Meta-análisis: Intervalos de confianza e Intervalos de predicción / Meta-analysis: Confidence intervals and Prediction intervals

En los informes meta-analíticos se suelen reportar varios tipos de intervalos, hecho que ha generado cierta confusión a la hora de interpretarlos. Los intervalos de confianza reflejan la incertidumbre relacionada con un número, el tamaño del efecto medio paramétrico. Los intervalos de predicción reflejan el tamaño paramétrico probable en cualquier estudio de la misma clase que los incluidos en un meta-análisis. Su interpretación y aplicaciones son diferentes. En este artículo explicamos su diferente naturaleza y cómo se pueden utilizar para responder preguntas específicas. Se incluyen ejemplos numéricos, así como su cálculo con el paquete metafor en R.(AU)

Several types of intervals are usually employed in meta-analysis, a fact that has generated some confusion when interpreting them. Confidence intervals reflect the uncertainty related to a single number, the parametric mean effect size. Prediction intervals reflect the probable parametric effect size in any study of the same class as those included in a meta-analysis. Its interpretation and applications are different. In this article we explain in de-tail their different nature and how they can be used to answer specific ques-tions. Numerical examples are included, as well as their computation with the metafor Rpackage.(AU)

Effect of perinatal consumption of low-calorie sweetener on maternal health: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Evidence regarding perinatal low-calorie (or artificial) sweetener (LCS) consumption and its effect on maternal health outcomes is limited and inconclusive. The primary outcomes of our systematic review and meta-analysis were the effect of preconception and pregnancy LCS exposure on reproductive and pregnancy outcomes. Secondary outcomes included long-term maternal health. METHODS: A systematic search of electronic databases, including PubMed, Embase, CINAHL, the Cochrane Library, Scopus, Web of Science, PsycINFO, ProQuest Health and Medical, ClinicalTrials.gov and Google Scholar, was conducted up to 20 November 2023. Primary studies, including clinical trials, cohort studies, case-control studies, which reported any LCS consumption during perinatal period and pregnancy and maternal health outcomes were eligible. A random effects model with restricted maximum likelihood estimation was used for the meta-analysis. We appraised the quality of the included studies using the National Institute of Health study quality appraisal tool and the overall quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation tool. RESULTS: A total of 19 eligible studies with 203,706 participants were included. LCS consumption during pregnancy was associated with 11% increased risk of preterm birth (RR = 1.11, 95% CI: 1.07-1.16, I2 = 0.01%) and 42% increased risk of gestational diabetes (RR = 1.42, 95% CI: 0.98-2.04, I2 = 67.60%) compared with no consumption, however, the effect size for gestational diabetes was not precise as the 95% CI indicated that the effect estimate could range from 2% lower risk to 204% (or 2.04 times) higher risk. We found no association between LCS consumption during pregnancy and gestational weight gain (standardized mean difference (SMD) = 0.04; 95% CI: -0.17 - 0.24, I2 = 41.31%) or gestational age at birth (SMD = 0.00; 95% CI: -0.13 - 0.14, I2 = 80.13%). The effect of LCS consumption on reproductive treatment outcomes were inconsistent. CONCLUSIONS: Based on the evidence available, LCS consumption in pregnancy was associated with increased risk of preterm birth and gestational diabetes. Robust research, such as well-designed randomized trials and large prospective cohort studies, is required to confirm the causal effect of LCS consumption during perinatal period on adverse maternal health outcomes.

Mind over chronic pain: A meta-analysis of cognitive restructuring in chronically ill adults.

OBJECTIVE: This meta-analysis synthesizes research on the impact of cognitive restructuring on chronic pain intensity, aiming to integrate diverse methodologies and findings while evaluating potential moderators. METHODS: Following PRISMA guidelines, we systematically searched multiple databases (PubMed, Web of Science, JSTOR, Sage, Social Science Research Network, PsycArticles, ScienceDirect, and Education Resources Information Center) until July 2023. Studies involving adults (≥18 years) diagnosed with chronic conditions who underwent cognitive restructuring to reduce chronic pain intensity, were included. Eligible studies compared this intervention with a control group. We excluded studies incorporating cognitive restructuring within broader interventions, lacking statistical data, or not written in English. Study quality was assessed using the Cochrane Risk of Bias tool (RoB 2). RESULTS: After reviewing 18,312 studies, we selected 11 studies published between 1991 and 2022, involving 693 participants with chronic conditions. A significant large overall effect size was found (d = 0.94, 95% CI 0.48 to 1.40). Moderation analyses revealed significant differences based on sex and study quality, with effects less pronounced among females and more substantial in higher-quality studies. CONCLUSION: Despite limitations such as statistical instability due to a small number of studies in certain moderator categories and methodological variability, this meta-analysis highlights the robust effects of cognitive restructuring on chronic pain intensity. The findings are valuable for guiding power calculations and future research expectations. Clinically, these results support the significant effect of cognitive restructuring in both individual and group settings, regardless of age, particularly when facilitated by teams that include psychologists.

Semaglutide for the prevention of atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist, is reported to have cardiac benefits, but its effects on preventing atrial fibrillation (AF) remain inconclusive. This study aimed to investigate whether semaglutide can prevent AF occurrence in patients with type 2 diabetes mellitus (T2DM), obesity, or overweight. METHODS: We searched MEDLINE, EMBASE, the Cochrane CENTRAL database, and clinicaltrials.gov from inception to December 29, 2023. Randomized controlled trials of semaglutide in patients with T2DM, obesity, or overweight were included. The primary outcome was AF occurrence. Relative risks (RRs) with 95 % confidence intervals (CIs) were calculated for the overall population and subgroups. RESULTS: Twenty-one trials comprising 25957 patients were included. In the overall pooled analysis, semaglutide decreased AF occurrence compared to control drugs (RR 0.70, 95 % CI 0.52-0.95). This result was consistent in trials using other antihyperglycemic medications as controls (RR 0.43, 95 % CI 0.21-0.89), but not in placebo-controlled trials (RR 0.77, 95 % CI 0.56-1.07). The outcome was favorable for patients with T2DM (RR 0.71, 95 % CI 0.52-0.97), but not for patients with overweight or obesity (RR 0.56, 95 % CI 0.18-1.73). Results varied by type of semaglutide, with oral semaglutide showing an RR of 0.49 (95 % CI 0.25-0.97) and subcutaneous semaglutide showing an RR of 0.77 (95 % CI 0.55-1.07). CONCLUSION: Semaglutide was associated with a reduced risk of AF occurrence in the overall analysis. Favorable outcomes were observed in subsets using other antihyperglycemic medications as controls, in patients with T2DM, and with oral semaglutide.

Factors associated with a placebo effect in Parkinson's disease in clinical trials: a meta-analysis.

OBJECTIVES: Outcomes of clinical trials of treatment in patients with Parkinson's disease (PD) may be influenced by placebo effects. The aim of this study was to determine the factors associated with placebo effects in Parkinson's disease (PD) for guidance with design of future clinical trials. METHODS: Factors associated with placebo effects in PD were examined in a meta-analysis using a random effects model with pooling of placebo effects on the Unified Parkinson's Disease Rating Scale part III (UPDRS III) or Movement Disorder Society sponsored revision of UPDRS III (MDS-UPDRS III). The following prespecified variables were included in the analyses: with or without drug at baseline, with or without a placebo run-in phase, with or without motor fluctuation, published year, number of study sites, placebo administration period, age, sex, disease duration, and daily levodopa dose. Publication bias was assessed by visual inspection of funnel plots and adjusted using the trim-and-fill method. RESULTS: Thirty-eight articles with a total of 4828 subjects satisfied the inclusion criteria. There was a significant placebo effect using UPDRS III or MDS-UPDRS III (SMD = - 0.25; 95% CI - 0.35 to - 0.14; p < 0.001, I2 = 92%). Subgroup and/or multivariate meta-regression analyses revealed that placebo effects were associated with advanced PD (p = 0.04), drug exposure at baseline (p < 0.001), placebo administration period (p < 0.001), and disease duration (p < 0.01). CONCLUSIONS: The results of this study are important as guidance in design of future clinical trials in which the influence of placebo effects is minimized.

Cold sub-mucosal injection versus traditional cold snare polypectomy for diminutive and small colorectal polyps: A systematic review and meta-analysis.

BACKGROUND: The guidelines recommend conventional cold snare polypectomy (C-CSP) for diminutive and small colorectal polyps (≤ 10 mm). However, it remains unclear whether CSP with sub-mucosal injection (SI-CSP) achieves comparable efficacy to C-CSP for managing these lesions. This study compares SI-CSP with C-CSP for patients with diminutive and small colorectal polyps. METHODS: An electronic literature search was conducted to retrieve articles comparing resection outcomes between SI-CSP and C-CSP in diminutive and small colorectal polyps (registration number INPLASY2023100096). Our primary outcomes of interest were the complete resection rate (CRR), complications (namely immediate bleeding, delayed bleeding and perforation) and polypectomy time. Mean differences with 95% confidence intervals (CI) were employed for continuous variables, while odds ratios (OR) with 95% CI were calculated for categorical variables. Data was analyzed using a random effects model and the I2 test was utilized to assess heterogeneity. RESULTS: Eight studies involving 1470 patients with 2223 polyps were included in our analysis. The CRR was not significantly higher in the SI-CSP group, with an OR of 95% CI 0.50 (0.22, 1.15). The incidences of immediate bleeding (OR 95% CI 0.60 [0.26-1.40]) and delayed bleeding (OR 95% CI 0.88 [0.32-2.42]) did not differ significantly between the two groups. On average, the mean polypectomy time was 64.75 seconds shorter in the C-CSP group (95% CI, - 102.96 to - 26.53). Notably, no perforation events were reported in the included studies. CONCLUSIONS: The use of SI-CSP was not superior to C-CSP in managing diminutive and small colorectal polyps and the procedure required significantly more time.

The Synergistic Anti-tumor Effects of Evodiamine based on Animal Model Experiments: A Systematic Review and Meta-analysis.

BACKGROUND: Evodiamine (EVO) is an alkaloid extracted from the dried and nearly ripe fruits of Euodia rutaecarpa and used as an anti-cancer, anti-inflammatory and anti-obesity agent. However, robust evidence of preclinical experiments has been lacking so far. Therefore, the purpose of this article was to investigate the effect of EVO in combination with other treatments on tumors in animal experiments. METHODS: A systematic review and meta-analysis were conducted to assess the anti-tumor effect of evodiamine-combined therapy. The search engine and electronic databases included PubMed, Scopus, China Knowledge Resource Integrated Database (CNKI), and SinoMed. The research method was based on the PRISMA checklist. RESULTS: A total of 7 studies and 108 animals were included. As a result, EVO combined therapy was found to be more effective than EVO monotherapy. The SMD was -25.64(95% CI: -5.77 -3.13) in tumor growth. In tumor weight, the SMD was -8.91(95% CI: -16.37, -1.44). CONCLUSION: EVO has the potential to alleviate the toxicity of chemotherapeutic agents, which increases the translatability to the clinical situation.

Vortioxetine for depression in adults: A systematic review and dose-response meta-analysis of randomized controlled trials.

AIM: Major depressive disorder (MDD) is a prevalent psychiatric condition and vortioxetine offers promising antidepressant effects due to its unique pharmacological profile. However, the dose-response relationships of vortioxetine for MDD is not well established. We aimed to conduct dose-response meta-analyses to fill this gap. METHODS: We systematically searched multiple electronic databases for randomized controlled trials of vortioxetine for MDD, with the last search conducted on 08 February, 2024. The dose-response relationship was evaluated using a one-stage random-effects dose-response meta-analysis with restricted cubic spline model. The primary outcome was efficacy (mean change in depression scale score), with secondary outcomes including response, dropout for any reasons (acceptability), dropout for adverse events (tolerability), and any adverse events (safety). RESULTS: The dose-response meta-analysis comprised 16 studies, with 4,294 participants allocated to the vortioxetine group and 2,299 participants allocated to the placebo group. The estimated 50% effective dose was 4.37 mg/day, and the near-maximal effective dose (95% effective dose) was 17.93 mg/day. Visual inspection of the dose-efficacy curve suggests that a plateau possibly had not been reached yet at 20 mg/day. Acceptability, tolerability and safety decreased as the dose increased. Subgroup analysis indicated that no significant differences were observed in acceptability, tolerability and safety among the dosage groups. CONCLUSIONS: Vortioxetine may potentially provide additional therapeutic benefits when exceeding the current licensed dosage without significantly impacting safety. Conducting clinical trials exceeding the current approved dosage appears necessary to fully comprehend its efficacy and risk.

Health Related Quality of life Amongst Refugees: A meta Analysis of Studies Using the SF-36.

The health of refugees has been widely documented, as has the impact of a range of factors throughout the migration journey from being exposed to violence to the impacts of immigration detention. This study adds to our understanding of health-related quality of life amongst refugees and asylum seekers by evaluating health-related quality of life as measured by the Short-Form 36 (SF-36) Health Survey using meta-analysis. The aims of this study were to (1) provide a summary and overview of health-related quality of life (as measured by the SF-36), including the extent to which this varies and (2) explore the factors that influence health-related quality of life (as measured by the SF-36) amongst refugees and asylum seekers. A search was undertaken of MEDLINE, CINAHL, PSYCINFO and SCOPUS, returning 3965 results. Papers were included if they sampled refugees (or asylum seeker or those with refugee-like experiences) and used the SF-36 (or its variants) as an outcome measure. Mean scores and standard deviations were pooled using a random effects model. The pooled sample size was 18,418. The pooled mean scores for the SF-36 physical summary measures was 54.99 (95% CI 46.01-63.99), while the mental health summary measure was 52.39 (95% CI 43.35-61.43). The pooled mean scores for each of the sub-scales ranged from 49.6 (vitality) to 65.54 (physical functioning). High heterogeneity was found between both summary measures and all sub-scales. In comparison to SF-36 results from general populations in high and middle income countries, these results suggest that refugee quality of life is generally poorer. However, this varied substantially between studies. One issue that is not well clarified by this review are the factors that contributed to health-related quality of life.

Transcriptome meta-analysis reveals the hair genetic rules in six animal breeds and genes associated with wool fineness.

Wool plays an irreplaceable role in the lives of livestock and the textile industry. The variety of hair quality and shape leads to the diversity of its functions and applications, and the finer wool has a higher economic value. In this study, 10 coarse and 10 fine ordos fine wool sheep skin samples were collected for RNA-seq, and coarse and fine skin/hair follicle RNA-seq datasets of other five animal breeds were obtained from NCBI. Weighted gene co-expression network analysis showed that the common genes were clustered into eight modules. Similar gene expression patterns in sheep and rabbits with the same wool types, different gene expression patterns in animal species with different hair types, and brown modules were significantly correlated with species and breeds. GO and KEGG enrichment analyses showed that, most genes in the brown module associated with hair follicle development. Hence, gene expression patterns in skin tissues may determine hair morphology in animal. The analysis of differentially expressed genes revealed that 32 highly expressed candidate genes associated with the wool fineness of Ordos fine wool sheep. Among them, KAZALD1 (grey module), MYOC (brown module), C1QTNF6 (brown module), FOS (tan module), ITGAM, MX2, MX1, and IFI6 genes have been reported to be involved in the regulation of the hair follicle cycle or hair loss. Additionally, 12 genes, including KAZALD1, MYOC, C1QTNF6, and FOS, are differentially expressed across various animal breeds and species. The above results suggest that different sheep breeds share a similar molecular regulatory basis of wool fineness. Finally, the study provides a theoretical reference for molecular breeding of sheep breeds as well as for the investigation of the origin and evolution of animal hair.

Resveratrol for inflammatory bowel disease in preclinical studies: a systematic review and meta-analysis.

Background: Inflammatory bowel disease (IBD) is a chronic condition that can be managed with treatment, but it is challenging to get IBD cured. Resveratrol, a non-flavonoid polyphenolic organic compound derived from various plants, has a potential effect on IBD. The current research was set out to investigate the therapeutic effects of resveratrol on animal models of IBD. Methods: A comprehensive search of PubMed, Embase, Web of Science, and Chinese databases was performed. The literature search process was completed independently by two people and reviewed by a third person. The risk of bias in the included literature was assessed using the Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Stroke (CAMARADES) 10-point quality checklist. The meta-analysis utilized Review Manager 5.4 software to evaluate the efficacy of resveratrol, with histopathological index as the primary outcome measure. Subgroup analysis was conducted based on this indicator. Additionally, meta-analyses were carried out on different outcomes reported in the literature, including final disease activity index, final body weight change, colon length, splenic index, and inflammatory factors. Results: After conducting a thorough literature search and selection process, a total of 28 studies were ultimately included in the analysis. It was found that over half of the selected studies had more than five items with low risk of bias in the bias risk assessment. Relevant datas from included literature indicated that the histopathological index of the resveratrol group was significantly lower than that of the control group (WMD = -2.58 [-3.29, -1.87]). Subgroup analysis revealed that higher doses of resveratrol (>80 mg/kg) had a better efficacy (WMD = -3.47 [-4.97, -1.98]). Furthermore, The data summary and quantitative analysis results of SI and colon length also showed that resveratrol was effective in alleviating intestinal mucosal pathological injury of IBD. In terms of biochemical indicators, the summary analysis revealed that resveratrol affected interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), transforming growth factor-ß (TGF-ß), interferon-γ (IFN-γ), malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), and prostaglandin E2 (PGE2) significantly. These effects may be attributed to the mechanism of resveratrol in regulating immune response and inhibiting oxidative stress. Conclusion: This review suggests that resveratrol demonstrated a notable therapeutic impact in preclinical models of IBD, particularly at doses exceeding 80 mg/kg. This efficacy is attributed to the protective mechanisms targeting the intestinal mucosa involved in the pathogenesis of IBD through various pathways. As a result, resveratrol holds promising prospects for potential clinical use in the future.

Comparative Profiles of the WATCHMAN™ and Amplatzer™ Cardiac Plug/Amplatzer™ Amulet™ Devices for Left Atrial Appendage Closure in Non-valvular Atrial Fibrillation: A Comprehensive Systematic Review and Meta-analysis.

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia marked by irregular and frequent tachycardic rhythms in the atria, affecting 1%-2% of the general population. The WATCHMAN™ device from Boston Scientific (Marlborough, MA, USA) and the Amplatzer™ Amulet™ device from Abbott (Chicago, IL, USA) are two devices used globally for left atrial appendage closure (LAAC) in non-valvular AF. A systematic search was conducted in PubMed, the Cochrane Library, and Elsevier's ScienceDirect literature databases to identify studies comparing the WATCHMAN™ procedure with Amulet™ device implantation for LAAC in patients with AF. The analyses were conducted using the random-effects model. A total of 20 studies were identified, with 18 falling into the category of observational studies and 2 being randomized controlled trials. A total of 6310 participants were included in this meta-analysis, with 3198 individuals (50.68%) assigned to the WATCHMAN™ procedure group and 3112 individuals (49.32%) allocated to the Amplatzer™ Cardiac Plug (ACP) group. The analysis revealed a higher risk of stroke associated with the WATCHMAN™ technique (relative risk [RR], 1.14), albeit without statistical significance. Conversely, the WATCHMAN™ approach led to a significantly lower risk of cardiac death (RR, 0.44; P = .04). Notably, the risks of all-cause mortality (RR, 0.89; 95% confidence interval [CI], 0.73-1.08; I 2 = 0%; P = .25) and major bleeding (RR, 0.93; 95% CI, 0.65-1.33; I 2 = 31%; P = .70) were clinically reduced with the WATCHMAN™ procedure, although statistical significance was not achieved. Compared to Amulet™ device implantation, WATCHMAN™ device implantation decreased the risk of cardiac mortality, while the risks of stroke, systemic embolism, all-cause mortality, and major bleeding were not statistically significant.

Abnormalities of brain structure and function in cervical spondylosis: a multi-modal voxel-based meta-analysis.

Background: Previous neuroimaging studies have revealed structural and functional brain abnormalities in patients with cervical spondylosis (CS). However, the results are divergent and inconsistent. Therefore, the present study conducted a multi-modal meta-analysis to investigate the consistent structural and functional brain alterations in CS patients. Methods: A comprehensive literature search was conducted in five databases to retrieve relevant resting-state functional magnetic resonance imaging (rs-fMRI), structural MRI and diffusion tensor imaging (DTI) studies that measured brain functional and structural differences between CS patients and healthy controls (HCs). Separate and multimodal meta-analyses were implemented, respectively, by employing Anisotropic Effect-size Signed Differential Mapping software. Results: 13 rs-fMRI studies that used regional homogeneity, amplitude of low-frequency fluctuations (ALFF) and fractional ALFF, seven voxel-based morphometry (VBM) studies and one DTI study were finally included in the present research. However, no studies on surface-based morphometry (SBM) analysis were included in this research. Due to the insufficient number of SBM and DTI studies, only rs-fMRI and VBM meta-analyses were conducted. The results of rs-fMRI meta-analysis showed that compared to HCs, CS patients demonstrated decreased regional spontaneous brain activities in the right lingual gyrus, right middle temporal gyrus (MTG), left inferior parietal gyrus and right postcentral gyrus (PoCG), while increased activities in the right medial superior frontal gyrus, bilateral middle frontal gyrus and right precuneus. VBM meta-analysis detected increased GMV in the right superior temporal gyrus (STG) and right paracentral lobule (PCL), while decreased GMV in the left supplementary motor area and left MTG in CS patients. The multi-modal meta-analysis revealed increased GMV together with decreased regional spontaneous brain activity in the left PoCG, right STG and PCL among CS patients. Conclusion: This meta-analysis revealed that compared to HCs, CS patients had significant alterations in GMV and regional spontaneous brain activity. The altered brain regions mainly included the primary visual cortex, the default mode network and the sensorimotor area, which may be associated with CS patients' symptoms of sensory deficits, blurred vision, cognitive impairment and motor dysfunction. The findings may contribute to understanding the underlying pathophysiology of brain dysfunction and provide references for early diagnosis and treatment of CS. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, CRD42022370967.

Folate Biomarkers, Folate Intake, and Risk of Death From All Causes, Cardiovascular Disease, and Cancer: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.

CONTEXT: Existing evidence on the relation between folate intake and biomarkers with mortality risk is controversial. OBJECTIVE: Previous cohort studies were examined regarding folate intake and biomarkers in relation to risk of all-cause, cardiovascular disease- (CVD), and cancer-related mortality through a systematic review and meta-analysis. DATA SOURCES: A systematic search was performed of the PubMed, Scopus, and ISI Web of Science databases up to July 2023. DATA EXTRACTION: Prospective cohort studies examining the association of folate biomarkers (in serum, plasma, red blood cells) and intake with risk of all-cause, CVD-, and cancer-related mortality were considered. A random-effects model was applied to combine study-specific risk estimates. Dose-response relations were assessed by 1-stage weighted mixed-effects meta-analysis. DATA ANALYSIS: A total of 25 cohorts with 423 304 participants, 36 558 all-cause, 12 662 CVD-, and 2426 cancer-related deaths were included. No significant association was observed between the highest levels of folate biomarkers and all-cause mortality risk (hazard ratio [HR], 0.91; 95% CI, 0.77-1.06; n = 17; I2 = 89.4%; P < .001), CVD-related mortality risk (HR, 0.97; 95% CI, 0.87-1.06; n = 11; I2 = 0.0%; P = .57), and cancer-related mortality risk (HR, 0.85; 95% CI, 0.69-1.05; n = 6; I2 = 57.8%; P = .04) compared with the lowest. Furthermore, each 10 nmol/L increase was marginally related to a 12% reduced all-cause mortality risk but not to CVD- and cancer-related mortality risk. A significant inverse association was found between highest intake of dietary folate and the lowest, and risk of all-cause (HR, 0.87; 95% CI, 0.78-0.96; n = 3; I2 = 63.6%; P = .06) and CVD (HR, 0.77; 95% CI, 0.57-0.93; n = 4; I2 = 80.2%; P = .002) mortality. CONCLUSIONS: This meta-analysis revealed a significant inverse relation between dietary folate intake and risk of all-cause and CVD mortality. Such an association was not found in the case of folate biomarkers. Further prospective studies are warranted to confirm these findings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42023401700.

The Effects of Vitamin D Supplementation During Pregnancy on Maternal, Neonatal, and Infant Health: A Systematic Review and Meta-analysis.

CONTEXT: Previous research linked vitamin D deficiency in pregnancy to adverse pregnancy outcomes. OBJECTIVE: Update a 2017 systematic review and meta-analysis of randomized controlled trials (RCTs) on the effect of vitamin D supplementation during pregnancy, identify sources of heterogeneity between trials, and describe evidence gaps precluding a clinical recommendation. DATA SOURCES: The MEDLINE, PubMed, Europe PMC, Scopus, Cochrane Database of Systematic Reviews, Web of Science, and CINAHL databases were searched. Articles were included that reported on RCTs that included pregnant women given vitamin D supplements as compared with placebo, no intervention, or active control (≤600 IU d-1). Risk ratios (RRs) and mean differences were pooled for 38 maternal, birth, and infant outcomes, using random effects models. Subgroup analyses examined effect heterogeneity. The Cochrane risk of bias tool was used. DATA EXTRACTION: Included articles reported on a total of 66 trials (n = 17 276 participants). DATA ANALYSIS: The median vitamin D supplementation dose was 2000 IU d-1 (range: 400-60 000); 37 trials used placebo. Antenatal vitamin D supplementation had no effect on the risk of preeclampsia (RR, 0.81 [95% CI, 0.43-1.53]; n = 6 trials and 1483 participants), potentially protected against gestational diabetes mellitus (RR, 0.65 [95% CI, 0.49-0.86; n = 12 trials and 1992 participants), and increased infant birth weight by 53 g (95% CI, 16-90; n = 40 trials and 9954 participants). No effect of vitamin D on the risk of preterm birth, small-for-gestational age, or low birth weight infants was found. A total of 25 trials had at least 1 domain at high risk of bias. CONCLUSION: Additional studies among the general pregnant population are not needed, given the many existing trials. Instead, high-quality RCTs among populations with low vitamin D status or at greater risk of key outcomes are needed. Benefits of supplementation in pregnancy remain uncertain because current evidence has high heterogeneity, including variation in study context, baseline and achieved end-line 25-hydroxyvitamin D level, and studies with high risk of bias. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022350057.

Efficacy and safety of monoamine reuptake inhibitors in attention deficit hyperactivity disorder: A Bayesian network meta-analysis.

The use of first-line drugs in clinical practice for attention deficit hyperactivity disorder (ADHD) is limited by their adverse effects. Many novel monoamine reuptake inhibitors (MRIs) with better safety profiles and comparable efficacy are also being tried for ADHD. This network meta-analysis (NMA) has evaluated the efficacy and safety of MRIs in ADHD. The data was extracted from 31 relevant clinical trials after a literature search on MEDLINE/PubMed, Embase, Scopus, Cochrane databases, and clinical trial registries. Quality assessment was performed using the risk of bias assessment tool (RoB2) by Cochrane Collaboration, and the random-effects model was used to estimate the effect size. Standardised mean difference (SMD) and 95% credible interval(95%CrI) were reported for the reduction in ADHD rating scale score. Network geometry was visualised, and node splitting was done for the closed triangles. Meta-regression was done for the duration of therapy. PRISMA-NMA guidelines were followed in selecting, analyzing, and reporting findings. The drugs showing significant reduction on the ADHD rating scale as compared to placebo are bupropion (SMD: 0.33; 95%CrI: 0.60,-0.059), dasotraline(SMD: 0.49; 95%CrI: 0.82,-0.16), venlafaxine(SMD: 0.71; 95%CrI: 1.3,-0.15), viloxazine(SMD: 0.45; 95%CrI: 0.77,-0.12). Other drugs (centanafadine, duloxetine, edivoxetine, reboxetine, tipepidine, vortioxetine) were no better than placebo in reducing symptom severity of ADHD. The efficacy of none of the drugs was found to be significantly different as compared to methylphenidate. Among all, duloxetine (OR:15; 95%CrI:1.8130) showed significantly more treatment-emergent adverse events than methylphenidate. In conclusion, venlafaxine, viloxazine, and bupropion are the most efficacious MRIs for ADHD symptom reduction as compared to placebo with high certainty of evidence.

Obstetric and perinatal outcomes of women with a history of recurrent pregnancy loss: a meta-analysis of cohort studies.

PURPOSE: To assess the risk of adverse obstetric and perinatal outcomes in subsequent pregnancies among women with a history of recurrent pregnancy loss (RPL). METHODS: Relevant studies were identified by searching the PubMed, Web of Science, and Embase databases. The pooled effect sizes were reported as odds ratios (OR) with their respective 95% confidence intervals (95% CI), and data analysis was performed using the random effects model. RESULTS: A total of 26 studies involving 4,730,728 women were included in this meta-analysis. The results reveal a significant increase in the prevalence of placenta accreta cases after RPL compared to women without RPL (pooled OR 4.04; 95% CI 1.16-14.15; 2 studies; I2 = 94%; P = 0.03). However, no elevated risk of aneuploidies (pooled OR 1.69, 95% CI 0.73-3.90; 5 studies; I2 = 48%; P = 0.22) or congenital anomalies (pooled OR 1.12, 95% CI 0.97-1.30; 7 studies; I2 = 13%; P = 0.12) in subsequent pregnancies of women with RPL was observed. Additionally, a moderate increase in the risk of various other obstetric and perinatal outcomes was found. The magnitude of the elevated risk of these adverse outcomes varied depending on the region. CONCLUSIONS: Women with a history of RPL exhibit a significantly elevated risk of placenta accreta in subsequent pregnancies, along with a moderate increase in the risk of various other adverse obstetric and perinatal outcomes. However, RPL does not signify an increased risk of aneuploidies or congenital anomalies in a consecutive pregnancy.

Postoperative outcomes of minimally invasive versus conventional nipple-sparing mastectomy with prosthesis breast reconstruction in breast cancer: a meta-analysis.

Breast cancer is the most common malignant tumor worldwide, and mastectomy remains the primary strategy for treating early stage breast cancer. However, the complication rates, surgical variables, and oncologic safety of minimally invasive nipple-sparing mastectomy (MINSM) have not been fully addressed. We systematically searched PubMed, Web of Science, Embase, and the Cochrane Library for randomized-controlled trials (RCTs) and non-RCTs that compared MINSM with conventional nipple-sparing mastectomy (CNSM), both followed by Prosthesis Breast Reconstruction (PBR). The main outcomes observed included overall complications, (Grade III) complications, skin and nipple necrosis, wound dehiscence, infection, seroma, hematoma, implant loss, and oncologic safety (positive margins and recurrence). Secondary outcomes included operation time, blood loss, hospital stay, cost-effectiveness, and patient satisfaction. Binary and continuous variables were compared using odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CI). A total of 10 studies involving 2,166 patients were included. There were no statistically significant differences between MINSM and CNSM in terms of skin necrosis, wound dehiscence, infection, seroma, hematoma, implant loss, or oncologic safety. However, MINSM significantly reduced overall complications (OR = 0. 74, 95% CI [0. 58, 0. 94], p = 0. 01) and (Grade III) complications (OR = 0. 47, 95% CI [0. 31, 0. 71], p = 0. 0003). Nipple necrosis events were also significantly reduced in the MINSM group (OR = 0. 49, 95% CI [0. 30, 0. 80], p = 0. 005). Patient satisfaction improved notably in the MINSM group. Additionally, compared with the CNSM group, the MINSM group had longer operating times (MD = 46. 88, 95% CI [19. 55, 74. 21], p = 0. 0008) and hospital stays (MD = 1. 39, 95% CI [0. 65, 2. 12], p < 0. 001), while intraoperative blood loss was significantly reduced (MD = -29. 05, 95% CI [-36. 20, -21. 90], p < 0. 001). Compared with CNSM, MINSM offers advantages in reducing complications and intraoperative blood loss, as well as improving aesthetic outcomes and patient satisfaction. Therefore, MINSM may become a viable option for breast surgery. Nevertheless, a long-term evaluation of the oncologic safety of this approach is necessary to ensure its efficacy and safety for patients.

Does Patellar Denervation with Electrocautery Benefits for Total Knee Arthroplasty without Patellar Resurfacing: A Meta-analysis of Randomized Controlled Trails.

To investigate the effects of patellar denervation (PD) and non-patellar denervation (NPD) after primary total knee arthroplasty (TKA) without patellar resurfacing, this study conducted systematic electronic searches in November 2023 using PubMed, Embase, Web of Science, Cochrane, and Scopus, adhering to Cochrane Collaboration recommendations. Only randomized controlled trials (RCTs) were included. Additionally, a manual search was performed to identify potentially eligible studies from the reference lists of review articles. Two researchers independently conducted literature reviews, data extraction, and risk of bias assessments. The outcome analysis encompassed the incidence of anterior knee pain (AKP), visual analogue scale (VAS), range of motion (ROM), American Knee Society Score (KSS), Oxford Knee Score (OKS), patellar score (PS), complications, and reoperations. Meta-analysis was executed using RevMan 5.3 software. To enhance the credibility of the study, TSA v0.9 software was utilized to perform power analysis on the overall efficacy of primary and secondary outcomes. Twelve studies involving 1745 patients (1587 knees) were included, with 852 undergoing PD and 893 undergoing NPD. Results indicated a superior reduction in AKP incidence in the PD group compared to the NPD group. Statistically significant differences were observed between PD and NPD in KSS, OKS, and PS. However, the upper limit of the 95% confidence interval for each outcome fell below the minimal clinically important difference (MCID). No significant differences were found in VAS and ROM between PD and NPD. Additionally, PD was not associated with an increased incidence of complications or reoperations. Within 12 months and beyond, PD was proven to be a beneficial intervention in reducing AKP following TKA without patellar resurfacing, achieved without an increase in complications or reoperations. Regarding KSS, OKS, and PS, the minimal advantage achievable through PD may not be clinically significant.

Once-weekly insulin icodec compared with daily basal insulin analogues in type 2 diabetes: Participant-level meta-analysis of the ONWARDS 1-5 trials.

AIM: To perform a participant-level post hoc meta-analysis of Phase 3a trials in type 2 diabetes (T2D) to characterize the hypoglycaemia safety and glycaemic efficacy of once-weekly insulin icodec (icodec). MATERIALS AND METHODS: All ONWARDS 1-5 randomized participants were pooled as overall T2D, insulin-naive, an insulin-experienced subgroups, and by once-daily trial comparator (degludec or glargine U100). The main outcomes included incidence and rates of clinically significant and severe hypoglycaemia. Additional endpoints included change in glycated haemoglobin (HbA1c) from baseline and HbA1c target achievement without clinically significant or severe hypoglycaemia. RESULTS: The meta-analysis comprised 3765 participants (1882 icodec vs. 1883 comparators). In the overall T2D pool, clinically significant hypoglycaemia incidence was similar in the icodec group versus the comparator group (17.9% vs. 16.2%, odds ratio [OR] 1.14, 95% confidence interval [CI] 0.94, 1.38); however, rates were low but significantly higher in the icodec group (1.15 vs. 1.00 episodes/participant-year of exposure, estimated rate ratio 1.51 [95% CI 1.24, 1.85]). Fewer severe hypoglycaemic episodes occurred with icodec than with comparators (8 vs. 18). A greater reduction in HbA1c occurred with icodec versus comparators, irrespective of subgroup (estimated treatment difference range [-0.10 to -0.29%]; all p < 0.05). Across subgroups, except for the insulin-experienced subgroup, the odds of achieving HbA1c <53 mmol/mol (7.0%) without clinically significant or severe hypoglycaemia were greater with icodec than with comparators (OR range 1.30-1.55; all p < 0.05). CONCLUSIONS: Icodec was associated with a similar incidence but higher rates of clinically significant hypoglycaemia (equating to one additional hypoglycaemic episode every 6 years) and fewer severe hypoglycaemic episodes versus comparators. Our findings also confirmed the greater efficacy of icodec that was demonstrated in the ONWARDS trial programme.