Direct Comparison Meta-analysis Research Articles

Combined Laparoscopic Uterine Artery Occlusion and Myomectomy versus Laparoscopic Myomectomy: A Direct-Comparison Meta-Analysis of Short- and Long-Term Outcomes in Women with Symptomatic Leiomyomas

ObjectiveTo ascertain the efficacy and safety of laparoscopic uterine artery occlusion (LUAO) during laparoscopic myomectomy (LM) on intra- and postoperative morbidity and to assess its impact on leiomyoma recurrence rates. Data SourcesMEDLINE, Scopus, Web of Science, and Cochrane Database were searched for relevant references from inception until December 2018, in line with PRISMA guidelines. Methods of Study SelectionTwo authors screened for study eligibility and extracted data. Randomized controlled trials (RCTs) and observational studies (OSs) comparing short- and long-term morbidity of LM with or without LUAO were included. The modified Jadad score and the methodologic index for nonrandomized studies were used to evaluate the quality of RCTs and OSs, respectively. Tabulation, Integration, and ResultsTwelve studies encompassing 750 LM and 873 LUAO-LM cases were included in the meta-analysis. The studies were of moderate quality. LUAO-LM appears to significantly decrease intraoperative blood loss, postoperative hemoglobin drop, and blood transfusion rate. A trend toward shorter hospital length of stay was demonstrated, whereas no significant difference in operation duration was observed. The combined procedure seemingly contributes to lower recurrence rate. No LUAO-related complications were reported. Moderate to high heterogeneity was observed for few outcomes. ConclusionThis is the first meta-analysis to date to provide a convincing overview of efficacy and safety of LUAO-LM. Although a medium risk of bias warrants some caution with interpretation of the results, LUAO-LM seemingly improves intra- and postoperative outcomes in women with symptomatic leiomyomas.

Which is the best treatment of osteoporotic vertebral compression fractures: balloon kyphoplasty, percutaneous vertebroplasty, or non-surgical treatment? A Bayesian network meta-analysis

BK, PVP, and NST are widely used to treat OVCFs, but preferable treatment is unknown. The aim of the current study was to use a Bayesian network meta-analysis to evaluate the relative benefits and risks of BK, PVP, and NST for patients with OVCFs. PubMed, EMBASE, and the Cochrane Library were screened. Based on the preplanned eligibility criteria, we screened and included randomized controlled trials that compared BK, PVP, and NST in treating patients with OVCFs. The risk of bias for individual studies was appraised. The data were pooled using a Bayesian network meta-analysis and a traditional direct comparison meta-analysis. Of the 1057 relevant studies, 15 were eligible and included. Compared with NST, PVP significantly reduced pain, Oswestry Disability Index (ODI), and Roland-Morris Disability Questionnaire (RMDQ). The comparative efficacy of BK and PVP was similar for pain (mean difference (MD) 0.51, 95% credible interval (CrI) - 0.35 to 1.4), ODI (MD 0.11, 95% CrI - 13 to 13), and RMDQ (MD 1.2, 95% CrI - 2.7 to 5.4). The European Quality of Life-5 Dimensions (EQ-5D) and Physical Component Summary subscales of the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36 PCS) did not differ significantly. There were also no substantial differences in the risks of subsequent vertebral fractures, adjacent vertebral fractures, and re-fractures at the treated level across all comparators. The results of pairwise meta-analyses were almost consistent with those of network meta-analyses. The treatment ranking indicated that PVP had the highest probability of being the most effective for pain, ODI, RMDQ, and EQ-5D. BK had the highest probability of improving SF-36 PCS and of reducing the risk of subsequent vertebral fractures and re-fractures at the treated level. NST was ranked first in preventing adjacent vertebral fractures. PVP was the most effective method for improving pain, functional status, and quality of life (based on EQ-5D). BK emerged as the best intervention for decreasing the risk of subsequent vertebral fractures and re-fractures at the treated level. NST could be ranked first in reducing adjacent vertebral fractures. The future directions of OVCFs treatment will depend on the outcomes of additional and larger randomized trials in comparing BK with PVP.

Protocol for a systematic review of venous coupler devices versus hand-sewn anastomosis for microsurgical free flap reconstruction

BackgroundA patent microvascular anastomosis is of paramount importance in free tissue transfer. Anastomotic coupler devices provide an alternative to technically demanding hand-sewn venous anastomosis. Various advantages of these devices have been discussed but previous systematic reviews had methodological flaws or did not perform a meta-analysis. This review aims to evaluate the quality of the evidence and quantify the efficacy and safety of venous couplers compared to hand-sewn anastomosis.MethodsA PRISMA-compliant systematic review and meta-analysis will be performed. A comprehensive search strategy has been developed and will be applied to the databases MEDLINE and Embase from inception to October 2018. All clinical studies using anastomotic coupler devices for venous anastomoses in free tissue transfer will be eligible for inclusion. Screening of studies and data extraction will be performed independently by two authors. Our primary outcome is anastomotic venous thrombosis. Secondary outcomes will include time to complete the venous anastomosis, tearing of veins, anastomotic leakage, flap loss/failure and fiscal outcomes. The risk of bias for included studies will be assessed by using the ROBINS-I tool, and recommendations based on the evidence will be made using the GRADE approach. Descriptive statistical analyses will be used and if two or more studies report the same outcome, data will be pooled for comparative analysis. A direct comparison meta-analysis will be performed if possible.DiscussionThere has been no comparison of coupled and hand-sewn venous anastomoses using a robust and validated methodology preceded by a protocol and performing meta-analysis. Included studies are expected to be mainly observational and prone to bias; however, there is value in summarising the evidence, assessing its risk of bias and performing meta-analysis to guide clinicians. By using a broad approach including all types of flaps, we foresee inherent differences regarding the unit of analysis and different anatomic sites. This will limit the validity of our conclusions but is unavoidable. We will seek unpublished data from authors and perform subgroup analysis where appropriate. Limitations and areas of uncertainty will be discussed to guide future research.Systematic review registrationPROSPERO CRD42018110111

Azithromycin or erythromycin? Macrolides for non-cystic fibrosis bronchiectasis in adults: A systematic review and adjusted indirect treatment comparison.

Non-cystic fibrosis (non-CF) bronchiectasis is a condition characterized by an airway inflammatory response to bacterial pathogens. Frequent exacerbations have a major influence on the quality of life. Macrolide antibiotics have not only antibacterial but also immune-regulation effects. It is proved that macrolides have a benefit in preventing exacerbations. However, it is still uncertain whether azithromycin or erythromycin is more effective and safe. The purpose of this study was to answer the following question: Which kind of macrolide antibiotic is more effective and safe in preventing non-CF bronchiectasis exacerbation? We conducted a systematic review to identify randomized clinical trials published up to May 2017 that reported on macrolides for non-CF bronchiectasis and an adjusted indirect treatment comparison (AITC) between macrolides to evaluate their efficacy and safety. The direct comparison meta-analysis found that macrolides decreased the rate of exacerbation of non-CF bronchiectasis (risk ratio (RR) = 0.45; 95% confidence interval (CI) 0.36–0.55) with heterogeneity (I 2 = 63.7%, p = 0.064). The AITC showed that azithromycin had a significantly lower bronchiectasis exacerbation rate than erythromycin (RR = 0.35; 95% CI: 0.403–0.947). Azithromycin increased the risk of diarrhea and abnormal pain. This meta-analysis suggested that long-term treatment with macrolides significantly reduced the incidence of non-CF bronchiectasis exacerbation. Moreover, azithromycin is more efficient than roxithromycin and erythromycin in preventing exacerbation.

The Impact of Saphenous Vein Sparing During Inguinal Lymphadenectomy on Postoperative Morbidity in Women With Vulval Cancer: An Updated Per-Groin Meta-analysis of Short-term Outcomes.

Inguinofemoral lymphadenectomy (IFL) is included in the standard surgical management of early-stage vulval cancer (VC) but is often accompanied by surgical complications. Efforts have been made to limit the postoperative morbidity by adopting more conservative IFL techniques without compromising the surgical outcomes. Saphenous vein (SV) preservation during IFL for VC appears to reduce the incidence of postoperative complications including lymphedema. To ascertain the efficacy of SV preservation, we aimed to revisit the impact of SV preservation on short-term per groin complications by updating on a previous meta-analysis to further guide current clinical practice. A systematic literature review was conducted to identify studies that reported postoperative complications following IFL with SV preservation and controls (SV ligation during IFL) in VC patients. We included articles in English language and avoided date restrictions. Direct-comparison meta-analysis was performed between the use of SV preservation and SV ligation for the short-term outcomes of lymphedema, cellulitis, and wound dehiscence/breakdown. Fixed- and random-effects models were fitted to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). Five studies were included in the final analysis. Direct-comparison per-groin meta-analysis between SV preservation and SV ligation significantly decreased the odds for developing lymphedema (OR, 0.363; 95% CI, 0.228-0.578; P < 0.001), cellulitis (OR, 0.481; 95% CI, 0.28-0.825; P = 0.008), and wound dehiscence/breakdown (OR, 0.296; 95% CI, 0.191-0.458; P < 0.001). When SV sparing was clearly the sole intervention, lymphedema was the only complication in which the positive effect of SV sparing is exerted (OR, 0.28; 95% CI, 0.149-0.526; P < 0.001). This per groin meta-analysis updates on the current evidence suggesting the SV sparing improves postoperative outcomes following IFL in VC patients. Where sentinel biopsy is not indicated, this risk-reducing strategy should be considered in selected VC patients undergoing IFL until a multicenter randomized controlled trial becomes available.

The Safety of Tranexamic Acid in Total Joint Arthroplasty: A Direct Meta-Analysis

BackgroundTranexamic acid (TXA) is effective in reducing blood loss in total joint arthroplasty (TJA), but concerns still remain regarding the drug's safety. The purpose of this direct meta-analysis was to evaluate and establish a basis for the safety recommendations of the combined clinical practice guidelines on the use of TXA in primary TJA. MethodsA search was completed for studies published before July 2017 on TXA in primary TJA. We performed qualitative and quantitative homogeneity testing and a direct comparison meta-analysis. We used the American Society of Anesthesiologists (ASA) score of 3 or greater as a proxy for patients at higher risk for complications in general and performed a meta-regression analysis to investigate the influence of comorbidity burden on the risk of arterial thromboembolic event and venous thromboembolic event (VTE). ResultsTopical, intravenous, and oral TXA were not associated with an increased risk of VTE after TJA. In addition, meta-regression demonstrated that TXA use in patients with an ASA status of 3 or greater was not associated with an increased risk of VTE after total knee arthroplasty. ConclusionAlthough most studies included in our analysis excluded patients with a history of prior thromboembolic events, our findings support the lack of evidence of harm from TXA administration in patients undergoing TJA. Moderate evidence supports the safety of TXA in patients undergoing total knee arthroplasty with an ASA score of 3 or greater. The benefits of using TXA appear to outweigh the potential risks of thromboembolic events even in patients with a higher comorbidity.

876: Sutures versus staples for skin closure after cesarean delivery. Does the type of suture matter? A direct and indirect comparison meta-analysis.

876: Sutures versus staples for skin closure after cesarean delivery. Does the type of suture matter? A direct and indirect comparison meta-analysis.

Meta-Analysis of Culprit-Only Versus Multivessel Percutaneous Coronary Intervention in Patients With ST-Segment Elevation Myocardial Infarction and Multivessel Coronary Disease

Recently, several randomized controlled trials (RCT) in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) have compared a strategy of routine multivessel percutaneous coronary intervention (PCI) performed either as a single procedure or as staged procedures to culprit-only PCI. All of these trials have been underpowered for clinical end points. We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for RCT comparing multivessel PCI with culprit-only PCI in patients with STEMI and MVD. The primary efficacy outcome was the composite rate of death or MI. Other efficacy outcomes included death, MI, and repeat revascularization. Safety outcomes were contrast-associated acute kidney injury, stroke, and major bleeding. Pairwise direct comparison and mixed-treatment comparison network meta-analyses were performed. Eleven trials that enrolled 3,150 patients with a total of 5,296 patient-years of follow-up were included. In direct comparison meta-analysis, single-procedure multivessel PCI was associated with a reduction in the risk of death or MI (rate ratio [RR] = 0.52; 95% confidence interval [CI] 0.37 to 0.73; p <0.001), due to less death (RR = 0.64; 95% CI 0.40 to 1.02; p = 0.06) and MI (RR = 0.42; 95% CI 0.25 to 0.69; p <0.0001) compared with culprit-only PCI. No heterogeneity (I2 = 0) was present between studies. In contrast, staged multivessel PCI did not significantly reduce death or MI compared with culprit-only PCI. Both multivessel PCI strategies reduced the risk of repeat revascularization without significant differences in safety outcomes. Results were consistent in the mixed-treatment comparison meta-analysis. In conclusion, the present meta-analysis suggests that single-procedure multivessel PCI may be the preferred strategy in patients with STEMI and MVD.

A systematic review and meta-analysis of adverse outcomes following non-buried versus buried Kirschner wires for paediatric lateral condyle elbow fractures.

PurposeFractures of the lateral condyle of the humerus in children are a common injury. If displaced or unstable they may require surgical reduction and fixation with Kirschner wires (K-wires). K-wires are placed using either an open or closed technique. The decision to bury or leave the ends extending through the skin is surgeon-dependent and based on factors including post-operative infection risk, bony union and ease of wire removal.MethodsWe performed a systematic review and meta-analysis of non-buried versus buried K-wires for lateral condyle elbow fractures in children in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. A comprehensive search strategy included Medline, Embase and CINAHL via NICE Evidence from database inception to June 2017. Two authors independently reviewed, included or excluded articles, extracted data and assessed for quality with the ROBINS-I tool. We performed direct comparison meta-analysis for all adverse events, post-operative infection and failure of bony union.ResultsThree studies were analysed comprising of 434 participants. There was a significantly reduced relative risk of adverse events in the non-buried group, equating to approximately 45% reduced risk (RR 0.55, 95% confidence interval 0.34 to 0.88). There were no significant differences in risk of post-operative infection or failure of bony union. All three cost-analyses in the included studies observed savings with non-buried K-wires.ConclusionNon-buried K-wires for lateral condyle elbow fractures convey a lower risk of adverse events and may be more cost-effective compared with buried K-wires. Non-buried K-wires do not appear to increase the risk of infection or failure of bony union. These findings are limited by a high risk of bias due to inherent methodological flaws in the design of included studies.

Interventions for obtaining and maintaining employment in adults with severe mental illness, a network meta-analysis.

Interventions for obtaining and maintaining employment in adults with severe mental illness, a network meta-analysis.

Prognostic value of KRAS codon 13 gene mutation for overall survival in colorectal cancer: Direct and indirect comparison meta-analysis.

The clinical significance of KRAS codon 13 mutation in patients with colorectal cancer (CRC) remains controversial. A systematic review and meta-analysis is necessary for a more precise estimation of the predictive role of KRAS codon 13 mutations in CRC patients. We performed a systematic search using the MEDLINE, EMBASE, and Cochrane library databases from January 2000 to November 2016. The prognostic value of KRAS codon 13 mutation for overall survival (OS) was investigated by measuring the hazard ratio (HR) and 95% confidence interval (CI). Data were analyzed with Review Manager Version 5.3 and the Canadian Agency for Drugs and Technologies in Health software. OS in CRC patients with KRAS codon 13 mutation was worse than that in CRC patients with KRAS wild-type (pooled HR = 1.37, 95% CI: 1.03-1.81, P = .03). Subgroup analysis of studies of enrolled CRC patients treated with antiepidermal growth factor receptor (EGFR) therapy showed no significant difference in OS associated with KRAS codon 13 mutation in comparison to KRAS wild-type (pooled HR = 1.57, 95% CI: 0.98-2.51, P = .06). In the indirect comparison, no statistically significant association was observed between codon 12 and 13 mutations for OS in CRC patients (pooled HR = 0.88, 95% CI: 0.65-1.20, P = .43). The current meta-analysis suggests that Codon 13 mutation of KRAS gene seems to correlate with the OS of patients with CRC, but has similar OS to those with KRAS wild-type in patients receiving anti-EGFR therapy. No difference was detected in the OS of CRC patients with codon 13 mutation versus codon 12 mutation.

Antipsychotic Drugs in Schizophrenia: Relative Effects in Patients With and Without Treatment Resistance.

How antipsychotic drugs compare in schizophrenia, and especially in medication-refractory schizophrenia, is a subject of considerable interest. Two network meta-analyses and 1 direct comparison meta-analysis recently compared antipsychotics in schizophrenia patients with and without documented treatment resistance. One network meta-analysis of antipsychotic drugs in non-refractory patients found clear efficacy advantages for clozapine, amisulpride, olanzapine, and risperidone. One network meta-analysis of antipsychotic drugs in refractory patients found a clear efficacy advantage for olanzapine; surprisingly, in this meta-analysis, clozapine was superior to first-generation but not second-generation antipsychotics. One direct comparison meta-analysis found clozapine generally superior to first- and second-generation antipsychotics, with advantages more clearly apparent in studies that were 3 months in duration or less. Drug discontinuation and adverse effect data from these meta-analyses are presented, and issues arising from the results are briefly discussed. At the risk of oversimplification, it appears that clozapine retains its preeminence in medication-refractory schizophrenia and that clozapine and olanzapine are both associated with superior efficacy outcomes in non-refractory patients. Interestingly, haloperidol, generally considered a reference neuroleptic and a reference comparator drug, fared poorly in most comparisons.

Systematic Literature Review Evidence of Pegaspargase for Treatment of Acute Lymphoblastic Leukemia (ALL)

Introduction: Advances in chemotherapeutic regimens have improved pediatric ALL survival rates from less than 10% in the 1960s to approximately 90% currently (Hunger et al NEJM 2015). Asparaginase (ASP), as a component of the multi-agent chemotherapy regimen has become a cornerstone treatment for ALL. Pegaspargase (Oncaspar, PEG) is a pegylated asparaginase with sustained asparaginase activity, offering less frequent administration and associated with less treatment-related anxiety compared to native E.coli L-asparaginase (Place et al Lancet Oncol 2015). Due to the ample amount of data available for PEG, a systematic literature review and quantitative synthesis of evidence was previously performed to assess the relative benefit of PEG versus native ASP in newly diagnosed ALL patients in terms of event free survival (EFS) and overall survival (OS) (Kilpatrick et al ICPE 2016). The main objective of this investigation was to update the literature review by identifying additional relevant scientific clinical evidence of PEG in first line treatment of ALL in pediatric patients, and to expand the investigation to include adult patients.Methods: All available evidence for newly diagnosed patients treated in pediatric and adult ALL protocols using PEG or native ASP was identified using a search algorithm. Randomized, observational and cohort studies were included. Outcomes were EFS and OS. Safety/immunogenicity was also examined. Feasibility was then explored in this order: direct comparison meta-analysis (MA) if at least two head-to-head trials were found, indirect comparison (network MA) if a common comparator could be identified or separate product MAs (pooled estimates) of PEG and native ASP using a random effects model. The individual product MA was analyzed for two important variables: risk category (standard & high risk) and by distinct age groups. Pooling was conducted, assuming normality, using the software Comprehensive Meta-Analysis, version 2.Results:There were 62 and 30 studies that met pre-specified inclusion criteria for abstraction for pediatric and adult populations, respectively. Some identified studies in both populations provided data for both asparaginases. Therefore, in pediatrics: 39 studies provided data for PEG and 41 for nativeASP, in adults: 10 studies provided data for PEG and 23 for nativeASP. Direct MA was not feasible as only one head-to-head study was identified. Also due to lack of common comparator, indirect MA was infeasible. Pooled estimate of EFS and OS data for pediatric ALL patients treated with PEG or native ASP is shown in table 1 below. Forest plot with pooled estimate of 5-year OS in adult ALL patients treated with PEG or native ASP is presented in figure 1, categorized by age group when available. Overall safety was consistent with product class for both asparaginases.Conclusions: A systematic literature review and quantitative synthesis constitute an important approach to critically appraise relevant research. Consistent with published data, better outcomes were observed in pediatric than adults patients. The result from this updated research synthesisdemonstrates a positive effectiveness profile of PEG in the treatment of newly diagnosed ALL patients with less frequent administration. [Display omitted] [Display omitted] DisclosuresLebedinsky:Shire: Employment. Hale:Shire: Employment. Patel:Shire: Employment. Casamayor:Shire: Other: Vendor; Quintiles: Employment. Wijnands:Shire: Other: Vendor; Quintiles: Employment. Desai:Shire: Employment.

TCT-462 Efficacy and Safety of Biodegradable Polymer Everolimus-eluting stents versus Durable Polymer Biolimus-eluting stents: A direct comparison meta-analysis of 8,476 patients from randomized trials

There is a paucity of data on long-term efficacy and safety of biodegradable polymer biolimus-eluting stent (BES) compared with durable polymer everolimus-eluting stent (EES) in patients undergoing percutaneous coronary intervention. Randomized controlled trials comparing EES with BES were

What's New in Hip Replacement.

Over the past year, there have been many changes in hip arthroplasty. Some of the new information further solidifies practices such as the use of tranexamic acid for blood conservation and the detection of infection through alpha defensins, and other studies have enhanced our knowledge of surgical approaches and the modes of failure of implants. Compared with the past, the biggest changes have not been in surgical materials or techniques but in how surgeons will practice in the future with respect to outcomes. ### Bearings Total hip arthroplasty is increasingly being utilized in younger, more active patients with long life expectancies. Researchers have conducted studies using different bearing couples in the hopes of improving the longevity of implants. In one report, the authors conducted a Level-I study to determine if there was a short-term to intermediate-term survivorship difference among common total hip arthroplasty bearings used in patients younger than 65 years of age1. This report described the survivorship of ceramic on ceramic, ceramic on highly cross-linked polyethylene, and metal on highly cross-linked polyethylene. Direct-comparison meta-analysis found no differences among the bearing surfaces in terms of the risk of revision. Network meta-analysis likewise found no differences in survivorship across the three implant types, suggesting that, at least in the short term, any of the bearing combinations functioned well in younger patients. Another randomized controlled trial compared the results of ceramic-on-ceramic bearing with those of ceramic-on-polyethylene bearings2. At the 10-year follow-up, there were no group differences (p > 0.48) in both the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) and the SF-12 (RAND 12-Item Health Survey). There were no failures or loss of fixation related to bearing surfaces or wear in either group. Comparing ceramic-on-ceramic bearings with ceramic-on-polyethylene bearings, there were few short-term differences in function or wear. These …

Meta-Analysis Comparing Complete Revascularization Versus Infarct-Related Only Strategies for Patients With ST-Segment Elevation Myocardial Infarction and Multivessel Coronary Artery Disease

Several recent randomized controlled trials (RCTs) demonstrated better outcomes with multivessel complete revascularization (CR) than with infarct-related artery-only revascularization (IRA-OR) in patients with ST-segment elevation myocardial infarction. It is unclear whether CR should be performed during the index procedure (IP) at the time of primary percutaneous coronary intervention (PCI) or as a staged procedure (SP). Therefore, we performed a pairwise meta-analysis using a random-effects model and network meta-analysis using mixed-treatment comparison models to compare the efficacies of 3 revascularization strategies (IRA-OR, CR-IP, and CR-SP). Scientific databases and websites were searched to find RCTs. Data from 9 RCTs involving 2,176 patients were included. In mixed-comparison models, CR-IP decreased the risk of major adverse cardiac events (MACEs; odds ratio [OR] 0.36, 95% CI 0.25 to 0.54), recurrent myocardial infarction (MI; OR 0.50, 95% CI 0.24 to 0.91), revascularization (OR 0.24, 95% CI 0.15 to 0.38), and cardiovascular (CV) mortality (OR 0.44, 95% CI 0.20 to 0.87). However, only the rates of MACEs, MI, and CV mortality were lower with CR-SP than with IRA-OR. Similarly, in direct-comparison meta-analysis, the risk of MI was 66% lower with CR-IP than with IRA-OR, but this advantage was not seen with CR-SP. There were no differences in all-cause mortality between the 3 revascularization strategies. In conclusion, this meta-analysis shows that in patients with ST-segment elevation myocardial infarction and multivessel coronary artery disease, CR either during primary PCI or as an SP results in lower occurrences of MACE, revascularization, and CV mortality than IRA-OR. CR performed during primary PCI also results in lower rates of recurrent MI and seems the most efficacious revascularization strategy of the3.

Safety and efficacy of dipeptidyl peptidase-4 inhibitors vs sulfonylurea in metformin-based combination therapy for type 2 diabetes mellitus: Systematic review and meta-analysis.

The purpose of this study was to compare the safety and efficacy of DPP-4 inhibitors versus sulfonylurea as adjunctive second-line therapy in patients with type 2 diabetes mellitus, inadequately controlled with metformin mono-therapy. A systematic review of published randomized controlled trials (RCTs) was performed in MEDLINE, EMBASE, PubMed and Cochrane library. Two reviewers independently selected the studies, extracted the data and assessed the risk of bias. Clinical outcomes were cardiovascular events, HbA1c % change from baseline, body weight and hypoglycemic event rate. A direct comparison meta-analysis using a random effect model was conducted to calculate mean differences in treatment effects and risk ratio between DPP-4 inhibitors and sulfonylurea. Ten RCTs on adult patients with type 2 diabetes and inadequate glycemic control were included in the final analysis. DPP-4 inhibitors compared to sulfonylureas produced a non-significant difference in HbA1c% change in 10,139 subjects, whereas a significant decrease in the rate of hypoglycemic events was observed in favor of DPP-4 inhibitors (RR= 0.12; P<0.00001) involving 10,616 patients, with at least one hypoglycemic event during the follow-up period (12-104 weeks). Body weight decreased by 2.2 kg (95% CI 1.7-2.7) with DPP-4 inhibitors, compared with sulfonylureas. There were insufficient data to assess a difference in the risk for cardiovascular events. The review shows that, in terms of clinical efficacy, there is no significant difference between DPP4-inhibitors and sulfonylurea when either is added to metformin mono-therapy. In contrast, the safety assessment analysis showed a significant decrease in the risk of hypoglycemic events in patients using DPP4-inhibitors.

Rotational vaginal delivery with Kielland's forceps: a systematic review and meta-analysis of effectiveness and safety outcomes.

The use of Kielland's forceps has declined significantly in the last three decades. There is a lack of quality evidence on potential benefits and harms associated with using these forceps. We have performed a systematic review of the literature and meta-analysis to assess the safety and efficacy of using Kielland's forceps. We have searched electronic databases for all clinical studies reporting primary data on using Kielland's forceps and assessed their risk of bias using the Newcastle-Ottawa Scale. We have pooled the event rate of adverse outcomes reported following the use of Kielland's forceps including a direct comparison to rotational ventouse. In total we included 23 studies. Direct comparison meta-analysis revealed higher failure rate with rotational ventouse compared with Kielland's. There was no statistically significant difference in the risk of adverse maternal outcomes between the two groups. There was higher risk of neonatal trauma in the ventouse group, but no significant difference in other neonatal outcomes. Kielland's forceps have a high success rate with relatively low adverse outcomes despite their use being controversial. In comparison to rotational ventouse, Kielland's forceps have higher efficacy with less risk of neonatal trauma.

Efficacy and safety of long-acting β-agonist/long-acting muscarinic antagonist combinations in COPD: a network meta-analysis

BackgroundThe place of long-acting β agonist/long-acting muscarinic antagonist (LABA/LAMA) combinations in stable patients with COPD is not well defined. The purpose of this study was to systematically review the efficacy...

Efficacy of high-dose ACTH versus low-dose ACTH in infantile spasms: A meta-analysis with direct and indirect comparison of randomized trials

To determine the influence of dose on the efficacy and safety of adrenocorticotropic hormone (ACTH) for infantile spasms. We searched six relative databases. Randomized controlled trials and crossover studies, which meet our inclusion criteria were considered for inclusion. The quality of included trials was evaluated with respect to sequence generation, allocation concealment, blinding and incomplete data. We performed both direct and indirect meta-analysis to evaluate the efficacy and safety of high-dose and low-dose of ACTH. Results: A total of 168 reports were retrieved, and after scrutiny seven reports of trials containing three head to head comparisons, two vigabatrin comparisons and two prednisone comparisons were included. In direct comparison meta-analysis, studies were homogenous (P >; 0.10). There was a trend towards more complete cessation of spasms in the low-dose ACTH treated group (RR: 0.86, 95% confidence interval [CI]: 0.57–1.31), though statistically not significant. Relapse was more frequent in low-dose ACTH groups (RR: 0.69, 95% CI: 0.22–2.19) but without demonstrating statistic difference. No difference was present for disappearance of hypsarrhythmia between high and low-dose ACTH (RR: 0.93, 95% CI: 0.57–1.54). In indirect meta-analysis the comparison of complete cessation of spasms between high-dose and low-dose ACTH from indirect meta failed to show any significant difference. There was no significant difference between two dosages with respect to relapse rates. High-dose ACTH produced more adverse effects than low-dose group. A low-dose ACTH therapy might be preferable for its comparative efficacy and lower risk of adverse effects.