Identifying patients who benefit more from perioperative immunotherapy combinations for resectable non-small cell lung cancer based on clinical and molecular characteristics: a meta-analysis of randomized clinical trials.

PURPOSE: This study aims to identify patient subgroups who benefit more from perioperative immunotherapy combined with chemotherapy (IO-CT) based on clinical and molecular characteristics in resectable non-small cell lung cancer (NSCLC). METHODS: Randomized controlled trials (RCTs) on perioperative IO-CT were searched. Beneficial differences of IO-CT regimens across different patient subgroups were assessed by pooling trial-specific ratios in event-free survival (EFS), overall survival (OS), pathological complete response (pCR), and major pathological response (MPR). RESULTS: Six studies (n = 3003) involving five IO-CT regimens were included. Compared to CT alone, all IO-CT regimens significantly improved EFS, OS, MPR, and pCR, but increased toxicity. Toripa-chemo showed the best EFS and nivo-chemo showed the best OS. Patients with PD-L1 ≥ 1% had more EFS benefits compared to those with PD-L1 < 1% (HR [hazard ratio]: 1.55, 95% CI 1.17-2.04). Squamous NSCLC patients had significantly more pCR and MPR benefits than non-squamous NSCLC patients (pCR: OR [odds ratio] 0.68, 95% CI 0.49-0.95; MPR: OR 0.61, 95% CI 0.45-0.82). Former smokers had significantly higher pCR benefits than non-smokers (OR: 2.18; 95% CI 1.21-3.92). Additionally, OS benefit was significantly higher in patients < 65 years compared to those ≥ 65 years (HR ratio: 0.59, 95% CI 0.36-0.95). For MPR, males benefited significantly more from IO-CT compared to females (OR: 1.69, 95% CI 1.18-2.42). CONCLUSION: Perioperative IO-CT is more effective but more toxic than CT alone in resectable NSCLC. Patients with PD-L1 ≥ 1%, squamous NSCLC, a history of smoking, age < 65 years and male gender may experience greater benefits from perioperative IO-CT.

The efficacy and safety of neoadjuvant immunochemotherapy in resectable stage I-III non-small cell lung cancer: a systematic review and network meta-analysis.

BACKGROUND: Neoadjuvant immunochemotherapy (NICT) is a new treatment method for resectable non-small-cell lung cancer (NSCLC). Network meta-analysis assessed efficacy, safety, and optimal treatment. METHODS: We searched for randomized controlled trials (RCTs) comparing NICT with neoadjuvant chemotherapy (NCT) in PubMed, Embase, Web of Science, Cochrane Library, and international conferences. Outcomes were surgical resection rate, pathological complete response(pCR),event-free survival (EFS), and Grade 3-5 treatment-related adverse events (TRAEs). RESULTS: RCTs of 3,387 patients, six treatment combinations, and two modalities were included. Meta-analysis showed that NICT yielded higher pCR and EFS rates than NCT. The toripalimab-chemotherapy combination had the highest surgical resection rate (OR = 1.68, 95% CI: 1.05-2.73), pCR (OR = 38.84, 95% CI: 11.05-268.19) and EFS (HR = 0.40, 95% CI: 0.28-0.58).This regimen worked well for patients with low programmed death-ligand 1 (PD-L1) expression or squamous cell pathology. For high PD-L1 expression and patients with NSCLC, neoadjuvant nivolumab with chemotherapy had the most efficacy. The incidence of treatment-related adverse events increased with longer treatment cycles, with perioperative nivolumab combined with chemotherapy showing the worst safety profile (RR = 1.32, 95% CI: 1.00-1.76), while neoadjuvant nivolumab combined with chemotherapy alone had the best safety profile (RR = 0.91, 95% CI: 0.68-1.21). Indirect comparison showed no survival benefit for neoadjuvant-adjuvant immunotherapy (HR = 0.93, 95% CI: 0.65-1.35). In the indirect comparison between the two immune checkpoint inhibitors(ICIs), although there was no significant difference in EFS (HR = 0.81, 95% CI: 0.61-1.08), PD-1 inhibitors may still be the most effective treatment option. CONCLUSIONS: NICT effectively and safely treats resectable NSCLC. The optimal treatment combination is typically toripalimab and chemotherapy. Treatment based on PD-L1 expression and pathological type is recommended.

Pharmacological Interventions for Attention-Deficit/Hyperactivity Disorder in Children and Adolescents with Tourette Disorder: A Systematic Review and Network Meta-Analysis.

Objective: To evaluate the comparative efficacy of pharmacological interventions for children and adolescents with a dual diagnosis of persistent tic disorders or Tourette disorder and attention-deficit/hyperactivity disorder (TD + ADHD). Methods: We searched CENTRAL, Embase, PubMed, PsycInfo, Web of Sciences, ClinicalTrials.gov, and WHO ICTRP up to September 2023 to identify double-blinded randomized controlled trials (RCTs) assessing pharmacological interventions for children and adolescents with TD + ADHD. Outcomes were change in ADHD symptoms (primary) and tics (secondary) severity. Standardized mean difference (SMD) was calculated and pooled in random-effects network meta-analysis. The Confidence in Network Meta-Analysis framework was adopted to determine certainty of evidence. Results: We included 8 RCTs involving 575 participants. Network meta-analyses demonstrated that α2 agonists (SMD, 95% confidence interval [CI] ADHD: -0.72 [-1.13 to -0.31]; TD: -0.70 [-0.96 to -0.45]) and stimulants + α2 agonists (ADHD: -0.84 [-1.54 to -0.13]; TD: -0.60 [-1.04 to -0.17]) were more efficacious than placebo for ADHD symptoms and tics severity. Stimulants alone were more efficacious than placebo for ADHD symptoms severity only, but they did not worsen tics (ADHD: -0.54 [-1.05 to -0.03]; TD: -0.22 [-0.49 to 0.05]). There were no significant differences between any pairs of medications that were found efficacious against placebo for ADHD symptoms or tics severity. Certainty in the evidence varied from low to very low. Conclusions: Stimulants are efficacious for ADHD symptoms severity and do not increase tics severity in TD + ADHD. α2 agonists are efficacious for both ADHD symptoms and tics severity in TD + ADHD. These findings should inform guidelines and help guide shared decision-making to choose a medication for children with TD + ADHD.

Is Cention-N comparable to other direct dental restorative materials? A systematic review with network meta-analysis of in vitro studies.

OBJECTIVES: To compare the performance of Cention-N® with direct restorative materials used at the daily practice (e.g., resin-based composites/RBC, glass ionomer cements/GIC, bioactive resins, silver amalgam) via a systematic review study. METHODS: The review followed the PRISMA-NMA recommendations, and the protocol of the review was published at osf.io/ybde8. The search was conducted in PubMed/MEDLINE, Scopus, Web of Science, Embase, Lilacs, and SciELO databases, as well as in the grey literature (Open Grey, Proquest, and Periódicos CAPES). Studies with an in vitro experimental design evaluating the characteristics and properties of Cention-N in comparison to other restorative materials were included. The risk of bias of included studies was assessed using the RoBDEMAT tool, and meta-analyses were conducted using Review Manager 5.4 and MetaInsight V3 tools. RESULTS: A total of 85 studies were included in the review, from which 79 were meta-analyzed. Several characteristics of direct restorative materials were analyzed, including physical (color change, degree of conversion, hardness, microleakage, polymerization rate, roughness, water solubility, water sorption), mechanical (bond strength to dentin, compressive strength, diametral tensile strength, flexural modulus, flexural strength, load-to-fracture, wear), and biological (alkalinizing effect, antibacterial activity, calcium and fluoride release) properties. SIGNIFICANCE: Cention-N presented similar physico-mechanical properties compared to RBCs, but a stronger behavior than GICs. Despite the Alkasite nature of Cention-N, GICs may still demonstrate the greatest fluoride releasing ability from all direct restorative materials. This review confirmed the adequate behavior of Cention-N when compared to several other more traditionally used materials, confirming its applicability for the permanent restoration of decayed or fractured teeth.

Levosimendana e Fibrilação Atrial: Uma Metanálise de Ensaios Clínicos Randomizados / Levosimendan and Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials

Resumo Fundamento A fibrilação atrial (FA) é uma complicação prevalente associada à levosimendana; no entanto, permanece incerto se existem disparidades nos efeitos da levosimendana na FA não pós-operatória e pós-operatória. Objetivos Este estudo teve como objetivo avaliar o efeito da levosimendana na FA não pós-operatória e pós-operatória conduzindo uma metanálise de ensaios clínicos randomizados (ECR). Métodos PubMed, Embase, Biblioteca Cochrane e outras bases de dados foram pesquisadas. Pares de revisores identificaram ECRs que compararam levosimendana e placebo ou outras terapias, e os resultados relataram dados de eventos de FA. Foram utilizados modelos de efeitos aleatórios (com nível de significância de 5%). Resultados Foram incluídos 29 ensaios elegíveis compreendendo 6.550 participantes, onze dos quais avaliaram a incidência de FA não pós-operatória e 18 incluíram FA pós-operatória. A análise revelou que a levosimendana elevou significativamente o risco de FA no grupo não pós-operatório (OR, 1,62; IC 95%: 1,19-2,20; p=0,002) e reduziu a incidência de FA no grupo pós-operatório (OR, 0,65; IC 95%: 0,44-0,96; p=0,03). A ocorrência de FA diminuiu mais significativamente em pacientes que usaram levosimendana após cirurgia cardíaca (OR, 0,53; IC 95%: 0,32-0,88; p=0,02) do que em pacientes que usaram levosimendana antes da cirurgia cardíaca (OR, 0,67; IC 95%: 0,42-1,06; p=0,09). O risco de FA foi significativamente elevado pela grande dose em bolus de levosimendana (dose em bolus ≥12 μg/kg) (OR, 1,44; IC 95%: 1,10-1,88; p=0,004) e diminuído pela pequena dose em bolus de levosimendana (dose em bolus <12 μg/kg) (OR, 0,64; IC 95%: 0,34-1,20; p=0,16). Conclusão A levosimendana foi associada a um aumento da incidência de FA não pós-operatória. O emprego da levosimendana foi eficaz na prevenção da FA pós-operatória.

Abstract Background Atrial fibrillation (AF) is a prevalent complication associated with levosimendan; however, it remains uncertain whether there are any disparities in the effects of levosimendan on non-postoperative and postoperative AF. Objectives This study aimed to evaluate the levosimendan effect on non-postoperative and postoperative AF by conducting a meta-analysis of randomized control trials (RCTs). Methods PubMed, Embase, Cochrane Library, and other databases were searched. Pairs of reviewers identified RCTs that compared levosimendan and placebo or other therapies, and the results reported AF events data. Random effects models were used (at a significance level of 5%). Results Twenty-nine eligible trials comprising 6550 participants were included, eleven of which evaluated the non-postoperative AF incidence, and 18 included postoperative AF. The analysis revealed that levosimendan elevated the AF risk significantly in the non-postoperative group (OR, 1.62; 95% CI: 1.19-2.20; p=0.002) and reduced the AF incidence in the postoperative group (OR, 0.65; 95% CI: 0.44-0.96; p=0.03). AF occurrence decreased more significantly in patients who used levosimendan after cardiac surgery (OR, 0.53; 95% CI: 0.32-0.88; p=0.02) than in patients who used levosimendan before cardiac surgery (OR, 0.67; 95% CI: 0.42-1.06; p=0.09). Moreover, The AF risk was significantly elevated by levosimendan large bolus dose (bolus dose≥12 μg/kg) (OR, 1.44; 95% CI: 1.10-1.88; p=0.004) and decreased by small bolus dose of levosimendan (bolus dose<12 μg/kg) (OR, 0.64; 95% CI: 0.34-1.20; p=0.16). Conclusion Levosimendan was linked to an increased non-postoperative AF incidence. The employment of levosimendan was effective in preventing postoperative AF.

Non-invasive treatments improve patient outcomes in chronic tinnitus: a systematic review and network meta-analysis.

OBJECTIVE: To investigate the relative effectiveness of various Non-Invasive Treatment Techniques (NITs) in chronic tinnitus management. METHODS: We searched PubMed, Embase and Cochrane Library databases from the time of data construction to December 31, 2022. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, NITs were evaluated, including Aacceptance and commitment therapy (A), Cognitive behavioral therapy (C), Sound therapy (S), Transcranial magnetic stimulation (T), Electrical stimulation therapy (E), Virtual reality therapy (V), tinnitus Retraining therapy (R), general psychotherapy (D), and Placebo (P). The outcome indicators included the Tinnitus Handicap Inventory (THI), Tinnitus Questionnaire (TQ), Hospital Anxiety and Depression Scale-anxiety-Depression (HADS-D), Insomnia Severity Index (ISI), Visual Analogue Scales-Loudness (VAS-L), and Visual Analogue Scales-Distress (VAS-D). Statistical analysis was performed using Stata 14.0 for NMA. RESULTS: This systematic review and meta-analysis included 22 randomized controlled trials comprising 2,354 patients. The treatment effects varied on each scale. For THI, S (86.9%) was the most effective, whereas P (6.5%) was the worst. For TQ, C (89.5%) was the most effective, whereas D (25.4%) was the worst. For HADS-D, A (82.4%) was the most effective, whereas D (9.47%) was the worst. For ISI, A (83.2%) was the most effective, whereas R (20.6%) was the worst. For VAS-L, S (73.5%) was the most effective, whereas E (18.9%) was the worst. For VAS-D, C (84.7%) was the most effective, whereas P (18.1%) was the worst. CONCLUSIONS: The combination of acoustics and cognitive behavioral therapy may be an effectively treat patients with chronic tinnitus. LEVEL OF EVIDENCE: How common is the problem? Level 2. Is this diagnostic or monitoring test accurate? (Diagnosis) Level 1. What will happen if we do not add a therapy? (Prognosis) Level 1. Does this intervention help? (Treatment Benefits) Level 1. What are the COMMON harms? (Treatment Harms) Level 1. What are the RARE harms? (Treatment Harms) Level 1. Is this (early detection) test worthwhile? (Screening) Level 1I.

Comparative effectiveness of first-line systemic treatments for metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis.

OBJECTIVES: No head-to-head trials had been performed to estimate the relative effectiveness of poly ADP-ribose polymerase inhibitor (PARPi) and androgen receptor signaling inhibitor (ARSi) in the first-line treatment for metastatic castration-resistant prostate cancer (mCRPC). We aimed to perform a systematic review and network meta-analysis to evaluate the comparative effectiveness of various systemic treatment agents for patients with mCRPC. METHODS: A comprehensive literature search was conducted for abstracts and full-text articles from the database's inception through April 27, 2023. The study concentrated on assessing radiographic progression-free survival (rPFS) for both overall and homologous recombination repair mutation (HRRm) population, with overall survival (OS) as the secondary measure. Under the Bayesian framework, the overall effect was pooled using the fixed-effects model in base case analysis. Scenario analysis using restricted mean survival time (RMST) methods was performed to test the robustness of the results. RESULTS: Nine studies with 6,830 patients and 8 unique treatment options were included. Network meta-analysis demonstrated that talazoparib in combination with enzalutamide (TALA + ENZA; overall population, hazard ratio [HR], 0.20; 95% credible interval [CrI]: 0.16-0.26; RMST, 3.51; 95% confidence interval [CI] 2.46-4.60; HRRm population, HR, 0.15; 95% CrI: 0.09-0.23; RMST, 4.14; 95% CI 2.84-5.39) was superior to other treatments in the first-line setting in terms of rPFS. The results of Bayesian framework and RMST models showed consistent efficacy ranks. When extrapolated to overall survival benefit, within the Bayesian framework, olaparib plus abiraterone acetate and prednisone (OLAP + AAP) achieved the highest OS benefit for the overall population, which was not statistically significant when compared to TALA + ENZA. However, TALA + ENZA achieved the highest OS benefit at 3 years by applying RMST. CONCLUSIONS: We suggest that talazoparib in combination with enzalutamide is probably a preferred treatment agent for the overall population and HRRm patients with mCRPC. Given the limitations of network framework and the modeling assumptions undertaken to finalize the analyses, results should be cautiously interpreted.

Network meta-analysis of pembrolizumab as monotherapy and in combination with chemotherapy for first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma / Metanálise em rede comparativa de pembrolizumabe como monoterapia e em combinação com quimioterapia para tratamento de primeira linha de carcinoma de células escamosas da cabeça e pescoço recorrente ou metastático

Pembrolizumab monotherapy or in combination with chemotherapy is approved as first-line treatment in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) based on improved overall survival (OS) versus EXTREME regimen in the KEYNOTE-048 trial. The clinical outcomes of pembrolizumab were compared with other recommended first-line treatments in R/M HNSCC in this study through a Bayesian network meta-analysis. A systematic literature review was conducted in July 2022, from which six trials that matched the KEYNOTE-048 patient eligibility criteria were included in the network. The OS and progression-free survival (PFS) outcomes were compared in the approved pembrolizumab indication (i.e., total population for pembrolizumab in combination with chemotherapy and combined positive score [CPS] ≥ 1 population for pembrolizumab monotherapy). A significant OS improvement was observed for pembrolizumab in combination with chemotherapy and pembrolizumab monotherapy versus EXTREME regimen (hazard ratio, 95% credible interval: 0.72, 0.60-0.86; 0.73, 0.60-0.88), platinum+5- FU (0.58, 0.43-0.76; 0.58, 0.44-0.78), and platinum+paclitaxel (0.53, 0.35-0.79; 0.53, 0.35-0.81), respectively. A non-significant numeric trend in OS improvement was observed versus the TPEx regimen. PFS was comparable with most first-line treatments and was improved versus platinum+5-FU (0.48, 0.36-0.64; 0.59, 0.45-0.79). Additional analyses in higher CPS subgroups also showed consistent results. Overall, our study results showed an improvement in OS outcomes versus alternative first-line treatments, consistent with the findings of the KEYNOTE-048 trial. These data support using pembrolizumab as a suitable firstline treatment option in R/M HNSCC.

Pembrolizumabe em monoterapia ou em combinação com quimioterapia é aprovado como tratamento de primeira linha em carcinoma de células escamosas recorrente/metastático de cabeça e pescoço (CECCP R/M) com base na melhora da sobrevida global (OS), em comparação com o esquema EXTREME no estudo KEYNOTE-048. Esse estudo comparou os resultados clínicos de pembrolizumabe com outros tratamentos recomendados de primeira linha em CECCP R/M por meio de uma metanálise de rede bayesiana. Uma revisão sistemática da literatura foi conduzida em julho de 2022, a partir da qual seis ensaios clínicos que atendiam aos critérios de elegibilidade de pacientes do KEYNOTE-048 foram incluídos na rede. Os desfechos de OS e sobrevida livre de progressão (PFS) foram comparados na indicação de pembrolizumabe (população total para pembrolizumabe em combinação com quimioterapia e população com escore positivo combinado [CPS] ≥ 1 em monoterapia com pembrolizumabe). Foi observada melhora significativa na OS para pembrolizumabe em combinação com quimioterapia e monoterapia com pembrolizumabe versus o esquema EXTREME (razão de risco, intervalo de confiança de 95%: 0,72, 0,60-0,86; 0,73, 0,60-0,88), platina+5-FU (0,58, 0,43-0,76; 0,58, 0,44-0,78) e platina+paclitaxel (0,53, 0,35-0,79; 0,53, 0,35-0,81), respectivamente. Uma tendência numérica não significativa de melhoria na OS foi observada em relação ao esquema TPEx. A PFS foi comparável com a maioria dos tratamentos de primeira linha e melhor em relação à platina+5-FU (0,48, 0,36-0,64; 0,59, 0,45-0,79). Análises adicionais em subgrupos com CPS mais elevado também mostraram resultados consistentes. No geral, os resultados de nosso estudo mostraram melhora nos desfechos de OS em comparação aos tratamentos de primeira linha alternativos, consistentes com os achados do estudo KEYNOTE-048. Esses dados apoiam o uso de pembrolizumabe como opção de tratamento em primeira linha em pacientes com CECCP R/M.

Effectiveness and safety of biological and target synthetic drugs treatment for psoriatic arthritis: a systematic review with network meta-analysis.

BACKGROUND: Psoriatic arthritis (PA) is a chronic inflammatory systemic arthritis that can result in loss of functional capacity and joint deformation. This systematic review assessed the effectiveness and safety of biological and target synthetic drugs for treating PA. METHODS: We searched for randomized clinical trials (RCTs) that evaluated the use of Adalimumab, Etanercept, Infliximab, Golimumab, Secukinumab, Certolizumab Pegol and Tofacitinib in the main general databases and clinical trial registers databases. The primary outcomes were ACR 50, PsARC, and serious adverse events. Two independent reviewers performed study selection and data extraction. Network meta-analyses were conducted using a random effects model and frequentist approach. The CINeMA software was used to assess the certainty of evidence. RESULTS: We included 33 RCTs (n = 11,034). The results from the network meta-analysis for the ACR 50 at 6-months follow-up showed that all drugs were superior to placebo, with Secukinumab (high certainty of evidence), Infliximab (very low certainty of evidence) and Adalimumab (high certainty of evidence) ranking the highest. Regarding the PsARC (at 6-months follow-up), all drugs, except for Golimumab (very low certainty of evidence), were superior to placebo, with Etanercept (low certainty of evidence), Infliximab (low certainty of evidence) and Certolizumab Pegol (low certainty of evidence) being the most effective drugs. There were no significant differences in the risk of serious adverse events between the drugs and placebo. Golimumab (very low certainty of evidence), Secukinumab (low certainty of evidence), and Adalimumab (very low certainty of evidence) ranked the highest for safety. CONCLUSIONS: In conclusion, based on the balance between efficacy and safety, Secukinumab and Adalimumab may be the preferred options among the evaluated drugs for treating patients with PsA. However, caution is necessary when interpreting the safety findings, as they are supported by evidence of low to very low certainty. Consequently, the balance between benefits and potential risks may change as new safety evaluation studies become available. PROTOCOL REGISTRATION: PROSPERO: CRD42022315577.

The efficacy of combining adjuvants with non-surgical periodontal therapy in individuals with type 2 diabetes: A Bayesian network meta-analysis.

AIM: This Bayesian network meta-analysis of randomized controlled trials assessed the effect of adjuvant periodontal treatment in both periodontal and HbA1c outcomes in adult individuals with type 2 diabetes (T2DM). MATERIALS AND METHODS: A systematic search was done up to February 2023 comparing sub-gingival debridement (SD) in combination with local or systemic adjuvant treatment with SD alone for individuals with T2DM. The primary outcomes were changes in absolute HbA1c levels and full-mouth probing depth reported at 3- to 6-month post-treatment. RESULTS: Seventy-two eligible publications evaluating 27 adjuvant treatments were retrieved. The combination of SD and systemic antibiotic metronidazole or SD and antioxidant alpha lipoic acid provided, respectively, 1.4% (95% credible interval [CrI] 0.48; 2.20) and 2.4% (95% CrI 1.50; 3.30) more significant improvement on HbA1c levels, and 0.89 mm (95% CrI 0.23; 1.50) and 0.92 mm (95% CrI 0.02; 0.92) greater periodontal probing depth reductions. Other adjuvant treatments provided added benefit to the periodontal outcomes without discernible effects on HbA1c. CONCLUSIONS: Adjuvant use of metronidazole or alpha lipoic acid was the best adjunct option to provide clinically meaningful HbA1c levels and probing depth reductions. However, no strong recommendation can be drawn due to the scarcity of studies for each adjuvant treatment and the low certainty of the resultant evidence.

Physical energies for the management of genitourinary syndrome of menopause: An overview of a systematic review and network meta-analysis.

BACKGROUND: Energy-based devices (laser and radiofrequency) have been used to treat genitourinary syndrome of menopause (GSM). OBJECTIVES: To evaluate the efficacy and safety of physical energy use in managing GSM symptoms. SEARCH STRATEGY: Five databases were searched from inception to December 2022. Language restrictions were not imposed. SELECTION CRITERIA: We included all Cochrane and non-Cochrane systematic reviews with or without meta-analyses that described postmenopausal women with symptoms of GSM treated with physical energy. DATA COLLECTION AND ANALYSIS: We performed a network meta-analysis using frequentist methods to calculate standardized mean differences (SMDs) and their corresponding 95% confidence intervals (CIs). Methodological and reporting quality were assessed using the Assessment of Multiple Systematic Reviews (AMSTAR 2). MAIN RESULTS: Nine reviews were included in the overview, six of which were meta-analyses. Four randomized controlled trials, representing 218 participants and nine different study arms, met the criteria for inclusion in our component network meta-analysis. Confidence in review findings was low in six reviews and critically low in three. Our network meta-analysis results showed that premarin (SMD 2.60, 95% CI 7.76-3.43), conjugated estrogens (SMD 2.13, 95% CI 1.34-2.91), carbon dioxide laser (SMD 1.71, 95% CI 1.10-2.31), promestriene (SMD 1.41, 95% CI 0.59-2.24), and vaginal lubricant (SMD 1.37, 95% CI 0.54-2.20) were more effective than sham for reducing sexual dysfunction, with a consequent increase in Female Sexual Function Index (FSFI). Two studies showed a high risk of bias, owing to a lack of blinding. CONCLUSION: Several gaps in the use of physical energy for managing GSM still need to be addressed. The small number of blind clinical trials made the results fragile.

Reabilitação protética de indivíduos maxilectomizados com prótese obturadora: análise pelo método de elementos finitos e revisão sistemática / Prosthetic rehabilitation of individuals maxillectomized with obturator prostheses: finite element analysis and systematic review

A prótese obturadora (PO) permite o restabelecimento estético e funcional de indivíduos maxilectomizados. Os objetivos deste estudo foram: 1. avaliar pelo método de elementos finitos (MEF), o comportamento biomecânico de infraestruturas metálicas de próteses parciais removíveis obturadoras (PPRO) para uma maxila com ressecção do tipo Classe II de Aramany, variando o tipo de conector maior; 2. realizar uma revisão sistemática com meta-análise em rede sobre a eficácia da PO, e outros tratamentos na qualidade de vida de seus usuários. No primeiro estudo, um modelo virtual simulando uma maxila Classe II de Aramany com ressecção óssea do lado esquerdo, e ausência dos dentes 24, 25, 26 e 27 foi construído no programa Rhinoceros® 7.0, a partir de duas tomografias. Em seguida, três infraestruturas de PPRO digitais foram confeccionadas variando o tipo de conector maior: grupo controle com conector maior tipo placa palatina com extensão reduzida (GC), conector maior tipo placa palatina com extensão total (ME), e conector maior tipo barra anteroposterior com extensão reduzida (AP). A análise de elementos finitos foi realizada no software Optistruct 2022, e os resultados analisados no HyperView 2022. Os resultados foram avaliados de forma qualitativa por meio da observação visual das imagens gráficas com variação dos gradientes de cores, de acordo com a distribuição de tensão, e quantitativa por meio da tensão de von Mises (σVM), tensão máxima principal (σmax), tensão mínima principal (σmin) e deslocamento (mm). No segundo estudo foi realizada uma revisão sistemática com meta-análise em rede (PROSPERO #CRD42023430827). Foram incluídos ensaios clínicos randomizados (ECRs) e estudos de intervenção não randomizados (EINRs) com pacientes reabilitados com prótese obturadora como um dos tratamentos de reabilitação. Sete desfechos reportados pelos pacientes foram analisados separadamente para cada desenho de estudo, de acordo com os questionários de QV: aparência, mastigação, dor, contato social, fala, deglutição e QV geral. Os dados foram convertidos para o questionário UW-QOL v4, exceto o contato social que foi convertido para o EORTC QLQ-H&N35. Foi usada meta-análise em rede Bayesiana modelo randômico para calcular as diferenças médias, e intervalos de credibilidade de 95% (Crl) para cada comparação entre tratamentos. A interpretação seguiu a certeza da evidência por meio da abordagem GRADE para meta-análise e a diferença mínima importante (DMI). A revisão incluiu 4 ECRs e 9 EINRs. Sete tratamentos foram avaliados: pré-cirúrgico (considerado sem tratamento), obturador pós-cirúrgico, obturador provisório, obturador convencional, obturador suportado por implante, obturador magnético e retalho, totalizando 120 comparações de tratamentos em todos os sete desfechos. Verificou-se pelos resultados do primeiro estudo que CG e AP apresentaram comportamentos semelhantes, já ME apresentou maiores valores de tensão para praticamente todos os componentes do sistema. Nenhum dos grupos apresentou valores de deslocamento significativos. Para a revisão sistemática, observou-se que a estimativa de efeito de alguns tratamentos alcançou a DMI, entretanto, o intervalo de credibilidade cruzou a linha de efeito nulo, com certeza da evidência muito baixa, portanto, nenhum tratamento foi mais eficaz que o outro. Para ambos os estudos, mais estudos laboratoriais e ensaios clínicos randomizados são incentivados para confirmar as evidências encontradas.

The obturator prosthesis (OP) allows the restoration of speech, aesthetics, and oral function in patients with maxilectomized individuals. The objectives of the study were: 1. to evaluate, using the finite element analysis (FEA) methodology, the biomechanical behavior of metallic infrastructures of removable partial denture obturator (RPDO) for a maxilla with Aramany Class II resection, varying the type of major connector; 2. carry out a systematic review with network meta-analysis on the effectiveness of the OP and other treatments on the quality of life of its users. In the first study, a virtual model simulating an Aramany Class II maxilla with bone resection on the maxillary left side and absence of teeth 24, 25, 26 and 27 was developed using the Rhinoceros® 7.0 program based on two tomography scans. After obtaining the virtual model, three infrastructures digital RPDOs were created varying the type of major connector: major connector with reduced coverage (RPDO1), major connector with extensive coverage (RPDO2) and major connector with anteroposterior bar (RPDO3). The FEA analysis was carried out using the Optistruct 2022 software, and the results were analyzed using the HyperView 2022 software. The results were evaluated qualitatively through visual observation of graphic images with variation of color gradients according to the stress distribution and quantitative von Mises stress (σVM), maximum principal stress (σmax), minimum principal stress (σmin) and displacement (mm). For the second study, the systematic review with network meta-analysis (PROSPERO #CRD42023430827). Randomized controlled trials (RCTs) and non-randomized studies of intervention (NRSIs) with obturator prosthesis as one of the treatments were included. Seven patient-reported outcomes were analyzed separately for each study design, according to the QOL questionnaires: appearance, chewing, pain, social contact, speech, swallowing and general QOL. Data were converted to the UW-QOL v4 questionnaire, except social contact, which was converted to the EORTC QLQ-H&N35. Network meta-analysis (NMA) Bayesian random model was used to calculate mean differences (MD) and 95% credibility intervals (Crl) for each treatment comparison. Interpretation followed the certainty of evidence through the GRADE approach for NMA and the least important difference (DMI). The review included 4 RCTs and 9 NRSIs. Seven treatments were evaluated: presurgical (considered no treatment), surgical obturator, interim obturator, obturator, implant-supported obturator, magnet obturator, and flap, totaling 120 treatment comparisons in all seven outcomes. The results of the first study indicate that RPDO1 and RPDO3 showed similar behaviors, while RPDO2 presented the highest stress values for all system components. None of the groups presented significant displacement values. In the systematic review, it was observed that the effect estimates of some treatments reached the DMI, however, for all treatment comparisons, the credibility interval crossed the null effect line with very low certainty of evidence. No treatment showed superiority compared to another for any outcome. For both studies, further laboratory studies and RCTs are encouraged to confirm the evidence.

Trastuzumab-emtansina versus otros regímenes anti-HER-2 en el cáncer de mama HER-2 positivo precoz o irresecable o metastásico: revisión sistemática y metaanálisis en red / Trastuzumab-emtansine versus other anti-HER2 regimens in early or unresectable or metastatic HER-2 positive breast cancer: systematic review and network meta-analysis

RESUMEN Objetivo. Nuestro objetivo fue estudiar la eficacia y la seguridad de trastuzumab-emtansina (T-DM1) en comparación con otras terapias anti-HER-2 en el cáncer de mama (CM) HER-2 positivo. Materiales y métodos. Realizamos un metaanálisis de red (NMA, por sus siglas en inglés) de ensayos clínicos aleatorizados (ECA). Nuestro estudio se centró en pacientes sometidos al tratamiento para el cáncer de mama localmente avanzado no resecable (CMLA) o cáncer de mama metastásico (CMm), que incluía esquemas con trastuzumab y taxanos. Además, consideramos casos dentro de los primeros 6 meses de tratamiento para el cáncer de mama temprano (CMT) HER-2 positivo. Resultados. Se incluyeron en nuestro análisis un total de 23 ECA y 41 reportes. En CMLA y CMm, no se observaron diferencias estadísticamente significativas en ninguna de las comparaciones entre T-DM1 y otras terapias anti-HER-2 positivo. Al evaluar la sobrevida libre de progresión (SLP), trastuzumab-deruxtecan (T-DXd) y PyroCap demostraron una mayor eficacia en comparación con otros tratamientos (Hazard Ratio [HR]: 3,57; intervalo de confianza al 95% [IC 95%]: 2,75-4,63 y HR: 1.82; IC 95%: 1,35-2,44; respectivamente), mientras que T-DM1 por sí solo mostró una efectividad superior en comparación con LapCap (HR: 0,65; IC 95%: 0,55-0,77), TrasCap (HR: 0,65; IC 95%: 0,46-0,91), LapCapCitu (HR: 0,60; IC 95%: 0,33-1,1), Nera (HR: 0,55; IC 95%: 0,39-0,77) y Cap (HR: 0,37; IC 95%: 0,28-0,49). Conclusiones. Este NMA estableció un ranking basado en la eficacia y seguridad comparativas entre las intervenciones disponibles. Aunque superior a otros esquemas, T-DM1 mostró una menor eficacia en la SLP y la tasa de respuesta objetiva, y una tendencia hacia una sobrevida global peor que T-DXd.

ABSTRACT Objective. We aimed to study the efficacy and safety of trastuzumab-emtansine (T-DM1) versus other anti-HER2 therapies in HER2+ breast cancer (BC). Materials and Methods. We performed a network meta-analysis (NMA) of randomized controlled trials (RCTs). Our study focused on patients undergoing treatment for unresectable locally advanced breast cancer (LABC) or metastatic breast cancer (mBC), which included regimens involving trastuzumab and taxanes. Additionally, we considered cases within the first 6 months of treatment for HER2+ early breast cancer (EBC). Results. A total of 23 RCTs and 41 reports were included in our analysis. LABC and mBC showed no statistically significant difference in any of the comparisons of T-DM1 versus the other anti-HER2+ therapies. When assessing progression-free survival (PFS), trastuzumab-deruxtecan (T-DXd) and PyroCap demonstrated greater efficacy compared to other treatments (Hazard Ratio [HR]: 3.57; 95% confidence interval [CI]: 2.75-4.63 and HR: 1.82; 95% CI: 1.35-2.44; respectively), while T-DM1 alone exhibited superior effectiveness compared to LapCap (HR: 0.65; 95% CI: 0.55-0.77), TrasCap (HR: 0.65; 95% CI: 0.46-0.91), LapCapCitu (HR: 0.60; 95% CI: 0.33-1.10), Nera (HR: 0.55; 95% CI: 0.39-0.77), and Cap (HR: 0.37; 95% CI: 0.28-0.49). Conclusions. NMA allows a ranking based on the comparative efficacy and safety among the interventions available. Although superior to other schemes, T-DM1 showed a lower efficacy performance in PFS and overall response rate and a trend towards worse overall survival than T-DXd.

Surgical management, use and efficacy of adjuvant dyes in idiopathic epiretinal membranes: a systemic review with network meta-analysis.

BACKGROUND: The epiretinal membrane (ERM) is a nonvascular fibrocellular tissue formed by cellular metaplasia and proliferation at the vitreoretinal surface and is generally treated by pars plana vitrectomy (PPV) with or without internal limiting membrane (ILM) peeling. This network meta-analysis aimed to compare the efficacy of all available ERM removal interventions and assessed the use and efficacy of surgical dyes in managing idiopathic ERMs. METHODS: MEDLINE, EMBASE, Cochrane CENTRAL, and the US National Library of Medicine were searched (June 28, 2023). Clinical studies that included patients with ERMs were included. Randomized controlled trials (RCTs) were also appraised using Cochrane risk of bias (ROB). RESULTS: Ten RCTs and ten non-RCTs were included in this study. A pairwise meta-analysis between ERM removal and combined ERM and ILM removal showed no significant difference in visual outcome (change in BCVA) 1 year postintervention (MD = - 0.0034, SE = 0.16, p = 0.832). Similarly, there was no significant difference in the central macular thickness postoperatively between the two groups (MD = - 4.95, SE = 11.11, p = 0.656) (Q = 4.85, df = 3, p = 0.182, I2 = 41.21%). The difference in ERM recurrence between the groups was also not statistically significant (OR = 4.64, p = 0.062, I2 = 0). In a network meta-analysis, there was no significant difference in visual outcomes between ERM removal only and other treatment modalities: combined ILM and ERM removal (MD = 0.039, p = 0.837) or watchful waiting (MD = 0.020, p = 0.550). In a network meta-analysis, there was no significant difference in the visual outcomes between ERM removal alone and dye-stained combined ERM and ILM peeling (MD = 0.122, p = 0.742 for brilliant blue G; BBG and MD = 0.00, p = 1.00 for membrane blue-dual; MBD). The probability of being a better surgical dye for better visual outcomes was 0.539 for the MBD group and 0.396 for the BBG group. The recurrence of ERM was not significantly different when the ILM was stained with any of the dyes. No study was judged on ROB assessment as having low ROB in all seven domains. CONCLUSION: The two types of surgical modalities provided comparable efficacy, with no significant differences between the outcomes. Among the dye-assisted ILM peeling methods, the membrane blue-dual dye was the most effective in providing better structural and functional outcomes.

Efficacy of pharmacological and non-pharmacological therapy on pain intensity and disability of older people with chronic nonspecific low back pain: a protocol for a network meta-analysis.

BACKGROUND: The purpose of this network meta-analysis (NMA) is to investigate the efficacy of pharmacological and non-pharmacological therapy on pain intensity and disability of older people with chronic nonspecific low back pain, providing comprehensive evidence for an informed decision-making. METHODS: We will perform a systematic search to identify randomized controlled trials of pharmacological and non-pharmacological interventions for older people with chronic nonspecific low back pain. MEDLINE, Cochrane Library, Embase, AMED, PsycINFO, and PEDro will be searched without language or date restrictions. Our primary outcomes are pain intensity and disability. Risk of bias will be assessed for all studies using the revised Cochrane risk-of-bias (RoB) tool 2.0. For each pairwise comparison between the different interventions, estimated mean differences and their 95% confidence intervals will be presented. Standard pairwise meta-analyses will be performed using random effects models in STATA version 16. The competing interventions will be ranked using the surface under the cumulative ranking curve (SUCRA) for the outcomes of interest at short and long terms. The confidence in the results from NMA will be assessed using the Confidence in Network Meta-Analysis (CINeMA) framework. DISCUSSION: This NMA compares efficacy of interventions for nonspecific chronic low back pain in older people. It will provide reliable evidence for patients, clinicians, stakeholders, and researchers in this field where competing therapies, many of extraordinarily little value, are commonly used in clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022312565.

Comparative assessment of efficacy and safety of approved oral therapies for overactive bladder: a systematic review and network meta-analysis

ABSTRACT Purpose: To compare the effectiveness and safety of marketed oral drugs for overactive bladder based on a systematic review and network meta-analysis approach. Methods: Pubmed, Embase, Web of Science, and the Cochrane Register of Clinical Trials databases were systematically searched. The search time frame was from database creation to June 2, 2022. Randomized controlled double-blind trials of oral medication for overactive bladder were screened against the protocol's entry criteria. Trials were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Stata 16.0 software. Result: A total of 60 randomized controlled double-blind clinical trials were included involving 50,333 subjects. Solifenacin 10mg was the most effective in mean daily micturitions and incontinence episodes, solifenacin 5/10mg in mean daily urinary urgency episodes and nocturia episodes, fesoterodine 8mg in urgency incontinence episodes/d and oxybutynin 5mg in voided volume/micturition. In terms of safety, solifenacin 5mg, ER-tolterodine 4mg, mirabegron, vibegron and ER-oxybutynin 10mg all showed a better incidence of dry mouth, fesoterodine 4mg, ER-oxybutynin 10mg, tolterodine 2mg, and vibegron in the incidence of constipation. Compared to placebo, imidafenacin 0.1mg showed a significantly increased incidence in hypertension, solifenacin 10mg in urinary tract infection, fesoterodine 4/8mg and darifenacin 15mg in headache. Conclusion: Solifenacin showed better efficacy. For safety, most anticholinergic drugs were more likely to cause dry mouth and constipation, lower doses were better tolerated. The choice of drugs should be tailored to the patient's specific situation to find the best balance between efficacy and safety.

Compared efficacy of rituximab, abatacept, and tocilizumab in patients with rheumatoid arthritis refractory to methotrexate or TNF inhibitors agents: a systematic review and network meta-analysis.

BACKGROUND: Our aim was to compare the efficacy of rituximab, tocilizumab, and abatacept in individuals with rheumatoid arthritis (RA) refractory to treatments with MTX or TNFi agents. METHODS: We searched 6 databases until January 2023 for phase 2-4 RCTs evaluating patients with RA refractory to MTX or TNFi therapy treated with rituximab, abatacept, and tocilizumab (intervention arm) compared to controls. Study data were independently assessed by two investigators. The primary outcome was considered as achieving ACR70 response. RESULTS: The meta-analysis included 19 RCTs, with 7,835 patients and a mean study duration of 1.2 years. Hazard ratios for achieving an ACR70 response at six months were not different among the bDMARDs, however, we found high heterogeneity. Three factors showing a critical imbalance among the bDMARD classes were identified: baseline HAQ score, study duration, and frequency of TNFi treatment in control arm. Multivariate meta-regression adjusted to these three factors were conducted for the relative risk (RR) for ACR70. Thus, heterogeneity was attenuated (I2 = 24%) and the explanatory power of the model increased (R2 = 85%). In this model, rituximab did not modify the chance of achieving an ACR70 response compared to abatacept (RR = 1.773, 95%CI 0.113-10.21, p = 0.765). In contrast, abatacept was associated with RR = 2.217 (95%CI 1.554-3.161, p < 0.001) for ACR70 compared to tocilizumab. CONCLUSION: We found high heterogeneity among studies comparing rituximab, abatacept, and tocilizumab. On multivariate metaregressions, if the conditions of the RCTs were similar, we estimate that abatacept could increase the chance of reaching an ACR70 response by 2.2-fold compared to tocilizumab.

Comparative assessment of efficacy and safety of approved oral therapies for overactive bladder: a systematic review and network meta-analysis.

bladder based on a systematic review and network meta-analysis approach. METHODS: Pubmed, Embase, Web of Science, and the Cochrane Register of Clinical Trials databases were systematically searched. The search time frame was from database creation to June 2, 2022. Randomized controlled double-blind trials of oral medication for overactive bladder were screened against the protocol's entry criteria. Trials were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Stata 16.0 software. RESULT: A total of 60 randomized controlled double-blind clinical trials were included involving 50,333 subjects. Solifenacin 10mg was the most effective in mean daily micturitions and incontinence episodes, solifenacin 5/10mg in mean daily urinary urgency episodes and nocturia episodes, fesoterodine 8mg in urgency incontinence episodes/d and oxybutynin 5mg in voided volume/micturition. In terms of safety, solifenacin 5mg, ER-tolterodine 4mg, mirabegron, vibegron and ER-oxybutynin 10mg all showed a better incidence of dry mouth, fesoterodine 4mg, ER-oxybutynin 10mg, tolterodine 2mg, and vibegron in the incidence of constipation. Compared to placebo, imidafenacin 0.1mg showed a significantly increased incidence in hypertension, solifenacin 10mg in urinary tract infection, fesoterodine 4/8mg and darifenacin 15mg in headache. CONCLUSION: Solifenacin showed better efficacy. For safety, most anticholinergic drugs were more likely to cause dry mouth and constipation, lower doses were better tolerated. The choice of drugs should be tailored to the patient's specific situation to find the best balance between efficacy and safety.

Alectinib for treating patients with metastatic ALK-positive NSCLC: systematic review and network metanalysis.

Aim: To compare the efficacy and safety of alectinib with other ALK inhibitors in treating patients with metastatic or locally advanced ALK-positive NSCLC. Methods: A systematic literature review was conducted up to November 2021. Network meta-analyses were performed using the frequentist method (random effects). GRADE evidence profile was conducted. Results: 13 RCTs were selected. For overall survival, alectinib was found to reduce the risk of death compared with crizotinib. In progression-free survival, alectinib reduced the risk of death or progression compared with crizotinib and ceritinib. Subgroup analysis by brain metastasis at baseline showed the superiority of alectinib over crizotinib and a similar effect compared with second-and third-generation inhibitors. Alectinib showed a good safety profile compared with the other ALK inhibitors.

This article reports the results of a systematic literature review with network meta-analysis (NMA) that aimed to compare the efficacy and safety of alectinib with other ALK inhibitors in treating patients with metastatic or locally advanced ALK-positive NSCLC. The results show that alectinib reduces the risk of death and the risk of progression compared with crizotinib. For progression-free survival, further significant reductions were observed when compared with ceritinib. For the other ALK inhibitors, no statistically significant differences were found. Subgroup analysis according to the presence of CNS metastases at baseline were consistent in showing the superiority of alectinib over crizotinib and the absence of statistically significant differences compared with second-and third-generation inhibitors. Alectinib showed a good safety profile compared with the other ALK inhibitors, reducing the frequency of adverse events (AEs) compared with ceritinib, and with no statistically significant differences compared with lorlatinib, brigatinib, ensartinib and crizotinib for the frequency of serious AEs or discontinuation of treatment due to AEs. The results of this study suggest clinically relevant insights in decision-making based on patient survival and progression-free survival. Furthermore, considering the importance of reducing the risk of intracranial progression and the need for available therapies for patients who will inevitably progress, alectinib could be considered as a first-line treatment for patients with ALK-positive NSCLC.

Incidence of adverse events and comparative tolerability of selective serotonin reuptake inhibitors, and serotonin and norepinephrine reuptake inhibitors for the treatment of anxiety, obsessive-compulsive, and stress disorders: a systematic review and network meta-analysis.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) show similar efficacy as treatments for anxiety, obsessive-compulsive, and stress-related disorders. Hence, comparisons of adverse event rates across medications are an essential component of clinical decision-making. We aimed to compare patterns of adverse events associated with SSRIs and SNRIs in the treatment of children and adults diagnosed with these disorders through a network meta-analysis. We searched MEDLINE, PsycINFO, Embase, Cochrane, websites of regulatory agencies, and international registers from inception to 09 September 2022, for randomized controlled trials assessing the efficacy of SSRIs or SNRIs. We analyzed the proportion of participants experiencing at least one adverse event and incidence rates of 17 specific adverse events. We estimated incidence rates and odds ratios through network meta-analysis with random effects and three-level models. We analyzed 799 outcome measures from 80 studies (n = 21 338). Participants in medication groups presented higher rates of adverse events (80.22%, 95% CI 76.13-83.76) when compared to placebo groups (71.21%, 67.00-75.09). Nausea was the most common adverse event (25.71%, CI 23.96-27.54), while weight change was the least common (3.56%, 1.68-7.37). We found higher rates of adverse events of medications over placebo for most medications, except sertraline and fluoxetine. We found significant differences between medications for overall tolerability and for autonomic, gastrointestinal, and sleep-related symptoms. Adverse events are a common reason that patients discontinue SSRIs and SNRIs. Results presented here guide clinical decision-making when clinicians weigh one medication over another. This might improve treatment acceptability and compliance.