Review Of Registries Research Articles

P0842 Paediatric Inflammatory Bowel Diseases: novel agents on the therapeutic horizon

Abstract Background The therapeutic landscape for inflammatory bowel disease (IBD) has advanced considerably over the past two decades with the development of monoclonal antibodies and advanced small molecules. However, only one advanced therapy class is approved for children with IBD. Long delays exist following adult approval, with a median delay of over seven years to paediatric approval (Figure 1).1 With the recent circulation of draft guidance for industry on drug development in paediatric IBD (pIBD) by the US Food and Drug Administration (FDA),2 an opportunity exists to improve clinical trial processes for drug approval in pIBD. The aim of this study is to summarize the landscape of pIBD clinical trials through a review of trial registries. Methods We conducted a cross-sectional review of publicly accessible data from Clinicaltrials.gov and ClinicalTrialsRegister.eu to identify investigational therapeutic agents as well as approved therapeutic agents for the treatment of pIBD. All interventional pIBD studies (<18 years and/or included a paediatric population) listed from the database’s inception to May 13, 2024, were considered for inclusion. Results A total of 3,493 records were identified from Clinicaltrials.gov (2,758) and ClinicalTrialsRegister.eu (735). One-hundred and sixteen completed trials were included in the review. Of those completed trials, 34 studies focused on biologic agents (29%). Novel small molecule agents (spingosine-1-phosphate agonists and Janus kinase inhibitors) were examined in 7 studies (6%). A further 118 IBD trials are actively recruiting paediatric patients. Sixty-five studies are randomised controlled trials and 53 are open-label studies. With regards to biologic agents, 17 trials are exploring the use of approved biologic agents in children and 34 trials are focusing on novel biologic agents. These include etrolizumab, golimumab, guselkumab, mirikizumab, risankizumab, ustekinumab, and vedolizumab. Sixteen trials are recruiting, examining small molecule therapies in pediatrics, to include upadacitinib, tofacitinib, etrasimod, and ozanimod. Conclusion Efforts to hasten the approvals of novel agents in pIBD is paramount to ensure timely access to effective medications. Whilst there is increasing trial activity in the pIBD landscape, approval by regulatory bodies continue to pose barriers. Consideration for novel trial designs and collaboration between research networks could reduce the delay in paediatric marketing approvals. Continued engagement with regulatory bodies and the international pIBD community offers a critical opportunity to advance drug approvals in children with IBD.

A systematic review of current national hospital-based stroke registries monitoring access to evidence-based care and patient outcomes.

National stroke clinical quality registries/audits support improvements in stroke care. In a 2016 systematic review, 28 registries were identified. Since 2016 there have been important advances in stroke care, including the development of thrombectomy services. Therefore, we sought to understand whether registries have evolved with these advances in care. The aim of this systematic review was to identify current, hospital-based national stroke registries/audits and describe variables (processes, outcome), methods, funding and governance). We searched four databases (21st May 2015 to 1st February 2024), grey literature and stroke organisations' websites. Initially two reviewers screened each citation; when agreement was satisfactory, one of four reviewers screened each citation. The same process was applied to full texts. If there were no new publications from registries identified in the original 2016 review, we contacted the registry leads. We extracted data using predefined categories on country (including income level), clinical/process variables, methods, funding and governance. We found 37 registries from 31 countries (28 high income, four upper-middle income, five lower-middle income) of which 16 had been identified in 2016 and 21 were new. Twenty-two of the same variables were collected by >50% of registries/audits (mostly acute care, including thrombectomy, and secondary prevention), compared with only four variables in 2016. Descriptions of funding, management, methods of consent and data privacy, follow-up, feedback to hospitals, linkage to other datasets and alignment of variables with guidelines were variably reported. Reasons for apparent termination of some registries was unclear. The total number of stroke registries has increased since 2016, and the number of variables collected has increased, reflecting advances in stroke care. However, some registries appeared to have ceased; the reasons are unclear.

Role of the Russian Heart Failure Society in Defining Views on Assessing the Severity and Implementing Optimal Methods of Treating CHF in the Russian Federation Over 25 years. Review of Registries and Multicenter Clinical Trials

An important objective of the creation of the Society of Experts in Heart Failure (SEHF) was to assess the level of diagnostics and approaches to the treatment of chronic heart failure (CHF) in the Russian Federation (RF), without which it was impossible to bring clinical practice to the optimal level and in consistency with the existing clinical guidelines. Thus, along with the development of Guidelines for the diagnosis and treatment of CHF, a series of registries and multicenter clinical trials (MCTs) was conducted to bring the indexes of real practice closer to the developed Guidelines. Numerous MCTs organized during the 25 years of the SEHF existence have significantly improved the substantiated and recommended therapy for CHF administered by practicing physicians in the Russian Federation. This article overviews the most important registries and MCTs that were conducted during the 25 years of the SEHF work and their effect on CHF diagnostics and treatment in the clinical practice in the RF.

Indigenous governance, ethics and data collection in Australian clinical registries.

To examine Indigenous Governance of Data processes in Australian clinical registries. Audit (via desktop review and interviews) of registries in the Australian Register of Clinical Registries from 17 January 2022 to 30 April 2023. The number of clinical registries collecting ethnicity data, reporting Aboriginal and/or Torres Strait Islander representation on registry governance or steering committees, and reporting human research ethics committee approval. A total of 107 clinical registries were reviewed. Of these registries, 65 (61%) collected ethnicity data; when these were grouped by geographical coverage, those most likely to collect ethnicity data were binational (24/40 [60%]), national (19/26 [73%]) or state based (19/26 [73%]). Of the registries that collected ethnicity data, 29 (45%) classified their ethnicity item as Aboriginal and/or Torres Strait Islander. Only eight clinical registries (7%) reported Aboriginal and/or Torres Strait Islander representation on their governance or steering committees. Human research ethics approval was reported in 94 registries (88%), with only 11 (12%) having Aboriginal human research ethics committee approval. Significant variability is evident in clinical registry recording of Indigenous governance of data, meaning that Aboriginal and Torres Strait Islander communities remain invisible in data which is used to inform policy, clinical models of care, health services and initiatives. Radical change is required to facilitate meaningful change in quality indicators for clinical registries nationally.

Core outcome Set for Cardio-oncology (COS-CO): development of a set of outcomes for the cardiovascular assessment and monitoring of cancer patients and survivors.

There is an increasing awareness of the evidence-based selection of outcomes to be measured in clinical trials and clinical practice. Currently, there is no core outcome set (COS) for cardio-oncology, which may hinder the (inter)national comparison of the effectiveness of research and the quality of cardio-oncology care. The aim of this study is to develop a standard and pragmatic patient-centred outcome set to assess and monitor cancer patients and survivors at risk of or with cardiovascular diseases. A list of outcome domains was generated through a review of registries and guidelines, and six patient interviews. The project team reviewed and refined the outcome domains prior to starting a two-round Delphi procedure conducted between January-June 2022. The panellists, including healthcare providers and researchers, were invited to rate the importance of the outcomes. 26 experts from 11 countries rated a list of 93 outcomes (round 1) and 63 outcomes (round 2) to gain consensus on a list of outcome measures, and of demographic factors, health status and treatment variables. The final COS includes 15 outcome measures, reflecting four core areas: life impact (n=2), pathophysiological manifestations (n=9), resource use/economic impact (n=1), and mortality/survival (n=3). Next, six demographic factors, 21 health status, three cardiovascular and nine cancer variables were included. This is the first international development of a COS for cardio-oncology. This set aims to facilitate (inter)national comparison in cardio-oncology care, using standardised parameters and meaningful patient-centred outcomes for research and quality of care assessments.

Septic complications are on the rise and aseptic loosening has decreased in total joint arthroplasty: an updated complication based analysis using worldwide arthroplasty registers

IntroductionA decade ago, a comprehensive study was conducted to investigate the reasons for revision surgeries and their respective frequencies in cases of total hip arthroplasty (THA) and total knee arthroplasty (TKA) based on a complication-based analysis of joint replacement registries. The aim of the present study was to determine whether the causes and risks of their occurrence have changed over the last ten years and to present an updated analysis.Materials and methodsA systematic review of national arthroplasty registries from seven countries examined the causes and rates of revisions of THA and TKA. The study focused on a descriptive analysis that provided an updated overview without statistical significance values.ResultsThe most common causes for revisions of THA were aseptic loosening (35.1%), deep infection (18.2%), dislocation/instability (15.9%), and periprosthetic fractures (11.4%). The most common causes for revisions of TKA were deep infection (21.6%), aseptic loosening (18.3%), instability (14.1%), and pain (10.9%).ConclusionThe findings of this study revealed significant shifts in the underlying causes of revision surgeries in the last decade. Notably, septic complications emerged as the predominant reason for revision of primary TKA, while they also gained prominence as a cause of failure of THA. Although aseptic loosening remains the primary cause for re-operation of THA, the relative risk has decreased for both THA and TKA.

Re-irradiation versus systemic therapy for the management of local-regionally recurrent head and neck cancer

PurposeThe optimal management of local-regionally recurrent head and neck cancer that is not amenable to surgical resection is uncertain. We sought to compare outcomes among patients treated with and without re-irradiation in this setting. Methods and MaterialsA review of institutional registries identified 65 patients with local-regionally recurrent squamous cell carcinoma of the head and neck who were ineligible for surgery. Forty patients (62 %) opted for re-irradiation with the remaining 25 patients (38 %) undergoing initial systemic therapy alone. All patients had measurable disease. Forty-three patients (66 %) were male and twenty-two (33 %) were female. The median age at the time of recurrence was 59 years (range, 39–84 years). The most common primary sites of disease were the oropharynx, (n = 25), oral cavity (N = 19), and nasopharynx (n = 11). The median interval from completion of prior radiation to the diagnosis of recurrent disease was 35 months (range, 2–102 months). ResultsRe-irradiation improved 2-year overall survival, (32 % versus 11 %), progression-free survival (31 % versus 7 %), and local–regional control (39 % versus 3 %) compared to systemic therapy alone (p < 0.05, for both). The likelihood of developing any new grade 3+ toxicity was significantly higher among patients treated by re-irradiation compared to those treated by systemic therapy (53 % vs. 28 %, p < 0.001). There were 3 treatment-related fatalities, all of which occurred in the re-irradiation group. The incidence of grade 3+ late toxicity was 48 % and 12 % for patients in the re-irradiation and systemic therapy cohorts, respectively (p < 0.001). ConclusionAlthough re-irradiation improved overall survival compared to systemic therapy for appropriately selected patients with local-regionally recurrent head and neck cancer, the relatively high risk of toxicity must be considered.

Comparison of revision rates and epidemiological data of a single total knee arthroplasty system of different designs (cruciate retaining, posterior stabilized, mobile bearing, and fixed bearing): a meta-analysis and systematic review of clinical trials and national arthroplasty registries

BackgroundThis study aimed to meta-analyze epidemiological data, revision rates, and incidences of different designs of a single Total Knee Arthroplasty System and compare these factors across different countries.MethodsA systematic review was conducted on clinical studies and arthroplasty registries of ATTUNE TKA from 1999 to 2020. The main endpoints analyzed were revision rates and epidemiological data.ResultsThe average age of patients was 67.8 years, with a gender distribution of 60% female and 40% male. The pooled average BMI was 29.4 kg/m2. Eight clinical studies showed a pooled revision rate per 100 observed CY of 0.5 (n = 1343 cases). Cumulative revision rates after 1, 3, and 5 years varied among registries, with the Swiss registry having the highest revision data (after 5 years: 6.3%) and the American registry having the lowest revision data (after 5 years: 1.7%). A comparison of the revision rates of mobile bearing and fixed bearing (41,200 cases) as well as cruciate retaining and posterior stabilized (n = 123,361 cases) showed no significant advantage in the first 5 years after implantation.ConclusionIn conclusion, pooled data from 41,200 cases of TKA with a single Total Knee Arthroplasty System in two arthroplasty registries revealed that there was no significant difference in revision rates between the mobile bearing and fixed bearing design within the first 5 years after implantation. In addition, a comparison of the revision rates in n = 123,361 cases showed no significant advantage for cruciate retaining or posterior stabilized in the first 5 years after implantation.

Tractor Injuries in the Upper Midwestern United States: a retrospective analysis of four trauma centers

ABSTRACT Objectives The purpose of the present study was to characterize the incidence, injury characteristics, and outcomes of patients presented to four trauma facilities located in the upper Midwest with tractor-related agricultural injuries. Methods We performed a retrospective review of the facility level trauma registries of four trauma centers located in North Dakota, South Dakota, and Minnesota between January 1, 2010 and December 31, 2021. We characterized the incidence, severity and outcomes of traumatic tractor-related agricultural injuries for pediatric and adult patients. We described the nature of these injuries by severity, anatomical site, type, age, sex, and length of stay (LoS). Injury severity was evaluated using Injury Severity Score (ISS) and Abbreviated Injury Scale (AIS). Results Findings indicated that farmers aged 65 and older experience polytraumatic, severe tractor-related agricultural injuries and fatalities. Of the 177 tractor patients analyzed, 40 patients were between the ages of 65 and 74 years and 45 patients were 75 and over. Male farmers aged 65 and older are injured year-round, many are discharged to skilled nursing facilities for additional care, are spending more time in the hospital, and have the highest rate of critical injuries out of all age groups. Moreover, the patients who died as a result of tractor-related agricultural injuries were men over 65 years. The most common tractor-related agricultural injuries include falls from tractors (n = 53), struck by object falling/propelled from tractor (n = 25), rollovers (n = 26), and runovers (n = 24). Falls from tractors accounted for 33% of all tractor-related upper extremity fractures, 36% of head injuries and 29% of chest injuries. Conclusion The findings from this study indicate that tractor-related agricultural injuries represent a significant problem in the upper Midwest. Older, male farm workers experience a higher incidence of tractor-related agricultural injuries, and all tractor-related fatalities occurred in individuals 65 years of age and older. These results underscore the need for further investigation into aging-related farm safety issues.

Cancer Research in sub-Saharan Africa: Progress in closing the gap

Cancer presents an escalating challenge in Sub-Saharan Africa (SSA), necessitating strategic interventions grounded in regionally relevant evidence-based medicine. Informed decision-making is critical to formulate effective strategies for cancer prevention, diagnosis, funding, and treatment within the SSA population. The aim of this study is to highlight ongoing clinical trials in SSA, emphasizing the continuous initiatives aimed at filling existing knowledge gaps. Further, the study seeks to assess whether SSA is progressing or stagnating in the global landscape of cancer research. A comprehensive review of research papers and online registries on clinical trials was executed, focusing on English-language journal articles retrieved from the PubMed database. Additionally, a quantitative, web-based, retrospective review was conducted on registered cancer studies in SSA over the past decade (2000-2023) from ClinicalTrials.gov and the Pan African Clinical Trials Registry (PACTR) databases. The review resulted in the inclusion of 71 articles from PubMed, alongside 104 and 140 clinical trials from ClinicalTrials.gov and PACTR databases, respectively. Aggregate findings from PubMed and clinical trial databases revealed that East Africa is the predominant contributor (37%) to cancer clinical trials, whereas Central Africa exhibited the lowest contribution (4%). Notably, PubMed indicated a predominant focus on cervical cancer in clinical trials. Between 2000 and 2015, less than 4% of global cancer clinical trials listed on ClinicalTrials.gov were performed in SSA; in subsequent years, there was an observable increase in the percentage of total trials performed in SSA. Analyses of funding sources revealed that 45% and 32% of clinical trials in SSA were supported by the United States and the United Kingdom, respectively. In the last two decades, the formation of entities like the African Consortium for Cancer Clinical Trials, spearheaded by BIO Ventures for Global Health in partnership with African ministries of health, cancer hospitals, private industry, research institutions, and global oncology experts, contributed to increasing the effective implementation of multicenter clinical trials in Africa. Noteworthy instances, such as the Burkitt's lymphoma and HypoAfrica studies, serve as examples of the results arising from these collaborative initiatives, reflecting substantial progress within SSA’s cancer research landscape.

The impact of nativity on uterine cancer survival in the public hospital system of Queens, New York

ObjectiveWe studied cis-women with uterine cancer presenting to the two Public Hospitals in Queens, New York from 2006 to 2015 to examine the relationship between nativity (birthplace) and survival. MethodsA retrospective review of tumor registries identified women diagnosed with uterine cancer between January 1, 2006, and December 31, 2015. Data from 259 women were available for this analysis. ResultsMost women were born outside the United States (US) (76% versus 24%). The majority of US-born women were black (68%). Seventy-seven women (30%) were born in Latin America, 76 in the Caribbean Islands (29%) and 44 in Asia/South Asia (17%). Most women presented with stage I/II disease (70%) and endometrioid/mucinous histology (68%) with no significant differences observed among nativity groups. Kaplan-Meier estimated survival curves stratified by birthplace demonstrated significant differences in survival distributions among the groups using the log-rank test (P < 0.0001). The most favorable survival curves were observed among all foreign-born women, whereas the least favorable survival was demonstrated in US-born women. Time to death was analyzed using the Cox proportional hazards model. Adjusting for age of diagnosis, insurance status, stage, and treatment modality, Latin American and Asia/South Asia birthplace was significantly associated with increased survival time. ConclusionAn immigrant health paradox was defined for foreign-born Latin American and Asian/South Asian women presenting to the two Public Hospitals of Queens, New York, as women born in these geographic regions were less likely to die at any given time compared to those born in the United States.

Trends in keratoplasty from central and northern India. Part II: Types of keratoplasty.

To report the types of keratoplasty and analyze trends over a period of two decades in central and northern India. This was a retrospective review of eye bank registries of six tertiary eye care centers located in central and north India from 2005 to 2021. The indications and various keratoplasty procedures were compared between 2005-2012 and 2013-2021 to analyze the trend. A total of 13,223 corneal grafts were performed, of which therapeutic penetrating keratoplasty (TPK) (5719, 43.3%) was the most common procedure, followed by optical penetrating keratoplasty (OPK) (5528, 41.8%), Descemet stripping endothelial keratoplasty (DSEK) (1279, 9.7%), deep anterior lamellar keratoplasty (DALK) (376, 2.8%), Descemet membrane endothelial keratoplasty (DMEK) (215, 1.6%), patch grafts (75, 0.6%), and keratoprostheses (31, 0.2%). Overall, OPK procedures decreased (-14.1%, P < 0.001), but TPK (+3.1%, P < 0.019), DSEK (+7.1%, P < 0.001), and DMEK (+1.9%, P < 0.001) procedures increased. Although there was an increasing trend in the use of DALK (+0.8%, P < 0.083) and keratoprostheses (+0.3%, P = 0.074) procedures, the trends were not statistically significant. In keeping with worldwide trends, an increasing trend in lamellar keratoplasties was observed in central and northern India during the past decade. The trend was significant for DSEK. However, as corneal ulcers and scars were the major indications for keratoplasty, TPK and OPK remained the most common procedures.

Trends in keratoplasty from central and Northern India. Part I: Indications for keratoplasty.

To report the indications for keratoplasty and analyze trends in two decades in India. This was a retrospective review of eye bank registries of six tertiary eye care centers located in central and northern India from 2005 to 2021. The patterns of corneal pathology and changes in trends were analyzed. Between 2005 and 2021, 13223 corneal grafts were performed in the six collaborating tertiary eye care centers. The most common indication for keratoplasty in both decades was corneal ulcer (41.1%), followed by corneal scar (25.5%), failed graft (12.0%), post-cataract surgery corneal edema (11.7%), corneal dystrophies (3.1%), corneal ectasia (1.8%), corneal trauma (0.3%), congenital corneal opacity (0.3%), and others (4.1%). An increasing trend was seen in corneal ulcers, failed grafts, and keratoconus. A reducing trend was seen in corneal scar and aphakic bullous keratopathy. There was no change in pseudophakic bullous keratopathy and Fuchs endothelial corneal dystrophy. Corneal ulcers, corneal scars, failed grafts, and post-cataract surgery corneal edema remained the foremost indications for keratoplasty in two decades in India. An increasing trend was seen in corneal ulcers and failed grafts which are of concern as these indications carry a poorer outcome. Capacity building in lamellar keratoplasty techniques is the need of the hour as pseudophakic bullous keratopathy was an important indication, and an increasing trend was noticed in keratoconus.

Current status of ECMO for massive pulmonary embolism.

Massive pulmonary embolism (MPE) carries significant 30-day mortality and is characterized by acute right ventricular failure, hypotension, and hypoxia, leading to cardiovascular collapse and cardiac arrest. Given the continued high mortality associated with MPE, there has been ongoing interest in utilizing extracorporeal membrane oxygenation (ECMO) to provide oxygenation support to improve hypoxia and offload the right ventricular (RV) pressure in the belief that rapid reduction of hypoxia and RV pressure will improve outcomes. Two modalities can be employed: Veno-arterial-ECMO is a reliable process to decrease RV overload and improve RV function, thus allowing for hemodynamic stability and restoration of tissue oxygenation. Veno-venous ECMO can support oxygenation but is not designed to help circulation. Several societal guidelines now suggest using ECMO in MPE with interventional therapy. There are three strategies for ECMO utilization in MPE: bridge to definitive interventional therapy, sole therapy, and recovery after interventional treatment. The use of ECMO in MPE has been associated with lower mortality in registry reviews, but there has been no significant difference in outcomes between patients treated with and without ECMO in meta-analyses. Considerable heterogeneity in studies is a significant weakness of the available literature. Applying ECMO is also associated with substantial multisystem morbidity due to a systemic inflammatory response, hemorrhagic stroke, renal dysfunction, and bleeding, which must be factored into the outcomes. The application of ECMO in MPE should be combined with an aggressive pulmonary interventional program and should strictly adhere to the current selection criteria.

Outcomes of chronic total occlussion recanalization in patients with prior bypass-surgery: an updated systematic review and meta-analysis of real world registries

Abstract Background Recanalization of chronic total occlusion (CTO) coronary lesions by percutaneous coronary intervention (PCI) in patients with prior coronary artery bypass grafting (CABG) is still considered a challenging scenario due to the complexity of coronary lesions as well as the requirement of CTO PCI advanced techniques. The aim of this study is to compare clinical outcomes of patients undergoing CTO PCI with and without CABG surgery. Methods We conducted a systematic review and meta-analysis of observational studies that compared in-hospital outcomes of CTO PCI in patients with vs. without prior CABG published in Medline from inception until December 2022. The results are synthesized in a quantitative manner with random effects models. Categorical variables were compared using the chi-square test, whereas continuous variables were compared using a 2-sample Student's t-test. Statistical heterogeneity was assessed by I2 statistics: I2 statistic &amp;gt;50% was considered substantial, and I2 &amp;gt;75% was considered considerable. The Review Manager Software version 5.3.5. (The Cochrane Collaboration, 2014) was used to calculate summary statistics (odds ratios [ORs] with 95% confidence intervals [CIs]). Results Eleven observational studies with a total of 35,666 patients were included, of whom 7,005 patients had a history of CABG. Prior CABG patients were older, (68.1 ± 9.0 vs. 64.1 ± 10.7 years; p &amp;lt; 0.001), and had more complex coronary lesions (J-CTO score: 3.2 ± 1.4 vs. 2.5 ± 1.4; p &amp;lt; 0.001). Prior CABG was associated with lower technical success (66.6% vs. 78.5%; OR 0.53 [95% CI: 0.43 to 0.65]; p &amp;lt; 0.00001, I2 = 84%) as well as lower procedural success (OR 0.64 [95% CI: 0.57 to 0.71]; p &amp;lt; 0.00001, I2 = 0%) as compared with patients with no prior CABG (Figure 1A and Figure 1B). Prior CABG patients had a higher incidence of in-hospital mortality (0.7% vs. 0.4%; OR: 2.00 [95% CI: 1.32 to 3.05]; p = 0.001, I2 = 9%, Figure 2A), coronary perforation (3.7% vs. 2.3%; OR: 1.64 [95% CI: 1.15 to 2.33]; p &amp;lt; 0.006, I2 = 74%, Figure 2B), and myocardial infarction (1.7% vs. 0.7%; OR: 2.57 [95% CI: 1.73 to 3.81]; p &amp;lt; 0.00001, I2 = 12%), but a lower incidence of cardiac tamponade (0.2% vs. 0.9%; OR: 0.36 [95% CI: 0.17 to 0.77]; p = 0.09, I2 = 0%, Figure 2C) compared with those without prior CABG. Both groups had a similar incidence of acute cerebrovascular events (0.2% vs. 0.1%; OR: 1.70 [95% CI: 0.75 to 3.88]; p = 0.21, I2 = 0%), major bleeding (1.4% vs. 1.2%; OR: 1.24 [95% CI: 0.96 to 1.61]; p = 0.09, I2 = 0%) and vascular complications (1.4% vs. 0.9%; OR: 1.50 [95% CI: 0.93 to 2.41]; p = 0.10, I2 = 0%). Conclusion Prior CABG patients undergoing CTO PCI presented a higher risk of in-hospital mortality and perioperative procedural complications although the risk of tamponade was lower.Figure 1A and Figure 1BFigure 2A, 2B and 2C

Standardized approach to extract candidate outcomes from literature for a standard outcome set: a case- and simulation study

AimsStandard outcome sets enable the value-based evaluation of health care delivery. Whereas the attainment of expert opinion has been structured using methods such as the modified-Delphi process, standardized guidelines for extraction of candidate outcomes from literature are lacking. As such, we aimed to describe an approach to obtain a comprehensive list of candidate outcomes for potential inclusion in standard outcome sets.MethodsThis study describes an iterative saturation approach, using randomly selected batches from a systematic literature search to develop a long list of candidate outcomes to evaluate healthcare. This approach can be preceded with an optional benchmark review of relevant registries and Clinical Practice Guidelines and data visualization techniques (e.g. as a WordCloud) to potentially decrease the number of iterations. The development of the International Consortium of Health Outcome Measures Heart valve disease set is used to illustrate the approach. Batch cutoff choices of the iterative saturation approach were validated using data of 1000 simulated cases.ResultsSimulation showed that on average 98% (range 92–100%) saturation is reached using a 100-article batch initially, with 25 articles in the subsequent batches. On average 4.7 repeating rounds (range 1–9) of 25 new articles were necessary to achieve saturation if no outcomes are first identified from a benchmark review or a data visualization.ConclusionIn this paper a standardized approach is proposed to identify relevant candidate outcomes for a standard outcome set. This approach creates a balance between comprehensiveness and feasibility in conducting literature reviews for the identification of candidate outcomes.

Clinical trials of neoadjuvant immune checkpoint inhibitors for early-stage operable colon and rectal cancer.

Immune checkpoint inhibitors (ICI) have become first-line treatment for metastatic colorectal cancer (CRC) with deficient mismatch repair (dMMR). Despite the remarkable response reported in preliminary trials, the role of ICI in patients with early-stage, operable CRC remains unclear. The aim of this study was to investigate trials on neoadjuvant ICI in operable CRC. Scoping review of clinical trial registries (Clinicaltrials.gov and EU clinical trial registers) and PubMed/Medline database of trials on neoadjuvant ICI for operable CRC was done up to December 2022. Some 40 trials investigating neoadjuvant ICI for early-stage, operable CRC were identified, including five published trials and three conference abstracts. Preclinical phase I/II trial predominated with only three clinical phase III trials. Few trials investigated neoadjuvant ICI as the only intervention (monotherapy). Trials in rectal cancer were designed for combined ICI with chemo(radio)therapy, only 8 trials stating an MSI/dMMR status for inclusion, one designed for MSS/pMMR only and, the rest agnostic for MMR status. Thirty-eight (95%) trials investigated programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors. PD-1/PD-L1 inhibitors were combined with vascular endothelial growth factor (VEGF) inhibitor or with cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) inhibitor, in two trials each, respectively. Pathological complete response as primary outcome after surgery was the most frequently used study endpoint. In rectal cancer, six trials included a "watch and wait" strategy for patients with complete clinical response. No "watch and wait" study design for colon cancer after neoadjuvant ICI were identified. High response rates from neoadjuvant ICI in early-stage colon and rectal cancer are reported in phase I/II studies. Contemporary trial designs are heterogeneous, with few comparable inclusion criteria, use of several drug combinations and durations and, wide variation of endpoints reported. Harmonizing clinical and translational aspects including survival data is needed for improved future trial designs with clinical impact.

PO-03-189 THROMBOEMBOLISM BEFORE VS AFTER PERCUTANEOUS CLOSURE OF PERI-DEVICE LEAKS RESULTING FROM PERCUTANEOUS LEFT ATRIAL APPENDAGE OCCLUSION

Recent studies have indicated that residual peri-device leaks after percutaneous left atrial appendage occlusion (LAAO) portend a higher risk of thromboembolic (TE) events. It is unknown whether eliminating these leaks via endovascular devices (e.g., coils, plugs) would improve clinical outcomes. To determine the TE risk in patients with incomplete LAAO before vs after leak closure with endovascular devices. This international, multicenter registry was designed as a retrospective review of individual prospective registries maintained at each participating center. All patients with peri-device leak≥3mm who underwent percutaneous closure were enrolled. A total of 238 LAAO patients with residual peri-device leak≥3mm were enrolled at 7 centers (age 74±9 years; 66.8% male; CHA2DS2-VASc 4.8±1.4; HAS-BLED 3.4 ± 1.1). The time between LAAO and leak closure was 11±9 months [221 patients-year (PY)]. Leaks were classified as moderate (3-4mm) in 174 patients (73.1%) or severe (≥5mm) in 64 (26.9%) patients. TE events occurred in 22 (9.2%) patients before leak closure, after a median of 8 months (IQR:6-21) post-LAAO (annualized rate: 9.9%). At the time of TE event, 13 (59.1%) patients were on ASA, 4 (18.2%) on warfarin, 4 (18.2%) on DAPT, and 1 (4.5%) on DOAC. Percutaneous leak closure was performed via endovascular coils or other vascular/septal occluders in 186 (78.1%) and 52 (21.9%) patients, respectively. Procedure time was 89±48 min; the mean volume of iodinated contrast medium used was 64±34mL. Major complications occurred in 2.5% (1 stroke, 1 air embolism, 4 pericardial effusions). Follow-up TEE after 3.4±1.9 months revealed complete LAA sealing or a negligible leak in 218 cases (91.6%); the remaining 20 patients had moderate (n=18) or severe (n=2) residual leak. During a mean follow-up after leak closure of 15±9 months (289PY); 9 (3.8%) patients developed TE events (annualized rate: 3.1%). Among them, 7 (77.8%) patients were on ASA, 1 (11.1%) on clopidogrel, and 1 (11.1%) on no antithrombotic therapy. TE incidence was significantly lower after leak closure (Hazard Ratio: 0.30; 95% Confidence Interval: 0.14-0.69; p=0.004). Kaplan Meier survival curves are reported in Figure 1 (log-rank p-value: 0.0023). Peri-device leaks≥3mm following percutaneous LAAO were associated with a high incidence of TE events. Percutaneous leak closure was safe and contributed to a significant thromboembolic risk reduction.

National Neurotrauma Registry Data in Low- and Middle-Income Countries - Current Status and Future Requirements Comment on "Neurotrauma Surveillance in National Registries of Low- and Middle-Income Countries: A Scoping Review and Comparative Analysis of Data Dictionaries".

Since 1990 National Trauma Registries, - taking the form of "not for profit" small and medium enterprises - have been integral to improvementsin major injury case fatality in high-income settings. This is laudable but unsatisfactory as globally most years of life lost to injury occur in low- and middle-income countries (LMICs). International Journal of Health Policy and Management, recently published a scoping review of neurotrauma registries in LMICs by Barthelemy et al; from this the commentary reflects on the state of the art and how these LMIC registries could be taken to "the next level" as meaningful tools for improving major injury patient care.

International primary knee arthroplasty registry review: findings from current reports.

International joint registries provide high volumes of information in relation to the performance of total knee arthroplasty on a global scale. Distillation of this data can be challenging, particularly with the establishment of more arthroplasty registries on a yearly basis. We therefore aim to present key information from these registries in relation to primary total knee arthroplasty. The specific questions of interest include: Which fixation type is superior in TKA? Does the level of constraint impact on clinical performance? How do partial knee replacements perform in the registries? Does patellar resurfacing lead to superior results? Are there any specific implants which perform particularly well or poorly? A comprehensive review of the major English-speaking knee arthroplasty registries across the globe was performed. Given the expanding large number of registries worldwide, it was not possible to perform a comprehensive review of all registries and so, a detailed review of the major English-speaking knee arthroplasty registries was included. Key trends and developments in implant performance were identified and presented in the current article. Total knee replacements have lower revision rates than both unicompartmental and patellofemoral joint replacement procedures. Patellofemoral joint replacements have the highest failure rate of all knee replacement procedures. Cruciate-Retaining (CR) TKR designs have superior outcomes to Posterior-Stabilized (PS) designs across all registries. Patellar resurfacing appears to confer an advantage over non-resurfaced patellas in primary TKR. We present current global trends in the utility and performance of TKA based on data from English-speaking arthroplasty registries.