A survey of experts to identify methods to detect problematic studies: Stage 1 of the INSPECT-SR Project.

Background: Randomised controlled trials (RCTs) inform healthcare decisions. Unfortunately, some published RCTs contain false data, and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs which have been conducted on a given topic. This means that any of these 'problematic studies' are likely to be included, but there are no agreed methods for identifying them. The INSPECT-SR project is developing a tool to identify problematic RCTs in systematic reviews of healthcare-related interventions. The tool will guide the user through a series of 'checks' to determine a study's authenticity. The first objective in the development process is to assemble a comprehensive list of checks to consider for inclusion. Methods: We assembled an initial list of checks for assessing the authenticity of research studies, with no restriction to RCTs, and categorised these into five domains: Inspecting results in the paper; Inspecting the research team; Inspecting conduct, governance, and transparency; Inspecting text and publication details; Inspecting the individual participant data. We implemented this list as an online survey, and invited people with expertise and experience of assessing potentially problematic studies to participate through professional networks and online forums. Participants were invited to provide feedback on the checks on the list, and were asked to describe any additional checks they knew of, which were not featured in the list. Results: Extensive feedback on an initial list of 102 checks was provided by 71 participants based in 16 countries across five continents. Fourteen new checks were proposed across the five domains, and suggestions were made to reword checks on the initial list. An updated list of checks was constructed, comprising 116 checks. Many participants expressed a lack of familiarity with statistical checks, and emphasized the importance of feasibility of the tool. Conclusions: A comprehensive list of trustworthiness checks has been produced. The checks will be evaluated to determine which should be included in the INSPECT-SR tool.

Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions.

INTRODUCTION: Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INveStigating ProblEmatic Clinical Trials in Systematic Reviews (INSPECT-SR) project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare-related interventions. METHODS AND ANALYSIS: The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: (1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, (2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, (3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in, (4) a consensus meeting to select checks to be included in a draft tool and to determine its format and (5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies and will help patients by protecting them from the influence of false data on their healthcare. ETHICS AND DISSEMINATION: The University of Manchester ethics decision tool was used, and this returned the result that ethical approval was not required for this project (30 September 2022), which incorporates secondary research and surveys of professionals about subjects relating to their expertise. Informed consent will be obtained from all survey participants. All results will be published as open-access articles. The final tool will be made freely available.

Editor's Choice -- European Society for Vascular Surgery (ESVS) 2024 Clinical Practice Guidelines on the Management of Abdominal Aorto-Iliac Artery Aneurysms.

OBJECTIVE: The European Society for Vascular Surgery (ESVS) has developed clinical practice guidelines for the care of patients with aneurysms of the abdominal aorta and iliac arteries in succession to the 2011 and 2019 versions, with the aim of assisting physicians and patients in selecting the best management strategy. METHODS: The guideline is based on scientific evidence completed with expert opinion on the matter. By summarising and evaluating the best available evidence, recommendations for the evaluation and treatment of patients have been formulated. The recommendations are graded according to a modified European Society of Cardiology grading system, where the strength (class) of each recommendation is graded from I to III and the letters A to C mark the level of evidence. RESULTS: A total of 160 recommendations have been issued on the following topics: Service standards, including surgical volume and training; Epidemiology, diagnosis, and screening; Management of patients with small abdominal aortic aneurysm (AAA), including surveillance, cardiovascular risk reduction, and indication for repair; Elective AAA repair, including operative risk assessment, open and endovascular repair, and early complications; Ruptured and symptomatic AAA, including peri-operative management, such as permissive hypotension and use of aortic occlusion balloon, open and endovascular repair, and early complications, such as abdominal compartment syndrome and colonic ischaemia; Long term outcome and follow up after AAA repair, including graft infection, endoleaks and follow up routines; Management of complex AAA, including open and endovascular repair; Management of iliac artery aneurysm, including indication for repair and open and endovascular repair; and Miscellaneous aortic problems, including mycotic, inflammatory, and saccular aortic aneurysm. In addition, Shared decision making is being addressed, with supporting information for patients, and Unresolved issues are discussed. CONCLUSION: The ESVS Clinical Practice Guidelines provide the most comprehensive, up to date, and unbiased advice to clinicians and patients on the management of abdominal aorto-iliac artery aneurysms.

Time Dependent Correlation Between Sac Behaviour and Re-intervention after Endovascular Aneurysm Repair.

OBJECTIVE: This study aimed to investigate the correlation between aneurysm sac behaviour and time to re-intervention after endovascular aneurysm repair (EVAR). METHODS: A retrospective observational cohort study of patients who underwent EVAR at a single centre between January 2008 and November 2011 and who were followed up for a mean of 6.6 ± 2.9 years was conducted. Based on sac appearances on pre-operative imaging and imaging at the end of follow up, patients were stratified into two groups: (1) sac regression; and (2) no sac regression. The no sac regression group was further subdivided into stable sac group and sac expansion group. Sac regression and expansion throughout follow up were defined as a decrease or increase in the abdominal aortic aneurysm sac diameter of ≥ 5 mm compared with the pre-operative size. A Cox proportional hazards model using multiple failure per subject data was used to identify sac behaviour as a predictor of re-intervention free time. RESULTS: Patients with sac regression had a higher probability of freedom from re-intervention compared with those with a stable or expanding aneurysm sac (94%, 57%, and 16% at 12 years, respectively; log rank, p < .001). Mean time to re-intervention was 11.3 years for the sac regression group, 8.8 years for the stable sac group, and 5.0 years for the sac expansion group (p < .001). In the stable sac group, the risk of re-intervention increased sharply six years after EVAR, whereas in the sac expansion group a sharp rise in re-intervention was noted 3.5 years after EVAR, reaching a plateau after year 6. CONCLUSION: A time dependent correlation between aneurysm sac behaviour and re-intervention was found. Such findings have implications for surveillance strategies.

Systematic Review and Meta-Analysis of the Effect of Anticoagulation on Outcomes After Endovascular Aneurysm Repair.

PURPOSE: Our objective was to investigate whether patients who receive anticoagulation therapy have different outcomes after endovascular aneurysm repair (EVAR) from those who do not. MATERIALS AND METHODS: We conducted a systematic review of studies that compared outcomes of EVAR in patients who were on therapeutic anticoagulation vs those who were not. We developed and reported the review in accordance with the PRISMA guidelines with a registered protocol (CRD42022375894). The Ovid interface was used to search Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (EMBASE), and Cochrane Central Register of Controlled Trials (CENTRAL) up to November 2022. The quality of studies was assessed with the Newcastle-Ottawa Scale (NOS) (maximum score=9), and the evidence was appraised with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. The hazard ratio (HR) and 95% confidence interval (CI) was the effect estimate in time-to-event meta-analyses, calculated using the inverse-variance statistical method and random-effects models. RESULTS: Sixteen studies qualified for inclusion reporting a total of 35 739 individuals. Anticoagulated patients had a statistically significantly higher hazard of death (HR=1.93, 95% CI=1.03-3.63), endoleak (HR=2.13, 95% CI=1.55-2.93), reintervention (HR=1.79, 95% CI=1.27-2.52), and aneurysm sac expansion (HR=2.72, 95% CI=1.57-4.72) than patients not receiving anticoagulation therapy. The median score on the NOS was 7 (range=4-9). The certainty of evidence was very low for mortality and reintervention and low for endoleak and sac expansion. CONCLUSIONS: Anticoagulation is a poor prognostic factor after standard EVAR and should be considered in decision-making, consent processes, and surveillance strategies. CLINICAL IMPACT: The number of individuals who take anticoagulation treatment has been rapidly increasing over the recent years. We aimed to investigate the effect of such treatment on outcomes after endovascular aneurysm repair (EVAR). Anticoagulated patients were found to have increased mortality, endoleak, and reintervention rates after EVAR compared to their non-anticoagulated counterparts. Anticoagulation therapy has a prognostic role in EVAR and should be considered in decision making and EVAR surveillance. Anticoagulated patients need to be informed of the higher failure rates of EVAR, and intensified surveillance strategies may need to be implemented in this patient cohort.

Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions.

Introduction: Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INSPECT-SR project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare related interventions. Methods and analysis: The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: 1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, 2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, 3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in 4) a consensus meeting to select checks to be included in a draft tool and to determine its format, 5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies, and will help patients by protecting them from the influence of false data on their healthcare.

Systematic Review With Meta-Analysis of Endovascular Versus Open Repair of Abdominal Aortic Aneurysm Repair in the Young.

PURPOSE: The purpose of this study was to investigate which treatment method for abdominal aortic aneurysm (AAA), endovascular or open repair, has better outcomes in young patients. MATERIALS AND METHODS: A systematic review was conducted to identify observational studies or randomized controlled trials (RCTs) that compared endovascular and open repair of intact AAA in young patients. MEDLINE, EMBASE, and CENTRAL were searched up to March 2022 using the Ovid interface. The risk of bias was assessed with the Newcastle-Ottawa scale (NOS), with a maximum score of 9, or version 2 of the Cochrane risk of bias tool. The certainty of evidence was assessed with the GRADE framework. Primary outcomes were perioperative, overall, and aneurysm-related mortality. Secondary outcomes were reintervention, hospital length of stay, and perioperative complications. Effect measures in syntheses were the odds ratio (OR), risk difference (RD), mean difference (MD), or hazard ratio (HR) and were calculated with the Mantel-Haenszel or inverse variance statistical method and random-effects models. RESULTS: Fifteen observational studies and 1 RCT were included, reporting a total of 48 976 young patients. Definitions of young ranged from 60 to 70 years. The median score on the NOS was 8 (range: 4-9), and the RCT was judged to be high risk of bias. The perioperative mortality was lower after EVAR (RD: -0.01, 95% CI: -0.02 to -0.00), but the overall and aneurysm-related mortality was not significantly different between EVAR and open repair (HR: 1.38, 95% CI: 0.81 to 2.33; HR: 4.68, 95% CI: 0.71 to 31.04, respectively), as was the hazard of reintervention (HR: 1.50, 95% CI: 0.88 to 2.56). The hospital length of stay was shorter after EVAR (MD: -4.44 days, 95% CI: -4.79 to -4.09), and the odds of cardiac (OR: 0.22, 95% CI: 0.13 to 0.35), respiratory (OR: 0.17, 95% CI: 0.11 to 0.26), and bleeding complications were lower after EVAR (OR: 0.26, 95% CI: 0.11 to 0.64). The level of evidence was low or very low. CONCLUSION: Patient preferences and perspectives should be considered during shared decision-making process considering the available evidence. EVAR may be considered in young and fit patients with a suitable anatomy. PROTOCOL REGISTRATION: PROSPERO, CRD42022325051. CLINICAL IMPACT: Uncertainty surrounds the optimal treatment strategy for abdominal aortic aneurysm in young patients. Meta-analysis of some 48,976 young patients showed that endovascular aneurysm repair (EVAR) has a lower perioperative mortality and morbidity and a shorter hospital and intensive care unit stay than open surgical repair, but the overall and aneurysm-related mortality in the short to medium term are not significantly different between EVAR and open repair. EVAR can be considered in young patients.

Systematic Review of the Effect of Cerebrospinal Fluid Drainage on Outcomes After Endovascular Descending Thoracic/Thoraco-Abdominal Aortic Aneurysm Repair.

OBJECTIVE: This study aimed to investigate whether prophylactic use of cerebrospinal fluid (CSF) drainage in endovascular descending thoracic aortic aneurysm (DTAA) and thoraco-abdominal aortic aneurysm (TAAA) repair contributes to a lower rate of post-operative spinal cord ischaemia (SCI). DATA SOURCES: MEDLINE, Embase, and CINAHL. REVIEW METHODS: A literature review was conducted in accordance with PRISMA guidelines (PROSPERO registration no. CRD42021245893). Risk of bias was assessed through the Newcastle-Ottawa scale (NOS), and the certainty of evidence was graded using the GRADE approach. A proportion meta-analysis was conducted to calculate the pooled rate and 95% confidence interval (CI) of both early and late onset SCI. Pooled outcome estimates were calculated using the odds ratio (OR) and associated 95% CI. The primary outcome was SCI, both early and lateonset. Secondary outcomes were complications of CSF drainage, length of hospital stay, and peri-operative (30 day or in hospital) mortality rates. RESULTS: Twenty-eight observational, retrospective studies were included, reporting 4 814 patients (2 599 patients with and 2 215 without CSF drainage). The NOS showed a moderate risk of bias. The incidence of SCI was similar in patients with CSF drainage (0.05, 95% CI 0.03 ‒ 0.08) and without CSF drainage (0.05, 95% CI 0.00 ‒ 0.14). No significant decrease in SCI was found when using CSF drainage (OR 0.67, 95% CI 0.29 ‒ 1.55, p = .35). The incidence rate of CSF drainage related complication was 0.10 (95% CI 0.04 ‒ 0.19). The 30 day and in hospital mortality rate with CSF drainage was 0.08 (95% CI 0.05 ‒ 0.12). The 30 day and in hospital mortality rate without CSF drainage and comparison with late mortality and length of hospital stay could not be determined due to lack of data. The quality of evidence was considered very low. CONCLUSION: Pre-operative CSF drainage placement was not related to a favourable outcome regarding SCI rate in endovascular TAAA and DTAA repair. Due to the low quality of evidence, no clear recommendation on pre-operative use of CSF drainage placement can be made.

Management of Inflammatory Bowel Disease Using E-health Technologies: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Technological advances have provided innovative, adaptive, and responsive models of care for inflammatory bowel diseases [IBD]. We conducted a systematic review to compare e-health interventions with standard care in management of IBD. METHODS: We searched electronic databases for randomised, controlled trials [RCT] comparing e-health interventions with standard care for patients with IBD. Effect measures were standardised mean difference [SMD], odds ratio [OR], or rate ratio [RR], calculated using the inverse variance or Mantel-Haenszel statistical method and random-effects models. Version 2 of the Cochrane tool was used to assess the risk of bias. The certainty of evidence was appraised with the GRADE framework. RESULTS: Fourteen RCTs [n = 3111; 1754 e-health and 1357 controls] were identified. The difference in disease activity scores (SMD 0.09, 95% confidence interval [CI]: -0.09-0.28) and clinical remission (odds ratio [OR] 1.12, 95% CI: 0.78-1.61) between e-health interventions and standard care were not statistically significant. Higher quality of life [QoL] [SMD 0.20, 95% CI: 0.05-0.35) and IBD knowledge [SMD 0.23, 95% CI: 0.10-0.36] scores were noted in the e-health group, and self-efficacy levels [SMD -0.09, 95% CI: -0.22-0.05] were comparable. E-health patients had fewer office [RR 0.85, 95% CI: 0.78-0.93] and emergency [RR 0.70, 95% CI: 0.51- 0.95] visits, with no statistically significant difference in endoscopic procedures, total health care encounters, corticosteroid use, and IBD related hospitalisation or surgery. The trials were judged to be at high risk of bias or to have some concerns for disease remission. The certainty of evidence was moderate or low. CONCLUSION: E-health technologies may have a role in value-based care in IBD.

Midterm changes in iliac limb apposition after endovascular aortic aneurysm repair.

BACKGROUND: Literature is scarce on the course of iliac endograft limb apposition after endovascular aortic aneurysm repair (EVAR), which is why this study was conducted. METHODS: A retrospective observational imaging study was performed to measure iliac apposition of endograft limbs on the first post-EVAR computed tomography angiography (CTA) scan and on the latest available follow-up CTA scan. With center lumen line reconstructions and CT-applied dedicated software, the shortest apposition length (SAL) of the endograft limbs was assessed as well as the distance between the end of the fabric and the proximal border of the internal iliac artery or the endograft-internal artery distance (EID). RESULTS: Ninety-two iliac endograft limbs were eligible for measurements, with a median follow-up of 3.3 years. At the first post-EVAR CTA, the mean SAL was 31.9±15.6 mm, and the mean EID was 19.5±11.8. At the last follow-up CTA, there was a significant decrease in apposition of 10.5±14.1 mm (P<0.001) and a significant increase in EID of 5.3±9.5 mm (P<0.001). A type Ib endoleak developed in three patients due to a reduced SAL. The apposition was <10 mm in 24% of limbs at the last follow-up vs. 3% at the first post-EVAR CTA. CONCLUSIONS: This retrospective study documented a significant decrease in post-EVAR iliac apposition over time, partly due to retraction of iliac endograft limbs at mid-term CTA follow-up. Further research is required to identify whether regular determination of iliac apposition may predict and prevent type IB endoleaks.

A Statistical Shape Model of Infrarenal Aortic Necks in Patients With and Without Late Type Ia Endoleak After Endovascular Aneurysm Repair.

PURPOSE: Hostile aortic neck characteristics, including short length, severe suprarenal and infrarenal angulation, conicity, and large diameter, have been associated with increased risk for type Ia endoleak (T1aEL) after endovascular aneurysm repair (EVAR). This study investigates the mid-term discriminative ability of a statistical shape model (SSM) of the infrarenal aortic neck morphology compared with or in combination with conventional measurements in patients who developed T1aEL post-EVAR. MATERIALS AND METHODS: The dataset composed of EVAR patients who developed a T1aEL during follow-up and a control group without T1aEL. Principal component (PC) analysis was performed using a parametrization to create an SSM. Three logistic regression models were created. To discriminate between patients with and without T1aEL, sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve (AUC) were calculated. RESULTS: In total, 126 patients (84% male) were included. Median follow-up time in T1aEl group and control group was 52 (31, 78.5) and 51 (40, 62.5) months, respectively. Median follow-up time was not statistically different between the groups (p=0.72). A statistically significant difference between the median PC scores of the T1aEL and control groups was found for the first, eighth, and ninth PC. Sensitivity, specificity, and AUC values for the SSM-based versus the conventional measurements-based logistic regression models were 79%, 70%, and 0.82 versus 74%, 73%, and 0.85, respectively. The model of the SSM and conventional measurements combined resulted in sensitivity, specificity, and AUC of 81%, 81%, and 0.92. CONCLUSION: An SSM of the infrarenal aortic neck determines its 3-dimensional geometry. The SSM is a potential valuable tool for risk stratification and T1aEL prediction in EVAR. The SSM complements the conventional measurements of the individual preoperative infrarenal aortic neck geometry by increasing the predictive value for late type Ia endoleak after standard EVAR. CLINICAL IMPACT: A statistical shape model (SSM) determines the 3-dimensional geometry of the infrarenal aortic neck. The SSM complements the conventional measurements of the individual pre-operative infrarenal aortic neck geometry by increasing the predictive value for late type Ia endoleaks post-EVAR. The SSM is a potential valuable tool for risk stratification and late T1aEL prediction in EVAR and it is a first step toward implementation of a treatment planning support tool in daily clinical practice.

Editor's Choice - Meta-Analysis of Compliance with Endovascular Aneurysm Repair Surveillance: The EVAR Surveillance Paradox.

OBJECTIVE: To compare the survival of patients who attended surveillance after endovascular aneurysm repair (EVAR) with those who were non-compliant. DATA SOURCES: MEDLINE and Embase were searched using the Ovid interface. REVIEW METHODS: A systematic review was conducted complying with the PRISMA guidelines. Eligible studies compared survival in EVAR surveillance compliant patients with non-compliant patients. Non-compliance was defined as failure to attend at least one post-EVAR follow up. The risk of bias was assessed with the Newcastle-Ottawa scale, and the certainty of evidence using the GRADE framework. Primary outcomes were survival and aneurysm related death. Effect measures were the hazard ratio (HR) or odds ratio (OR) and 95% confidence interval (CI) calculated using the inverse variance or Mantel-Haenszel statistical method and random effects models. RESULTS: Thirteen cohort studies with a total of 22 762 patients were included. Eight studies were deemed high risk of bias. The pooled proportion of patients who were non-compliant with EVAR surveillance was 43% (95% CI 36 - 51). No statistically significant difference was found in the hazard of all cause mortality (HR 1.04, 95% CI 0.61 - 1.77), aneurysm related mortality (HR 1.80, 95% CI 0.85-3.80), or secondary intervention (HR 0.66, 95% CI 0.31 - 1.41) between patients who had incomplete and complete follow up after EVAR. The odds of aneurysm rupture were lower in non-compliant patients (OR 0.63, 95% CI 0.39 - 1.01). The certainty of evidence was very low for all outcomes. Subgroup analysis for patients who had no surveillance vs. those with complete surveillance showed no significant difference in all cause mortality (HR 1.10, 95% CI 0.43 - 2.80). CONCLUSION: Patients who were non-compliant with EVAR surveillance had similar survival to those who were compliant. These findings question the value of intense surveillance in all patients post-EVAR and highlight the need for further research on individualised or risk adjusted surveillance.