Project description:BackgroundAngiotensin receptor blockers (ARBs) and β blockers are widely used in the treatment of Marfan syndrome to try to reduce the rate of progressive aortic root enlargement characteristic of this condition, but their separate and joint effects are uncertain. We aimed to determine these effects in a collaborative individual patient data meta-analysis of randomised trials of these treatments.MethodsIn this meta-analysis, we identified relevant trials of patients with Marfan syndrome by systematically searching MEDLINE, Embase, and CENTRAL from database inception to Nov 2, 2021. Trials were eligible if they involved a randomised comparison of an ARB versus control or an ARB versus β blocker. We used individual patient data from patients with no prior aortic surgery to estimate the effects of: ARB versus control (placebo or open control); ARB versus β blocker; and indirectly, β blocker versus control. The primary endpoint was the annual rate of change of body surface area-adjusted aortic root dimension Z score, measured at the sinuses of Valsalva.FindingsWe identified ten potentially eligible trials including 1836 patients from our search, from which seven trials and 1442 patients were eligible for inclusion in our main analyses. Four trials involving 676 eligible participants compared ARB with control. During a median follow-up of 3 years, allocation to ARB approximately halved the annual rate of change in the aortic root Z score (mean annual increase 0·07 [SE 0·02] ARB vs 0·13 [SE 0·02] control; absolute difference -0·07 [95% CI -0·12 to -0·01]; p=0·012). Prespecified secondary subgroup analyses showed that the effects of ARB were particularly large in those with pathogenic variants in fibrillin-1, compared with those without such variants (heterogeneity p=0·0050), and there was no evidence to suggest that the effect of ARB varied with β-blocker use (heterogeneity p=0·54). Three trials involving 766 eligible participants compared ARBs with β blockers. During a median follow-up of 3 years, the annual change in the aortic root Z score was similar in the two groups (annual increase -0·08 [SE 0·03] in ARB groups vs -0·11 [SE 0·02] in β-blocker groups; absolute difference 0·03 [95% CI -0·05 to 0·10]; p=0·48). Thus, indirectly, the difference in the annual change in the aortic root Z score between β blockers and control was -0·09 (95% CI -0·18 to 0·00; p=0·042).InterpretationIn people with Marfan syndrome and no previous aortic surgery, ARBs reduced the rate of increase of the aortic root Z score by about one half, including among those taking a β blocker. The effects of β blockers were similar to those of ARBs. Assuming additivity, combination therapy with both ARBs and β blockers from the time of diagnosis would provide even greater reductions in the rate of aortic enlargement than either treatment alone, which, if maintained over a number of years, would be expected to lead to a delay in the need for aortic surgery.FundingMarfan Foundation, the Oxford British Heart Foundation Centre for Research Excellence, and the UK Medical Research Council.
Project description:PurposeThe infundibulo-pelvic angle (IPA) is reportedly a predictor of successful ureteroscopy for lower pole renal stones, however there is uncertainty at which IPA success is likely. We therefore aimed to perform a meta-analysis and determine at which the angle of likely success and failure.MethodsWe performed a systematic review and meta-analysis as per Cochrane guidelines in accordance to the PRISMA statement. The review was registered with PROSPERO prior to commencement (ID: CRD42022296732). We included studies reporting on outcomes of ureteroscopy for lower pole stones, with IPA. We excluded patients undergoing alternative treatments for lower pole stones, anatomical abnormalities and studies with < 10 patients. We assessed bias with the Newcastle-Ottawa scale. We performed meta-analysis in R, and summarised the findings as per GRADE.ResultsOverall, there were 13 studies included, with 10 included for meta-analysis. These studies covered n = 1964 patients (71% stone free). Overall, the stone free patients had a significantly less acute mean IPA (52o ± 9o), compared to the non-stone free patients (39o ± 7o), on meta-analysis (REM MD = -13.0, 95% CI: -18.7 to -7.2, p < 0.001). On examination of forest plots, at IPA < 30o no patients were stone free, whilst > 50o all were stone free. Risk of bias was moderate, and certainty of evidence was 'very low'.ConclusionWith a very low certainty of evidence, we demonstrate that at an IPA of < 30o no patient is stone free, whilst > 50o all patients (in this review) are stone free. More evidence is therefore needed.
Project description:ObjectiveTo investigate the potential beneficial and adverse effects of routine ureteric stent placement after ureteroscopy.DesignSystematic review and meta-analysis of randomised controlled trials.Data sourcesCochrane controlled trials register (2006 issue 2), Embase, and Medline (1966 to 31 March 2006), without language restrictions. Review methods We included all randomised controlled trials that reported various outcomes with or without stenting after ureteroscopy. Two reviewers independently extracted data and assessed quality. Meta-analyses used both fixed and random effects models with dichotomous data reported as relative risk and continuous data as a weighted mean difference with 95% confidence intervals.ResultsNine randomised controlled trials (reporting 831 participants) were identified. The incidence of lower urinary tract symptoms was significantly higher in participants who had a stent inserted (relative risk 2.25, 95% confidence interval 1.14 to 4.43, for dysuria; 2.00, 1.11 to 3.62, for frequency or urgency) after ureteroscopy. There was no significant difference in postoperative requirement for analgesia, urinary tract infections, stone free rate, and ureteric strictures in the two groups. Because of marked heterogeneity, formal pooling of data was not possible for some outcomes such as flank pain. A pooled analysis showed a reduced likelihood of unplanned medical visits or admission to hospital in the group with stents (0.53, 0.17 to 1.60), although this difference was not significant. None of the trials reported on health related quality of life. Cost reported in three randomised controlled trials favoured the group without stents. The overall quality of trials was poor and reporting of outcomes inconsistent.ConclusionsPatients with stents after ureteroscopy have significantly higher morbidity in the form of irritative lower urinary symptoms with no influence on stone free rate, rate of urinary tract infection, requirement for analgesia, or long term ureteric stricture formation. Because of the marked heterogeneity and poor quality of reporting of the included trials, the place of stenting in the management of patients after uncomplicated ureteroscopy remains unclear.
Project description:ObjectiveThis meta-analysis aimed to demonstrate the effect of methylene blue (MB) in patients with distributive shock.DesignMeta-analysis.MethodsAccording to the Prospective International Register of Systematic Reviews (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched the relevant randomised controlled trials (RCTs) via PubMed, Embase and Cochrane Library from the date of database inception to 19 April 2023. The primary outcome was mortality during follow-up, and secondary outcomes included mean arterial pressure (mm Hg), mechanical ventilation time (hours), intensive care unit (ICU) length of stay (LOS) (days), hospital LOS (days) and heart rate (times/min).ResultsThis study included six RCTs with 265 participants. The study showed no significant difference in mortality between the MB and placebo groups (ORs: 0.59; 95% CI 0.32 to -1.06). However, MB reduced the duration of mechanical ventilation (mean difference (MD): -0.68; 95% CI -1.23 to -0.14), ICU LOS (MD: -1.54; 95% CI -2.61 to -0.48) and hospital LOS (MD: -1.97; 95% CI -3.92 to -0.11).ConclusionsThe use of MB may not reduce mortality in patients with distributive shock, but may shorten the duration of mechanical ventilation, ICU LOS and hospital LOS. More clinical studies are needed to confirm these findings in the future.Trial registration numberCRD42023415938.
Project description:BackgroundLaparoscopic cholecystectomy (LC) in patients admitted with acute cholecystitis is considered the preferred, feasible and safe mode of managing gallstone disease. The objective of this study is to evaluate the role of single-dose pre-operative prophylactic antibiotics in patients undergoing emergency LC for mild to moderate acute cholecystitis.MethodsAll randomized control trials (RCTs) reporting the use of single-dose pre-operative prophylactic antibiotics in patients undergoing acute cholecystectomy were retrieved from the search of standard medical electronic databases and analysis was conducted by using the principles of meta-analysis on the statistical software RevMan version 5.ResultsStandard medical databases search produced only 3 RCTs on 781 patients undergoing acute cholecystectomy. There were 384 patients in single dose pre-operative antibiotics group whereas 397 patients were recruited in the no-antibiotics group. In the random effects model analysis, the use of single-dose preoperative prophylactic antibiotics in patients undergoing acute cholecystectomy for mild to moderate cholecystitis failed to demonstrate any extra advantage of reducing the risk of [risk ratio (RR) =0.69; 95% confidence interval (CI): 0.46-1.03; Z=1.80; P=0.07] infective complications. There was no heterogeneity [Tau2 =0; Chi2 =1.74, df =2 (P=0.42; I2=0%)] among included studies.ConclusionsA preoperative single dose of prophylactic antibiotics in patients undergoing acute LC for mild to moderate acute cholecystitis does not offer extra benefits to reduce infective complications.
Project description:BackgroundWhether biliary drainage should be performed before surgery in jaundiced patients is a topic of debate. Published studies on the effect of preoperative biliary drainage show great discrepancies in their conclusions, and the use of different drainage methods is an important factor. The aim of the present study was to investigate the effect of preoperative biliary stents (PBS) on postoperative outcomes in patients following pancreaticoduodenectomy (PD).MethodsMEDLINE, EMBASE, Science Citation Index Expanded, and the Cochrane database were searched up to October 2019 to identify all published articles related to the topic. A meta-analysis was performed to compare postoperative outcomes in patients with and without PBS. Quality assessment and data extraction from included studies were performed by 2 independent authors. Statistical analysis was performed using RevMan 5.2 software.ResultsTwenty-seven studies involving 10,445 patients were included in the analysis. Biliary drainage was performed in 5769 patients (PBS group), and the remaining 4676 patients underwent PD directly (direct surgery [DS] group). Overall mortality, severe complications, abdominal hemorrhage, bile leakage, intra-abdominal abscess, and pancreatic fistula were not significantly different between the PBS and DS groups. However, overall morbidity, delayed gastric emptying, and wound infection were significantly higher in the PBS group compared to the DS group. Subgroup analysis indicated that the adverse effect of PBS on postoperative complications was more evident with increased stent proportion.ConclusionsPreoperative biliary stenting increases overall morbidity, delayed gastric emptying, and wound infection rates in patients following PD. Thus, preoperative biliary drainage via stent placement should be avoided in patients waiting for PD.
Project description:BackgroundHigh placebo responses have limited drug development in eosinophilic oesophagitis. The optimal configuration of trial outcomes is uncertain.AimsTo inform more efficient future trial designs, to characterise clinical, endoscopic and histologic placebo responses in eosinophilic oesophagitis randomised controlled trials (RCTs).MethodsWe updated a Cochrane systematic review and meta-analysis, searching multiple databases to January 1, 2024, to identify placebo-controlled RCTs evaluating medical therapies for patients with eosinophilic oesophagitis. The primary outcome was the pooled proportion of study-defined clinical, endoscopic and histologic responders and remitters randomised to placebo, using an intention-to-treat approach and random-effects model. Sources of heterogeneity were explored using meta-regression.ResultsWe included 25 RCTs. The pooled proportion of clinical response was 41.0% [95% CI: 29.7%-52.8%] with substantial heterogeneity (I2 = 74.9%). On meta-regression, older age and a higher probability of being randomised to placebo reduced the likelihood of clinical response to placebo. The pooled proportion of histologic remission defined as a peak eosinophil count [PEC] ≤ 6 eosinophils per high power field [HPF] or ≤ 1 eosinophil/HPF was 4.3% [95% CI: 2.6%-6.2%] (I2 = 23.6%) and 1.3% [95% CI: 0.5%-2.5%] (I2 = 0%), respectively. The standardised mean difference in the Eosinophilic Oesophagitis Endoscopic Reference Score to placebo was -0.25 [95% CI: -0.41, -0.10].ConclusionsOver 40% of patients in eosinophilic oesophagitis trials respond clinically to placebo, and this is associated with trial design factors such as randomisation ratio and trial population. Objective endoscopic and histologic measures are associated with very low placebo responses.
Project description:Virtual reality (VR), a technology that provides a stimulated sensory experience, has recently been implemented in various fields of medicine. Several studies have investigated the efficacy of VR on preoperative anxiety. The purpose of this meta-analysis was to validate whether VR could relieve preoperative anxiety in patients undergoing surgery. Electronic databases were searched to identify all randomized controlled trials (RCTs) investigating the effect of VR on preoperative anxiety. The primary outcome was defined as the preoperative anxiety scores. We estimated the effect size using the standard mean difference (SMD) with a 95% confidence interval (CI) using a random effect model. Ultimately, 10 RCTs, with a total of 813 patients, were included in the final analysis. Preoperative anxiety was significantly lower in the VR group than in the control group (SMD -0.64, 95% CI -1.08 to -0.20, p = 0.004). In a subgroup analysis, the preoperative anxiety scores were lower in the VR group than in the control group in pediatric patients (SMD -0.71, 95% CI -1.14 to -0.27, p = 0.002), whereas a significant difference was not observed between the two groups in adult patients (p = 0.226). The results of this meta-analysis indicated that VR could decrease preoperative anxiety, especially in pediatric patients.
Project description:Preoperative fasting leads to metabolic stress and causes insulin resistance in patients undergoing cardiac surgery. The aim of this study was to assess the effect of preoperative oral carbohydrate loading (OCH) on outcome in patients undergoing planned cardiac surgery by systematically reviewing the literature and synthesizing evidence from randomized controlled trials (RCTs). Systematic search of PubMed/MEDLINE/Embase/Cinahl/Web of Science/ClinicalTrials databases was performed to identify relevant RCTs from databased inception until 05/03/2020. We included studies that compared outcome measures between OCH with control (placebo or standard starvation). We conducted a random-effect meta-analysis of clinical and biochemical parameters. Nine studies (N = 9) were included with a total of 507 patients. OCH significantly decreased aortic clamping duration (n = 151, standardized mean difference (SMD) = -0.28, 95% confidence interval (CI) = -0.521 to -0.038, p = 0.023 and differences in means (DM) = -6.388, 95%CI = -11.246 to -1.529, p = 0.010). Patients from treatment groups had shorter intensive care unit (ICU) stay (n = 202, SMD = -0.542, 95%CI = -0.789 to -0.295, p < 0.001 and DM = -25.925, 95%CI = -44.568 to -7.283, p = 0.006) and required fewer units of insulin postoperatively (n = 85, SMD = -0.349, 95%CI = -0.653 to -0.044, p = 0.025 and DM = -4.523, 95%CI = -8.417 to -0.630, p = 0.023). The necessity to use inotropic drugs was significantly lower in the OCH group (risk ratio (RR) = 0.795, 95%CI = 0.689 to 0.919, p = 0.002). All other primary outcomes did not reveal a significant effect. Preoperative OCH in patients undergoing cardiac surgery demonstrated a 20% reduction in the use of inotropic drugs, a 50% reduction of the length of ICU stay, a 28% decrease in aortic clamping duration and a 35% decrease of postoperative insulin requirement.