, particularly among older adults.

Maintenance of zilucoplan efficacy in patients with generalised myasthenia gravis up to 24 weeks: a model-informed analysis.

Background: Clinical efficacy of zilucoplan has been demonstrated in a 12-week, placebo-controlled, phase III study in patients with acetylcholine receptor autoantibody-positive generalised myasthenia gravis (gMG). However, placebo-controlled zilucoplan data past 12 weeks are not available. Objectives: Predict the treatment effect of zilucoplan versus control (placebo or standard of care) in patients with gMG up to 24 weeks. Design: A model-informed analysis (MIA) within a Bayesian framework. Methods: Part 1 of the MIA comprised a control meta-regression using aggregate data on control response over time from randomised studies and a national myasthenia gravis (MG) registry. In Part 2, a combined Bayesian analysis of individual patient-level data from the phase II (NCT03315130), RAISE (NCT04115293) and RAISE-XT (NCT04225871) studies of zilucoplan was conducted using posterior distributions from Part 1 as informative priors. Population mean treatment effect in the change from baseline (CFB) at week 24 in MG-Activities of Daily Living (MG-ADL) and quantitative MG (QMG) scores for zilucoplan versus control were assessed. Results: At week 24, the predicted mean CFB in MG-ADL score was -4.55 (95% credible interval: -6.04, -3.13) with zilucoplan versus -2.00 (-3.35, -0.64) with control (difference: -2.55 [-3.76, -1.40]). The probability of a favourable treatment effect as measured by MG-ADL score at week 24 with zilucoplan versus control was >99.9%. There was an 82.8% probability that the difference in the predicted mean CFB in MG-ADL score at week 24 was greater than the clinically meaningful threshold (⩾2.0-point improvement). Comparable results were observed with QMG. Conclusion: This MIA demonstrates the maintenance of efficacy with zilucoplan versus control up to 24 weeks. Through combining real-world evidence with data from randomised studies, this novel method to estimate long-term treatment efficacy facilitated reduced exposure to placebo in the phase III RAISE study. This methodology could be used to reduce the length of future placebo-controlled studies.

Relationship between magnesium dosage and the preventive effect on cisplatin-induced nephrotoxicity: meta-analysis and meta-regression analysis.

BACKGROUND: Cisplatin (CDDP) is an anticancer drug used to treat several types of cancer. CDDP-induced nephrotoxicity (CIN) is a serious adverse effect of CDDP treatment. Although magnesium sulfate (Mg) premedication has been proven to prevent CIN, the relationship between Mg dosage and its preventive effects on CIN are unknown. Therefore, we have evaluated this relationship using meta-analysis and meta-regression analysis to optimize cancer chemotherapies, including CDDP. METHODS: We selected candidate studies, generated a forest plot to evaluate the preventive effects of Mg on CIN, and performed subgroup analyses. Moreover, a meta-regression analysis was conducted to reveal the relationship between Mg dosage and its preventive effects on CIN. RESULTS: We identified 17 related studies and the total odds ratio (OR) of Mg premedication on CIN was 0.26 and the 95% confidence interval (95% CI) was 0.17-0.41 (p < 0.00001) although funnel plot suggested asymmetry. In subgroup analysis by forest plot, total OR with 95% CI of low Mg dosage administration (less than 10 mEq) and high Mg dosage administration (10 mEq or higher) was 0.35 (0.16-0.77, p = 0.0169) and 0.12 (0.07-0.21, p < 0.0001), respectively. In addition, meta-regression analysis was performed on Mg dosage and the OR of related studies, indicating a relationship between Mg dosage and OR (p = 0.0349). CONCLUSION: This study has revealed that premedication with Mg prevented CIN in a dose-dependent manner.

The effects of chicory inulin-type fructans supplementation on weight management outcomes: systematic review, meta-analysis and meta-regression of randomized controlled trials.

BACKGROUND: Excess body weight and adiposity can adversely affect metabolic health. Prebiotics such as inulin-type fructans (ITF) from chicory root are known to modulate gut microbiota and may improve body weight regulation. OBJECTIVE: This study aimed to assess evidence for chicory ITF supplementation to support weight management. METHODS: Eligible articles (initial search to 2021, updated to February 2023) were searched from EMBASE, MEDLINE (PubMed), and Cochrane Library. Data on primary (body weight) and secondary outcomes [body mass index (BMI), total fat mass, body fat percentage and waist circumference] were extracted by two reviewers independently. Random-effects model using inverse variance method was utilized. Subgroup analysis (health status, ITF-type) and meta-regression (dose and duration) were evaluated. RESULTS: A total of 32 eligible studies were included. Chicory ITF significantly reduced body weight [mean difference (MD) -0.97 kg, 95% confidence interval (95% CI: -1.34, -0.59); n = 1184] compared with placebo. ITF favored overall effects reduction in BMI (MD: -0.39 kg/m2; 95% CI: -0.57 to -0.20; n = 985), fat mass (MD: -0.37 kg; 95% CI: -0.61 to -0.13; n = 397), waist circumference (MD: -1.03 cm; 95% CI: -1.69 to -0.37; n = 604), and for intervention duration >8 wk, body fat percentage (MD: -0.78%; 95% CI: -1.17 to -0.39; n = 488). Except for considerable heterogeneity in body weight (I2 = 73%) and body fat percentage (I2 = 75%), all other outcomes had negligible to moderate heterogeneity. Significant reduction in body weight, BMI and waist circumference was evident irrespective of participants' health status. There was minimal evidence that dose, duration, or type of ITF influenced the magnitude of reductions in outcomes. CONCLUSIONS: Chicory ITF supplementation may benefit weight management by reducing body weight, BMI, fat mass, waist circumference, and to a certain extent body fat percentage. PROSPERO REGISTRATION NUMBER: CRD42020184908.

The effect of physical exercise on circulating neurotrophic factors in healthy aged subjects: A meta-analysis and meta-regression.

Vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and insulin-like growth factor-1 (IGF-1) may help the brain resist both functional and structural neurodegeneration, which is critical for maintaining cognitive and neurological health in older adults. This meta-analysis and meta-regression seek to elucidate the impact of physical activity on these biomarker levels in healthy seniors, as well as to examine the influence of several moderator factors, including age, sex, period length, and time, for the first time. The standardized mean effect metric was used to assess the influence of weights, which reflected each group's relative importance in comparison to baseline data. The study looked at potential moderating factors including age, gender, and physical activity levels. The analysis of 11 studies indicated no significant effect of physical activity on VEGF levels [0.328, CI 95 % (-0.871 to 1.52); I2 = 0.00; p = 0.592; Q = 4.14]. Physical activity had a substantial impact on brain-derived neurotrophic factor (0.827, 95 % confidence interval: 0.487 to 1.16; I2 = 0.00; p = 0.00; Q = 78.46), with females showing particularly notable effects (Tau2 = 0.327, Tau = 0.571, I2 = 80.90 %, Q = 68.05, df = 15, p = 0.00). Physical activity also had a substantial effect on insulin-like growth factor 1 (0.276, 95 % confidence interval: 0.065 to 0.487; I2 = 0.00; p = 0.10; Q = 8.35), indicating that it positively influences IGF-1 levels. Overall, while physical exercise has a significant effect on BDNF and IGF-1, more research is needed to fully understand its impact on vascular endothelial growth factor and to investigate how individual characteristics may influence exercise outcomes.

Health state utility values of type 2 diabetes mellitus and related complications: a systematic review and meta-regression.

BACKGROUND: This study aimed to synthesize and quantitatively examine Health State Utility Values (HSUVs) for Type 2 Diabetes Mellitus (T2DM) and its complications, providing a robust meta-regression framework for selecting appropriate HSUV estimates. METHOD: We conducted a systematic review to extract HSUVs for T2DM and its complications, encompassing various influencing factors. Relevant literature was sourced from a review spanning 2000-2020, supplemented by literature from PubMed, Embase, and the Web of Science (up to March 2024). Multivariate meta-regression was performed to evaluate the impact of measurement tools, tariffs, health status, and clinical and demographic variables on HSUVs. RESULTS: Our search yielded 118 studies, contributing 1044 HSUVs. The HSUVs for T2DM with complications varied, from 0.65 for cerebrovascular disease to 0.77 for neuropathy. The EQ-5D-3L emerged as the most frequently employed valuation method. HSUV differences across instruments were observed; 15-D had the highest (0.89), while HUI-3 had the lowest (0.70) values. Regression analysis elucidated the significant effects of instrument and tariff choice on HSUVs. Complication-related utility decrement, especially in diabetic foot, was quantified. Age <70 was linked to increased HSUVs, while longer illness duration, hypertension, overweight and obesity correlated with reduced HSUVs. CONCLUSION: Accurate HSUVs are vital for the optimization of T2DM management strategies. This study provided a comprehensive data pool for HSUVs selection, and quantified the influence of various factors on HSUVs, informing analysts and policymakers in understanding the utility variations associated with T2DM and its complications.

The relationship between treatment-related changes in total hip BMD measured after 12, 18, and 24 mo and fracture risk reduction in osteoporosis clinical trials: the FNIH-ASBMR-SABRE project.

There is a strong association between total hip bone mineral density (THBMD) changes after 24 mo of treatment and reduced fracture risk. We examined whether changes in THBMD after 12 and 18 mo of treatment are also associated with fracture risk reduction. We used individual patient data (n = 122 235 participants) from 22 randomized, placebo-controlled, double-blind trials of osteoporosis medications. We calculated the difference in mean percent change in THBMD (active-placebo) at 12, 18, and 24 mo using data available for each trial. We determined the treatment-related fracture reductions for the entire follow-up period, using logistic regression for radiologic vertebral fractures and Cox regression for hip, non-vertebral, "all" (combination of non-vertebral, clinical vertebral, and radiologic vertebral) fractures and all clinical fractures (combination of non-vertebral and clinical vertebral). We performed meta-regression to estimate the study-level association (r2 and 95% confidence interval) between treatment-related differences in THBMD changes for each BMD measurement interval and fracture risk reduction. The meta-regression revealed that for vertebral fractures, the r2 (95% confidence interval) was 0.59 (0.19, 0.75), 0.69 (0.32, 0.82), and 0.73 (0.33, 0.84) for 12, 18, and 24 mo, respectively. Similar patterns were observed for hip: r2 = 0.27 (0.00, 0.54), 0.39 (0.02, 0.63), and 0.41 (0.02, 0.65); non-vertebral: r2 = 0.27 (0.01, 0.52), 0.49 (0.10, 0.69), and 0.53 (0.11, 0.72); all fractures: r2 = 0.44 (0.10, 0.64), 0.63 (0.24, 0.77), and 0.66 (0.25, 0.80); and all clinical fractures: r2 = 0.46 (0.11, 0.65), 0.64 (0.26, 0.78), and 0.71 (0.32, 0.83), for 12-, 18-, and 24-mo changes in THBMD, respectively. These findings demonstrate that treatment-related THBMD changes at 12, 18, and 24 mo are associated with fracture risk reductions across trials. We conclude that BMD measurement intervals as short as 12 mo could be used to assess fracture efficacy, but the association is stronger with longer BMD measurement intervals.

In this study, we looked at how changes in hip bone density over time relate to the risk of fractures in people taking osteoporosis medications. We analysed data from over 122 000 participants across 22 different clinical trials. We found that the increase in bone density measured after 12, 18, and 24 mo of treatment was linked to the risk of fractures. Specifically, greater improvements in bone density were associated with fewer fractures in the spine, hips, and other bones. Using statistical methods, we calculated the strength of this association. We discovered that the later, we measured BMD in people taking the medication, the stronger the link between improved bone density and reduced fracture risk became. Our findings suggest that bone density measurements after 12 mo of treatment could help predict how well a medication will prevent fractures. However, the best predictions came from bone density changes measured over longer periods.

Exploring the association between ambient air pollution and COVID-19 risk: A comprehensive meta-analysis with meta-regression modelling.

Introduction: Air pollution is speculated to increase the risk of Coronavirus disease-2019 (COVID-19). Nevertheless, the results remain inconsistent and inconclusive. This study aimed to explore the association between ambient air pollution (AAP) and COVID-19 risks using a meta-analysis with meta-regression modelling. Methods: The inclusion criteria were: original studies quantifying the association using effect sizes and 95 % confidence intervals (CIs); time-series, cohort, ecological or case-crossover peer-reviewed studies in English. Exclusion criteria encompassed non-original studies, animal studies, and data with common errors. PubMed, Web of Science, Embase and Google Scholar electronic databases were systemically searched for eligible literature, up to 31, March 2023. The risk of bias (ROB) was assessed following the Agency for Healthcare Research and Quality parameters. A random-effects model was used to calculate pooled risk ratios (RRs) and their 95 % CIs. Results: A total of 58 studies, between 2020 and 2023, met the inclusion criteria. The global representation was skewed, with major contributions from the USA (24.1 %) and China (22.4 %). The distribution included studies on short-term (43.1 %) and long-term (56.9 %) air pollution exposure. Ecological studies constituted 51.7 %, time-series-27.6 %, cohorts-17.2 %, and case crossover-3.4 %. ROB assessment showed low (86.2 %) and moderate (13.8 %) risk. The COVID-19 incidences increased with a 10 µg/m3 increase in PM2.5 [RR = 4.9045; 95 % CI (4.1548-5.7895)], PM10 [RR = 2.9427: (2.2290-3.8850)], NO2 [RR = 3.2750: (3.1420-3.4136)], SO2 [RR = 3.3400: (2.7931-3.9940)], CO [RR = 2.6244: (2.5208-2.7322)] and O3 [RR = 2.4008: (2.1859-2.6368)] concentrations. A 10 µg/m3 increase in concentrations of PM2.5 [RR = 3.0418: (2.7344-3.3838)], PM10 [RR = 2.6202: (2.1602-3.1781)], NO2 [RR = 3.2226: (2.1411-4.8504)], CO [RR = 1.8021 (0.8045-4.0370)] and O3 [RR = 2.3270 (1.5906-3.4045)] was significantly associated with COVID-19 mortality. Stratified analysis showed that study design, exposure period, and country influenced exposure-response associations. Meta-regression model indicated significant predictors for air pollution-COVID-19 incidence associations. Conclusion: The study, while robust, lacks causality demonstration and focuses only on the USA and China, limiting its generalizability. Regardless, the study provides a strong evidence base for air pollution-COVID-19-risks associations, offering valuable insights for intervention measures for COVID-19.

Virtual reality exposure therapy for social anxiety disorders: a meta-analysis and meta-regression of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Virtual reality exposure therapy offers a unique opportunity to treat social anxiety disorder. This meta-analysis aims to evaluate the effectiveness of virtual reality exposure therapy compared to waitlist comparators or other interventions for individuals with social anxiety disorder in alleviating anxiety symptoms. METHODS: A three-step comprehensive search for the randomized controlled trials of virtual reality exposure therapy was conducted from inception to 7 December 2023. The overall effect was measured using Hedges' g and determined using t-statistics at a significance level of p < 0.05. Sensitivity, subgroup, and meta-regression analyses were carried out. RESULTS: A total of 17 randomized control trials were retrieved from nine electronic databases. Virtual reality exposure therapy has greater efficacy than waitlist comparators in reducing anxiety symptoms at post-intervention and follow-up assessment. Virtual reality exposure therapy demonstrates a similar effect to other interventions at post-intervention and follow-up assessment. We observed a greater effect for participants with symptomatic social anxiety when we combined the intervention with cognitive behavioral therapy compared to its counterpart. Meta-regression analyses found no significant covariate. CONCLUSIONS: Overall, virtual reality exposure therapy can provide supplementary therapy for improving anxiety symptoms. Additional high-quality and large-scale trials with long-term follow-up are needed.

Association between depressive duration and cognitive decline in middle-aged and older adults: Evidence from the Health and Retirement Study 2010-2018.

BACKGROUND: Depression has been found to be associated with cognitive decline, but whether longer depressive durations lead to more severe cognitive declines has not been investigated. We aimed to estimate the association between depressive duration and cognitive decline in middle-aged and older Americans based on a large-scale representative population study. METHODS: We included 27,886 participants from the Health and Retirement Study (HRS) in 2010-2018. Four datasets with 2-, 4-, 6-, and 8-year consecutive interviews were further derived which involving persistent depressed and persistent depression-free individuals. Multiple linear regressions were constructed to estimate the effects of each depressive duration on the decline in global cognition, memory and mental status. Meta-regressions were performed to test the linear trends and to explore the heterogeneity between sex, age and baseline cognitive function along with subgroup analyses. RESULTS: Depressive durations of 2, 4, 6, and 8 years were associated with reductions in global cognitive scores of 0.62 points (95% CI: 0.51-0.73), 0.77 points (95% CI: 0.60-0.94), 0.83 points (95% CI: 0.55-1.10), and 1.09 points (95% CI: 0.63-1.55), respectively, indicating a linear trend (P = 0.016). More pronounced associations were observed in middle-aged adults and females. Similar patterns were found in the associations between depressive duration and two subdomains, i.e., memory and mental health. LIMITATIONS: This study is essentially a cross-sectional study and therefore cannot provide causal associations. CONCLUSIONS: Longer depressive durations were linearly related to more severe cognitive declines. Timely intervention for depression targeted middle-aged adults can more effectively alleviate cognition-related burdens.

crossnma: An R package to synthesize cross-design evidence and cross-format data using network meta-analysis and network meta-regression.

BACKGROUND: Although aggregate data (AD) from randomised clinical trials (RCTs) are used in the majority of network meta-analyses (NMAs), other study designs (e.g., cohort studies and other non-randomised studies, NRS) can be informative about relative treatment effects. The individual participant data (IPD) of the study, when available, are preferred to AD for adjusting for important participant characteristics and to better handle heterogeneity and inconsistency in the network. RESULTS: We developed the R package crossnma to perform cross-format (IPD and AD) and cross-design (RCT and NRS) NMA and network meta-regression (NMR). The models are implemented as Bayesian three-level hierarchical models using Just Another Gibbs Sampler (JAGS) software within the R environment. The R package crossnma includes functions to automatically create the JAGS model, reformat the data (based on user input), assess convergence and summarize the results. We demonstrate the workflow within crossnma by using a network of six trials comparing four treatments. CONCLUSIONS: The R package crossnma enables the user to perform NMA and NMR with different data types in a Bayesian framework and facilitates the inclusion of all types of evidence recognising differences in risk of bias.

"Let's talk about sex, inflammaging, and cognition, baby": A meta-analysis and meta-regression of 106 case-control studies on mild cognitive impairment and Alzheimer's disease.

Background: Chronic inflammation is recognised as an important component of Alzheimer's disease (AD), yet its relationship with cognitive decline, sex-differences, and age is not well understood. This study investigated the relationship between inflammatory markers, cognition, sex, and age in individuals with mild cognitive impairment (MCI) and AD. Methods: A systematic review was performed to identify case-control studies which measured cognitive function and inflammatory markers in serum, plasma, and cerebrospinal fluid in individuals with MCI or AD compared with healthy control (HC) participants. Meta-analysis was performed with Hedges' g calculated in a random effects model. Meta-regression was conducted using age, sex, and mini-mental status exam (MMSE) values. Results: A total of 106 studies without a high risk of bias were included in the meta-analysis including 18,145 individuals: 5625 AD participants, 3907 MCI participants, and 8613 HC participants. Combined serum and plasma meta-analysis found that IL1ß, IL6, IL8, IL18, CRP, and hsCRP were significantly raised in individuals with AD compared to HC. In CSF, YKL40, and MCP-1 were raised in AD compared to HC. YKL40 was also raised in MCI compared to HC. Meta-regression analysis highlighted several novel findings: MMSE was negatively correlated with IL6 and positively correlated with IL1α in AD, while in MCI studies, MMSE was negatively correlated with IL8 and TNFα. Meta-regression also revealed sex-specific differences in levels of IL1α, IL4, IL6, IL18, hsCRP, MCP-1, and YKL-40 across AD and MCI studies, and age was found to account for heterogeneity of CRP, MCP-1, and IL4 in MCI and AD. Conclusion: Elevated levels of IL6 and YKL40 may reflect microglial inflammatory activity in both MCI and AD. Systemic inflammation may interact with the central nervous system, as poor cognitive function in individuals with AD and MCI was associated with higher levels of serum and plasma proinflammatory cytokines IL6 and TNFα. Moreover, variations of systemic inflammation between males and females may be modulated by sex-specific hormonal changes, such as declining oestrogen levels in females throughout the menopause transition. Longitudinal studies sampling a range of biospecimen types are needed to elucidate the nuances of the relationship between inflammation and cognition in individuals with MCI and AD, and understand how systemic and central inflammation differentially impact cognitive function.

Survival After Transarterial Radioembolization in Patients with Unresectable Intrahepatic Cholangiocarcinoma: An Updated Meta-analysis and Meta-regression.

PURPOSE: Transarterial radioembolization (TARE) has emerged as a promising therapeutic approach for unresectable intrahepatic cholangiocarcinoma (ICCA). We updated our previous meta-analysis with meta-regression to explore the efficacy of TARE in the context of ICCA. METHODS: We searched PubMed and Scopus for studies published up to September 1, 2023. The primary outcome was overall survival. Secondary outcomes were tumor overall response rate, severe adverse events, and downstaging to surgery. Meta-analysis employed a random-effects model, and meta-regression was utilized to explore sources of heterogeneity. RESULTS: We included 27 studies, involving 1365 patients. Pooled survival estimates at 1, 2, and 3 years were 52.6%, 27%, and 16.8%, respectively. Meta-regression revealed that the proportion of patients naïve to treatment was the only pre-TARE predictor of survival (1-, 2-, and 3-year survival of 70%, 45%, and 36% for treatment-naïve patients, mean survival 19.7 months vs. 44%, 18%, and 7% for non-naïve patients, mean survival 12.2 months). Overall response according to RECIST 1.1 and mRECIST was 19.6% and 67%, respectively. Effective downstaging to surgery was possible in varying rates (3-54%); the mean survival in these patients was 34.8 months (1-, 2-, and 3-year survival of 100%, 87%, and 64%). About 45.7% of patients experienced adverse events, but only 5.9% were severe. CONCLUSIONS: Our study benchmarked the survival rates of patients undergoing TARE for unresectable ICCA and showed that this is a valid option in these patients, especially if naïve to previous treatments. Downstaging to surgery is feasible in selected patients with promising results.

Effect of dietary ß-mannanase supplementation on growth performance, intestinal morphology, digesta viscosity, and nutrient utilization in broiler chickens: Meta-analysis and meta-regression.

Objective: The present study aimed to investigate the effectiveness of dietary ß-mannanase supplementation on growth performance, intestinal morphology, digesta viscosity, and dietary nutrient utilization in broiler chickens through a meta-analysis. The effects were further examined by a meta-regression analysis with activity levels of ß-mannanase in broiler diets. Methods: A total of 23 studies, which conducted in 11 countries and completed between December 2003 and August 2023, were finally selected for this meta-analysis. The standardized mean difference (SMD) and its 95% confidence interval (CI) were calculated as the effect size metrics using random effect model, with I2 value being utilized to measure heterogeneity. Investigated measurements included body weight gain (BWG), feed intake (FI), feed conversion ratio (FCR), villus height (VH), crypt depth (CD), VH:CD ratio, digesta viscosity, nitrogen-corrected metabolizable energy (AMEn), apparent ileal digestibility (AID), and apparent total tract retention (ATTR) of dry matter (DM), gross energy (GE), and nitrogen (N). All statistical analyses were performed using R version 4.3.3. Results: Results revealed significant positive effects of dietary ß-mannanase supplementation on BWG (P = 0.005), FCR (P < 0.001), VH (P < 0.001), VH:CD (P < 0.001), digesta viscosity (P < 0.001), AMEn (P = 0.011), AID of GE (P = 0.002) and N (P = 0.003), and ATTR of DM (P = 0.019), GE (P = 0.002), and N (P = 0.005) in broiler chickens. In the meta-regression analysis, increasing activity levels of ß-mannanase in broiler diets increased VH:CD (P < 0.001, R2 = 79.2%) and AID of N (P = 0.038, R2 = 67.4%). Conclusion: the current meta-analysis indicates that dietary ß-mannanase supplementation improves energy and nutrient utilization in broiler diets possibly by decreasing digesta viscosity and enhancing intestinal morphology in broiler chickens. These beneficial effects can contribute to improved growth performance in broiler chickens.

A Meta-Analytical Way of Systematizing the Use of Hyaluronan Gels for the Relief of Osteoarthritis, Compared with New Treatment Alternatives.

Hyaluronic acid, in the form of a gel or viscoelastic colloidal solution, is currently used for the viscosupplementation of joints affected by osteoarthritis, but its effectiveness is under debate in relation to newer alternatives. Based on meta-analytical arguments, the present article reinforces the opinion that there are still no decisive arguments for its complete replacement but for its use adapted to the peculiarities of the disease manifestation and of the patients. A "broad" comparison is first made with almost all alternatives studied in the last decade, and then a meta-regression study is performed to compare and predict the effect size induced by viscosupplementation therapy and its main challenger of clinical interest, the platelet-rich plasma treatment. If they are computerized, the developed models can represent tools for clinicians in determining the appropriateness of the option or not for viscosupplementation in a manner adapted to the pain felt by the patients, to their age, or to other clinical circumstances. The models were generated using algorithms implemented in the R language and assembled in different R packages. All primary data and necessary R scripts are provided in accordance with the philosophy of reproducible research. Finally, we adhere in a documented way to the opinion that HA-based products, currently under circumspection, are still clinically useful.

A meta-analysis of the meat physicochemical parameters of broiler chickens fed insect-based diet.

A total of 23 studies were identified in a literature search performed in the Scopus, Science Direct and Google Scholar databases for meta-analysis. The criteria used include studies that were published from 2015 to 2023 and those reporting the effects of insect meal utilisation in poultry diets. Data on live weight (LW), carcass weight (CW), moisture, meat pH, lightness (L*), redness (a*), yellowness (b*), proximate composition (protein, fat and ash content) and shear force in broilers were subjected to OpenMEE software, and data were pooled using a random-effect model. Subgroup analysis and meta-regression were performed to ascertain the influence of dietary insect meals on the response of meat aspects and the source of heterogeneity, respectively, using the following moderators (insect species, dosage level, feeding duration and age at slaughter). The results indicated that dietary insect meal did not affect LW, CW, meat L*, pH, shear force, moisture, fat and ash content. In contrast, dietary insect meal increased the a* of the meat (standardised mean differences (SMDs) = 1.03; 95% confidence intervals (CIs) = 0.484-1.578; p ≤ 0.001), b* (SMD = 1.117; 95% CI = 0.334-1.90; p = 0.005), and meat protein content (SMD = 0.365; 95% CI = 0.031-0.7; p = 0.032). The subgroup analysis showed that insect meal dosage of ≤10% and age at slaughtered ≤35 days had improved the LW, CW and meat L*. In addition, the meat a*, protein and ash content were also influenced by insect species, dosage levels and age at slaughter. In conclusion, ≤10% of either Hermetia illucens or Tenebrio molitor can be included in broiler diets without compromising the LW, CW, meat pH, colour, shear force, moisture, fat and ash content in broilers. The study therefore indicated that insect meals have a bright future as an alternative protein source in poultry diets.

Towards optimized methodological parameters for maximizing the behavioral effects of transcranial direct current stimulation.

Introduction: Transcranial direct current stimulation (tDCS) administers low-intensity direct current electrical stimulation to brain regions via electrodes arranged on the surface of the scalp. The core promise of tDCS is its ability to modulate brain activity and affect performance on diverse cognitive functions (affording causal inferences regarding regional brain activity and behavior), but the optimal methodological parameters for maximizing behavioral effects remain to be elucidated. Here we sought to examine the effects of 10 stimulation and experimental design factors across a series of five cognitive domains: motor performance, visual search, working memory, vigilance, and response inhibition. The objective was to identify a set of optimal parameter settings that consistently and reliably maximized the behavioral effects of tDCS within each cognitive domain. Methods: We surveyed tDCS effects on these various cognitive functions in healthy young adults, ultimately resulting in 721 effects across 106 published reports. Hierarchical Bayesian meta-regression models were fit to characterize how (and to what extent) these design parameters differentially predict the likelihood of positive/negative behavioral outcomes. Results: Consistent with many previous meta-analyses of tDCS effects, extensive variability was observed across tasks and measured outcomes. Consequently, most design parameters did not confer consistent advantages or disadvantages to behavioral effects-a domain-general model suggested an advantage to using within-subjects designs (versus between-subjects) and the tendency for cathodal stimulation (relative to anodal stimulation) to produce reduced behavioral effects, but these associations were scarcely-evident in domain-specific models. Discussion: These findings highlight the urgent need for tDCS studies to more systematically probe the effects of these parameters on behavior to fulfill the promise of identifying causal links between brain function and cognition.

Growth performance, antioxidant status, intestinal morphology, and body composition of Nile tilapia (Oreochromis niloticus) supplemented with essential oils: A meta-analysis.

This study aimed to evaluate the effects of dietary supplementation with essential oils (EOS) on growth performance, antioxidant status in blood serum, intestinal morphology, and whole-body composition of Nile tilapia (Oreochromis niloticus) through a meta-analytic approach. The search and collection of scientific articles were conducted using the PRISMA methodology, and 45 full-text scientific articles were obtained. The data used in the meta-analysis were extracted from these 45 documents. The effect size was assessed through weighted mean differences (WMD) using Der-Simonian and Laird random effects models. Dietary supplementation with EOS increased (P < 0.001) final weight, body weight gain, specific growth rate, feed intake, protein efficiency ratio, and survival but decreased (P < 0.001) feed conversion ratio. In blood serum, EOS supplementation decreased (P < 0.001) the concentration of malondialdehyde and increased (P < 0.001) the concentration of catalase, superoxide dismutase, and glutathione peroxidase. In the foregut, midgut, and hindgut, greater (P < 0.01) villus height, villus width, and number of goblet cells were observed in response to EOS supplementation. EOS supplementation increased (P < 0.01) crude protein content and decreased (P < 0.05) crude lipid content in the whole-body. In conclusion, essential oils can be used as a dietary additive to improve growth performance, antioxidant status in blood serum, and intestinal morphology in Nile tilapia. Likewise, supplementation with essential oils increases the protein content and decreases the fat content in the whole-body of Nile tilapia.