Cumulative Ranking Curve Values Research Articles

Assessment of Postnatal Corticosteroids for the Prevention of Bronchopulmonary Dysplasia in Preterm Neonates

The safety of postnatal corticosteroids used for prevention of bronchopulmonary dysplasia (BPD) in preterm neonates is a controversial matter, and a risk-benefit balance needs to be struck. To evaluate 14 corticosteroid regimens used to prevent BPD: moderately early-initiated, low cumulative dose of systemic dexamethasone (MoLdDX); moderately early-initiated, medium cumulative dose of systemic dexamethasone (MoMdDX); moderately early-initiated, high cumulative dose of systemic dexamethasone (MoHdDX); late-initiated, low cumulative dose of systemic dexamethasone (LaLdDX); late-initiated, medium cumulative dose of systemic dexamethasone (LaMdDX); late-initiated, high cumulative dose of systemic dexamethasone (LaHdDX); early-initiated systemic hydrocortisone (EHC); late-initiated systemic hydrocortisone (LHC); early-initiated inhaled budesonide (EIBUD); early-initiated inhaled beclomethasone (EIBEC); early-initiated inhaled fluticasone (EIFLUT); late-initiated inhaled budesonide (LIBUD); late-initiated inhaled beclomethasone (LIBEC); and intratracheal budesonide (ITBUD). PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, World Health Organization's International Clinical Trials Registry Platform (ICTRP), and CINAHL were searched from inception through August 25, 2020. In this systematic review and network meta-analysis, the randomized clinical trials selected included preterm neonates with a gestational age of 32 weeks or younger and for whom a corticosteroid regimen was initiated within 4 weeks of postnatal age. Peer-reviewed articles and abstracts in all languages were included. Two independent authors extracted data in duplicate. Network meta-analysis used a bayesian model. Primary combined outcome was BPD, defined as oxygen requirement at 36 weeks' postmenstrual age (PMA), or mortality at 36 weeks' PMA. The secondary outcomes included 15 safety outcomes. A total of 62 studies involving 5559 neonates (mean [SD] gestational age, 26 [1] weeks) were included. Several regimens were associated with a decreased risk of BPD or mortality, including EHC (risk ratio [RR], 0.82; 95% credible interval [CrI], 0.68-0.97); EIFLUT (RR, 0.75; 95% CrI, 0.55-0.98); LaHdDX (RR, 0.70; 95% CrI, 0.54-0.87); MoHdDX (RR, 0.64; 95% CrI, 0.48-0.82); ITBUD (RR, 0.73; 95% CrI, 0.57-0.91); and MoMdDX (RR, 0.61; 95% CrI, 0.45-0.79). Surface under the cumulative ranking curve (SUCRA) value ranking showed that MoMdDX (SUCRA, 0.91), MoHdDX (SUCRA, 0.86), and LaHdDX (SUCRA, 0.76) were the 3 most beneficial interventions. ITBUD (RR, 4.36; 95% CrI, 1.04-12.90); LaHdDX (RR, 11.91; 95% CrI, 1.64-44.49); LaLdDX (RR, 6.33; 95% CrI, 1.62-18.56); MoHdDX (RR, 4.96; 95% CrI, 1.14-14.75); and MoMdDX (RR, 3.16; 95% CrI, 1.35-6.82) were associated with more successful extubation from invasive mechanical ventilation. EHC was associated with a higher risk of gastrointestinal perforation (RR, 2.77; 95% CrI, 1.09-9.32). MoMdDX showed a higher risk of hypertension (RR, 3.96; 95% CrI, 1.10-30.91). MoHdDX had a higher risk of hypertrophic cardiomyopathy (RR, 5.94; 95% CrI, 1.95-18.11). This study suggested that MoMdDX may be the most appropriate postnatal corticosteroid regimen for preventing BPD or mortality at a PMA of 36 weeks, albeit with a risk of hypertension. The quality of evidence was low.

Efficacy and safety of liver support devices in acute and hyperacute liver failure: a systematic review and network meta-analysis

Acute liver failure (ALF) is a potentially life-threatening condition. Liver support therapies can be applied as a bridging-to-transplantation or bridging-to-recovery; however, results of clinical trials are controversial. Our aim was to compare liver support systems in acute and hyperacute liver failure with network meta-analysis. After systematic search, randomized controlled trials (RCT) comparing liver support therapies in adults with acute or hyperacute liver failure were included. In-hospital mortality was the primary outcome, the secondary outcomes were hepatic encephalopathy and mortality-by-aetiology. A Bayesian-method was used to perform network meta-analysis and calculate surface under the cumulative ranking curve (SUCRA) values to rank interventions. Eleven RCTs were included. BioLogic-DT and molecular adsorbent recirculating system (MARS) resulted in the lowest mortality (SUCRAs: 76% and 73%, respectively). In non-paracetamol-poisoned patients, BioLogic-DT, charcoal hemoperfusion and MARS may be equally efficient regarding mortality (SUCRAs: 53%, 52% and 52%, respectively). Considering hepatic encephalopathy, extracorporeal liver assist device (ELAD) may be the most effective option (SUCRA: 78%). However, in pairwise meta-analysis, there were no statistically significant differences between the interventions in the outcomes. In conclusion, MARS therapy seems to be the best available option in reducing mortality. Further research is needed on currently available and new therapeutic modalities. (CRD42020160133).

Diagnostic values of F-18 FDG PET or PET/CT, CT, and US for Preoperative Lymph Node Staging in Thyroid Cancer: A Network Meta-Analysis.

This study compared the diagnostic performance of three different imaging modalities for preoperative lymph node (LN) staging in thyroid cancer patients, using a network meta-analysis (NMA). PubMed and Embase were searched to identify studies evaluating the performance of F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET or PET/CT), computed tomography (CT), and ultrasonography (US) for preoperative LN staging in thyroid cancer patients. The NMA included both patient- and lesion-based analyses. The surface under the cumulative ranking curve (SUCRA) values was used to decide on the most effective diagnostic method. A total of 3,571 patients from 19 direct comparison studies using three different imaging modalities for preoperative LN staging in thyroid cancer patients were included. US showed the highest SUCRA values for positive predictive values (PPV), negative predictive values (NPV), and accuracy in detection of all cervical LN metastasis. F-18 FDG PET or PET/CT and US showed the highest SUCRA values for PPV and sensitivity, respectively, for central LN, and the highest SUCRA value of specificity and sensitivity, respectively, for lateral LN. The results from this NMA indicate that F-18 FDG PET or PET/CT, CT, and US have complementary diagnostic roles for preoperative staging in thyroid cancer patients. Using NMA, we comprehensively compared the different diagnostic values and limitations of F-18 FDG PET or PET/CT, CT, and US for the preoperative LN staging in thyroid cancer patients.

Investigation on the Efficiency of Chinese Herbal Injections for Treating Non-small Cell Lung Cancer With Vinorelbine and Cisplatin Based on Multidimensional Bayesian Network Meta-Analysis.

Background: As non-small cell lung cancer (NSCLC) seriously threatens human health, several clinical studies have reported that Chinese herbal injections (CHIs) combined with vinorelbine and cisplatin (NP) are beneficial. This multidimensional network meta-analysis was performed to explore the preferable options among different CHIs for treating NSCLC. Methods: A literature search was performed in several databases to identify randomized controlled trials (RCTs) of CHIs in the treatment of NSCLC from inception to January 31, 2019. Final included studies met the eligibility criteria and methodological quality recommendations. Data analysis was performed using Stata 13.0 and WinBUGS 14.0 software. Each outcome was presented as an odds ratio and the surface under the cumulative ranking curve value (SCURA). The “scatterplot3d” package in R 3.6.1 software was used to perform multidimensional cluster analysis. Results: Ultimately, 97 eligible RCTs involving 7,440 patients and 14 CHIs were included in this network meta-analysis. Combined with NP chemotherapy, Kanglaite injection plus NP exhibited a better impact on the clinical effectiveness rate (SCURA probability: 78.34%), and Javanica oil emulsion injection plus NP was better in the performance status (95.44%). Huachansu injection plus NP was dominant in reducing thrombocytopenia (92.67%) and gastrointestinal reactions (92.52%). As to multidimensional cluster analysis, Shenmai injection plus NP was superior considering improving the clinical effectiveness rate, performance status and relieving leukopenia. Conclusions: The combination of CHIs and NP has a better impact on patients with NSCLC than NP alone. Among them, Shenmai injection plus NP, Kanglaite injection plus NP and Javanica oil emulsion injection plus NP were notable. Nevertheless, more multicenter and better designed RCTs are needed to validate our findings.

Relative performance of various biomaterials used for maxillary sinus augmentation: A Bayesian network meta-analysis.

ObjectivesTo assess the histomorphometric outcomes obtained in randomized clinical trials (RCTs) with different biomaterials used for maxillary sinus augmentation (MSA).Materials and MethodsA search of the existing medical literature until October 1, 2019, was performed. Inclusion criteria were (a) RCTs assessing a two‐stage MSA from the lateral approach using autologous bone or biomaterials for grafting and (b) reported histomorphometric outcomes based on crestal bone core biopsy samples. The Bayesian method was used to perform pairwise meta‐analyses and network meta‐analysis (NMA). The primary outcome, the new bone percentage (NB %), was calculated as mean differences with 95% credible intervals. The interventions were ranked by their posterior probability by calculating the surface under the cumulative ranking curve values.ResultsThirty‐four RCTs (842 MSAs) were included in the analysis with a normal healing period (5–8 months). All comparisons were presented in a league table. On the basis of the ranking probability, the most effective bone grafting material for NB% was bovine xenograft + bone marrow concentrate (BMC) (81%), followed by bovine xenograft + platelet‐rich plasma (PRP) (77%), bioactive glass ceramic + autologous bone 1:1 (70%), nanocrystalline hydroxyapatite in silica gel (70%), and bioactive glass ceramic (70%). Autologous bone graft alone took the twelfth position with 57%.ConclusionWithin the limitations of the present NMA, the analysis did not confirm autologous bone alone as the gold standard for MSA and showed superiority of composite grafts such as bovine xenograft + BMC after 5–8 months of healing.

Comparative Efficacy of Glucagon-like Peptide 1 Receptor Agonists and Sodium Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular Events in Type 2 Diabetes: A Network Meta-analysis.

The comparative efficacy of different glucagon-like peptide 1 receptor agonists and sodium glucose cotransporter 2 inhibitors for prevention of major adverse cardiovascular events (MACE) in type 2 diabetes with or without cardiorenal disease is undefined. PubMed and Embase were searched for relevant randomized trials. We conducted network meta-analysis within the Bayesian framework. Effect sizes were measured using hazard ratio (HR) and 95% confidence interval (CI). We calculated surface under the cumulative ranking curve (SUCRA) values to rank drug interventions for different type 2 diabetic subgroups. Albiglutide (HR 0.76, 95% CI 0.63-0.93) and subcutaneous semaglutide (HR 0.71, 95% CI 0.52-0.95), with the maximum SUCRA values, significantly reduced MACE versus lixisenatide in people with diabetes with cardiovascular disease; albiglutide (HRs: 0.69 and 0.72), with the maximum SUCRA value, significantly reduced MACE versus dapagliflozin and exenatide in people with diabetes with heart failure; and canagliflozin (HRs: 0.72 and 0.72) and liraglutide (HRs: 0.68 and 0.68), with the maximum SUCRA values, significantly reduced MACE versus exenatide and lixisenatide in people with diabetes with chronic kidney disease. In preventing MACE in type 2 diabetes, subcutaneous semaglutide and albiglutide are most effective for diabetes with cardiovascular disease, albiglutide is most effective for diabetes with heart failure, and canagliflozin and liraglutide are most effective for diabetes with chronic kidney disease.

Target Lesion Failure With Current Drug-Eluting Stents: Evidence From a Comprehensive Network Meta-Analysis.

The aim of this study was to investigate the efficacy and safety of currently used drug-eluting stents (DES). Head-to-head comparisons among newer DES have shown conflicting results. For this network meta-analysis, randomized controlled trials comparing different types of currently used DES were searched in PubMed, Scopus, and proceedings of international meetings. The primary endpoint was target lesion failure (TLF) at 1 year and at long-term follow-up. Seventy-seven trials with 99,039 patients were selected for this network meta-analysis. Among the 10 DES included in the meta-analysis, 4 received the most extensive investigation: Orsiro, XIENCE, Nobori/BioMatrix, and Resolute. At 1 year, the Orsiro stent was associated with lower rates of TLF compared with XIENCE (odds ratio [OR]: 0.84; 95% confidence interval [CI]: 0.71 to 0.98; p=0.03), Resolute (OR: 0.81; 95%CI: 0.68 to 0.95; p=0.01), and Nobori/BioMatrix (OR: 0.81; 95%CI: 0.67 to 0.98; p=0.03). Orsiro had the highest probability to be the best (70.8%), with a surface under the cumulative ranking curve value of 95.9%. However, after a median follow-up period of 50months (range: 24 to 60months), no significant difference was apparent in the rates of TLF between any DES, although Orsiro still ranked as the best stent (58.6% probability to be the best). In addition, Orsiro had a lower rate of long-term definite stent thrombosis compared with Nobori/BioMatrix (OR: 0.60; 95%CI: 0.36 to 0.98; p=0.04) and lower rates of definite and probable stent thrombosis compared with Resolute (OR: 0.66; 95%CI: 0.45 to 0.99; p=0.04). No differences in cardiac mortality between any DES were observed. Orsiro is associated with a lower 1-year rate of TLF compared with XIENCE, Resolute, and Nobori/BioMatrix but with an attenuation of the efficacy signal at long-term follow-up.

Comparative effects on pain arising from injury to the knee meniscus in adults: A systematic review and network meta-analysis

Objective: To identify the most effective pain management method for meniscus injuries by comparing pain relief observed with several common interventions including combined different combinations of surgery and exercise, surgery alone, supervised exercise alone and home exercise alone. Methods: PubMed, Embase, CINAHL, Cochrane Library, Web of Science, SportDiscus, and PEDro were searched from database inception through October 15, 2020. Randomized controlled trials investigating the effect of surgery and exercise for meniscus injuries by using the visual analogue scale (VAS) assessment were eligible for inclusion. Primary outcome was mean change in VAS score from baseline. Comparisons between interventions were made through use of random-effects network meta-analysis over the short-term (three months) and mid-term (12 months). Relative ranking of therapies was assessed by the surface-under-the-cumulative ranking possibilities. All reference lists of included studies were hand-searched. Results: We investigated six RCTs (total n = 796 patients). No significant difference was found between different treatments of pain control in three months and 12 months. The surface under the cumulative ranking curves suggested that supervised exercise combined with surgery was considered most likely to overshadow other treatments in reducing short-term pain (surface under cumulative ranking curve (SUCRA) values: 98.1; mean ranks: 1.1) and mid-term pain (SUCRA values: 97.2; mean rank: 1.1). Conclusion: There is not sufficient evidence to identify any preferred or more effective surgical and/or exercise-based treatment program.

Prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis with a combination of pharmacological agents based on rectal non-steroidal anti-inflammatory drugs: A systematic review and network meta-analysis.

Rectally administered non-steroidal anti-inflammatory drugs (NSAIDs) are effective but suboptimal in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis or PEP. New trials with the combination of rectal NSAIDs and other pharmacological agents have been conducted. This network meta-analysis (NMA) aimed to determine the relative efficacy of combination regimens and identify an optimal regimen for preventing PEP. We performed a systematic and comprehensive search to identify and analyze all the randomized controlled studies published until October 15, 2019, examining rectal NSAIDs and their combination with other pharmacological agents for the prevention of PEP. The primary outcome was the frequency of PEP. We conducted an NMA to combine the direct and indirect comparisons of rectal NSAIDs and their combination with other pharmacological agents. The NMA included 24 studies evaluating 14 regimens in 11321 patients. According to predictive interval plot and surface under the cumulative ranking curve values, indomethacin+lactated Ringer's solution, followed by diclofenac+nitrate and indomethacin+normal saline, is the most efficacious combination of pharmacological agents for the overall prevention of PEP. Rectal indomethacin alone is the most efficacious agent for prevention of moderate to severe PEP, and rectal diclofenac is the most useful agent for prevention of PEP among the high-risk group. Rectal indomethacin with intravenous hydration and rectal diclofenac with sublingual nitrate are the most efficacious combination regimens for the overall prevention of PEP.

Indirect Treatment Comparison of CC-486 Versus Azacitidine (AZA) As Maintenance Therapy for Acute Myeloid Leukemia (AML)

Introduction: For medically fit patients with AML, intensive chemotherapy (IC) is used to induce complete remission (CR). Following CR, some patients may be considered for curative-intent hematopoietic stem cell transplantation. For others, the aim of treatment is to prevent relapse, which usually occurs within 1 year from CR. Post CR, treatment may include consolidation therapy, consisting of chemotherapy given soon after CR is achieved. In addition, maintenance therapy with intravenous (IV) or subcutaneous (SC) injection of AZA has shown evidence of statistically significant improvement in unadjusted time to relapse, though not in unadjusted overall survival (OS), vs placebo (PBO) in randomized controlled trials (RCTs) (Wei. 2019). In the QUAZAR AML-001 trial, maintenance with CC-486, an oral hypomethylating agent, resulted in significant improvements in unadjusted time to relapse and OS vs PBO (Wei et al. 2019). No head-to-head trials have compared CC-486 with AZA. Objective: To assess the relative efficacy of CC-486 compared with AZA. Methods: A systematic literature review was conducted to identify RCTs assessing AML maintenance therapy with AZA, for comparison with CC-486. Bayesian network meta-analysis (NMA) compared endpoints of CC-486 and AZA. Hazard ratios (HR), 95% credible intervals (CrI), and surface under the cumulative ranking curve (SUCRA) values were calculated. The impact of differences in potential treatment-effect-modifying characteristics between populations in the NMA was explored using anchored matching-adjusted indirect comparison (MAIC). The NMA was repeated using CC-486 vs PBO efficacy from the MAIC, to satisfy the assumption of clinical similarity necessary in NMA (Hoaglin et al. 2011). Results: Four RCTs evaluating OS outcomes that could be compared were identified: QUAZAR AML-001 (CC-486) (Wei et al. 2019), HOVON 97 AML (SC AZA) (Huls et al. 2019), UK NCRI AML16 (SC AZA) (Burnett et al. 2015), and QoLESS-AZA-MLE (SC and IV AZA, included in sensitivity analysis) (Oliva et al. 2019). Other efficacy and safety endpoints were not analyzed owing to lack of comparable data among the 4 identified RCTs. Results of the NMA indicated CC-486 was associated with statistically significant improvement in OS vs SC AZA (HR 0.744; CrI 0.557, 0.998); SC AZA was not statistically different from PBO (HR 0.926; CrI 0.771, 1.120). SUCRA values associated CC-486 with the best OS (98.8%). In a sensitivity analysis, CC-486 was associated with statistically significant improvement in OS vs SC or IV AZA (HR 0.741; CrI 0.556, 0.992). In the MAIC, a structured process was used to evaluate the need for adjustment due to differences in trial populations in the NMA. Populations for each trial were compared (Table). Per methodological guidance (Phillippo et al. 2016), the MAIC sought to adjust characteristics with evidence of (a) treatment-effect-modifying status on the scale of parameters entering the NMA and (b) substantial imbalance across populations. Using the QUAZAR individual patient data, univariate analyses were conducted to determine prognostic and effect-modifying status of variables (Table). For each SC AZA trial, a multivariate Cox model was estimated, including all significant prognostic variables reported, and effect modifiers that remained significant when controlling for prognostic variables and improved model fit. Among variables reported for UK NCRI, no effect modifiers enhanced the multivariate model; for HOVON, treatment interactions with age > 81 years (the oldest age in HOVON) and absolute neutrophil count (ANC) did. MAIC was therefore conducted by re-weighting QUAZAR patients to match means/shares of the HOVON patients, adjusting for mean age, % aged > 81 years, % poor cytogenetic risk, and mean ANC. Effective sample size was 411 (−13% vs N = 472 in QUAZAR). Frequency-weighted, unadjusted (including only a treatment covariate) Cox regression was conducted. After adjusting for effect-modifying differences, the OS improvement of CC-486 vs PBO observed in QUAZAR was maintained in the HOVON population. Incorporating the adjusted HR from the MAIC in the NMA, CC-486 continued to be associated with statistically significant improvement in OS vs SC AZA (HR 0.753; CrI 0.563, 0.998). Conclusion: Maintenance CC-486 appears to significantly improve OS compared with SC AZA for patients with AML who have achieved CR after IC, based on a systematic analysis of RCT outcomes. Disclosures Tabah: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Huggar:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company; Karyopharm Therapeutics: Current equity holder in publicly-traded company; FibroGen: Current equity holder in publicly-traded company. Wang:Medicus Economics: Current Employment; Bristol Myers Squibb: Research Funding. Johnson:Medicus Economics: Current Employment; BMS: Research Funding. Copher:Bristol Myers Squibb: Current Employment. O'Connell:Bristol-Myers Squibb: Consultancy; Other biopharmaceutical manufacturers: Consultancy; Medicus Economics, LLC: Current Employment. Leblanc:AbbVie, Agios, Amgen, AstraZeneca, CareVive, BMS/Celgene, Daiichi-Sankyo, Flatiron, Helsinn, Heron, Otsuka, Medtronic, Pfizer, Seattle Genetics, Welvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; American Cancer Society, BMS, Duke University, NINR/NIH, Jazz Pharmaceuticals, Seattle Genetics: Research Funding; UpToDate: Patents & Royalties: Royalties; Agios, AbbVie, and Bristol Myers Squibb/Celgene: Speakers Bureau; AstraZeneca: Research Funding.

What Is the Relative Effectiveness of the Various Surgical Treatment Options for Distal Radius Fractures? A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

Many acceptable treatment options exist for distal radius fractures (DRFs); however, a simultaneous comparison of all methods is difficult using conventional study designs. We performed a network meta-analysis of randomized controlled trials (RCTs) on DRF treatment to answer the following questions: Compared with nonoperative treatment, (1) which intervention is associated with the best 1-year functional outcome? (2) Which intervention is associated with the lowest risk of overall complications? (3) Which intervention is associated with the lowest risk of complications requiring operation? Ten databases were searched from inception to July 25, 2019. Search and analysis reporting adhered to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Included studies were English-language RCTs that assessed at least one surgical treatment arm for adult patients with displaced DRFs, with less than 20% loss to follow-up. We excluded RCTs reporting on patients with open fractures, extensive bone loss, or ipsilateral upper extremity polytrauma. Seventy RCTs (n = 4789 patients) were included. Treatments compared were the volar locking plate, bridging external fixation, nonbridging external fixation, dynamic external fixation, percutaneous pinning, intramedullary fixation, dorsal plating, fragment-specific plating, and nonoperative treatment. Subgroup analyses were conducted for intraarticular fractures, extraarticular fractures, and patients with an average age greater than 60 years. Mean (range) patient age was 59 years (56 to 63) and was similar across all treatment groups except for dynamic external fixation (44 years) and fragment-specific plating (47 years). Distribution of intraarticular and extraarticular fractures was approximately equal among the treatment groups other than that for intramedullary fixation (73% extraarticular), fragment-specific plating (66% intraarticular) [13, 70], and dorsal plating (100% intraarticular). Outcomes were the DASH score at 1 year, total complications, and reoperation. The minimum clinically important different (MCID) for the DASH score was set at 10 points. The analysis was performed using Bayesian methodology with random-effects models. Rank orders were generated using surface under the cumulative ranking curve values. Evidence quality was assessed using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology. Most studies had a low risk of bias due to randomization and low rates of incomplete follow-up, unclear risk of bias due to selective reporting, and high risk of bias due to lack of patient and assessor blinding. Studies assessing bridging external fixation and/or nonoperative treatment arms had a higher overall risk of bias while studies with volar plating and/or percutaneous pinning treatment arms had a lower risk of bias. Across all patients, there were no clinically important differences in terms of the DASH score at 1 year; although differences were found, all were less than the MCID of 10 points. Volar plating was ranked the highest for DASH score at 1 year (mean difference -7.34 [95% credible interval -11 to -3.7) while intramedullary fixation, with low-quality evidence, also showed improvement in DASH score (mean difference -7.75 [95% CI -14.6 to -0.56]). The subgroup analysis revealed that only locked volar plating was favored over nonoperative treatment for patients older than 60 years of age (mean difference -6.4 [95% CI -11 to -2.1]) and for those with intraarticular fractures (mean difference -8.4 [95% CI -15 to -2.0]). However, its clinical importance was uncertain as the MCID was not met. Among all patients, intramedullary fixation (odds ratio 0.09 [95% CI 0.02 to 0.84]) and locked volar plating (OR 0.14 [95% CI 0.05 to 0.39]) were associated with a lower complication risk compared with nonoperative treatment. For intraarticular fractures, volar plating was the only treatment associated with a lower risk of complications than nonoperative treatment (OR 0.021 [95% CI < 0.01 to 0.50]). For extraarticular fractures, only nonbridging external fixation was associated with a lower risk of complications than nonoperative treatment (OR 0.011 [95% CI < 0.01 to 0.65]), although the quality of evidence was low. Among all patients, the risk of complications requiring operation was lower with intramedullary fixation (OR 0.06 [95% CI < 0.01 to 0.85) than with nonoperative treatment, but no treatment was favored over nonoperative treatment when analyzed by subgroups. We found no clinically important differences favoring any surgical treatment option with respect to 1-year functional outcome. However, relative to the other options, volar plating was associated with a lower complication risk, particularly in patients with intraarticular fractures, while nonbridging external fixation was associated with a lower complication risk in patients with extraarticular fractures. For patients older than 60 years of age, nonoperative treatment may still be the preferred option because there is no reliable evidence showing a consistent decrease in complications or complications requiring operation among the other treatment options. Particularly in this age group, the decision to expose patients to even a single surgery should be made with caution. Level I, therapeutic study.

Which is the best analgesia treatment for total knee arthroplasty: Adductor canal block, periarticular infiltration, or liposomal bupivacaine? A network meta-analysis

Study objectiveTo review all randomized controlled trials (RCTs) comparing the analgesic efficacy of adductor canal block (ACB), periarticular infiltration (PAI), and any other mode of these treatments in analgesia, such as PAI with liposomal bupivacaine (LB), continuous adductor canal block (cACB) or ACB + PAI, after total knee arthroplasty (TKA). DesignSystematic review and network meta-analysis of RCTs. PatientsWe searched PubMed, Embase, and the Cochrane database to detect all relevant RCTs on investigating the analgesic effects of ACB, PAI and LB for TKA published until April 2020. InterventionsUse of different analgesic methods of ACB, PAI, cACB, ACB + PAI and LB. MeasurementsThe primary endpoint was visual analog scale (VAS) score at rest and movement. The secondary endpoints were opioids consumption, length of hospitalization and knee range of motion (ROM). We used Cochrane risk of bias to assess the quality of evidence for outcomes. ResultsForty-two studies involving 3785 patients with 5 different methods containing ACB, PAI, ACB + PAI, continuous ACB (cACB), LB, were evaluated. According to surface under the cumulative ranking curve value, 24 h resting VAS score was the lowest the ACB + PAI (88.4%), followed by cACB (73.4%); Resting VAS score at 48 h and movement VAS score at 24 h and 48 h was the lowest in the cACB (99.9%, 92% and 100%). Total opioids consumption was the least in LB (81.4%) before cACB (60.8%). ROM was the largest in the ACB + PAI (84.1%) before cACB (78.8%). ConclusionAlthough all analgesic methods available were not evaluated, and further studies are needed to establish our results, the 24 h resting VAS score was lowest in ACB + PAI and 48 h resting and movement VAS score was lowest in cACB.Clinical trial registration: PROSPERO (CRD 42020168102).

Fecal Microbiota Transplantation May Be the Best Option in Treating Multiple Clostridioides difficile Infection: A Network Meta-Analysis.

IntroductionClostridioides difficile (formerly Clostridium) infection (CDI) is the most common cause of healthcare-associated diarrhea with high mortality and recurrence rate; furthermore, the treatment of recurrent cases is a challenge. In this network meta-analysis, we aimed to compare all available therapies against multiple recurrent CDI (mrCDI) and rank them by efficacy.MethodsAfter a systematic search, randomized controlled trials (RCT) with any interventions against mrCDI were included. Data were extracted to the study database using Excel. Risk of bias assessment was performed with the Cochrane RoB 2 tool. The primary outcome was the clinical cure of CDI and the secondary outcome was the recurrence of CDI. A Bayesian method was performed to investigate the efficacy rank order of therapies. We registered our protocol with the Prospero Center for Reviews and Dissemination (registration no. CRD42020160365).ResultsSix RCTs with seven interventions were included in the quantitative synthesis. According to the surface under the cumulative ranking curve values, fecal microbiota transplantation (FMT) after a short course of vancomycin therapy (83%) shows the highest efficacy for clinical cure. Tolevamer and vancomycin + FMT seemed to be the most effective in preventing recurrence (87% and 75%, respectively).ConclusionVancomycin + FMT is perhaps the most effective option for the treatment and prevention of mrCDI, while tolevamer is also effective in preventing recurrence.Electronic Supplementary MaterialThe online version of this article (10.1007/s40121-020-00356-9) contains supplementary material, which is available to authorized users.

Role of Neoadjuvant and Adjuvant Radiotherapy in Resectable Esophageal and Esophagogastric Junction Cancers: A Systematic Review and Network Meta-Analysis

For patients with resectable esophageal and esophagogastric junction cancers, neoadjuvant and adjuvant radiotherapy with or without chemotherapy is widely used to improve the effect of surgery. This study is to evaluate the effect of radiotherapy adding to surgery and identify the optimized treatment model. According to pre-specified searching strategy and inclusion/exclusion criteria, we systematically screened electronic databases (PubMed, Embase and Cochrane Library) for relevant studies up to February 2020. Only phase II and III randomized controlled trials comparing the following treatments were included: surgery alone, surgery preceded by neoadjuvant radiotherapy (NRT) or neoadjuvant chemoradiotherapy (NCRT), surgery followed by adjuvant radiotherapy (ART) or adjuvant chemoradiotherapy (ACRT). Overall survival (OS) was identified as the measurement of effectiveness. A network meta-analysis was conducted to synthesize the evidence under the Bayesian framework. The relative effects of all possible comparisons were made. Ranking analysis was performed to support the decision in clinical practice. Fourteen eligible trials with 2904 patients were included and 10 comparisons were generated. The results were shown in table 1. Compared with surgery alone, only NCRT showed favorable OS with significant difference (hazard ratio (HR) 0.75, 95% credible interval 0.65-0.87), while NRT (HR 0.76, 0.43-1.31), ACRT (HR 0.74, 0.49-1.12) and ART (HR 0.9, 0.67-1.22) provided no significant survival advantage. Ranking analysis showed that the surface under the cumulative ranking curve (SUCRA) value in NCRT was 0.79, which was the highest among all five treatments, followed by ACRT (0.74), NRT (0.66), ART (0.41), and surgery alone (0.14). For resectable esophageal and esophagogastric junction cancers, NCRT may be the optimal strategy, while NRT or ART or ACRT may not improve OS compared with surgery alone. Table 1. Pooled hazard ratios (95% credible intervals) for overall survival in the network meta-analysis.Abstract 3531; TableNCRT_SNRT_SSS_ACRTS_ARTNCRT_SNCRT_S1 (0.56, 1.75)1.33 (1.15, 1.54)0.98 (0.65, 1.5)1.19 (0.86, 1.68)NRT_S1(0.57, 1.78)NRT_S1.32 (0.76, 2.34)0.97 (0.49, 2)1.19 (0.64, 2.3)S0.75 (0.65, 0.87)0.76 (0.43, 1.31)S0.74 (0.49, 1.12)0.9 (0.67, 1.22)S_ACRT1.02 (0.67, 1.53)1.03 (0.5, 2.02)1.35 (0.89, 2.04)S_ACRT1.22 (0.74, 2)S_ART0.84 (0.6, 1.16)0.84 (0.43, 1.57)1.12 (0.82, 1.5)0.82 (0.5, 1.36)S_ART Open table in a new tab

Network Meta-Analysis of Drug Therapies for Lowering Uric Acid and Mortality Risk in Patients with Heart Failure.

This network meta-analysis aimed to assess the current efficacy of decreasing the uric acid (UA) level with drugs to reduce mortality in patients with heart failure (HF). Electronic literature searches using EMBASE and MEDLINE of studies published from 1 Jan 1950 to 26 Dec 2019 were conducted for randomized controlled trials or non-randomized cohort studies that included at least one group of patients who took UA-lowering drugs and with a study outcome of all-cause mortality. A random-effects network meta-analysis was performed within a frequentist framework. Hierarchy of treatments was expressed as the surface under the cumulative ranking curve (SUCRA) value, which is in proportion to mean rank (best is 100%). Nine studies, which included seven different types of groups, were eligible for analysis. The "untreated uricemia" group in which patients had hyperuricemia but without treatment had a significantly higher risk of mortality than the "no uricemia" group in which patients had no hyperuricemia (relative risk (RR)(95% confidence interval (CI), 1.43 (1.08-1.89)). The "start-allo" group wherein patients started to take allopurinol did not have a significantly lower risk of mortality than the "untreated uricemia" group (RR (95% CI), 0.68 (0.45-1.01)). However, in the "start-allo" group the SUCRA value was comparable to that in the "no uricemia" group (SUCRA: 65.4% for "start-allo"; 64.1% for "no uricemia"). Results suggested that allopurinol therapy was not associated with a significantly improved prognosis in terms of mortality but could potentially counteract the adverse effects associated with longstanding hyperuricemia in HF patients.

Comparison of First-Line Treatments for Patients With Extensive-Stage Small Cell Lung Cancer

Combinations of chemotherapy with immunotherapy or bevacizumab in first-line treatments of extensive-stage small cell lung cancer (ES-SCLC) have been evaluated in various clinical trials. However, it remains unclear what the optimal combination regimen is. To clarify which first-line combination regimen is associated with the best tumor response among patients with ES-SCLC. Electronic databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) were systematically searched to extract eligible literature from database inception to December 2019. Head-to-head randomized clinical trials on first-line treatments for patients with ES-SCLC were included with outcomes and toxic effects reported, including objective response rate (ORR, involving complete response and partial response), disease control rate (DCR, involving complete response, partial response, and stable disease), progression-free survival (PFS), overall survival (OS), and treatment related adverse events (TRAEs) of grades 3 to 5. Of 199 eligible articles, 14 were included. Data were independently extracted and collected by 2 reviewers based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Data were pooled using a random-effects model. Main outcomes were OS, PFS, DCR, ORR, and TRAEs of grades 3 to 5. A total of 3 phase 2 and 11 phase 3 randomized clinical trials involving 4838 patients were included. Programmed cell death ligand 1 (PD-L1) inhibitor (durvalumab and atezolizumab) plus etoposide-based chemotherapy, compared with etoposide-based chemotherapy alone, showed the most favorable OS (hazard ratio, 1.40; 95% CI, 1.09-1.80) and the best DCR (odds ratio [OR], 0.42; 95% CI, 0.21-0.81). Bevacizumab plus etoposide-based chemotherapy provided the best PFS compared with etoposide-based chemotherapy alone (hazard ratio, 1.54; 95% CI, 1.09-2.27), although this was not translated into OS benefit. The addition of PD-L1 inhibitors to etoposide-platinum chemotherapy caused no more toxic effects in general (compared with etoposide-based chemotherapy alone: OR, 1.14; 95% CI, 0.36-2.31), while bevacizumab plus etoposide-platinum regimen induced the most TRAEs grades 3 to 5 among all first-line treatments (eg, compared with irinotecan-platinum regimen: OR, 4.24; 95% CI, 1.26-14.57). Based on the surface under the cumulative ranking curve value, PD-L1 inhibitor plus etoposide-platinum had the highest probability of being ranked first for OS (0.87) and DCR (0.97). The findings of this systematic review and network meta-analysis suggest that the combination of a PD-L1 inhibitor (durvalumab and atezolizumab) and etoposide-based chemotherapy may be an optimal first-line treatment option for patients with ES-SCLC patients.

Interventions for Preventing Chemotherapy-Induced Alopecia: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

Chemotherapy-induced alopecia (CIA) is a common adverse effect among patients undergoing chemotherapy. Patients experiencing CIA suffer psychological distress and even refuse or discontinue chemotherapy. A variety of interventions have been applied to prevent CIA. However, the best intervention option remains unknown. To evaluate and determine the comparative effects of all available interventions for preventing CIA. A comprehensive literature search of four English and 3 Chinese electronic databases was performed to identify potential studies from database inception to August 2018. Two reviewers conducted data selection, data extraction, and risk of bias assessment independently. The consistency model was used to conduct a network meta-analysis based on a frequentist framework to evaluate the relative effects of different interventions. Rankings of interventions were evaluated by the surface under the cumulative ranking curve values. Seventeen eligible trials including 1378 patients were included. Scalp cooling (odds ratio, 0.13; 95% confidence interval, 0.07-0.25) and scalp compression (odds ratio, 0.13; 95% confidence interval, 0.03-0.52) had significant effects relative to usual care. Ranking of efficacy indicated that scalp cooling was the most effective, followed by scalp compression with tourniquets, topical Chinese medicinal herbs, oral Chinese medicinal herbs, minoxidil, and usual care. The results of this study indicate that scalp cooling is the most effective method to prevent CIA during chemotherapy. Our results could provide a reference to prevent CIA. Updated studies with high quality, sufficient sample sizes, and direct comparison between interventions are needed in the future.

Psychological interventions for chronic non-specific low back pain: protocol of a systematic review with network meta-analysis

IntroductionPsychological factors such as fear avoidance beliefs, depression, anxiety, catastrophic thinking and familial and social stress, have been associated with high disability levels in people with chronic low back pain...

Evaluation of different surgical dressings in reducing postoperative surgical site infection of a closed wound: A network meta-analysis

To evaluate the effects of different surgical dressings in reducing surgical site infection (SSI) and identify the optimal dressings. Randomized controlled trials investigating the application of surgical dressings were retrieved from electronic databases, including MEDLINE, EMBASE, and the Cochrane Library. The odds ratios (ORs) of the SSI rate were compared by direct meta-analysis, and the surface under the cumulative ranking (SUCRA) curve values were calculated based on the Bayesian theorem. A node-splitting model was applied to analyse the consistency of the comprehensive comparison results. Twenty-two studies containing 5487 participants were pooled for the comprehensive comparison. Among all the studies included, 9 types of surgical dressings were identified for comparison. The results of the direct meta-analysis revealed that novel dressings significantly reduced the overall SSI rate with an OR of 1.026 (95% CI: 1.013-1.040, p<0.001), which was determined to have low heterogeneity (I2=32.1%). Specifically, 3 types of dressings presented significant effects in reducing SSI, namely, mupirocin-containing (OR=1.076, 95% CI: 1.014-1.142, p=0.015), dialkylcarbamoyl-chloride-containing (OR=1.047, 95% CI: 1.012-1.083, p=0.008) and vitamin E (VE)-silicone-containing (OR=1.129, 95% CI: 1.016-1.255, p=0.025) dressings. Network meta-analysis demonstrated that the VE-silicone dressing (SUCRA=0.37) was the optimal dressing, followed by the mupirocin dressing, with a SUCRA of 0.31. The present network meta-analysis identified the superiority of VE-silicone and mupirocin dressings in preventing SSI. The evidence-based results provide suggestions and directions for future investigations on surgical dressings. More large-scale trials with rigorous designs are warranted to clarify the clinical value of novel dressings in surgical incision management.

Efficacy of noninvasive respiratory support modes as postextubation respiratory support in preterm neonates: A systematic review and network meta-analysis.

Multiple noninvasive respiratory support (NRS) modalities are used for postextubation support in preterm neonates. Seven NRS modalities were compared-constant flow continuous positive airway pressure (CPAP) (CF-CPAP) (bubble CPAP; ventilator CPAP), variable flow CPAP (VF-CPAP), high flow nasal cannula (HFNC), synchronized noninvasive positive pressure ventilation (S-NIPPV), nonsynchronized NIPPV (NS-NIPPV), bilevel CPAP (BiPAP), noninvasive high-frequency oscillation ventilation (nHFOV). Systematic review and network meta-analysis (NMA) using the Bayesian random-effects approach. MEDLINE, EMBASE, CENTRAL, WHO-ICTRP were searched. Requirement of invasive mechanical ventilation within 7 days of extubation. A total of 33 studies with 4080 preterm neonates were included. S-NIPPV, NS-NIPPV, nHFOV, and VF-CPAP were more efficacious in preventing reintubation than CF-CPAP (risk ratio [RR] [95% credible intervals {CrI}]: 0.22 [0.12, 0.35]; 0.44 [0.27, 0.67]; 0.42 [0.18, 0.81]; 0.73 [0.52, 0.99]). Surface under the cumulative ranking curve (SUCRA) value ranked S-NIPPV to be the best postextubation intervention (SUCRA: 0.98). S-NIPPV was more effective than NS-NIPPV, BiPAP, VF-CPAP, and HFNC (RR [95% CrI]: 0.52 [0.24, 0.97]; 0.32 [0.14, 0.64]; 0.30 [0.16, 0.50]; 0.24 [0.12, 0.41]). NS-NIPPV resulted in lesser reintubation compared to VF-CPAP and HFNC (RR [95% CrI]: 0.61 [0.36, 0.97]; 0.49 [0.27, 0.80]). BiPAP, VF-CPAP, and HFNC had comparable efficacies. The overall quality of evidence was very low to moderate. Results of this NMA indicate that S-NIPPV might be the most effective and CF-CPAP the least effective NRS modality for preventing extubation failure.