Quality Of Randomized Controlled Trials Research Articles

Development of a risk of bias assessment tool specifically for meta-analysis of trials for surgical site infection

Background: Surgical site infections (SSIs) significantly impact patient outcomes, with rates reaching up to 20% after surgery, leading to higher morbidity, prolonged hospital stays, and increased costs. The assessment of randomized controlled trials (RCTs) related to SSIs has been challenging due to the lack of a specialized Risk of Bias (RoB) tool, as existing tools like the RoB-2 are not surgery-specific. To address this gap, we developed an adapted SSI-specific RoB-2 tool. Methods: This tool was created through a four-stage consensus process involving surgeons, trial statisticians, and methodologists with extensive experience in international SSI trials. Results: The process identified ten critical domains relevant to assessing RCTs on SSI interventions. Of these, eight domains were prioritized as essential for the final tool, while two were considered desirable but less critical due to the challenges of blinding in surgical contexts. Conclusion: The adapted RoB-2 tool is tailored to the unique aspects of SSI trials, offering a more focused and practical means of evaluating RCT quality. It not only improves the assessment of existing studies but also guides the design of future RCTs, enhancing the quality of evidence in SSI research. The tool's application in meta-analyses will likely lead to more reliable and generalizable results, informing clinical practice and policy decisions related to SSI prevention and management.

Risk of new vertebral compression fractures and serious adverse effects after vertebroplasty: a systematic, critical review and meta-analysis of randomized controlled trials.

Osteoporotic vertebral fractures (OVFs) significantly impact morbidity, mortality, functionality, and quality of life. Vertebroplasty, a widely utilized treatment for OVFs, has its efficacy and safety debated due to varying outcomes reported across clinical trials and meta-analyses. This study aims to critically review and conduct a meta-analysis of randomized controlled trials (RCTs) focusing on the safety of vertebroplasty, specifically its association with serious adverse effects and the development of new vertebral fractures, while exploring potential confounders. We conducted a systematic review and meta-analysis by searching PubMed, Web of Science, and EMBASE. The search was updated to February 23, 2024. We included published RCTs comparing vertebroplasty to conservative treatment (CT) or placebo/active control, focusing on new fractures and serious adverse effects. The primary outcomes were "incidence of new fractures" and "serious adverse effects". We applied the Dersimonian-Laird method with a random effects model to estimate risk ratios (RRs) of the primary outcomes, using the I2 statistic to assess heterogeneity among studies. Sensitivity analyses were conducted when significant heterogeneity was detected. Subgroup analyses were performed based on the characteristics of the control groups, risk of bias based on The Cochrane Risk of Bias Tool 2, time from fracture onset, and multicentric versus single-center trials. In total, 14 RCTs encompassing 1,413 patients were analyzed. High and unclear risk of bias were observed in 15 and 25 items, respectively. No significant difference was observed in the incidence of new vertebral fractures between vertebroplasty and the control groups [RR =1.05, 95% confidence interval (CI): 0.71-1.56; I2=55%; P<0.01]. However, vertebroplasty was associated with a significantly lower incidence of serious adverse effects (RR =0.53, 95% CI: 0.31-0.91; I2=0%; P=0.93). Subgroup analyses revealed no significant differences based on control types, risk of bias, or number of institutions involved. Notably, early vertebroplasty (within 6 weeks of symptom onset) showed a protective effect against new vertebral fractures (RR =0.60, 95% CI: 0.38-0.92; I2=0%; P=0.53). The sensitivity analysis showed that one study influenced the observed heterogeneity but did not significantly modify the pooled estimate. Vertebroplasty is not associated with an increased risk of developing new vertebral fractures and may reduce the risk of serious adverse effects compared to placebo or CT. Early intervention post-fracture appears beneficial. However, the limited number and quality of RCTs call for further high-quality studies.

How is the quality of randomized controlled trials (RCTs) for acupuncture treatment of post-stroke aphasia? A report quality assessment.

This study aimed to assess the quality of randomized controlled trials (RCTs) that have reported the use of acupuncture for the treatment of post-stroke aphasia (PSA). We systematically searched PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang data Information Site, and China Science and Technology Journal Database from January 2013 to June 2023. RCTs utilizing acupuncture as an intervention for the treatment of post-stroke aphasia were included in this study. The overall quality score (OQS) of RCTs was independently evaluated by two researchers using the Consolidated Standards for Reporting Trials (CONSORT) and the Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) guidelines, with the agreement between researchers calculated using Cohen's kappa statistics. In conclusion, we included 38 RCTs in this study. The median OQS of the 38 RCTs was 13 (minimum 8, maximum 20) based on the CONSORT statement. Out of all CONSORT items, 10 (27%) had a positive rate of greater than 80%, while 17 (46%) had a positive rate of less than 10%. The median OQS of the 38 RCTs was 12 (minimum 6, maximum 14) based on the STRICTA guideline. Within the STRICTA guideline, 6 items (35%) had a positive rate of greater than 80%, and 3 items (18%) had a positive rate of less than 10%. Most items based on the CONSORT and STRICTA guidelines were observed to have a perfect or good degree of agreement. The overall reporting quality of RCTs for acupuncture treatment of PSA was found to be suboptimal. Notably, the reporting quality of the STRICTA guideline is higher compared to the CONSORT statement. Therefore, strict adherence to both the CONSORT and STRICTA statements is recommended to enhance the quality of RCT reports on acupuncture treatment for post-stroke aphasia.

Evaluating Compliance of Randomized Controlled Trial Abstracts in Plastic Surgery Journals with CONSORT Guidelines Using GPT-4 AI

Background: The quality of reporting in randomized controlled trials (RCTs) is crucial for accurate interpretation and synthesis of evidence. The Consolidated Standards of Reporting Trials (CONSORT) guidelines provide a standardized framework for reporting RCT abstracts. This study aimed to evaluate the adherence of RCT abstracts published in three major plastic surgery journals to the CONSORT tool guideline for reporting abstracts, utilizing Generative Pre-trained Transformer 4 artificial intelligence (GPT-4 AI) technology. Methods: Abstracts of RCTs published between 2010 and 2023 were collected. The GPT-4 AI model was utilized to assess the abstracts based on the CONSORT criteria. Descriptive statistics were used to report the compliance scores and identify areas where abstracts lacked compliance. Results: Of the initially identified 500 abstracts, a total of 371 RCT abstracts met the inclusion criteria and were analyzed. The mean CONSORT score was 10.05 (±2.22), with a median score of 10.72. Specific areas where abstracts lacked compliance included trial design (39.6%), participant details (28.8%), intervention descriptions (15.6%), randomization process (25.3%), and the number of participants analyzed (33.4%). Trial registration (18.3%) and funding information (15.1%) were also frequently missing. Conclusions: Our study’s innovative use of the GPT-4 AI model for analysis demonstrated the potential of AI technology in streamlining and enhancing the evaluation of research compliance. We advocate for heightened awareness and more rigorous application of CONSORT guidelines among authors, reviewers, and journal editors. Emphasizing the role of AI technology in the evaluative process can further improve the reporting quality of future RCTs in plastic surgery, contributing to more reliable and transparent research in the field.

A Comparison Between Volar Locking Plates and Percutaneous Pinning in the Treatment of Distal Radius Fractures: A Systematic Review

Percutaneous fixation with Kirschner wires and open reduction and internal fixation with volar locking plates are the most common surgical techniques for managing distal radius fractures (DRFs). As the superiority of either technique is yet to be established, we aimed to conduct an updated systematic review to compare these techniques for the optimal management of unstable DRFs. We conducted a comprehensive literature search to identify studies comparing fixation outcomes for DRFs between groups treated with Kirschner wires and those treated with volar locking plates. Only randomized controlled trials (RCTs) were included. The revised Cochrane risk-of-bias tool was used to assess the methodological quality of RCTs. Meta-analyses were performed only on outcome measures that were reported at the same time points using the same metrics across three or more RCTs. Evaluated outcomes included the Disabilities of the Arm, Shoulder, and Hand (DASH) score, grip strength, wrist range of motion, and radiological outcomes. We also assessed the Patient-Rated Wrist Evaluation (PRWE) score and incidence of complications. Fourteen RCTs with 2,226 patients were included in the meta-analysis. DASH scores were significantly lower in the plating group at all time points. PRWE outcomes favored the plating group at follow-ups greater than 1 year. There were no significant differences in radiological outcomes or incidence of complications between the two groups. Although the plating group provided marginally better functional outcomes at 1 year after surgery, the K-wire group remained a viable alternative. The reported differences should be interpreted cautiously because of the inherent variability of the included RCTs. High-quality RCTs with strict inclusion criteria and standard postoperative protocols are essential to generalize our results across all age groups and fracture types to overcome our study's limitations. Therapy/Prevention, Etiology/Harm II.

The differential effects of eicosapentaenoic acid and docosahexaenoic acid on cardiovascular risk factors: an updated systematic review of randomized controlled trials.

Cardiovascular disease remains a major global health concern. The combination of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been shown to beneficially modify a range of cardiovascular risk factors. However, whether EPA and DHA have differential effects or potencies is currently unclear. A systematic review of randomized controlled trials (RCTs) that compared ≥2 g/day of near pure EPA and DHA was conducted. A total of 24 publications from nine unique RCTs were included. EPA and DHA both lower triglyceride levels, with DHA most likely having a slightly greater effect. Furthermore, both EPA and DHA increase high density lipoprotein (HDL) 2 cholesterol, which is cardioprotective, with the increase being greater with DHA. DHA appears to increase low density lipoprotein (LDL) cholesterol; however, DHA also increases LDL particle size, which would render LDL less atherogenic. DHA seems more effective than EPA in decreasing heart rate and blood pressure. Both EPA and DHA alter platelet function decreasing thrombogenicity, although they may have different actions on platelets. Both EPA and DHA decrease F2-isoprostanes, interpreted as a reduction in oxidative stress. They both decrease inflammatory gene expression and promote an anti-inflammatory oxylipin profile. These are all favorable effects with regard to cardiovascular disease risk. Effects of EPA and DHA on blood glucose are inconsistent. This review is constrained by the small number of high quality RCTs that directly compare EPA to DHA and report on outcomes other than blood lipids. There is a need for additional high-quality research to assess the independent effects of EPA and DHA on cardiovascular risk factors (e.g., inflammation, blood pressure, vascular function, platelet function) in larger and more diverse study populations.

Scaffolds for Osteochondral Lesions of the Talus: Systematic Review and Meta-Analysis of the Last Ten Years Literature.

Scaffolds are widely used devices for the treatment of osteochondral lesions of the talus (OCLT), aimed at enhancing mechanical stability and fostering chondrogenic differentiation. A systematic review and meta-analysis were performed to evaluate the safety, and clinical and radiological results of scaffolds for OCLT management. On 2 January 2024, a search was performed in four databases (PubMed, Embase, Web of Science, and Scopus), according to PRISMA guidelines. The risk of bias in the included studies was also evaluated. Thirty clinical studies were included in the qualitative analysis: 12 retrospective case series, 3 retrospective comparative studies, 9 prospective case series, 1 prospective comparative study, and 1 Randomized Controlled Trial (RCT). Natural scaffolds, such as bilayer collagen (COLL)I/III and hyaluronic scaffolds, were the most employed. Only minor adverse events were observed, even if more serious complications were shown, especially after medial malleolar osteotomy. An overall clinical and radiological improvement was observed after a mean of 36.3 months of follow-up. Patient age and Body Mass Index (BMI), lesion size, and location were correlated with the clinical outcomes, while meta-analysis revealed significant improvement in clinical scores with hyaluronic scaffolds compared to microfracture alone. This study highlights the safety and positive clinical outcomes associated with the use of scaffolds for OCLT. In the few available comparative studies, scaffolds have also demonstrated superior clinical outcomes compared to microfractures alone. Nevertheless, the analysis has shown the limitations of the current literature, characterized by an overall low quality and scarcity of RCTs.

Fragility Index Analysis of the 2018 Clinical Practice Guidelines on Tranexamic Acid Use in Total Joint Arthroplasty

BackgroundThe 2018 American Association of Hip and Knee Surgeons clinical practice guideline (CPG) ‘tranexamic acid use in total joint arthroplasty’ evaluated the efficacy and safety of tranexamic acid in primary total joint arthroplasty. The following review assessed the statistical fragility of the randomized controlled trial (RCT) outcomes on which the CPG recommendations were based using a fragility analysis. MethodsAll dichotomous outcomes from the RCTs used to guide the CPG from its associated network, and direct meta-analyses were analyzed. Fragility and reverse fragility indices (FI and rFI) and quotients were calculated for each outcome. The mean indices and quotients were calculated for each guideline question, outcome category, and comparison of tranexamic dose, formulation, and administration timing. ResultsThis review evaluated 403 dichotomous outcomes on transfusion and complication rates associated with tranexamic acid (TXA) administration. The mean FI of significant outcomes of the CPG was 5.23, and the mean rFI of nonsignificant outcomes was 5.80. Outcomes assessing complication rates had a mean rFI of 6.48. Most outcomes on transfusion in categories comparing TXA to placebo administration had higher mean FIs than rFIs, and all outcomes comparing transfusion risk associated with different TXA formulations and doses had higher mean rFIs than FI or no associated significant outcomes. ConclusionsThe rFI and FIs calculated for this CPG are comparable to or higher than mean values reported across orthopaedic literature, indicating the relative statistical stability of its included outcomes. As we learn more about fragility analyses and their potential applications, this type of statistical analysis shows promise as a useful tool to incorporate into future guidelines to assess the quality of RCTs and evaluate the strength of recommendations.

Evidence-Based Review of Randomized Controlled Trials of Interventions for Mental Health Management Post-Moderate to Severe Traumatic Brain Injury.

To present an evidence-based review of randomized controlled trials (RCTs) evaluating interventions for mental health post-moderate to severe traumatic brain injury (post-MSTBI), as part of an extensive database that has been conceptualized as a living systematic review. Systematic searches were conducted for RCTs published in the English language in MEDLINE, PubMed, Scopus, CINAHL, EMBASE, and PsycINFO, up to and including December 2022, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The methodological quality of RCTs was assessed using the Physiotherapy Evidence Database scale, and the level of evidence was assigned using a modified Sackett scale. Eighty-seven RCTs examining mental health interventions and outcome measures post-MSTBI were included. These studies collectively enrolled 6471 participants. A total of 41 RCTs (47.1%) were conducted in the United States and 56 studies (64.4%) were published after 2010. A total of 62 RCTs (71.3%) examined nonpharmacological interventions and 25 RCTs (28.7%) examined pharmacological interventions. Effective pharmacological treatments included desipramine and cerebrolysin; methylphenidate and rivastigmine showed conflicting evidence. Cognitive behavioral therapy (CBT) was found to be effective for hopelessness, stress, and anxiety, compared to usual care; however, it may be as effective as supportive psychotherapy for depression. CBT combined with motivational interviewing may be as effective as CBT combined with nondirective counseling for depression, stress, and anxiety. Acceptance and commitment therapy was effective for anxiety, stress, and depression. Tai Chi, dance, and walking appeared to be effective for depression and stress, while other nonpharmacological treatments such as peer mentoring showed limited effectiveness. This evidence-based review provides a comprehensive overview of the research landscape of RCTs addressing mental health post-MSTBI. The findings from these RCTs may be valuable for health care professionals, researchers, and policymakers involved in the field of mental health and neurorehabilitation.

Systematic Review of Volume and Methodological Quality of Randomised Trials in Acute Pancreatitis

Abstract Background This systematic review assessed the volume and methodological quality of randomised controlled trials (RCTs) in relation to management of acute pancreatitis (AP). Methods The PUBMED, MEDLINE, CENTRAL databases were systematically searched for RCTs published across 3 time periods: &lt;1996(P1), 1996-2008 (P2), &gt;2008(P3). RCT quality was assessed using the Cochrane Risk of Bias (RoB) 2 tool, sample size recalculation, and for spin (interpretation of non-statistically significant results as relevant, making the study appear to be positive). Results Overall, 263 RCTs with 23,232 patients with AP were included. The average number of RCTs per year increased from 1.4, 6.0, to 10.6 in P1, P2, and P3, respectively. The RoB assessment showed low, some, and high concerns in overall RoB in 21%, 56% and 24% of all RCTs. Selective reporting bias improved over time. Sample size calculation reporting significantly increased through the three time periods (17%, 38% and 47%, p &lt; 0.001). Spin was identified in 68 RCTs (26% of all RCTs). Conclusion The quantity and quality of published RCTs relating AP management has increased over time, however significant shortcomings of methodological quality persist. Significant improvements in the conduct and reporting of randomised trials in AP are required to improve the evidence base in this field.

Evaluation of the reporting quality of randomized controlled trials of acupuncture for depression based on CONSORT statement, STRICTA criteria and SHARE checklist

To evaluate the reporting quality of randomized controlled trials (RCTs) of acupuncture for depression. Systematic searches were performed in PubMed, the Cochrane Library, EMbase, CNKI, Wanfang, SinoMed and VIP Database for RCTs of acupuncture in treatment of depression. The search time was from the establishment of database to December 1, 2023, and the language restriction was Chinese and English. The reporting quality of RCTs of acupuncture for depression was evaluated using the CONSORT statement, the international standardization for trial reporting, STRICTA, the international standard for clinical trial interventions of acupuncture, and SHARE, the guideline and checklist for reporting sham acupuncture controls. According to the CONSORT statement items, the items with the reporting rate less than 50% was accounted for 54.05% of all of the items for Chinese articles, and there were 8 and 1 items with a reporting rate of 0% and 100%, respectively. For the English articles, the items with the reporting rate less than 50% was accounted for 35.14% of all of the items, and there were 3 and 7 items with a reporting rate of 0% and 100%, respectively. The reporting rate of 15 items in Chinese and English articles was greater than 50%, e.g. structured abstract, background and purpose. Based on STRICTA criteria, the reporting rate of either Chinese or English articles was relatively high. The items for Chinese articles with the reporting rate less than 50% was accounted for 23.53% of all of the items, and there were 1 and 4 items with a reporting rate of 0% and 100%, respectively. For English articles, the items with the reporting rate less than 50% was accounted for 11.76% of all of the items, and there was 1 item with a reporting rate of either 0% or 100%. In compliance with SHARE checklist, the reporting rate was low for either Chinese or English articles. The items with the reporting rate less than 50% was accounted for 57.89% of all of the items for Chinese articles, and there were 2 and 0 items with a reporting rate of 0% and 100%, respectively. For English articles, the items with the reporting rate less than 50% was accounted for 52.63% of all of the items, and there was 1 item with a reporting rate of 0% and 100%, respectively. The overall reporting quality of RCTs of acupuncture for depression is low currently. It is urgent to enhance the reporting of the details on sham acupuncture control especially. It is suggested that RCTs should be reported strictly in compliance with the CONSORT statement, STRICTA criteria, and SHARE checklist in the future.

Virtual reality technology reduces the pain and anxiety of children undergoing vein puncture: a meta-analysis

BackgroundPain management is an important part of nursing care for children. The objective of this study was to systematically assess the impact of virtual reality (VR) technology on alleviating the pain and anxiety experienced by children during venipuncture procedures.MethodsThis study searched Pubmed, Web of Sciences, Scopus, The Cochrane Library, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Embase, Medline, China National Knowledge Infrastructure (CNKI), Wanfang, Weipu and China biomedical databases on the randomized controlled trials (RCTs) of virtual reality technology for relieving pain and anxiety associated with venous puncture for children up to July 6, 2024. Risk of bias tool recommended by Cochrane library was used to evaluate the RCT quality. RevMan 5.3 software was used for statistical analysis.ResultsA total of 10 RCTs involving 874 children were included. 429 children received VR intervention during vein puncture. VR was beneficial to reduce the children’s self-reported pain scores [SMD=-0.48, 95% CI (− 0.61, − 0.35)], children’s caregivers reported needle-related pain level [SMD=-0.93, 95% CI (-1.45, − 0.42)], children’s self-reported anxiety scores [SMD=-0.45, 95% CI (− 0.65, − 0.25)], children’s caregivers reported needle-related anxiety level [SMD=-0.47, 95% CI (− 0.73, − 0.21)]. Egger regression tests indicated that there were no publication biases in the synthesized outcomes (all P > 0.05).ConclusionsVR technology has been shown to effectively mitigate the pain and anxiety experienced by children during venipuncture. Despite the positive findings, more research is needed to better understand the role of VR in children undergoing venipuncture.

Abstracts of randomized controlled trials in splint therapy for temporomandibular disorders: Reporting quality and spin.

Poor reporting quality and spin in randomized controlled trial (RCT) abstracts can lead to misinterpretation and distorted interpretation of results. This methodological study aimed to assess the reporting quality and spin among RCT abstracts on splint therapy for temporomandibular disorders (TMD) and explore the association between spin and potentially related factors. The authors searched PubMed for RCTs on splint therapy for TMD. The reporting quality of each abstract was assessed using the original 16-item CONSORT for abstracts checklist. The authors evaluated the presence and characteristics of spin only in abstracts with nonsignificant primary outcomes according to pre-determined spin strategies. Logistic regression analyses were performed to identify factors associated with the presence of spin. A total of 148 abstracts were included in the reporting quality evaluation. The mean overall CONSORT score (OCS) was 5.86 (score range: 0-16). Only interventions, objectives and conclusions were adequately reported. Of the 61 RCT abstracts included for spin analysis, spin was identified in 38 abstracts (62.3%), among which 32 abstracts (52.3%) had spin in the Results section and 21 (34.4%) had spin in the Conclusions section. A significantly lower presence of spin was found in studies with exact p-value reporting (OR: 0.170; 95% CI: 0.032-0.887; p = .036) and a two-arm comparison design (OR: 11.777; 95% CI: 2.171-63.877; p = .004). The reporting quality of RCT abstracts on splint therapy for TMD is suboptimal and the prevalence of spin is high. More awareness and joint efforts are needed to improve reporting quality and minimize spin.

Efficacy and Safety of Hyaluronic Acid Fillers With or Without Lidocaine in the Treatment of Nasolabial Folds: An Updated Systematic Review and Meta-Analysis.

To update the evidence on the effectiveness and safety of hyaluronic acid gel combined with lidocaine for treating nasolabial folds. We searched electronic databases including PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science using subject headings and keywords associated with hyaluronic acid and lidocaine in the context of nasolabial folds. Inclusion criteria were met by randomized controlled trials (RCTs) comparing the efficacy and safety of hyaluronic acid gel with or without lidocaine. Outcomes measured included visual pain analog scale (VAS) scores, wrinkle severity scale scores, and adverse events. The quality of RCTs was evaluated using the Cochrane Randomized Controlled Trials Scale, which encompasses criteria such as randomization, allocation concealment, blinding, dropout, and withdrawal rates, and was assessed by two independent reviewers. No significant difference in overall wrinkle severity rating scale scores was observed between HA with lidocaine and HA without lidocaine [MD=0.08, 95% CI (-0.09, 0.24), P=0.36]. However, there was a significant reduction in pain scale scores (VAS) [SMD=-2.47, 95% CI (-4.15, -0.79), P=0.004]; no significant differences were noted in the ncidence of at least one adverse event [RR=0.97, 95% CI (0.90, 1.05), P=0.51]; and there were no significant differences in swelling [RR= 0.99, 95% CI (0.92, 1.06), P=0.80], erythema [RR=1.01, 95% CI (0.91, 1.11), P=0.91], bruising [RR=0.99, 95% CI (0.89, 1.13), P=0.86], itching [RR=1.03, the 95% CI (0.88, 1.21), P=0.74], induration [RR=1.04, 95% CI (0.92, 1.17), P=0.55], and papules [RR=0.77, 95% CI (0.58, 1.02), P=0.07]. There was a significantly lower incidence of tenderness [RR=0.91, 95% CI (0.86, 0.97), P=0.002] only in the control group. Sensitivity analysis confirmed the stability of results across all outcome indicators with low sensitivity and high confidence. Subgroup analysis indicated higher wrinkle severity scores among East Asians compared to Europeans and Americans. HA containing lidocaine significantly reduces pain and is comparable in effectiveness and safety of HA without lidocaine. The clinical effects appear more pronounced in East Asians. Due to the limited number of related studies, further research is necessary. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

P-336 Efficacy of Gonadotrophin (GnRH) antagonists for endometriosis-associated pelvic pain - A systematic review and meta-analysis

Abstract Study question Are Gonadotropin-releasing hormone (GnRH) antagonists effective and safe in managing pain associated with endometriosis? Summary answer GnRH antagonists seem effective and safe in managing endometriosis-associated pain for at least 12 weeks of use. There is uncertainty with the evidence. What is known already GnRH agonists are commonly used as effective second-line treatment for endometriosis-associated pain. However, these agonists have drawbacks and are not well-tolerated by many women. GnRH antagonists, offer potential advantages over the agonists while providing similar efficacy. They lack the initial stimulatory effects thereby avoiding the initial flare-up of symptoms, which is common with agonists. Furthermore, unlike agonists, which are mainly available as injections, the antagonist are also available as oral preparations, which allow titration of doses. In-vitro and animal studies have shown antagonists to induce regression of endometriotic lesions by apoptosis. However, their efficacy in relieving endometriosis-related pains remains uncertain. Study design, size, duration Extensive electronic search was conducted by the Cochrane Gynaecology and Fertility group, up to October 2023 to identify randomised controlled trials (RCTs) evaluating efficacy of GnRH antagonists in managing endometriosis-related pains compared with placebo and/or GnRH agonists. The main searched databases included CENTRAL, MEDLINE and EMBASE. Screening and selection of suitable studies were undertaken. Study eligibility criteria included treatment for ≥12 weeks, laparoscopically confirmed endometriosis and assessment of pelvic pain scores as the primary endpoint. Participants/materials, setting, methods Primary end-point was a change in endometriosis-related pain score after 12-week treatment with GnRH antagonists compared with placebo and/or GnRH agonists. Changes in pain and quality of life (QoL) scores and adverse-events of GnRH-antagonists were compared between the antagonist versus the agonist/placebo groups. Data were analysed using RevMan software (V5.4) to calculate the standard mean difference (SMD) for continuous data, and the risk ratios (RRs) with 95% confident intervals (95% CI) for categorical data. Main results and the role of chance Seven eligible RCTs (n = 3043) were included, all of which compared GnRH-antagonist versus placebo, and only three also compared versus GnRH-agonist (leuprorelin). The GnRH-antagonists included ASP1707, Elagolix, Linzagolix and Relugolix. Meta-analysis of overall pelvic pain data from seven RCTs (n = 1684) showed significantly greater reduction in pain scores after 12 weeks of GnRH-antagonist versus placebo at low (SMD -0.29 95%CI -0.39 to -0.19; I2=0) and high doses (SMD-0.53 95%CI -0.63 to -0.43, I2=38%). Similarly, meta-analysis of other pains (dysmenorrhoea, non-menstrual pain, and dyspareunia) showed significantly greater pain score reduction with GnRH-antagonists versus placebo. Meta-analysis of overall pelvic pain from two RCTs (n = 263) comparing GnRH-antagonist versus leuprorelin showed comparable reduction in pain scores after 12 weeks at low (SMD 0.33 95%CI 0.09 to 0.58, I2=44%) and high doses (SMD 0.06 95%CI -0.19 to 0.30, I2=0%). Similarly, meta-analysis of other forms of pain revealed comparable reductions of pain scores between both drugs. Meta-analysis of QoL data (2RCTs, n = 259) revealed significantly greater improvements in scores with leuprorelin versus antagonists at low (SMD 0.74 95% CI 0.46 to 1.01; I2=98%) and high doses (SMD 0.35, 95%CI, 0.09 to 0.60, I2=97%). The most frequently reported treatment-related side-effects were hot-flushes, headaches and nasopharyngitis. No life-threatening side-effects were reported. Limitations, reasons for caution There was high heterogeneity between studies (e.g. differences in antagonists and pain scoring systems). No information was provided on prior endometriosis surgery, which is a confounding factor. Additionally, declared COI by authors of all trials could introduce high risk of bias. Evidence certainty was therefore deemed low to very low. Wider implications of the findings GnRH-antagonists seem to offer a promising treatment for endometriosis-related pain, with comparable efficacy to the agonists, but with several potential advantages. However, given the low quality and uncertainty of the evidence in this meta-analysis, high quality RCTs with robust designs are needed before making any firm recommendations for clinical practice. Trial registration number not applicable

Modified Atkins Diet in Adolescents and Adults with Drug Resistant Epilepsy: A Systematic Review and Meta-Analysis.

Epilepsy is one of the common neurological diseases which affects 65-70 million people worldwide. Modified Atkins diet (MAD) as a therapy is used as one of the treatments to reduce the seizures occurrence in epileptic patients. The purpose of this purpose is to review all evidence regarding the efficacy of the MAD from randomized controlled trials (RCTs) in adolescents and adults with drug resistant epilepsy (DRE). The total of three databases were searched (PubMed, Embase, and Cochrane Library) till 31 January 2023. Only RCTs with MAD as a one of the treatment arms were included in meta-analysis. The proportion of reduction of seizures in patients with epilepsy and relative risk to identify the relationship between MAD (as risk) to decrease the epileptic seizure was used as outcomes. The Jadad score with three domains was used to estimate the quality of RCTs included for meta-analysis. Only three RCTs were included following the stringent inclusion criteria in current meta-analysis. The pooled proportion from 142 patients going through MAD therapy shows the reduction in epileptic seizure ≥50%, by the random effect model was 0.23 (95% confidence interval [CI], 0.10 to 0.37). Our meta-analysis underlines a significant efficacy of MAD compared to the control group in seizure reduction ≥50%, The pooled relative risk was 6.47 (95% CI, 1.60 to 26.14; p-value <0.05). MAD therapy was efficacious and had better compliance for seizure reduction in subjects with DRE.

Durable effects of acupuncture for tension-type headache: A systematic review and meta-analysis

BackgroundAcupuncture may be effective in treating tension-type headache (TTH). The durability of its effects after treatment completion remains inconclusive. MethodsWe searched multiple databases and references from previous reviews for randomized controlled trials (RCTs) which investigated the effectiveness of acupuncture for TTH. We assessed the methodological quality of RCTs using the Cochrane Risk of Bias 2.0 (RoB 2) tool. Primary outcome was response rate, defined as the proportion of participants who reported at least a 50% reduction in monthly headache days from baseline after completion of treatment. Secondary outcomes included headache days, headache intensity, and analgesic use. Safety outcomes were also evaluated. ResultsA total of seven RCTs involving 3,221 participants with frequent episodic and chronic TTH were included. Individuals receiving acupuncture reported a significantly higher response rate versus sham acupuncture (SA) immediately and at 1–6 months after completion of treatment (P<0.05). Compared with SA, post-treatment results of headache days and headache intensity appeared consistent on the whole, showing associations favoring acupuncture. However, no significant reduction in analgesic use was found post-treatment. Acupuncture showed no superiority over physical training or relaxation training in headache days and headache intensity. Moreover, no serious adverse events associated with acupuncture were reported. ConclusionLimited evidence suggested that acupuncture might provide durable post-treatment effects in the management of frequent episodic and chronic TTH for up to 6 months compared with SA,with no severe treatment-related adverse events reported.

#2564 Terlipressin given by continuous infusion versus boluses in the treatment of hepatorenal syndrome: a systematic review and meta-analysis

Abstract Background and Aims Hepatorenal syndrome (HRS) is one of the complications among patients with cirrhosis. Available guidelines recommended terlipressin with albumin as part of HRS management. To date there is no consensus on whether terlipressin should be given via bolus or continuous intravenous infusion. This study aims to compare the effectiveness and safety of continuous intravenous infusion versus intravenous boluses of terlipressin in the treatment of patients with HRS and cirrhosis. Method A comprehensive search for databases of randomized controlled trials (RCTs) comparing continuous intravenous infusion versus intravenous boluses of terlipressin among adult patients with hepatorenal syndrome was done. PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were searched using relevant terms including hepatorenal syndrome, acute kidney injury, cirrhosis, terlipressin, bolus, and continuous infusion until December 2023. Response to therapy defined as decrease in serum creatinine or regression of acute kidney injury was the primary outcome of interest, while safety in terms of drug-related events, mortality, and transplant-free survival were the secondary outcomes. Data extraction was performed using a standardized data form. The reviewers independently screened the studies and assessed the methodological quality using the Cochrane Risk of Bias tool and any discrepancies were resolved by consensus among the authors. Random-effects meta-analysis was done using Review Manager 5.4. Results A total of three studies, one high quality and two moderate quality RCTs, were included in the review, involving a total of 240 patients. Pooled analysis showed that continuous infusion was as effective or better than bolus infusion in achieving the primary outcome (RR 1.12, 95% CI 0.95-1.32, I2 = 0%). In one study, 28- and 90-day mortality were not significantly different, while 90-day transplant-free survival was not significantly different between continuous and bolus groups from another trial (53% vs 69% p = 0.26). Higher incidence of adverse events were also reported in the bolus group, RR 0.37, 95% CI 0.13-1.04 (p = 0.06). Conclusion There is limited evidence to suggest that continuous infusion of terlipressin may demonstrate resolution of acute kidney injury more frequently than bolus infusion, and that continuous infusion is associated with decreased adverse events. Larger randomized controlled trials with higher quality are needed to ascertain the effects on mortality, need for renal replacement therapy, and transplant-free survival.

Regulatory patterns of Chinese patent medicine for lipid metabolism disorders in patients with type 2 diabetes mellitus complicated by ischemic stroke: A systematic review and network meta-analysis.

To investigate the regulatory patterns of Chinese patent medicine (CPM) interventions on lipid metabolism disorders in patients with type 2 diabetes mellitus (T2DM) complicated by ischemic stroke. Two researchers independently searched 8 major databases and created a comprehensive database containing all randomized controlled trials (RCTs) that investigated the application of "blood-activating and stasis-removing" CPM in the treatment of stroke combined with T2DM until October 1, 2022. The collected data were compiled and organized in Excel. Quality assessment was performed using the Cochrane 5.3 bias risk assessment tool, and the network meta-analysis was conducted using R software. A total of 12 articles were included in the final analysis, covering 4 types of CPM: Naoxintong Capsules (NXT), Tongmai Jiangtang Capsules, Tongxinluo Capsules (TXL), and Yindan Xinnaotong Soft Capsules. Among these, CPM formulations containing herbs with blood-activating and stasis-removing properties were the most commonly used. The results of the network meta-analysis are as follows: (1) the combination of 3 CPM formulations showed superior efficacy in improving total cholesterol levels compared to conventional Western medicine treatment (CT). In particular, Yindan Xinnaotong Soft Capsules + CT (surface under the cumulative ranking curve [SUCRA] = 97.24%) demonstrated the highest efficacy, followed by NXT + CT (SUCRA = 66.23%), and then TXL + CT (SUCRA = 55.16%). (2) TXL + CT treatment exhibited the most promising efficacy in improving triglyceride levels (P < .05), while the effects of the other 3 CPM formulations were not statistically significant. (3) In terms of improving low-density lipoprotein levels, NXT + CT (SUCRA = 82.27%) showed better efficacy than TXL + CT (SUCRA = 73.99%), while the effects of the other 2 CPM formulations were not statistically significant. (4) The combination of CPM formulations and CT resulted in a lower incidence of adverse reactions compared to CT (P < .05). The treatment of patients with T2DM complicated by ischemic stroke commonly involved the use of "blood-activating and stasis-removing" herbal medicines. These herbal medicines have shown effectiveness in regulating patients' blood lipid levels. However, it is crucial to acknowledge that the analysis was influenced by variations in the number and quality of RCTs involving different CPM formulations. Therefore, additional validation through large-scale, high-quality RCT studies is required.

Milestones in Surgical Complication Reporting – Twenty years of Clavien-Dindo Classification &amp; ten years of Comprehensive Complication Index (CCI®)

Abstract Background Standardized outcome reporting is key for proper assessment of surgical procedures. A recent consensus conference recommended the Clavien-Dindo classification (CDC) and the Comprehensive Complication Index (CCI®) for assessing postoperative morbidity. However, their use in randomized controlled trials (RCTs) has not been assessed, and several challenging scenarios for grading complications require consensus-based guidance. Aims The aim of this study was to assess the use of the CDC and CCI® in RCTs and to provide guidance on their standardized and consistent application. Methods We identified all RCTs that used the CDC or CCI® as a primary or secondary outcome. In addition, we asked 163 international surgeons to independently grade complications of 20 clinical cases covering seven challenging scenarios. Finally, a core group of five experts used this information do develop consistent recommendations. Results Up to July 2023, 1424 RCTs used the CDC or CCI® to assess postoperative morbidity. Annual use was steadily increasing with now over 200 new RCTs per year. Eighty-nine (55%) surgeons completed the survey. Complications requiring multiple interventions, complications of complications, complications occurring prior to referral, and expected and unrelated complications should all be counted as separate complications and included in the CCI®. Invasive diagnostics without findings should not be considered as a complication since purely diagnostic. Conclusion We observed an extensive and steadily increasing use of CDC and CCI® in RCTs, highlighting the importance of their consistent application. Provided by the original developers of the CDC and CCI® and based on an international survey of their frequent users, the current consensus offers much-needed guidance for challenging scenarios. This will further improve the consistency and accuracy of complication reporting, leading to higher quality RCTs, improved cost estimations, and better quality control, ultimately benefiting all stakeholders.