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)

Genetic predisposition of BDNF (rs6265) gene is susceptible to Schizophrenia: A prospective study and updated meta-analysis / Asociación entre el gen BDNF (rs6265) y predisposición a la esquizofrenia: estudio prospectivo y metaanálisis actualizado

Introduction: Genetic polymorphism in the BDNF gene has been found to cause neuronal alterations and has been identified as a causal factor for many neuropsychiatric disorders. Therefore, various neurological case–control studies and meta-analyses have been conducted to find the possible link between BDNF and susceptibility to schizophrenia. Method: This meta-analysis gathered data from 25 case–control studies including a total of 8384 patients with schizophrenia and 8821 controls in order to identify the relationship between the rs6265 single nucleotide polymorphism and the disease, evaluating the combined odds ratio and 95% confidence intervals under 5 different genetic models. Validation followed the “Leave one out” method, and we used the Egger test and Begg's funnel plot to identify publication bias. Results: Research into the rs6265 (G/A) polymorphism revealed a non-significant association with schizophrenia in all 5 genetic models; in the subgroup analysis, no association was found between white and Asian populations, with a p value > .05. Conclusions: Overall, the updated meta-analysis revealed that rs6265 exonic polymorphisms do not increase susceptibility to this disease. However, to better understand the pathogenesis of the disease, there is a need for further case–control studies into the BDNF polymorphism including larger sample sizes and different ethnic groups.(AU)

Introducción: Se sabe que los polimorfismos del gen BDNF provocan alteraciones neuronales y parecen ser un factor causal en muchos trastornos neuropsiquiátricos. Es por ello que se han llevado a cabo varios metaanálisis y estudios de casos y controles con el objetivo de evaluar la posible relación entre BDNF y la esquizofrenia. Método: Realizamos un metaanálisis de 25 estudios de casos y controles, que incluyó un total de 8.384 pacientes con esquizofrenia y 8.821 controles. Se analizó la relación entre el polimorfismo de nucleótido simple rs6265 y la esquizofrenia mediante odds ratios combinados y sus intervalos de confianza del 95% con 5 modelos genéticos diferentes. Utilizamos el método de validación cruzada dejando uno fuera («leave one out»), la prueba de Egger y el gráfico en embudo de Begg para identificar posibles sesgos de publicación. Resultados: Los estudios sobre el polimorfismo rs6265 (G/A) muestran una asociación no significativa con la esquizofrenia en los 5 modelos genéticos. En el análisis por subgrupos, no se encontró relación con las poblaciones caucásica y asiática (p > 0,05). Conclusiones: La presencia de polimorfismos rs6265 no aumenta la predisposición a desarrollar esquizofrenia. Sin embargo, se deben realizar más estudios de casos y controles sobre polimorfismos de BDNF, con muestras más numerosas y con individuos de diferentes grupos étnicos, para comprender mejor los mecanismos patogénicos de la enfermedad.(AU)

Resultados tras 5 años de cirugía o abordaje percutáneo en coronariopatía grave. Metanálisis de ensayos aleatorizados con reconstrucción del tiempo hasta el evento / Results beyond 5-years of surgery or percutaneous approach in severe coronary disease. Reconstructed time-to-event meta-analysis of randomized trials

Introducción y objetivos: Existe controversia sobre la mejor estrategia de revascularización en la enfermedad coronaria avanzada, incluidas la enfermedad del tronco coronario y la enfermedad multivaso. Varios metanálisis han comparado resultados a 5 años, pero no hay resultados después del quinto año. Se realizaron una revisión sistemática y un metanálisis de ensayos clínicos aleatorizados para comparar los resultados después del quinto año entre la cirugía de revascularización coronaria (CABG) y la intervención coronaria percutánea (ICP) con stents farmacoactivos.MétodosSe analizaron los ensayos clínicos publicados entre 2010 y 2023. El objetivo primario fue la mortalidad por cualquier causa. Las bases de datos originales se reconstruyeron a partir de las curvas de Kaplan-Meier simulando un metanálisis individual. Se realizaron comparaciones en ciertos puntos de corte (5 y 10 años). Se calculó la diferencia del tiempo medio de supervivencia restringida. Se aplicó el modelo de efectos aleatorios y de DerSimonian-Laird.ResultadosSe analizó a 5.180 pacientes. Durante los 10 años de seguimiento, las ICP muestran una mayor incidencia de mortalidad (HR=1,19; IC95%, 1,04-1,32; p=0,008). La ICP muestra un mayor riesgo de mortalidad a 5 años (HR=1,2; IC95%, 1,06-1,53; p=0,008), mientras que no hubo diferencias de 5 a 10 años (HR=1,03; IC95%, 0,84-1,26; p=0,76). La esperanza de vida de los pacientes sometidos a CABG fue ligeramente mayor (2,4 meses más).ConclusionesEntre los pacientes con enfermedad coronaria avanzada, incluidas la enfermedad del tronco coronario y la enfermedad multivaso, hubo mayor mortalidad tras una ICP que tras la CABG a los 10 años de seguimiento. En concreto, la ICP tiene mayor mortalidad durante los primeros 5 años y un riesgo comparable de 5 a 10 años. (AU)

Introduction and objectives: There is controversy about the optimal revascularization strategy in severe coronary artery disease (CAD), including left main disease and/or multivessel disease. Several meta-analyses have analyzed the results at 5-year follow-up but there are no results after the fifth year. We conducted a systematic review and meta-analysis of randomized clinical trials, comparing results after the fifth year, between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) using drug-eluting stents in patients with severe CAD.MethodsWe analyzed all clinical trials between January 2010 and January 2023. The primary endpoint was all-cause mortality. The databases of the original articles were reconstructed from Kaplan-Meier curves, simulating an individual-level meta-analysis. Comparisons were made at certain cutoff points (5 and 10 years). The 10-year restricted median survival time difference between CABG and PCI was calculated. The random effects model and the DerSimonian-Laird method were applied.ResultsThe meta-analysis included 5180 patients. During the 10-year follow-up, PCI showed a higher overall incidence of all-cause mortality (HR, 1.19; 95%CI, 1.04-1.32; P=.008)]. PCI showed an increased risk of all-cause mortality within 5 years (HR, 1.2; 95%CI, 1.06-1.53; P=.008), while no differences in the 5–10-year period were revealed (HR, 1.03; 95%CI, 0.84-1.26; P=.76). Life expectancy of CABG patients was slightly higher than that of PCI patients (2.4 months more).ConclusionsIn patients with severe CAD, including left main disease and/or multivessel disease, there was higher a incidence of all-cause mortality after PCI compared with CABG at 10 years of follow-up. Specifically, PCI has higher mortality during the first 5 years and comparable risk beyond 5 years. (AU)

Comparison of inflammatory markers, coagulation indicators and outcomes between influenza and COVID-19 infection amongst children: A systematic review and meta-analysis.

Background: Influenza and COVID-19 patients share similar features and outcomes amongst adults. However, the difference between these diseases is not explored in paediatric age group especially in terms of inflammatory markers, coagulation profile and outcomes. Hence, we did this review to compare the inflammatory, coagulation features and outcomes between influenza and COVID-19 infected children. Methods: Literature search was done in PubMed Central, Scopus, EMBASE, CINAHL, Cochrane library, Google Scholar & ScienceDirect from November 2019 to May 2022. Risk of bias assessment was done through Newcastle Ottawa scale. Meta-analysis was done using random-effects model and the final pooled estimate was reported as pooled odds ratio (OR) or standardized mean difference (SMD) along with 95 % confidence interval (CI) depending on the type of outcome. Results: About 16 studies were included with most studies having higher risk of bias. Influenza paediatric patients had significantly higher erythrocyte sedimentation rate (ESR) (pooled SMD = 0.60; 95%CI: 0.30-0.91; I2 = 0 %), lactate dehydrogenase (LDH) (pooled SMD = 2.01; 95%CI: 0.37-3.66; I2 = 98.4 %) and prothrombin time (PT) (pooled SMD = 2.12; 95%CI: 0.44-3.80; I2 = 98.3 %) when compared to paediatric COVID-19 patients. There was no significant difference in terms of features like CRP, procalcitonin, serum albumin, aPTT, mortality and need for mechanical ventilation. Conclusion: Inflammatory markers like ESR, LDH and PT was significantly higher in influenza patients when compared to COVID-19 in children, while rest of the markers and adverse clinical outcomes were similar between both the groups. Identification of these biomarkers has helped in understanding the distinctness of COVID-19 and influenza virus and develop better management strategies.

Acupuncture for cognitive impairment after stroke: A systematic review and meta-analysis.

Objective: Acupuncture as an alternative therapy for post-stroke cognitive impairment (PSCI) has emerged as a research focus. The inclusion of additional external treatments in many previous studies prevents a clear, direct assessment of acupuncture's impact on PSCI. In order to prevent patients from developing hypersensitivity to other treatments and misinterpreting acupuncture's true therapeutic value, this study establish stricter intervention criteria and exclude therapies beyond acupuncture. The review aimed to offering a clearer evaluation of acupuncture's efficacy and safety in PSCI treatment. Methods: This research involved a comprehensive search for randomized controlled trials (RCTs) across eight databases, adhering to the Cochrane Systematic Reviewer's Handbook 5.1.0 for risk-of-bias and quality assessments. A meta-analysis was conducted using RevMan 5.3 software. Results: The inclusion of 18 publications, totaling 1361 patients, was achieved. The meta-analysis demonstrated a significantly higher overall efficacy of acupuncture for PSCI compared to controls (OR = 4.06, 95 % CI 2.86-5.76, Z = 7.82). Notable statistical differences were observed in the Montreal Cognitive Assessment scores (MD = 2.32, 95 % CI 1.68-2.97, Z = 7.10) and the Mini-Mental State Examination scores (MD = 2.02, 95 % CI 1.06-2.98, Z = 4.13) between the groups. Improvements in the Barthel Index scores were noted for the experimental group (MD = 5.70, 95 % CI 4.68-6.72, Z = 10.92). Conclusion: Integrating acupuncture with Western medications offers significant benefits for treating PSCI over Western medications alone. However, the long-term efficacy of acupuncture in PSCI treatment and its potential in reducing recurrence rates remain undetermined. Further high-standard RCTs are essential to explore acupuncture's effectiveness in PSCI treatment more thoroughly.

The ultrasound-guided versus standard technique for peripheral intravenous catheter placement by nurses: A systematic review and meta-analysis.

Aim: To comprehensively evaluate the efficacy of Ultrasound-guided technique for peripheral intravenous catheter placement by nurses in their daily practice. Background: Peripheral intravenous catheter insertion is a common clinical procedure in healthcare settings. Ultrasound-guided peripheral intravenous placement has emerged in recent decades and was recognized as particularly useful in some specific patient groups. Methods: Studies that had compared the ultrasound-guided and traditional approaches were eligible for inclusion and further analysis. The primary outcome was the success rate on the first intravenous insertion attempt. The secondary outcomes included the time needed for successful insertion, and the average number of attempts to establish the IV access. We systematically assess all studies using Cochrane Collaboration's Risk of Bias tool and the Newcastle-Ottawa Scale. We calculated the odds ratio and standardized mean difference with 95 % confidence intervals for the outcomes. Data were analyzed and visualized on Review Manager 5.3.4 and Stata 16.0. Results: 23 studies were included (17 randomized controlled trials and six cohort studies) with a population of 2051 patients offered ultrasound-assisted technique and 2479 treated with the conventional approach for comparison. The former approach was associated with a higher success rate on the first attempt in comparison (OR = 2.95, 95 % CI: 1.86, 4.69). This technique also took less time and less acupuncture to patients' skin (SMD = -0.62, 95 % CI: 1.01, -0.23; SMD = -0.55, 95 % CI: 0.92, -0.18). In the sub-group analyses, children were more likely to benefit from ultrasound guided technique. Ultrasound guided technique demonstrated consistent and significant benefits in emergency clinical settings. Hospitals from different geographical locations exhibited similar trends in the three outcomes. Year of publication and study design revealed inconsistent and insignificant outcomes. Conclusions: Ultrasound-guided technique can be a safer, faster, and more effective alternative to the traditional approach for nurses to establish intravenous access across different clinical settings and age groups.

Effect of Meditation, Mindfulness-Based Stress Reduction, and Relaxation Techniques as Mind-Body Medicine Practices to Reduce Blood Pressure in Cardiac Patients: A Systematic Review and Meta-Analysis.

Elevated blood pressure is one of the major risk factors for cardiovascular diseases. Available evidence on mind-body medicine (MBM) techniques on blood pressure is inconclusive and provides conflicting results. The objective of the current systematic review and meta-analysis is to evaluate the effect of MBM techniques on blood pressure in patients with cardiovascular disease. Randomized control trials (RCTs) done between the years 2000 and 2020 on cardiovascular disease, using MBM techniques such as meditation, mindfulness-based stress reduction and relaxation techniques were searched through electronic databases such as PubMed, Cumulative Index to Nursing & Allied Health (CINAHL), EMBASE and Cochrane Library. Three authors independently performed article selection, data extraction and validation. Meta-analysis was performed using a random effect model and standardized mean difference (SMD) with 95% confidence interval (CI) estimated for the effect size. Fifteen RCTs with 927 patients were included in the meta-analysis. Heterogeneity among the studies was very high for all analyses (I2>94%). For studies comparing systolic blood pressure, MBM interventions show a significant (p=0.01) effect when compared to conventional treatment, an overall estimated effect size of SMD - 0.78 (95% CI: -1.36, -0.20). For studies comparing the diastolic blood pressure, MBM intervention did not show any significant effect when compared to the conventional treatment, an overall effect size of SMD -0.26 (95% CI: -0.91, 0.39). The findings of the meta-analysis suggest that MBM interventions may improve systolic blood pressure alone in patients with cardiac diseases. With high heterogeneity and low quality of the included studies, more robust evidence is required before suggesting MBM as an effective treatment modality for reducing blood pressure in cardiovascular diseases.

The prevalence of post traumatic and associated factors among nurses during COVID_19 pandemics: a systematic review and meta-analysis.

BACKGROUND: Despite the negative outcomes, exposure to a crisis may cause people to experience positive changes. This study aims to analyze the prevalence of post-traumatic growth (PTG) and its relevant factors among nurses during the COVID-19 pandemic. METHOD: The research protocol was registered with PROSPERO (CRD42022329671), and PRISMA steps were taken in this study. PubMed, Scopus and ProQuest were explored on 1/9/2022 to create the research database. According to the inclusion criterion, all studies analyzing the prevalence of post-traumatic growth through the PTG Inventory were considered eligible. They were all qualitatively assessed through the modified version of the Quality Assessment Checklist for prevalence studies. RESULTS: A total of 15 papers met the inclusion criterion (n = 22756). According to the research results, the prevalence of PTG was randomly calculated ES [95% Conf. Interval = 0.15 [0.12-0.17]), and heterogeneity was reported I2 = 98.52% (P = 0.000). The results also indicated that the mean score of PTGI decreased in nurses as their work experience and mean age increased. However, the effect was not statistically significant for the mean age (P = 0.06). According to the results, the PTGI score decreased in nurses with more work experience, a finding which was statistically significant (P = 0.04). CONCLUSION: This meta-analysis determined a 15% prevalence rate of PTG in nurses. Psychological interventions should be developed and applied to older nurses with more work experience in order to mitigate the harm caused by the pandemic and its consequent crises.

The effect of cognitive load, ego depletion, induction and time restriction on moral judgments about sacrificial dilemmas: a meta-analysis.

Greene's influential dual-process model of moral cognition (mDPM) proposes that when people engage in Type 2 processing, they tend to make consequentialist moral judgments. One important source of empirical support for this claim comes from studies that ask participants to make moral judgments while experimentally manipulating Type 2 processing. This paper presents a meta-analysis of the published psychological literature on the effect of four standard cognitive-processing manipulations (cognitive load; ego depletion; induction; time restriction) on moral judgments about sacrificial moral dilemmas [n = 44; k = 68; total N = 14, 003; M(N) = 194.5]. The overall pooled effect was in the direction predicted by the mDPM, but did not reach statistical significance. Restricting the dataset to effect sizes from (high-conflict) personal sacrificial dilemmas (a type of sacrificial dilemma that is often argued to be best suited for tests of the mDPM) also did not yield a significant pooled effect. The same was true for a meta-analysis of the subset of studies that allowed for analysis using the process dissociation approach [n = 8; k = 12; total N = 2, 577; M(N) = 214.8]. I argue that these results undermine one important line of evidence for the mDPM and discuss a series of potential objections against this conclusion.

Cerebrospinal fluid/serum albumin ratio in patients with Lewy body disease: a systematic review and meta-analysis.

Background: Abnormal cerebrospinal fluid (CSF)/serum albumin ratio (Qalb) levels have been observed in patients with cognitive impairment. Few studies have specifically focused on Lewy Body Disease (LBD), and the results were controversial. Thus, we conducted this systematic review and meta-analysis to investigate Qalb levels in patients with LBD by including data from different studies. Method: We systematically searched PubMed, Embase, Cochrane Library, and Web of Science databases for a collection of studies containing studies comparing Qalb levels in patients with LBD and healthy controls (including healthy controls and other dementia subtypes). In the initial search, 86 relevant papers were retrieved. Standardized mean differences (SMD) in Qalb levels were calculated using a random effects model. Results: A total of 13 eligible studies were included. Mean Qalb levels were significantly higher in patients with LBD compared to healthy older adults [standardized mean difference (SMD): 2.95, 95% confidence interval (CI): 0.89-5.00, Z = 2.81, p = 0.005]; and were significantly higher in patients with LBD than in patients with Alzheimer's disease (AD) (SMD: 1.13, 95% CI: 0.42-1.83, Z = 3.15, p = 0.002);whereas mean Qalb levels were significantly higher in patients with frontotemporal lobar degeneration (FTLD) compared to those with AD (SMD: 1.13, 95% CI,0.14-2.13, Z = 2.24, p = 0.03). Conclusion: Qalb levels were significantly elevated in LBD patients compared with normal older adults and were higher than those in AD patients and FTLD patients, which helped in the differential diagnosis of LBD from other neurodegenerative diseases. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024496616.

The risk of endocrine immune-related adverse events induced by PD-1 inhibitors in cancer patients: a systematic review and meta-analysis.

Objective: Endocrinopathies are the most common immune-related adverse events (irAEs) observed during therapy with PD-1 inhibitors. In this study, we conducted a comprehensive systematic review and meta-analysis to evaluate the risk of immune-related endocrinopathies in patients treated with PD-1 inhibitors. Methods: We performed a systematic search in the PubMed, Embase, and Cochrane Library databases to retrieve all randomized controlled trials (RCTs) involving PD-1 inhibitors, spanning from their inception to November 24, 2023. The comparative analysis encompassed patients undergoing chemotherapy, targeted therapy, or receiving placebo as control treatments. This study protocol has been registered with PROSPERO (CRD42023488303). Results: A total of 48 clinical trials comprising 24,514 patients were included. Compared with control groups, patients treated with PD-1 inhibitors showed an increased risk of immune-related adverse events, including hypothyroidism, hyperthyroidism, hypophysitis, thyroiditis, diabetes mellitus, and adrenal insufficiency. Pembrolizumab was associated with an increased risk of all aforementioned endocrinopathies (hypothyroidism: RR=4.76, 95%CI: 3.55-6.39; hyperthyroidism: RR=9.69, 95%CI: 6.95-13.52; hypophysitis: RR=5.47, 95%CI: 2.73-10.97; thyroiditis: RR=5.95, 95%CI: 3.02-11.72; diabetes mellitus: RR=3.60, 95%CI: 1.65-7.88; adrenal insufficiency: RR=4.80, 95%CI: 2.60-8.88). Nivolumab was associated with an increased risk of hypothyroidism (RR=7.67, 95%CI: 5.00-11.75) and hyperthyroidism (RR=9.22, 95%CI: 4.71-18.04). Tislelizumab and sintilimab were associated with an increased risk of hypothyroidism (RR=19.07, 95%CI: 5.46-66.69 for tislelizumab and RR=18.36, 95%CI: 3.58-94.21 for sintilimab). For different tumor types, both hypothyroidism and hyperthyroidism were at high risks. Besides, patients with non-small cell lung cancer were at a higher risk of thyroiditis and adrenal insufficiency. Patients with melanoma were at a higher risk of hypophysitis and diabetes mellitus. Both low- and high-dose group increased risks of hypothyroidism and hyperthyroidism. Conclusion: Risk of endocrine irAEs may vary in different PD-1 inhibitors and different tumor types. Increased awareness and understanding of the risk features of endocrine irAEs associated with PD-1 inhibitors is critical for clinicians. Systematic review registration: crd.york.ac.uk/prospero, identifier PROSPERO (CRD42023488303).

Association of IL­6 and MMP­3 gene polymorphisms with adolescent idiopathic scoliosis: A systematic review and meta­analysis.

The pathogenesis of adolescent idiopathic scoliosis (AIS) remains unclear. It has been found that interleukin-6 (IL-6) rs1800795 locus and matrix metalloproteinase-3 (MMP-3) rs3025058 locus gene polymorphisms may be associated with AIS susceptibility, which has been controversial and needs to be further confirmed by updated meta-analysis. The aim of the present study was to investigate the association of MMP-3 rs3025058 and IL-6 rs1800795 single nucleotide polymorphisms (SNPs) with susceptibility to AIS. All relevant articles that met the criteria were retrieved and included, and the publication dates were limited from January 2005 to December 2023. The allele frequencies and different genotype frequencies of IL-6 rs1800795 and MMP-3 rs3025058 loci in each study were extracted and statistically analyzed by ReviewManager 5.4 software, and the odds ratio (OR) and 95% confidence interval (95% CI) of different genetic models were calculated. The results of the meta-analysis showed that there was no significant association between the gene polymorphism of IL-6 rs1800795 locus and the pathogenesis of AIS. The allele 5A and genotype 5A5A of MMP-3 rs3025058 SNP were associated with AIS susceptibility (5A vs. 6A, OR=1.18; 95% CI, 1.04-1.33; 5A5A vs. 6A6A, OR=1.65; 95% CI, 1.23-2.21; and 5A5A vs. 5A6A + 6A6A, OR=1.54; 95% CI, 1.19-1.99). Results of subgroup analysis revealed that the allele 5A and genotype 5A5A of MMP-3 rs3025058 SNP were associated with AIS susceptibility in the Caucasian population, and the susceptibility of AIS was associated with the genotype 5A5A of MMP-3 rs3025058 SNP in an Asian population. There was no significant association between the gene polymorphism of IL-6 rs1800795 locus and the pathogenesis of AIS, while the allele 5A of MMP-3 rs3025058 locus was associated with the susceptibility to AIS, especially in the Caucasian population.

Efficacy and safety of PD-1/PD-L1 inhibitor-based immune combination therapy versus sorafenib in the treatment of advanced hepatocellular carcinoma: a meta-analysis.

Objective: To systematically evaluate the safety and efficacy of PD-1/PD-L1 inhibitor-based immunotherapy (hereafter referred to as "combination immunotherapy") compared with that of sorafenib in the treatment of hepatocellular carcinoma (HCC). Methods: Databases such as PubMed, Embase, and the Cochrane Library were searched from the date of their establishment to September 2023 to identify randomized controlled trials (RCTs) of combination immunotherapy versus sorafenib for the treatment of advanced HCC. Two reviewers independently evaluated the quality of the included studies, extracted the data, and cross-checked the information. The meta-analysis was performed using RevMan 5.3 software. Results: A total of 5 RCTs were included. The results of the meta-analysis showed the following: (1) Effectiveness. Compared to sorafenib, combination immunotherapy significantly improved overall survival (OS, HR = 0.69, 95% CI: 0.58 ~ 0.82, p < 0.01) and progression-free survival (PFS, HR = 0.62, 95% CI: 0.50 ~ 0.78, p < 0.001) in patients with advanced HCC. (2) Safety. Both groups had comparatively high incidences of adverse events (AEs), but the difference in any treatment-related adverse events was not significant between the two arms (OR = 0.98, 95% CI: 0.95 ~ 1.02, p = 0.34). The difference in the incidence of grade 1-2 adverse reactions was statistically significant (OR = 0.66, 95% CI = 0.49-0.90, p = 0.001). There were no differences in grade 3/4 TRAEs or grade 5 TRAEs (OR = 1.46, 95% CI = 0.78 ~ 2.71, p = 0.24; OR = 1.08, 95% CI = 0.73 ~ 1.58, p = 0.71). Conclusion: Combined immunotherapy can significantly prolong the OS and PFS of patients with advanced HCC without increasing the incidence of adverse effects in terms of safety, but the incidence of AEs in different systems is different.

Risk factors for cervical instability in rheumatoid arthritis: a meta-analysis.

Introduction: The aim of the study was to evaluate the risk factors for cervical instability in rheumatoid arthritis (RA). Material and methods: Computer searches were conducted in PubMed, Embase, Cochrane Library, the China National Knowledge Infrastructure (CNKI) database, the Wan Fang database, the Chinese Scientific Journal Databases (VIP) database, and the Chinese Biomedical Literature database (CBM) from their establishment until November 2022. Results: A total of 8 articles were included in this study, including 1 cross-sectional study, 5 case-control studies, and 2 cohort study, including 3078 patients with RA. Meta-analysis results showed that: male sex (OR = 1.70, 95% CI: 1.19-2.42), course of disease (OR = 1.72, 95% CI: 1.29-2.28), long-term glucocorticosteroid use (OR = 2.84, 95% CI: 1.97-2.40), Steinbrocker staging (OR = 2.30, 95% CI: 1.61-3.28), disability at baseline (OR = 24.57, 95% CI: 5.51-109.60), peripheral joint destruction (OR = 2.24, 95% CI: 1.56-3.21), Steinbrocker stage I-IV progression to disability (OR = 20.08, 95% CI: 4.18-96.53), and previous joint surgery (OR = 1.54, 95% CI: 1.06-2.26) are the main risk factors for cervical instability in RA. Conclusions: There are many risk factors for cervical instability in RA. In clinical practice, special attention should be paid to patients who are male, have a longer course of disease, have long-term glucocorticosteroid use, have previous joint surgery, have peripheral joint damage, and develop disability in Steinbrocker stage I-IV. Attention should be paid to the high-risk groups mentioned above, and effective measures such as early screening and full monitoring should be taken to prevent the occurrence of cervical instability in RA.

Clinical evaluation of maxillary sinus floor elevation with or without bone grafts: a systematic review and meta-analysis of randomised controlled trials with trial sequential analysis.

Introduction: Our goal was to systematically review the current evidence comparing the relative effectiveness of two maxillary sinus floor elevation (MSFE) approaches (internal and external) without bone grafts with that of conventional/grafted MSFE in patients undergoing implantation in the posterior maxilla. Material and methods: Medical databases (PubMed/Medline, Embase, Web of Science, and Cochrane Library) were searched for randomised controlled trials published between January 1980 and May 2023. A manual search of implant-related journals was also performed. Studies published in English that reported the clinical outcomes of MSFE with or without bone material were included. The risk of bias was assessed using the Cochrane Handbook Risk Assessment Tool. Meta-analyses and trial sequence analyses were performed on the included trials. Meta-regression analysis was performed using pre-selected covariates to account for substantial heterogeneity. The certainty of evidence for clinical outcomes was assessed using GRADEpro GDT online (Guideline Development Tool). Results: Seventeen studies, including 547 sinuses and 696 implants, were pooled for the meta-analysis. The meta-analysis showed no statistically significant difference between MSFE without bone grafts and conventional MSFE in terms of the implant survival rate in the short term (n = 11, I2 = 0%, risk difference (RD): 0.03, 95% confidence intervals (CI): -0.01-0.07, p = 0.17, required information size (RIS) = 307). Although conventional MSFE had a higher endo-sinus bone gain (n = 13, I2 = 89%, weighted mean difference (WMD): -1.24, 95% CI: -1.91- -0.57, p = 0.0003, RIS = 461), this was not a determining factor in implant survival. No difference in perforation (n = 13, I2 = 0%, RD = 0.03, 95% CI: -0.02-0.09, p = 0.99, RIS = 223) and marginal bone loss (n = 4, I2 = 0%, WMD = 0.05, 95% CI: -0.14-0.23, p = 0.62, no RIS) was detected between the two groups using meta-analysis. The pooled results of the implant stability quotient between the two groups were not robust on sensitivity analysis. Because of the limited studies reporting on the visual analogue scale, surgical time, treatment costs, and bone density, qualitative analysis was conducted for these outcomes. Conclusions: This systematic review revealed that both non-graft and grafted MSFE had high implant survival rates. Owing to the moderate strength of the evidence and short-term follow-up, the results should be interpreted with caution.

The prognostic value of cancer stem cell markers in thyroid cancer: a systematic review.

Introduction: Thyroid cancer stem cells (TCSCs) play a crucial role in the pathogenesis, metastasis, and therapeutic response of thyroid cancer, making them promising biomarkers and potential targets for clinical intervention. This systematic review aims to qualitatively assess the impact of commonly used TCSC markers on the prognosis of thyroid cancer using qualitative methods. Methods: In total, the analysis encompassed five articles. Results: Six TCSC markers were involved, among which CD133, CD44, CD24, CD15 and ALDH1 were associated with the prognosis of thyroid cancer. Conclusions: However, the utility of these TCSC markers in clinical practice for predicting the prognosis of thyroid cancer requires further research to provide additional evidence supporting their effectiveness.

Interventions to mitigate cancer-related medical financial hardship: A systematic review and meta-analysis.

BACKGROUND: This study systematically reviewed interventions mitigating financial hardship in patients with cancer and assessed effectiveness using a meta-analytic method. METHODS: PubMed, Cochrane, Scopus, CINAHL, and Web of Science were searched for articles published in English during January 2000-April 2023. Two independent reviewers selected prospective clinical trials with an intervention targeting and an outcome measuring financial hardship. Quality appraisal and data extraction were performed independently by two reviewers using a quality assessment tool. A random-effects model meta-analysis was performed. Reporting followed the preferred reporting items for systematic review and meta-analyses guidelines. RESULTS: Eleven studies (2211 participants; 55% male; mean age, 59.29 years) testing interventions including financial navigation, financial education, and cost discussion were included. Financial worry improved in only 27.3% of 11 studies. Material hardship and cost-related care nonadherence remained unchanged in the two studies measuring these outcomes. Four studies (373 participants; 37% male, mean age, 55.88 years) assessed the impact of financial navigation on financial worry using the comprehensive score of financial toxicity (COST) measure (score range, 0-44; higher score = lower financial worry) and were used for meta-analysis. There was no significant change in the mean of pooled COST score between post- and pre-intervention (1.21; 95% confidence interval, -6.54 to 8.96; p = .65). Adjusting for pre-intervention COST, mean change of COST significantly decreased by 0.88 with every 1-unit increase in pre-intervention COST (p = .02). The intervention significantly changed COST score when pre-intervention COST was ≤14.5. CONCLUSION: A variety of interventions have been tested to mitigate financial hardship. Financial navigation can mitigate financial worry among high-risk patients.

Pharmacologic and Nutritional Interventions for Early Alzheimer's Disease: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Background: Early intervention is essential for meaningful disease modification in Alzheimer's disease (AD). Objective: We aimed to determine the efficacy and safety of pharmacologic and nutritional interventions for early AD. Methods: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched from database inception until 1 September 2023. We included randomized controlled trials that evaluated the efficacy of interventions in early AD. Only interventions that demonstrated efficacy compared to placebo were included in the network meta-analysis (NMA). Then we performed frequentist fixed-effects NMA to rank the interventions. GRADE criteria were used to evaluate the level of evidence. Results: Fifty-eight trials including a total of 33,864 participants and 48 interventions were eligible for inclusion. Among the 48 interventions analyzed, only 6 (12.5%) treatments- ranging from low to high certainty- showed significant improvement in cognitive decline compared to placebo. High certainty evidence indicated that donanemab (standardized mean difference [SMD] -0.239, 95% confidence interval [CI] -0.343 to -0.134) and lecanemab (SMD -0.194, 95% CI -0.279 to -0.108) moderately slowed the clinical progression in patients with amyloid pathology. Additionally, methylphenidate, donepezil, LipiDiDiet, and aducanumab with low certainty showed significant improvement in cognitive decline compared to placebo. However, there was no significant difference in serious adverse events as reported between the six interventions and placebo. Conclusions: Only 12.5% of interventions studied demonstrated efficacy in reducing cognitive impairment in early AD. Donanemab and lecanemab have the potential to moderately slow the clinical progression in patients with amyloid pathology. Further evidence is required for early intervention in AD.

Dose-dependent effect of tart cherry on selected cardiometabolic risk factors: A GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials.

AIMS: This study aimed to clarify the effectiveness of tart cherries on anthropometric, lipid, and glycemic indices. We also aimed to clarify the appropriate dosage for this effect and suggest directions for future studies. METHODS: PubMed, Scopus, and Web of Science were searched until May 2022. Twelve eligible trials were included. The pooled results were reported as weighted mean differences (WMD) and 95 % confidence intervals (CIs). The Cochrane risk of bias and GRADE tools were used to assess the risk of bias and certainty of the evidence, respectively. RESULTS: Tart cherry generally showed no significant effects on cardiometabolic risk factors. But subgroup analysis revealed that tart cherry significantly lowered total cholesterol (WMD: -0.33 mmol/l; 95 % CI: -0.55, -0.10), triglyceride (WMD: -0.19 mmol/l; 95 % CI: -0.26, -0.12), and low-density lipoprotein cholesterol (WMD: -0.36 mmol/l; 95 % CI: -0.58, -0.14), in unhealthy populations. Additionally, subgroup analysis indicated that the favorable effects of tart cherry were more pronounced in a single dose, longer duration, elderly, and obese individuals. Dose-response analysis revealed that 20 ml concentrate has the greatest effect in reducing total cholesterol (WMD: -0.40 mmol/l; 95 % CI: -0.61, -0.19), triglyceride (WMD: -0.23 mmol/l; 95 % CI: -0.33, -0.13), and elevating high-density lipoprotein cholesterol (WMD: 0.20 mmol/l; 95 % CI: 0.17, 0.22). CONCLUSIONS: Tart cherry supplementation did not have significant effects on anthropometric and glycemic indices, but can improve lipid profile, especially in a single dose, longer duration, and in elderly, obese, and unhealthy individuals.