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.

Association of 10 Polymorphisms in PLA2R1 and HLA DQA1 Genes with Primary Membranous Nephropathy Risk: A Meta-Analysis and a Meta-Regression.

Background: Although, several studies have assessed the association of the phospholipase A2 receptor (PLA2R) and HLA-DQA1 SNPs with primary membranous nephropathy (PMN), results were inconsistent and between-studies heterogeneity needs to be investigated. Objectives: The aim of this review was to summarize existing data on the contribution of 10 SNPs in the PLA2R and HLA-DQA1 genes to PMN susceptibility and to investigate the between-studies heterogeneity by subgroup analyses and meta-regressions. Design: This study was performed according to the PRISMA guidelines for systematic reviews and meta-analyses. Data sources and methods: An electronic literature search for eligible studies among all papers published prior to January 10, 2024, was conducted through PubMed, EMBASE, Web of science and Scopus databases. Meta-analyses together with subgroup analyses and meta-regressions were performed for the 10 following SNPs: rs4664308, rs3749117, rs3749119, rs35771982, rs3828323, rs16844715, rs1511223, rs6757188, rs2715918, and rs2187668. Results: Combined analyses revealed a significant increase in PMN risk conferred by the following alleles: rs4664308*A, rs3749117*T, rs3749119*C, rs35771982*G, rs3828323*C, rs16844715*C, rs1511223*A, rs2715918*A, and rs2187668*A, all P-values < .001. Moreover, the PLA2R-rs4664308/HLA-DQA1-rs2187668 interaction was significantly associated with an increased PMN risk, P < .001. However, there was a substantial between-studies heterogeneity for some SNPs. Subgroup analyses by ethnicity for the 9 PLA2R SNPs did not show any cross-ethnic disparity. Inversely, the risk conferred by the HLA-DQA1 rs2187668*A allele was significantly higher in Caucasians (OR [95% CI] = 3.929 [3.251-4.748]) than in Asians (OR [95% CI] = 2.537 [1.94-3.318], P = .007. Besides, meta-regressions revealed for the majority of investigated SNPs significant correlations of the effect size with albumin, 24-hours proteinuria, serum creatinine, and eGFR levels. Hence, the influence on PMN risk conferred by the PLA2R and HLA-DQA1 SNPs was rather noted in patients with a severe disease. Conclusion: This meta-analysis showed that 9 out of the 10 investigated SNPs in PLA2R and HLA-DQA1 genes were associated with increased PMN risk. Heterogeneity could be due to disparate patient groups in terms of disease presentation for almost all SNPs, and ethnicity for the HLA-DQA1 rs2187668 SNP. Registration: This review has been registered on PROSPERO: CRD42024506729. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024506729.

Genetic factors in primary membranous nephritis Why was the study done? Primary membranous nephritis (PMN) is the most common etiology of adult-onset nephrotic syndrome. Understanding risk factors, particularly genetic ones, would provide a better understanding of its pathophysiological mechanisms in order to prevent and treat patients more effectively. What did the researchers do? The research team summarized published data on genetic factors associated with PMN including phospholipase A2 receptor (PLA2R) and HLA-DQA1 genes. What did the researchers find? The total number of included studies was 27. Nine out of ten genetic factors were found to be associated with PMN risk. Moreover, we noted significant interaction between PLA2R and HLA-DQA1 in potentializing PMN risk. Nevertheless, there was a significant between-studies heterogeneity which was found to be explained in part by disease severity. What do the findings mean? This study has identified some important some genetic factors associated with PMN together with confounding factors that could influence the aforementioned association.

A bayesian network meta-analysis to explore modifying factors in randomized controlled trials: what works for whom to reduce depression in nursing home residents?

BACKGROUND: Reviews of depression interventions in nursing home residents resulted in positive findings. However, because of the heterogeneity of the studies, it remains unclear what works for whom. Considering moderator effects may contribute to a comprehensive understanding of depression treatment in residents. Therefore, this study aims to review depression interventions, examining moderator effects of (1) residents' factors, and (2) components specific of interventions. METHODS: A Bayesian network meta-analysis of randomized controlled trials primarily aimed at reducing depressive symptoms among residents was conducted. First, intervention types, e.g., exercise interventions, were compared to care as usual. Second, meta-regression analyses were conducted for moderator effects of residents' factors (i.e., severity of depressive symptoms, physical dependency, and cognitive impairment) and components identified as specific to an intervention (e.g., music, creativity, positivity). RESULTS: Our search across six databases resulted in 118 eligible studies: 16 on neurobiological interventions, 102 on non-pharmacological interventions. Compared to care as usual, cognitive interventions, such as cognitive behavioral therapy and goal-oriented therapy, showed the strongest effects (MD = -1.00, 95% CrI [-1.40 to -0.66]). Furthermore, the severity of depressive symptoms moderated the effect of interventions (ƅ = -0.63, CrI 95% [-1.04 to -0.22]), while none of fifteen identified intervention-specific components did. In residents with a depression diagnosis, there were larger effect sizes for interventions including daily structure, psychoeducation, healthy food, creativity, positivity, and an activating/encouraging environment, whereas interventions focusing on distraction and relaxation had larger effect sizes in those residents without. CONCLUSIONS: By examining the moderator effects, we provided an integrative perspective on the observed variations in effects across different target groups, and components of depression interventions. This approach underscores the complex nature of interventions, emphasizing the need for continued transdisciplinary research, and the exploration of potential moderators. Future investigations should carefully assess residents' factors and choose interventions and their components accordingly.

Policy solutions for addressing carbon leakage: Insights from meta-regression analysis.

Carbon leakage has become a key issue in global climate initiatives. This study aims to examine the effectiveness of various policy solutions for mitigating carbon leakage, as explored extensively in the literature. Employing a meta-regression analysis, this paper analyzes 416 leakage ratio estimates extracted from 39 economic studies published in English and Chinese between 2004 and 2022. These estimates evaluate the effects of diverse climate policies and modeling assumptions on carbon leakage. The results confirm that both 'intra-region' and 'cross-border' anti-leakage policies significantly impact carbon policy regions. The findings imply to policymakers that, although the implementation of border carbon adjustments provokes international debate under current WTO regulations, the 'intra-region' policies, which are more politically feasible, can achieve comparable effectiveness.

Quantitative assessment of baseline imbalances in evolocumab and alirocumab trials: a meta-epidemiological study.

BACKGROUND: Baseline imbalances have been identified in randomized trials of evolocumab and alirocumab. Our aim was to quantitatively assess (1) the presence of systematic baseline differences, and (2) the relationship of baseline differences with effects on low-density lipoprotein-cholesterol (LDL-c) and clinical outcomes in the trials. METHODS: We performed a meta-epidemiological study. PubMed, Embase, regulatory reports, ClinicalTrials.gov and company websites were searched for trials. Seven baseline characteristics (mean age, LDL-c, BMI, percentage males, diabetics, smokers, and hypertensives) and five outcomes (LDL-c, major adverse cardiac events, serious adverse events, any adverse events, all-cause mortality) were extracted. We calculated (1) range and distribution of baseline imbalances (sign-test), (2) pooled baseline differences and heterogeneity (meta-analysis), (3) differences in SDs around continuous variables (sign-test and pooling), and (4) the relationship of baseline differences with outcomes (meta-regression). The comparisons of PCSK9-inhibitor groups with either placebo or ezetimibe were analysed separately and combined. RESULTS: We identified 43 trials with 63,193 participants. Baseline characteristics were frequently missing. Many trials showed small baseline imbalances, but some large imbalances. Only baseline BMI showed a statistically significant lower pooled mean for the drug versus placebo groups (MD -0.16; 95% CI -0.24 to -0.09). Heterogeneity in baseline imbalances was present in six placebo- and five ezetimibe-comparisons. Heterogeneity was statistically significant for BMI, males, diabetics and hypertensives in the combined comparisons. There was a statistically significant preponderance for larger SDs in the PCSK9-inhibitor versus control groups (sign-test age 0.014; LDL-c 0.014; BMI 0.049). Meta-regression showed clinically relevant relationships of baseline imbalances in age, BMI and diabetics with the risk of any adverse events and the risk of mortality. Two relationships were statistically significant: A higher mean BMI in the drug versus control group with a decreased risk of mortality (beta - 0.56; 95% CI -1.10 to -0.02), and a higher proportion of diabetics with an increased risk of any adverse events (beta 0.02; 95% 0.01 to 0.04). CONCLUSIONS: Heterogeneous baseline imbalances and systematically different SDs were present in evolocumab and alirocumab trials, so study groups cannot be assumed to be comparable. These findings raise concerns about the design and conduct of the randomization procedures.

Estimating the heat-related mortality and morbidity burden in the province of Quebec, Canada.

BACKGROUND: As climate change increases the frequency and intensity of extreme heat events, there is an urgent need to quantify the heat-related health burden. However, most past studies have focussed on a single health outcome (mainly mortality) or on specific heatwaves, thus providing limited knowledge of the total pressure heat exerts on health services. OBJECTIVES: This study aims to quantify the heat-related mortality and morbidity burden for five different health outcomes including all-cause mortality, hospitalizations, emergency department (ED) visits, ambulance transports and calls to a health hotline, using the province of Quebec (Canada) as a case study. METHODS: A two-step statistical analysis was employed to estimate regional heat-health relationships using Distributed Lag Non-Linear Models (DLNM) and pooled estimates using a multivariate meta-regression. Heat burden was quantified by attributable fraction (AF) and attributable number (AN) for two temperature ranges: all heat (above the minimum mortality/morbidity temperature) and extreme heat (above the 95th percentile of temperature). RESULTS: Higher temperatures were associated with greater risk ratios for all health outcomes studied, but at different levels. Significant AF ranging from 2 to 3% for the all heat effect and 0.4-1.0% for extreme heat were found for all health outcomes, except for hospitalizations that had an AF of 0.1% for both heat exposures. The estimated burden of all heat (and extreme heat) every summer across the province was 470 (200) deaths, 225 (170) hospitalizations, 36 000 (6 200) ED visits, 7 200 (1 500) ambulance transports and 15 000 (3 300) calls to a health hotline, all figures significant. DISCUSSION: This new knowledge on the total heat load will help public health authorities to target appropriate actions to reduce its burden now and in the future. The proposed state-of-the-art framework can easily be applied to other regions also experiencing the adverse effects of extreme heat.

Meta-analysis of antimicrobial activity of Allium, Ocimum, and Thymus spp. confirms their promising application for increasing food safety.

Biopreservation strategies such as the use of Mediterranean plant extracts to ensure food safety are promising to deal with the emergence of antimicrobial resistances and the overreliance on food chemical additives. In the last few decades, antimicrobial susceptibility testing (AST) for evaluating the in vitro antibacterial potential of plant extracts against the most relevant foodborne pathogens has been widely reported in the literature. The current meta-analysis aimed to summarise and analyse the extensive evidence available in the literature regarding the in vitro antimicrobial capability of Allium, Ocimum and Thymus spp. extracts against foodborne pathogens. A systematic review was carried out to gather data on AST results of these extracts against Listeria monocytogenes, Staphylococcus aureus, Salmonella spp., Escherichia coli and Bacillus cereus, including inhibition diameters (ID) and minimum inhibitory concentrations (MIC). A total of 742 records were gathered from a raw collection of 2,065 articles. Weighted mixed-effect linear models were adjusted to data to obtain pooled ID, pooled MIC and the relationship between both model estimations and observations. The pooled results revealed B. cereus as the most susceptible bacteria to Allium sativum (pooled ID = 20.64 ± 0.61 mm) by diffusion methods and S. aureus (pooled MIC = 0.146 mg/mL) by dilution methods. Diffusion methods did not yield conclusive results for Ocimum spp. extracts; however, the lowest pooled MIC was obtained for S. aureus (0.263 mg/mL). Among the foodborne pathogens evaluated, B. cereus showed the highest sensitivity to Thymus spp. extracts by both diffusion and dilution methods (pooled ID = 28.90 ± 2.34 mm and MIC = 0.075 mg/mL). The methodology used for plant extraction was found to not significantly affect MIC values (p > 0.05). Overall, the antimicrobial effectiveness of the studied extracts against Gram-positive and Gram-negative bacteria was demonstrated. Finally, the robustness of the meta-regression model was confirmed, also revealing an inversely proportional correlation between the ID and MIC measurements (p < 0.0001). These results provide a robust scientific basis on the factors affecting the in vitro antimicrobial efficacy of extracts from Mediterranean plants. They also provide valuable information for stakeholders involved in their industrial application in food, including producers, regulatory agencies and consumers which demand green-labelled foods.

Integration of Antioxidant Activity Assays Data of Stevia Leaf Extracts: A Systematic Review and Meta-Analysis.

Stevia rebaudiana Bertoni, a no-calorie natural sweetener, contains a plethora of polyphenols that exert antioxidant properties with potential medicinal significance. Due to the variety of functional groups, polyphenols exhibit varying solubility depending on the nature of the extraction solvents (water, organic, or their mixtures, defined further on as hydroalcoholic extracts). In the present study, we performed a systematic review, following PRISMA guidelines, and meta-analysis, synthesizing all available data from 45 articles encompassing 250 different studies. Our results showed that the total phenolic content (TPC) of hydroalcoholic and aqueous extracts presents higher values (64.77 and 63.73 mg GAE/g) compared to organic extracts (33.39). Total flavonoid content (TFC) was also higher in aqueous and hydroalcoholic extracts; meta-regression analysis revealed that outcomes in different measuring units (mg QE/g, mg CE/g, and mg RUE/g) do not present statistically significant differences and can be synthesized in meta-analysis. Using meta-regression analysis, we showed that outcomes from the chemical-based ABTS, FRAP, and ORAC antioxidant assays for the same extract type can be combined in meta-analysis because they do not differ statistically significantly. Meta-analysis of ABTS, FRAP, and ORAC assays outcomes revealed that the antioxidant activity profile of various extract types follows that of their phenolic and flavonoid content. Using regression meta-analysis, we also presented that outcomes from SOD, CAT, and POX enzymatic antioxidant assays are independent of the assay type (p-value = 0.905) and can be combined. Our study constitutes the first effort to quantitatively and statistically synthesize the research results of individual studies using all methods measuring the antioxidant activity of stevia leaf extracts. Our results, in light of evidence-based practice, uncover the need for a broadly accepted, unified, methodological strategy to perform antioxidant tests, and offer documentation that the use of ethanol:water 1:1 mixtures or pure water can more efficiently extract stevia antioxidant compounds.

Health Effects of Occupational and Environmental Exposures to Nuclear Power Plants: A Meta-Analysis and Meta-Regression.

PURPOSE OF REVIEW: Numerous epidemiological studies have shown increased health risks among workers and residents living near nuclear power plants exposed to radiation levels meeting regulatory dose limits. This study aimed to evaluate the association between radiation exposure and disease risks among these populations exposed to radiation levels meeting the current regulatory dose limits. RECENT FINDINGS: We searched four databases (Cochrane Library, PubMed, ScienceDirect, and Web of Science) for studies published before August 2023, screened eligible studies (inclusion and exclusion criteria based on population, exposure, comparator, and outcome framework), and collected data on exposure indicators and disease risks. We applied random-effects models of meta-analysis to estimate the pooled effects and meta-regression to assess the dose-response relationship (radiation dose rate for workers and distance for residents). We identified 47 studies, 13 with worker and 34 with resident samples, covering 175 nuclear power plants from 17 countries, encompassing samples of 480,623 workers and 7,530,886 residents. Workers had a significantly lower risk for all-cancer and a significantly higher risk for mesothelioma. Residents had significantly higher risks for all-cancer, thyroid cancer, and leukemia. Notably, children under 5 years old showed the highest risk for all-cancer. Our meta-regression showed a significantly positive dose-response relationship between cumulative dose of radiation exposure and risk for circulatory disease among workers. Our findings demonstrated higher risks for mesothelioma for workers and all-cancer, thyroid cancer, and leukemia for residents exposed to low-dose radiation from nuclear power plants. Some included studies did not adjust for cancer risk confounders, which could overestimate the association between radiation exposure and cancer risk and increase the risk of bias.

Amount and frequency of psychotherapy as predictors of treatment outcome for adult depression: A meta-regression analysis.

BACKGROUND: It is not clear whether the amount and frequency of psychotherapy is associated with treatment effects for adult depression. We investigated whether a number of indicators of the amount and frequency of psychotherapy were related to the treatment effects in randomized controlled trials (RCTs) comparing individual, face-to-face psychotherapy to a control group (e.g., care-as-usual [CAU] or waitlist condition [WL]). METHODS: Four databases were systematically searched, and meta-regression analyses conducted to assess the relationship between the effect size (Hedges' g) of the treatment and number of sessions, duration of psychotherapy, total contact time with the therapist, and number of sessions per week. RESULTS: We included 176 studies (210 comparisons) with 15,158 participants. We did not find a relationship between the effect size, and number of sessions, or total contact time. There was a small negative association between duration of treatment and the effect size, an additional week of treatment was related to a 0.014 decrease in the effect size. In addition, there was a strong association between number of sessions per week and the effect size, an increase from one to two sessions per week was related to an effect size higher by 0.596. Both associations were no longer significant when controlling for characteristics of studies. LIMITATIONS: The current findings are correlational, future research should thus address this question in an RCT. CONCLUSIONS: We should deliver brief therapies, and thus shorten waiting lists. More sessions, if necessary, should be delivered with higher frequency and over a shorter period of time.

No Change in Complications Following Thyroidectomy Despite Increase in Thyroid Cancer Surgeries: A Meta-Regression Analysis.

PURPOSE: The increase in thyroid cancer incidence has inevitably led to an increase in thyroid cancer surgeries. This meta-regression analysis aimed to determine if the rate of post-thyroidectomy complications changes by year. MATERIALS AND METHODS: PubMed and Embase databases were used to perform a systematic literature search of studies published from January 1, 2005, using the keywords "thyroidectomy" and "complication." A meta-regression was performed for post-thyroidectomy hypocalcemia and bleeding. RESULTS: This meta-analysis included 25 studies involving 927751 individuals. Through the years of publications in this study, there was no significant difference in the proportion of post-thyroidectomy hypocalcemia and bleeding (p=0.9978, 0.6393). CONCLUSION: Although the number of thyroid surgeries has recently increased, the incidence of post-thyroidectomy hypocalcemia and bleeding did not significantly increase.

Impact of Humectants on Physicochemical and Functional Properties of Jerky: A Meta-Analysis.

This study aimed to determine the effects of humectants on moisture content, water activity, tenderness, color, microbiological analysis, protein denaturation, and oxidation of jerky. A thorough search for papers published in scientific journals that examined the impacts of humectants on jerky was carried out using Web of Science, Google Scholar, PubMed, and Science Direct. Only 14 studies matched inclusion requirements. They were used in the meta-analysis to synthesise quantitative findings. In the current investigation, jerky produced with beef, poultry, goat, or pork was used. The standardised mean difference (SMD) between treatments with humectants and controls was examined to investigate the effects of humectants using random-effects models. Heterogeneity was investigated using meta-regression. A subgroup analysis was carried out for significant factors. Results revealed that the addition of humectants had no significant impact on water activity, pH, fat, ash, CIE L*, or CIE a* (p>0.05). However, humectant addition significantly increased moisture (SMD=1.28, p<0.05), CIE b* (SMD=1.67, p<0.05), and overall acceptability (SMD=1.73, p<0.05). It significantly decreased metmyoglobin (SMD=-0.96, p<0.05), shear force (SMD=-0.84, p<0.05), and protein (SMD=-1.61, p<0.05). However, it was difficult to get a firm conclusion about how humectants affected the myofibrillar fragmentation index, total plate count, and 2-thiobarbituric acid-reactive substances because there were fewer than ten studies. To sum up, the proper use of humectants in jerky demands careful attention to both type and quantity, needing a delicate balancing act with other contributing factors.

Enrollment, adherence and retention rates among musculoskeletal disorders rehabilitation practitioners in knowledge translation studies: a systematic review and meta-regression.

BACKGROUND: Practitioners' enrollment, adherence, and retention rates influence estimates of effectiveness in knowledge translation (KT) studies and remain important concerns for implementation researchers. This review aimed to systematically summarize the current evidence on feasibility measures as gauged by enrollment, adherence, and retention rates in KT evaluation studies targeting rehabilitation practitioners treating musculoskeletal disorders (MSDs). METHODS: We searched five electronic databases from the inception to October 2022. We included KT studies that 1) had designs recommended by the Effective Practice and Organisation of Care, 2) targeted rehabilitation practitioners managing patients with MSDs, 3) delivered KT interventions according to the Expert Recommendations for Implementing Change classification, and 4) reported on the feasibility measures (e.g., enrollment, adherence, and retention). Descriptive statistics were conducted to report on study-, practitioners- and intervention-related factors influencing enrollment, adherence, and retention rates. Meta-regression weighted by the sample size of included studies was used to estimate the effect of factors on overall enrollment, adherence, and retention rates. RESULTS: Findings from 33 KT studies reported weighted enrolment, adherence, and retention rate of 82% (range: 32%-100%), 74% (range: 44%-100%), and 65% (range: 36%-100%) respectively for both intervention and control groups. Factors positively influencing enrollment, adherence, and retention rates included designing short study period with short duration intervention. CONCLUSIONS: Intense (e.g., high frequency, short duration) single KT intervention was more appealing for practitioners. Future evaluation studies should clearly report follow-up data, and practitioners' prior training, Results may not apply to non-MSD healthcare providers.

A Mechanistic Analysis of the Neural Modulation of the Inflammatory System Through Vagus Nerve Stimulation: A Systematic Review and Meta-analysis.

OBJECTIVE: We aimed to conduct a systematic review and meta-analysis assessing the antiinflammatory effects of various VNS methods while exploring multiple antiinflammatory pathways. MATERIALS AND METHODS: We included clinical trials that used electrical stimulation of the vagus nerve and assessed inflammatory markers up to October 2022. We excluded studies lacking control groups, those with combined interventions, or abstracts without full text. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Cochrane Handbook for Systematic Reviews. For each inflammatory marker, a random-effects meta-analysis using the inverse variance method was performed. Methods used include transcutaneous auricular VNS (taVNS), transcutaneous cervical VNS (tcVNS), invasive cervical VNS (iVNS), and electroacupuncture VNS (eaVNS). Main reported outcomes included tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1ß, C-reactive protein (CRP), and IL-10. Risk of bias was evaluated using the Cochrane Collaboration Tool (RoB 2.0). RESULTS: This review included 15 studies, involving 597 patients. No statistically significant general VNS effect was observed on TNF-α, IL-6, and IL-1ß. However, CRP, IL-10, and interferon (IFN)-γ were significantly modulated by VNS across all methods. Subgroup analysis revealed specific stimulation techniques producing significant results, such as taVNS effects in IL-1ß and IL-10, and iVNS in IL-6, whereas tcVNS and eaVNS did not convey significant pooled results individually. Cumulative exposure to VNS, higher risk of bias, study design, and pulse width were identified as effect size predictors in our meta-regression models. CONCLUSIONS: Pooling all VNS techniques indicated the ability of VNS to modulate inflammatory markers such as CRP, IL-10, and IFN-γ. Individually, methods such as taVNS were effective in modulating IL-1ß and IL-10, whereas iVNS modulated IL-6. However, different VNS techniques should be separately analyzed in larger, homogeneous, and powerful studies to achieve a clearer and more consistent understanding of the effect of each VNS method on the inflammatory system.

Biomechanical strength of triceps tendon repairs: systematic review and meta-regression analysis of human cadaveric studies.

PURPOSE: It is unclear which triceps tendon repair constructs and techniques produce the strongest biomechanical performance while minimizing the risk of gap formation and repair failure. We aimed to determine associations of construct and technique variables with the biomechanical strength of triceps tendon repairs. PubMed, Embase, Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov were systematically searched for peer-reviewed studies on biomechanical strength of triceps tendon repairs in human cadavers. 6 articles met the search criteria. Meta-regression was performed on the pooled dataset (123 specimens). Outcomes of interest included gap formation, failure mode, and ultimate failure load. Covariates were fixation type; number of implants; and number of sutures. Stratification by covariates was performed. We found no association between fixation type and ultimate failure load; however, suture anchor fixation was associated with less gap formation compared with transosseous direct repair (ß = - 1.1; 95% confidence interval [CI]:- 2.2, - 0.04). A greater number of implants was associated with smaller gap formation (ß = - 0.77; 95% CI: - 1.3, - 0.28) while a greater number of sutures was associated with higher ultimate failure load ( ß= 3; 95% CI: 21, 125). In human cadaveric models, the number of sutures used in triceps tendon repairs may be more important than the fixation type or number of implants for overall strength. If using a transosseous direct repair approach to repair triceps tendon tears, surgeons may choose to use more sutures in their repair in order to balance the risk of larger gap formation when compared to indirect repair techniques. LEVEL OF EVIDENCE: Level III.

The Relationship Between Vitamin D Intake and Serum 25-hydroxyvitamin D in Young Children: A Meta-Regression to Inform WHO/FAO Vitamin D Intake Recommendations.

BACKGROUND: This work was commissioned by the World Health Organization and Food and Agriculture Organization to inform their update on the vitamin D requirements for children aged <4 y. OBJECTIVES: The objective of this work was to undertake multilevel and multivariable dose-response modeling of serum 25-hydroxyvitamin D (25OHD) to total vitamin D intake in children aged <4 y with the goal of deriving updated vitamin D requirements for young children. METHODS: Systematically identified randomized controlled trials among healthy children from 2 wk up to 3.9 y of age provided with daily vitamin D supplements or vitamin D-fortified foods were included. Linear and nonlinear random effects multilevel meta-regression models with and without covariates were fitted and compared. Interindividual variability was included by simulating the individual serum 25OHD responses. The percentage of individuals reaching set minimal and maximal serum 25OHD thresholds was calculated and used to derive vitamin D requirements. RESULTS: A total of 31 trials with 186 data points from North America, Europe, Asia, and Australasia/Oceania, with latitudes ranging from 61°N to 38°S, and with participants of likely mostly light or medium skin pigmentation, were included. In 29 studies the children received vitamin D supplements and in 2 studies the children received vitamin D-fortified milk with or without supplements. The dose-response relationship between vitamin D intake and serum 25OHD was best fitted with the unadjusted quadratic model. Adding additional covariates, such as age, did not significantly improve the model. At a vitamin D intake of 10 µg/d, 97.3% of the individuals were predicted to achieve a minimal serum 25OHD threshold of 28 nmol/L. At a vitamin D intake of 35 µg/d, 1.4% of the individuals predicted to reach a maximal serum 25OHD threshold of 200 nmol/L. CONCLUSIONS: In conclusion, this paper details the methodological steps taken to derive vitamin D requirements in children aged <4 y, including the addition of an interindividual variability component.

Association of adipokine levels with obesity in periodontal health and disease: A systematic review with meta-analysis and meta-regression.

This study aimed to investigate the levels of serum, gingival crevicular fluid (GCF), and salivary adipokines and their possible relationship with periodontitis and obesity. An electronic search was conducted in the following databases: PubMed/ Medline, Scopus, and EBSCOhost through February 2023. Two independent reviewers screened the titles, abstracts, and full text of all the studies. Studies comparing the levels of adipokines in GCF, serum, and/or saliva in subjects with obesity and periodontitis (group 1), subjects with normal weight and periodontitis (group 2), and subjects with obesity and gingival health (group 3) were included. Meta-analyses and meta-regression were performed on the data from included studies. Seventeen studies with study participants ranging from 30 to 120 were included with subjects in each group ranging from 10 to 40. There was a significant increase in levels of serum TNF-α, leptin, IL-6, and CRP between groups 1 and 2 (p < .05). In GCF, TNF-α and resistin levels were significantly higher (p < .05) in Group 1 vs. 2. Serum level of leptin was higher for group 1 vs. 3 (p < .05). Meta-regression analysis revealed that the obesity definition (body mass index (BMI) cut-off value >25 or >30) was significant for serum resistin (p < .05) and GCF resistin (p < .05) between group 1 and 2. The current analysis indicates that both periodontitis and obesity can modulate the pro-inflammatory cytokines at systemic and local levels. This bidirectional interaction of periodontitis and obesity via the inflammation pathway seems likely plausible. Further studies are required to elucidate this mechanism in more detail.

Implementing Multilevel Network Meta-Regression for Time-To-Event Outcomes: A Case Study in Relapsed Refractory Multiple Myeloma.

OBJECTIVES: Multilevel network meta-regression (ML-NMR) leverages individual patient data (IPD) and aggregate data from a network of randomized controlled trials (RCTs) to assess the comparative efficacy of multiple treatments, while adjusting for between-study differences. We provide an overview of ML-NMR for time-to-event outcomes and apply it to an illustrative case study, including example R code. METHODS: The case study evaluated the comparative efficacy of idecabtagene vicleucel (ide-cel), selinexor+dexamethasone (Sd), belantamab mafodotin (BM), and conventional care (CC) for patients with triple-class exposed relapsed/refractory multiple myeloma in terms of overall survival. Single-arm clinical trials and real-world data were naively combined to create an aggregate data artificial RCT (aRCT) (MAMMOTH-CC versus DREAMM-2-BM versus STORM-2-Sd) and an IPD aRCT (KarMMa-ide-cel versus KarMMa-RW-CC). With some assumptions, we incorporated continuous covariates with skewed distributions, reported as median and range. The ML-NMR models adjusted for number of prior lines, triple-class refractory status, and age and were compared using the leave-one-out information criterion. We summarized predicted hazard ratios and survival (95% credible intervals) in the IPD aRCT population. RESULTS: The Weibull ML-NMR model had the lowest leave-one-out information criterion. Ide-cel was more efficacious than Sd, BM, and CC in terms of overall survival. Effect modifiers had minimal impact on the model, and only triple-class refractory was a prognostic factor. CONCLUSIONS: We demonstrate an application of ML-NMR for time-to-event outcomes and introduce code that can be used to aid implementation. Given its benefits, we encourage practitioners to utilize ML-NMR when population adjustment is necessary for comparisons of multiple treatments.

The association between inflammatory biomarkers and low back disorder: a systematic review and meta-analysis.

INTRODUCTION: Low back disorder (LBD) is a major cause of disability worldwide. Inflammation results in proliferation of cytokines or consequent degradation products (collectively known as inflammatory biomarkers) that activate pain pathways which can result in non-specific LBD. This systematic review and meta-analysis aim to evaluate the relationship between inflammatory biomarkers and clinical outcomes in patients with LBD. METHODS: The PRISMA guideline was followed for the systematic reivew. Three online databases were searched. Four RCTs and sixteen observational studies with 1142 LBD patients were analysed. The primary outcomes were back and leg pain scores, back-specific disability scores and expression of inflammatory biomarkers. Standardized mean difference (SMD) and their 95% confidence intervals (CI) were evaluated. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to summarize the strength of evidence. RESULTS: Four RCTs and sixteen observational studies were included in the analysis of 1142 patients with LBD. There was a statistically significant reduction in back pain score and IL-1 beta and increase in the expression of CTX-1 and IL-10 levels post treatment. There was a significant relationship between increase in the expression of MCP- and reduction in the expression of hsCRP with increase in back pain. Significant relationship was also observed between increase in the expression of MCP-1 and reduction in the expression of IL-6 with increase in leg pain. Increase in the expression of IL-8 and reduction in the expression of hsCRP was also associated with increased disability score. CONCLUSION: Inflammatory biomarkers play a significant role in the pathogenesis of LBD. CTX-1, IL-10 and IL-1 beta may be responsible for the decrease in back pain scores post treatment. There is a relationship between MCP-1, IL-6, IL-8 and hsCRP with clinical and functional assessments for LBD. Further studies will improve understanding of the pathogenesis of LBD and aid in targeted management strategies.

Rebound Inverts the Staphylococcus aureus Bacteremia Prevention Effect of Antibiotic Based Decontamination Interventions in ICU Cohorts with Prolonged Length of Stay.

Could rebound explain the paradoxical lack of prevention effect against Staphylococcus aureus blood stream infections (BSIs) with antibiotic-based decontamination intervention (BDI) methods among studies of ICU patients within the literature? Two meta-regression models were applied, each versus the group mean length of stay (LOS). Firstly, the prevention effects against S. aureus BSI [and S. aureus VAP] among 136 studies of antibiotic-BDI versus other interventions were analyzed. Secondly, the S. aureus BSI [and S. aureus VAP] incidence in 268 control and intervention cohorts from studies of antibiotic-BDI versus that among 165 observational cohorts as a benchmark was modelled. In model one, the meta-regression line versus group mean LOS crossed the null, with the antibiotic-BDI prevention effect against S. aureus BSI at mean LOS day 7 (OR 0.45; 0.30 to 0.68) inverted at mean LOS day 20 (OR 1.7; 1.1 to 2.6). In model two, the meta-regression line versus group mean LOS crossed the benchmark line, and the predicted S. aureus BSI incidence for antibiotic-BDI groups was 0.47; 0.09-0.84 percentage points below versus 3.0; 0.12-5.9 above the benchmark in studies with 7 versus 20 days mean LOS, respectively. Rebound within the intervention groups attenuated and inverted the prevention effect of antibiotic-BDI against S. aureus VAP and BSI, respectively. This explains the paradoxical findings.