Randomized Controlled Trials Research Articles

The effectiveness and safety of botulinum toxin injections for managing motor disorders of patients with Parkinson's disease: A meta-analysis of randomized controlled trials.

This study aimed to assess the effectiveness and safety of botulinum toxin (BTX) injections for managing motor disorders in patients with Parkinson's disease (PD). An electronic search was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data from available randomized controlled trials (RCTs) assessing BTX injections for motor disorders in PD patients were extracted for meta-analysis. Ultimately, 215 patients from eight RCTs were enrolled. Pooled analyses indicated that BTX was more effective than placebo in improving tremor (standardized mean difference [SMD] = 0.96, 95% CI [0.34, 1.58], p < 0.01), whereas no notable differences were observed between BTX and placebo regarding freezing of gait (SMD = 0.66, 95% CI [-0.26, 1.58], p = 0.162), United Parkinson's Disease Rate Scale (UPDRS) III score (SMD = -0.20, 95% CI [-1.17, 0.76], p = 0.68) and clinical global impression (CGI) score (SMD = 0.84, 95% CI [-0.74, 2.42], p = 0.298). Adverse events related to BTX injections were comparable to placebo (OR = 1.74, 95% CI [0.59, 5.14], p = 0.32). The current evidence suggests that BTX is effective and safe in treating PD tremor but fails to provide therapeutic benefits for freezing of gait and motor functional scores in PD patients. Furthermore, the limited number of included studies and heterogeneity in BTX intervention protocols suggest more research is needed, with additional standardized RCTs, to better understand and optimize BTX injections for motor disorders in PD.

A systematic review and meta-analysis of the effectiveness of interventions targeting the parent-child relationship in families of children with an intellectual disability.

The review aimed to investigate the effectiveness of parent-child relationship interventions for families of children with intellectual disability up to 12 years old. Quasi-experimental or randomised controlled trials (RCTs) of interventions targeting the parent-child relationship where ≥50% of children had an intellectual disability were included. Meta-analyses of parent-child relationship outcomes and child outcomes used standardised mean difference as the effect size. Twenty-seven papers were included (N = 1325). Parent-child relationship outcomes improved significantly (n = 1325; g = 1.08, 95% CI: 0.64, 1.52) with a large effect size that was robust to sensitivity analyses. Child developmental outcomes improved significantly (n = 1082; g = 0.65, 95% CI: 0.23, 1.07), and indicated a large effect size for child socialisation and communication. Findings suggest that interventions targeting parent-child relationship quality are associated with substantial improvements in parent-child relationship and may improve child outcomes related to socialisation and communication.

Enhanced recovery after surgery for hip and knee arthroplasty: A systematic review and meta-analysis on randomized control trials

ObjectivesThis review aimed to compare the efficacy and safety of enhanced recovery after surgery (ERAS) versus traditional care in patients who underwent total hip arthroplasty (THA) and total knee arthroplasty (TKA). MethodsAll randomized controlled trials (RCTs) were acquired via a comprehensive search of multiple databases. A meta-analysis was performed using Cochrane Collaboration's RevMan 5.4 software to calculate effect sizes. ResultsThis meta-analysis included 850 patients in the ERAS group and 845 patients in the control group (patients who received traditional care). The outcomes suggested no significant difference in operative time, intraoperative blood loss, visual analogue scale, 30-day readmission rate, and mortality rate between the two groups. However, the ERAS group was associated with a significant decrease in transfusion rate, hospital length of stay, and postoperative complications. Moreover, the ERAS group had higher Hospital for Special Surgery scores and satisfaction rates. ConclusionsPatients who underwent THA and TKA would benefit more from ERAS than traditional care.

Comparison of the Efficacy of Cephalosporins and Non-cephalosporins in Preventing Surgical Site Infections in Colorectal Surgery Patients: An Updated Systematic Review and Meta-Analysis.

This study aims to compare the efficacy of cephalosporin and non-cephalosporin antibiotics in preventing surgical site infections (SSIs) in patients undergoing colorectal surgery, providing a scientific basis for the selection of perioperative antibiotics through systematic review and meta-analysis. Adhering to the PRISMA guidelines, this research employed an extensive literature search strategy across multiple databases to identify relevant studies, including randomized controlled trials (RCTs) and observational studies. Inclusion criteria were studies on adults undergoing colorectal surgery who received preoperative prophylaxis with either cephalosporin or non-cephalosporin antibiotics. Exclusion criteria included preoperative diagnosis of infectious diseases and preoperative use of antimicrobial agents. Meta-analysis was conducted using RevMan 5.3 software to assess the effectiveness of both antibiotic classes in preventing SSIs, including subgroup analyses. Eight studies met the inclusion criteria, comprising 872 patients. Meta-analysis revealed that the incidence of SSI in the cephalosporin group was lower than in the non-cephalosporin group (14.8% vs 25.1%), with statistical significance (OR = 1.94, 95% CI: 1.38-2.74, PP = =0.0001). However, no significant difference in SSI risk was observed between the groups within 30days (OR = =1.92, 95% CI: 1.08-3.42). Subgroup analysis indicated that higher-quality studies were associated with larger effect sizes. This study suggests that cephalosporin antibiotics may be superior to non-cephalosporins in preventing SSIs following colorectal surgery, especially in the short term. However, their long-term efficacy in SSI prevention may be similar. The selection of perioperative antibiotics should consider factors such as the antimicrobial spectrum, pharmacokinetic properties, and bacterial resistance.

In Vivo Imaging Techniques for the Human Scalp: A Systematic Review of the Literature.

Scalp inflammation and alopecia are distressing conditions for which patients regularly present to dermatology. Although some diagnoses can be made clinically, others require biopsy, which carries the risk of pain, infection, bleeding, and scarring. This review examines the existing literature regarding noninvasive in vivo imaging techniques and their evidence and utility in evaluating scalp pathology, with a focus on the diagnostics of hair conditions. A systematic literature search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines without timeframe restrictions. The PubMed and Clarivate (Web of Science) databases were searched using the terms ("imaging" OR "in-vivo imaging" OR "non-invasive imaging" OR "non-invasive in vivo imaging" "imaging," "in-vivo imaging) AND ("human scalp disorders" OR "scalp" OR "hair loss" OR "alopecia"). Peer-reviewed randomized control trials (RCTs), prospective studies, retrospective studies, and case series or reports discussing in vivo imaging of the scalp published before 2022 were selected. Forty-two studies were included and discussed; modalities included laser devices (n = 27), ultrasound (US) (n = 13), infrared thermography (n = 1), skin capacitance imaging (SCI), and ultraviolet light-enhanced visualization (ULEV) (n = 1). The most common laser devices used were reflectance confocal microscopy (RCM), multiphoton microscopy (MPM), and optical coherence tomography (OCT). US techniques included high-frequency US (HFUS) and US biomicroscopy (UBM). Quality imaging of the scalp in the setting of alopecic, neoplastic, and inflammatory diseases is highly sought after. Many of these noninvasive imaging techniques show promise, each with individual advantages and disadvantages in imaging-specific conditions. Ultimately, noninvasive imaging techniques may be used to optimize patient management and minimize morbidity associated with scalp biopsies.

Chronic Non-bacterial Osteomyelitis (CNO) In Childhood: A Review.

Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone disorder mostly affecting children and adolescents. Although it is considered a rare disease, CNO is likely to be the single most common autoinflammatory bone disease in childhood, underdiagnosed and underreported due to a lack of awareness of the condition in both medics and patients and the absence of validated diagnostic criteria. The exact underlying pathogenesis of CNO remains unknown, making targeted treatment difficult. This issue is exacerbated by the lack of any randomised control trials, meaning that treatment strategies are based solely on retrospective reviews and case series. This review summarises the current concepts in pathophysiology, the clinical features that help differentiate important differential diagnoses, and an approach to investigating and managing children with CNO. Ultimately, the timely and thorough investigation of children and young people with CNO is vitally important to exclude important mimics and initiate appropriate management that can prevent the complications of persistent inflammatory bone disease.

Neuroplasticity Alterations Induced by Isotretinoin use in RARA Gene Polymorphism is Associated with Increased Risk of Depression and Suicidal Ideation in Patients with Vitamin D Deficiency: A Systematic Review and Meta-Analysis

Rationale: Isotretinoin is widely used for severe acne treatment, but concerns have emerged regarding its potential association with depression and suicidal ideation. Previous studies have produced mixed findings, necessitating a comprehensive evaluation of the evidence. This systematic review and meta-analysis aim to clarify the association between isotretinoin use and the onset of depression or suicidal ideation, focusing on genetic predispositions, particularly in patients with vitamin D deficiency. Objectives: This review assesses the risk of depression and suicidal ideation in patients treated with isotretinoin for severe acne compared to those not using isotretinoin. A secondary focus is placed on identifying specific genetic factors, such as polymorphisms in the RARA and LEP genes, that may predispose patients to these psychiatric side effects. Eligibility Criteria: Randomized controlled trials (RCTs), cohort studies, and case-control studies comparing isotretinoin users to non-users were included. Exclusion criteria included studies that lacked a comparator group or did not report psychiatric outcomes (depression or suicidal ideation). Outcomes: The primary outcome was the incidence of depression or suicidal ideation among isotretinoin users compared to non-users. Secondary outcomes examined the influence of genetic polymorphisms, specifically in the RARA and LEP genes, on the risk of developing psychiatric side effects. Risk of Bias: Risk of bias was assessed using the Cochrane Risk of Bias tool for randomized trials and the Newcastle-Ottawa Scale for observational studies. The overall quality of the included studies was moderate to high. Synthesis Methods: A random-effects meta-analysis was performed to pool odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity was assessed using the I² statistic, and sensitivity analyses were conducted to ensure the robustness of the findings. Included Studies: Fifteen studies were included, comprising 3 randomized controlled trials, 7 cohort studies, and 5 case-control studies, with a total of 8,000 isotretinoin users and 10,000 non-users. The studies were conducted in diverse clinical settings with a follow-up range of 6 months to 5 years. Synthesis of Results: The pooled analysis demonstrated a significant association between isotretinoin use and an increased risk of depression (OR: 1.3, 95% CI: 1.1–1.5, p &lt; 0.05). Specific genetic polymorphisms, particularly in the RARA and LEP genes, were identified as potential risk factors for developing depression among isotretinoin users, particularly in patients with concurrent vitamin D deficiency. Conclusions: Isotretinoin use is associated with an increased risk of depression, particularly in individuals with specific genetic polymorphisms such as RARA and LEP. Clinicians should consider conduct precision medicine genetic testing testing for these polymorphisms before initiating isotretinoin treatment and closely monitor patients for psychiatric alterations, mood changes, especially those with with vitamin D deficiency or genetic predisposition to depression

The role of metformin in modulating cardiometabolic risk in obese pediatric populations with metabolic syndrome: A systematic review

Introduction: Obesity significantly increases the risk of developing cardiometabolic complications, which are precursors to cardiovascular diseases (CVD). In children and adolescents, metabolic dysfunctions such as insulin resistance, dyslipidemia, and hypertension are key contributors to early-onset cardiovascular risk. Metformin, a well-established antidiabetic agent, has shown potential benefits in addressing these metabolic imbalances. However, the long-term impact of metformin on cardiovascular outcomes in obese pediatric patients remains unclear. Aim: This systematic review aims to evaluate the effect of metformin on cardiometabolic parameters in obese children and adolescents with metabolic syndrome, focusing on insulin sensitivity, body mass index (BMI), blood pressure, and lipid profiles. Methods: A systematic review was conducted by searching databases including PubMed, Cochrane Library, Embase, and Web of Science. The inclusion criteria targeted randomized controlled trials (RCTs), cohort studies, systematic reviews, and meta-analyses published between 2004 and 2024. Pediatric patients aged 6-18 years with obesity and metabolic syndrome were included. The primary outcomes assessed were BMI, insulin sensitivity, lipid profiles, blood pressure, and cardiovascular outcomes. Results: A total of 23 studies, including 10 RCTs and 1 meta-analysis, were reviewed, involving 777 patients. Metformin demonstrated consistent improvements in insulin sensitivity and BMI in obese children and adolescents. Several studies reported modest reductions in BMI, improved insulin resistance, and better lipid profiles. However, variability in results was observed regarding long-term cardiovascular outcomes. While metformin reduced systolic blood pressure and carotid intimal-medial thickness (CIMT), the long-term impact on preventing major cardiovascular events remained inconclusive. Discussion: Metformin’s benefits on cardiometabolic risk factors in obese children are primarily attributed to its effects on insulin sensitivity, lipid metabolism, and inflammatory pathways. Its ability to activate AMP-activated protein kinase (AMPK) leads to improved metabolic profiles and reduced inflammation and is crucial for mitigating obesity-related cardiovascular risks. Despite these positive effects, the evidence for long-term prevention of cardiovascular events is limited and requires further exploration. Conclusions: Metformin offers significant short-term benefits in improving BMI, insulin sensitivity, and cardiometabolic parameters in obese children and adolescents. However, its long-term efficacy in preventing cardiovascular events remains uncertain. Further studies are necessary to establish its role in long-term cardiovascular protection in pediatric populations

Effects of two non-drug interventions on pain and anxiety in the nursing process of burn patients: a literature review with meta-analysis

BackgroundBurns are a global health issue causing significant mortality and high medical costs. Non-pharmacological interventions such as music therapy and virtual reality (VR) therapy have shown potential in alleviating pain and anxiety in burn patients. This study systematically evaluates the impact of these interventions using a network meta-analysis.MethodsA systematic review and network meta-analysis were conducted according to PRISMA 2020 guidelines and registered in PROSPERO (CRD42024566536). Searches in PubMed, Cochrane Library, Web of Science, and Embase up to November 22, 2023, identified randomized controlled trials (RCTs) involving music therapy or VR therapy in burn patients. The Cochrane Risk of Bias Tool (2.0) assessed study quality. Data were analyzed using StataMP-64 software.ResultsSeventeen RCTs with 1,119 burn patients were included. Both music therapy and VR therapy significantly reduced pain and anxiety compared to control groups. Music therapy was more effective for pain reduction (SUCRA: 85.4%), while VR therapy was superior for anxiety relief (SUCRA: 79.5%).ConclusionMusic therapy and VR therapy effectively reduce pain and anxiety in burn patients. Integrating these interventions into burn care can enhance patient outcomes. Further research is needed to confirm these findings and optimize individualized treatment plans.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, PROSPERO (CRD42024566536).

Sodium-glucose cotransporter-2 inhibitors in acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trials.

We aimed to assess the efficacy and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus placebo, initiated within the hospitalization period, in addition to habitual treatment, for treating adult patients with confirmed acute myocardial infarction (AMI). We also conducted subgroup analysis by diabetes mellitus (DM) status and type of AMI. We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs). The primary outcome was hospitalization for heart failure (HF). The secondary outcomes were all-cause death, cardiovascular death, and serious adverse events (AEs). We pooled risk ratios (RR) with a 95% confidence interval (CI) for binary outcomes. The between-study variance was assessed using tau2 statistics. We included five RCTs, encompassing 11,211 patients. SGLT2i significantly reduced the risk of hospitalization for HF compared to placebo (RR 0.73; 95% CI [0.61, 0.88]). However, the risk of all-cause death (RR 1.05; 95% CI [0.78, 1.41]) and cardiovascular death (RR 1.04; 95% CI [0.84, 1.29]) was similar between the groups, as well as the risk of serious AEs (RR 1.01; 95% CI [0.90, 1.14]). In the subgroup analysis by DM status and type of AMI, there were no significant subgroup differences for the outcomes of hospitalization for HF and all-cause death. In patients with AMI, treatment with SGLT2i is safe and significantly reduces the risk of hospitalization for HF, but it has no impact on all-cause death and cardiovascular death compared to placebo.

Effectiveness of long-acting buprenorphine - A systematic review.

To analyse the evidence of the effectiveness of long-acting injection buprenorphine (LAI-B) in the management of opioid use disorder (OUD). Databases were searched for studies reporting on the effectiveness of LAI-B for the treatment of OUD. Risk of bias was assessed, and a narrative synthesis of data was presented. The study adhered to PRISMA guidelines and was registered with PROSPERO (CRD42023396033). Eighteen studies were included in the final review: two double-blind randomised control trials, two open-label randomised control trials, two retrospective cohort studies, one non-controlled pilot study, and eleven observational studies. In comparative trials, LAI-B was superior to placebo and superior or non-inferior to treatment as usual. LAI-B was positively associated with improvements in abstinence rates and patient-centred outcomes. There was limited data on the long-term effects of continuous LAI-B prescription. LAI-B is an effective treatment for OUD with advantages over existing forms of treatment. Patients reported high levels of medication satisfaction and there were no significant safety concerns. This review highlights the need for future research on long-term effectiveness outcomes, with participants of more varied demographics and psychiatric comorbidity, which is more reflective of the OUD population seen in community clinical settings.

Comparison of interrupted and uninterrupted anticoagulation strategies for cardiac implantable electronic device insertion: a systematic review and meta-analysis

Abstract Introduction Up to 35% of patients who are candidates for a cardiac implantable electronic device (CIED) receive chronic anticoagulation. However, guidelines on anticoagulant management in the perioperative period of CIED insertion differ worldwide. It is uncertain whether interrupting or continuing anticoagulation in these settings provides optimal outcomes. Purpose To assess the effects of interrupting versus continuing chronic anticoagulation with either warfarin or a direct oral anticoagulant (DOAC) in the perioperative setting of CIED insertion. Methods CENTRAL, MEDLINE, Embase, Web of Science, and two trial registries were searched from inception to 26 November 2021. Randomised controlled trials (RCTs) assessing interrupting chronic warfarin or DOAC therapy, with or without heparin bridging, versus continuing anticoagulation in adults undergoing CIED insertion were included. Comparisons were divided into two categories: interrupted versus uninterrupted warfarin and interrupted versus uninterrupted DOAC. Outcomes were expressed as risk ratios (RR) with 95% confidence intervals (95%CI). Inverse variance random-effects models were used for the meta-analyses. Risk of bias (RoB) was assessed using the Cochrane RoB2 tool, and certainty of evidence (CoE) per outcome was assessed with GRADE methods. Results Ten RCTs (n=2221) were included: five RCTs (n=1267) used warfarin; four RCTs (n=954) used DOACs. One additional RCT using warfarin was ongoing without any outcome data available. Bleeding events included device-pocket haematoma, haemothorax, cardiac tamponade, and non-tamponade pericardial effusion. Interrupted versus uninterrupted warfarin: The evidence is very uncertain on the effect of interrupted warfarin on device-pocket haematoma (RR 1.89, 95%CI 0.85 to 4.20, 5 RCTs, very low CoE) and bleeding events (RR 1.94, 95%CI 0.86 to 4.41, 5 RCTs, very low CoE). Interrupted warfarin may result in little to no difference in thromboembolic events (RR 0.85, 95%CI 0.18 to 4.11, 5 RCTs, low CoE) and ischaemic stroke (RR 1.01, 95%CI 0.11 to 9.61, 2 RCTs, low CoE). Interrupted warfarin may reduce all-cause mortality (RR 0.35, 95%CI 0.04 to 2.93, 3 RCTs, low CoE). Interrupted versus uninterrupted DOAC: The evidence is very uncertain on the effect of interrupted DOAC on device-pocket haematoma (RR 1.15, 95%CI 0.58 to 2.28, 4 RCTs, very low CoE) and bleeding events (RR 1.14, 95%CI 0.58 to 2.21, 4 RCTs, very low CoE). Interrupted DOAC may result in little to no difference in thromboembolic events (RR 0.98, 95%CI 0.06 to 15.63, 3 RCT, low CoE) and ischaemic stroke (RR 0.98, 95%CI 0.06 to 15.63, 2 RCTs, low CoE). Interrupted DOAC may reduce all-cause mortality slightly (RR 0.49, 95% CI 0.04 to 5.39, 2 RCTs, low CoE). Conclusion Interrupting anticoagulation with either warfarin or DOACs in patients undergoing CIED insertion produced similar outcomes as uninterrupted anticoagulation.Figure 1.Figure 2.

Sub-Saharan Africa's contribution to clinical trials in international acute coronary syndromes and heart failure guidelines

Abstract Introduction There is a growing burden of acute coronary syndrome (ACS) and heart failure (HF) in sub-Saharan Africa (SSA), yet outcomes remain poor compared to high-income countries (HICs). Global clinical guidelines are pivotal to the delivery of evidence based cardiovascular care, however their applicability to populations in SSA remains unclear. Purpose To evaluate the extent to which populations from SSA contribute to pharmacotherapeutic randomised clinical trials informing international ACS and HF clinical guidelines. Methods We extracted details on pharmacotherapeutic randomised control trials (RCTs) contributing to Class I or II guideline recommendations from the 2023 European Society of Cardiology (ESC) guidelines for ACS and the 2021 ESC guidelines for HF. Data on RCTs contributing to these guidelines were extracted from the ClinicalTrials.gov or published articles. We analysed the proportion of RCTs which had a contribution from countries in each World Bank income group. Then we specifically assessed the contribution of SSA countries to clinical trials and analysed temporal trends. Results Of 119 RCTs from the ESC HF guidelines and the 343 pharmacotherapy RCTs from the ESC ASC guidelines 75.9% were exclusively conducted in high-income countries, 22.2% of the trials included at least one site from a middle-income country and none included sites from a low-income country (figure 1). The global distribution of HF (figure 2a) and ACS (figure 2b) pharmacotherapy guidelines is demonstrated in figure 2. The only country represented from SSA was South Africa which is an upper middle-income country. A site from South Africa was included in 17 (14.2%) HF RCTs and 28 (8.2%) ACS RCTs. There has been a significant increase in the proportion HF RCTs conducted in SSA, increasing from 2.6% between 1990 and 1999 to 50% since 2020 (OR 28.8, 95% CI 2.6 – 983.4, p-value for trend&amp;lt; 0.0001). For ACS RCTs, the proportion of trials conducted in SSA increased from 1.8% pre 1990 to 23.4% during 2000-2009 (OR 15.9, 95% CI 4.2 - 112.9, p value for trend = 0.003) then declined to 11.3% from 2010-2019. Conclusions There is a marked under-representation of SSA countries in ACS and HF pharmacotherapy RCTs, despite the region's escalating cardiovascular disease burden. South Africa is the sole contributor from the region, with all other SSA countries absent. This finding could potentially affect the applicability and generalisability of global guidelines to populations in SSA with distinct clinical presentations and healthcare challenges.Figure 1 Figure 2

Impact of selective reporting bias on stroke trials: potential compromise in evidence synthesis - A cross-sectional study

BackgroundAccurate reporting of outcomes is crucial for interpreting the results of randomized controlled trials (RCTs). However, selectively reporting outcomes in publications to achieve researchers’ anticipated results still occurs frequently. This study aims to investigate the prevalence of selective reporting of outcomes in RCTs on treating acute ischemic stroke (AIS), identify factors contributing to this issue, and assess its potential impact on the degree and direction of intervention effect.MethodsA search was conducted in MEDLINE, Embase, and the Cochrane Library to collect interventional RCTs on AIS published from 2020 to 2022. Full texts of RCTs were reviewed, and only those reporting International Clinical Trials Registry Platform primary registry numbers were included. Registration information of the RCTs was extracted from the registry platforms and compared with the publications’ details to assess the selective reporting of outcomes. Bayesian multilevel logistic regression was used to analyze the reasons behind selective reporting.ResultsAmong the total of 159 AIS RCTs identified, 82 (51.6%) were ultimately included, as they reported registration numbers, which encompassed 819 outcomes. Among them, 72 RCTs (87.8%) and 497 outcomes (60.7%) exhibited selective reporting. Omission-type selective reporting (downgrading, omitting, or ambiguously reporting) accounted for 36.4%, while addition-type selective reporting (upgrading, adding, or altering the measurement scope of outcomes) comprised 63.6%. Omission-type selective reporting correlated with negative results (OR: 7.39; 95% CI: 4.08—13.44), whereas addition-type selective reporting correlated with positive results (OR: 2.07; 95% CI: 1.34—3.26) and publication in journals that are not in the top quartile of the Journal Citation Reports (OR: 2.48; 95% CI: 1.15—5.38).ConclusionsRegistered interventional AIS RCTs still face significant issues regarding selective reporting of outcomes. Therefore, it is necessary to further evaluate the influence of selective reporting bias on the positive results obtained from individual AIS RCTs and the systematic reviews based on these RCTs.

Unlocking equity: assessing for gaps in cardiovascular guidelines for pregnant women

Abstract Introduction Cardiovascular disease is the primary contributor to pregnancy-related fatalities in the United States, displaying a gradual rise over the years. Pregnancy introduces unique physiological changes that can impact pre-existing cardiovascular conditions and trigger new complications. Considerable inequalities in pregnancy-related mortality built on race and ethnicity are unmistakable, with the highest rates observed in black non-Hispanic women. Purpose This study aims to evaluate current gaps in racial/ethnic minority participation in randomized control trials (RCTs) cited in major cardiology guidelines. Methods Citations in the 2018 ESC Guidelines for the Management of Cardiovascular Diseases During Pregnancy were evaluated for RCTs. The American Heart Association and American College of Cardiology guidelines were also examined. Manuscripts and supplementary data were examined for participant-level racial or ethnic data, including age, race, and ethnicity. Results Thirteen RCTs, representing 20,665 participants, spanning the period from 2002 to 2017, were reviewed. European guidelines referenced thirteen of the RCTS, while American guidelines referenced two RCTs. The average age of participants was 31 years old. Most of the trials were conducted in Europe (46%). Forty-six percent of RCTs reported race/ethnicity breakdowns, with pooled participation showing a majority of non-Hispanic white participants (76.7%), with limited representation from other racial groups (table). Eight trials focused on hypertension, two on venous thromboembolism, and one on heart failure. Conclusion Pregnant women are frequently excluded from RCTs due to concerns about potential harm to the developing fetus. Consequently, current guidelines lack robust RCTs tailored to pregnant women with various cardiovascular diseases. The underrepresentation of ethnic minorities in cardiovascular disease trials contributes to a scarcity of evidence-based recommendations for managing these conditions during pregnancy and postpartum. Future clinical practice guidelines should advocate for a more personalized and evidence-based approach to managing cardiovascular diseases in pregnancy.

Remote monitoring of implantable cardioverter defibrillators: a systematic review and meta-analysis of randomised controlled trials

Abstract Background Remote monitoring (RM) of implantable cardioverter defibrillators (ICD) has been widely adopted as the standard follow-up strategy [1]. Observational data [2,3] has suggested morbidity and mortality reduction associated with RM compared to traditional in-person ICD follow-up, however, randomised controlled trials (RCTs) demonstrate heterogeneous results. Purpose To assess the impact of RM of ICDs on morbidity and mortality through a systematic review and meta-analysis of RCTs comparing RM versus in-person follow-up. Methods PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and reference lists were searched for RCTs evaluating RM compared to in-person follow-up of patients with ICDs or cardiac resynchronisation therapy with defibrillator (CRT-D) devices. Meta-analyses of all-cause mortality, cardiovascular (CVD) hospitalisation and inappropriate ICD shock rates were performed. Results Literature search identified 1011 relevant publications, out of which 15 RCTs [4-18] involving a total of 7579 patients (13 RCTs reporting mortality rate, 7 RCTs reporting CVD hospitalisation rate, 6 RCTs reporting inappropriate ICD shock rate) met the inclusion criteria. Pooled analyses demonstrated that RM is not associated with a significant reduction in all-cause mortality (OR 0.95; 95% CI 0.78-1.16; p=0.60)(Figure 1, panel a) or odds of CVD hospitalisation (OR 0.95; 95% CI 0.72-1.25; p=0.70) (Figure 1, panel b). RM was, however, shown to be associated with significantly lower odds of receiving an inappropriate ICD shock compared to the control group (OR 0.63; 95% CI 0.46-0.88; p=0.006) (Figure 1, panel c). The IN-TIME study (the only RCT that independently reached statistical significance in terms of RM effect on mortality) enrolled patients exclusively with a Biotronik ICD or CRT-D; this raised the question as to whether the choice of vendor had an impact on mortality. Our subgroup analysis of the Biotronik device studies demonstrated that there was no significant all-cause mortality benefit (OR 0.87, 95% CI 0.59-1.27; p=0.46). Conclusions This meta-analysis of 15 RCTs including 7579 patients suggests that RM of ICDs is associated with a reduction in inappropriate ICD shocks, without a significant reduction in mortality or CVD hospitalisation when compared to in-person follow-up. Further studies comparing different RM processing and alert response models are warranted.

Direct oral anticoagulants or warfarin in patients with left ventricular thrombus: a meta-analysis of randomized clinical trials

Abstract Background/Introduction There are limited randomized controlled trials (RCTs) data on the use of direct oral anticoagulants (DOAC) versus warfarin in patients with left ventricular (LV) thrombus. Current AHA and ESC guidelines recommend oral anti-coagulants (either DOAC or warfarin) for 3 to 6 months without any preference. Purpose We aimed to compare outcomes with DOACs versus warfarin in patients with LV thrombus. Methods A comprehensive literature search was performed from inception to 02/01/2024 of the PubMed database. RCTs of adult patients comparing DOAC to warfarin were evaluated for mortality, major bleeding, stroke, and LV thrombus resolution. Meta-analytic Odds ratio (OR) with 95% confidence intervals (CI) were calculated using DerSimonian-Laird method. Results From 100 studies, four RCTs with 188 subjects (95 DOAC and 93 warfarin) were included with mean age of 53.4 years, 69.5% males, and mean follow up 5.03 months. There was no difference in mortality (OR= 0.67 [95% CI 0.15-3.06]; p=0.60; I2=0%; 3 trials), stroke (OR= 0.46 [95% CI 0.09-2.44]; p=0.37; I2=0%; 4 trials), major bleeding (OR= 0.43 [95% CI 0.12-1.55]; p=0.20; I2=0%; 4 trials), and LV thrombus resolution (OR= 1.33 [95% CI 0.45-3.95]; p=0.61; I2=0%; 2 trials) with use of DOAC compared to warfarin (Figure Panel A to D). Overall, there was no evidence of publication bias using either funnel plot or eggers test (p &amp;gt; 0.05). Conclusions In this meta-analysis of 4 RCTs, there was similar efficacy and safety of DOAC and warfarin in patients with LV thrombus. However, the evidence is limited by small sample size with lesser precision in the estimates. Future large-scale trials are needed to confirm these findings.

Efficacy and safety of P2Y12 inhibitors plus aspirin versus aspirin alone in ischemic stroke or high-risk transient ischemic attack: a meta-analysis of randomized controlled trials

Abstract Background Patients with mild ischemic stroke or transient ischemic attack (TIA) have an increased risk of recurrent stroke within 90 days after the onset of the initial thrombotic event. Antiplatelet therapy plays an essential role in reducing the risk of stroke recurrence. However, data regarding the efficacy and safety of dual antiplatelet therapy (DAPT) with P2Y12 inhibitors (clopidogrel/ticagrelor) and aspirin versus aspirin monotherapy is limited. Purpose We performed an updated systematic review and meta-analysis to evaluate the effectiveness of DAPT versus aspirin monotherapy in patients with mild ischemic stroke or TIA in the light of new published evidence. Moreover, we investigated whether antiplatelet therapy started within 72 hours is effective in reducing recurrent stroke as compared to the conventionally used 24-hour time window for initiating DAPT. Methods PubMed/MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) that compared DAPT with aspirin plus clopidogrel to aspirin alone started within 24 hours or 72 hours in patients with acute mild ischemic stroke or high-risk TIA from inception to December 31st, 2023. A random-effects model was used to pool risk ratios (RRs) and 95% confidence intervals (CIs) for clinical endpoints. Results Five RCTs with 27,563 patients were included in this study. DAPT significantly reduced the risk of recurrent stroke by 23% (RR: 0.77; 95% CI: 0.70-0.83; p&amp;lt;0.00001), ischemic stroke by 26% (RR: 0.74; 95% CI: 0.68-0.81; p&amp;lt;0.00001), and major adverse cardiovascular events (MACE) by 23% (RR: 0.77; 95% CI: 0.71-0.84; p&amp;lt;0.00001). However, DAPT was associated with a significantly increased risk of moderate or severe bleeding (RR: 2.19; 95% CI: 1.38-3.48; p=0.0009) and hemorrhagic stroke (RR: 2.08; 95% CI: 1.13-3.82; p=0.02). No significant differences were observed for all-cause death (RR: 1.28; 95% CI: 0.95-1.71; p=0.10), cardiovascular death (RR: 1.38; 95% CI: 0.81-2.33; p=0.23), and myocardial infarction (RR: 1.63; 95% CI: 0.77-3.46; p=0.20). We performed sensitivity analysis based on the hazard ratio reported by RCTs which showed comparable results. Subgroup analysis based on treatment onset time (therapy initiation within 24 hours of thrombotic event vs therapy initiation within 72 hours of thrombotic event) showed that both strategies were effective in reducing the risk of recurrent stroke. Subgroup analysis based on the duration of DAPT (21 days vs. 90 days) showed that DAPT for 90 days was associated with an increased risk of moderate or severe bleeding as compared to therapy lasting for 21 days. Conclusion DAPT with P2Y12 inhibitors and aspirin reduces the risk of recurrent stroke and MACE but is associated with an increased risk of moderate or severe bleeding.

Intensive blood pressure lowering after endovascular thrombectomy in acute ischaemic stroke: an updated systematic review and meta-analysis of randomized controlled trials

Abstract Background Endovascular thrombectomy is an effective treatment in those with acute ischemic stroke. However, following successful reperfusion there are still many uncertainties as to the factors which influence patient outcome. Effective blood pressure management in this cohort has been elicited as one of these factors, with worse outcomes seen at both the high and low extremes. Purpose Pinpointing an optimal systolic blood pressure target after this procedure is still uncertain. We aimed to perform an updated meta-analysis of randomised controlled trials (RCTs) to evaluate the safety and efficacy of intensive blood pressure management as compared to conventional blood pressure management in this patient population. Methods We searched various electronic databases, including Embase, MEDLINE (via PubMed), and CENTRAL, to retrieve relevant RCTs evaluating a strategy of intensive blood pressure management after endovascular thrombectomy compared to conventional management. We pooled risk ratio (RR) with 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) with 95% CI for continuous outcomes, using RevMan 5.4. Results The meta-analysis included 4 RCTs with a total of 1560 patients. According to the analysis, intensive blood pressure management was associated with a statistically significant decrease in the number of patients showing functional independence (modified Rankin scale mRS score=0-2) at 90 days (RR 0.81; CI = 0.72-0.91; I2 = 12%). Regarding 90-day mortality, the pooled results from three RCTs showed no statistically significant difference between the intensive blood pressure management group and the conventional blood pressure management group (RR 1.17; CI = 0.90-1.52; I2 = 0%). There was no statistically significant difference between the two groups regarding the incidence of intracerebral haemorrhage (ICH) (RR 1.05; CI = 0.90-1.23; I2 = 0%) and the incidence of symptomatic intracerebral haemorrhage (sICH) (RR 1.10; CI = 0.76-1.60; I2 = 0%). Conclusion The meta-analysis showed no benefit of intensive lowering of blood pressure in terms of functional independence at 90 days, mortality rates, and incidence of ICH. Future large-scale trials should focus on other interventions to improve prognosis in these patients.Figure 1Figure 2

A meta-analysis of randomised controlled trials comparing optical coherence tomography-guided against angiography-guided revascularisation

Abstract Optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) offers more in-depth assessment of plaque morphology, vessel sizing and post-PCI stent deployment characteristics than angiography guidance alone. Previous studies have demonstrated superiority of OCT-guided compared to angiography-guided PCI in stent implantation and expansion, with no difference in safety outcomes. Despite this, adoption of OCT-guided PCI remains low in clinical practice due to its increased procedural time, larger contrast volume, and added cost. Two large multicentre international randomised controlled trials (RCTs) were recently published. We therefore aimed to perform an up-to-date meta-analysis of RCTs comparing OCT-guided revascularisation against angiography-guided revascularisation on hard clinical outcomes. A comprehensive search of PubMed/MEDLINE and Ovid/Embase was performed, of which only RCTs were included. Two authors identified relevant articles and extracted the data independently. Any disagreements were resolved by a third author. Clinical outcome data was extracted from each study and then pooled to determine the overall risk ratio (RR) and confidence interval (CI) collectively. This was calculated with random-effects model using the Mantel-Haenszel method. All reported P values are two-sided, with significance set at P&amp;lt;0.05. A total of ten RCTs involving a total of 5062 patients were included. After an average follow-up of 20 months, there was no significant difference in the trial-defined composite endpoint between OCT-guided versus angiography guided revascularisation [6.8% versus 7.9%, RR 0.85, 95% CI (0.69 to 1.03), P=0.10, heterogeneity (I2)=0%]. There was also no significant difference in cardiac death [1.0% versus 1.6%, RR 0.61, 95% CI (0.36 to 1.02), P=0.06, heterogeneity (I2)=0%, Figure 1a], myocardial infarction [3.2% versus 3.7%, RR 0.86, 95% CI (0.65 to 1.15), P=0.31, I2=0%, Figure 1b] and target lesion or vessel repeat revascularisation [3.8% versus 4.1%, RR 0.95, 95% CI (0.72 to 1.25), P=0.70, I2=0%, Figure 1c] between the two arms. However, the OCT-guided revascularisation arm was associated with a significantly lower rate of stent thrombosis [0.8% versus 1.5%, RR 0.57, 95% CI (0.33 to 0.97), P=0.04, I2=0%, Figure 1d] than the angiography-guided revascularisation arm. The number-needed-to-treat (NNT) by OCT-guided revascularisation to reduce one additional stent thrombosis event was 143. In conclusion, our findings show the use of OCT-guided revascularisation led to a significant reduction in stent thrombosis compared to angiography-guided revascularisation, but there was no difference in cardiac death, myocardial infarction and repeat revascularisation. The NNT for stent thrombosis was 143 patients. Further research is needed to identity those subgroups most likely to benefit from OCT-guided revascularisation before it can be more widely adopted to significantly impact on clinical care.