Clinical Research Collaboration Research Articles

A worldwide look into Long COVID-19 management: an END-COVID survey

BackgroundLong COVID is a heterogeneous clinical syndrome characterised by a variety of reported symptoms and signs. Its clinical management is expected to differ significantly worldwide.MethodsA survey-based study investigating Long COVID-related standard operating procedures (SOPs) has been conducted by the European Respiratory Society (ERS) END-COVID clinical research collaboration with the support of other international societies (ALAT, APSR, CHEST, ESCMID, PATS). A global analysis of the results is provided here, alongside with sub-population analysis based on continents, national income levels, type of involved healthcare professionals and inclusion or exclusion of paediatric patients.Findings1015 healthcare professionals from 110 different countries worldwide participated in this study, the majority of them being respiratory physicians (60.6%). A dedicated Long COVID programme was present in 55.4% of the investigated institutions, with hospital admission during the acute infection being the main inclusion criteria to access them. Consistent differences in Long COVID-related procedures were identified among centres, mainly regarding the multidisciplinary approach, the availability of telemedicine and psychological support, the type of requested exams and the total amount of visits in the centre.InterpretationLong COVID management shows important differences related to geographical areas and national income levels. SOPs were significantly different when centres were managed by a pulmonologist or when paediatric patients were included.FundingERS has received funding to conduct this study by AstraZeneca UK Limited, Novartis Pharma AG, F. Hoffmann-La Roche Ltd, and Boehringer Ingelheim International GmbH.

Abstract PO1-14-01: Clonal Architecture of circulating tumor DNA predicts Early Progression on Tamoxifen With or Without Palbociclib in Hormone Receptor-Positive Advanced Breast Cancer: NCCH1607/PATHWAY trial

Abstract Objective: Some patients with poor prognosis hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC) experience early disease progression on the combination of CDK4/6 inhibitors and endocrine therapy. We aimed to determine whether clonal architecture assessed by circulating tumor DNA (ctDNA) could identify patients at higher risk of early progression on tamoxifen therapy with or without palbociclib. Methods: PATHWAY trial is a randomized, placebo-controlled, Asian international, double-blind, phase 3 study evaluating palbociclib plus tamoxifen (PAL+TAM) versus placebo plus tamoxifen (PLB+TAM) in pre/perimenopausal and postmenopausal women with HR+/HER2- ABC (NCT03423199). The study was conducted as a Clinical Research Collaboration with the National Cancer Center Hospital as the regulatory study sponsor and Pfizer providing drug and financial support. The primary endpoint was investigator assessed progression-free survival (PFS). Genomic profiling by next-generation sequencing was an exploratory endpoint to characterize molecular alterations in ctDNA and correlate these with clinical outcomes. Plasma samples were collected at cycle 1-day 1 (pre-treatment) and cycle 2-day 15 and sequenced with the Guardant360 assay (Guardant Health). Patients were included if they had a minimum of 14 days of treatment in the first cycle. The variant allele frequency (VAF) was defined as number of mutant molecules at a specific nucleotide location over the total number of molecules present in the background at a specific given genomic location. We assessed the gene with highest VAF as the dominant clone allele frequency (DCAF). The association of changes in ctDNA alterations with PFS was evaluated to identify biomarkers of early progression. Results: Pre-treatment plasma was successfully sequenced in 177 of the 184 patients; 88 patients treated with PAL+TAM, and 89 with PLB+TAM. ctDNA was detected in 144 (81.4%) patients; the median number of genetic abnormalities was 2 (range, 0-19). PIK3CA, TP53, ERBB2, ESR1, AKT1, EGFR and PTEN were the genes with highest VAF as the dominant clone (24.3%, 11.9%, 4.5%, 4.5%, 3.4%, 3.4%, 3.4%, respectively). The median DCAF was 1.79 (range, 0.1-81.23); PAL+TAM, 2.53 (range, 0.1-63.5) and PLB+TAM, 1.65 (range, 0.08-81.23). Patients with ≥ 2 detectable genomic alterations and DCAF ≥ 1.8% had worse PFS (hazard ratio (HR) 1.93 [95% confidence interval (CI): 1.375 to 2.721], p = 0.0003 and HR 1.95 [95% CI: 1.345 to 2.834], p < 0.0001, respectively) compared to all other patients. In addition, we evaluated whether changes of clonal architecture in ctDNA at early treatment time point (ie. Cycle 2 Day 15) are associated with PFS. Patients with increased DCAF had worse PFS on both PAL+TAM (HR 2.80 [95% CI: 0.552 to 14.15], p = 0.04) and PLB+TAM (HR 2.02 [95% CI: 1.022 to 3.990], p = 0.01). All patients with high pretreatment DCAF (≥ 1.8%) and increase in DCAF progressed within 1 year (n=5, 2 patients treated with PAL+TAM, and 3 with PLB+TAM). Conclusion: Evaluation of clonal architecture in ctDNA could support identification of HR+/HER2- ABC patients with poorer prognosis, who may be at higher risk of early progression, regardless of CDK4/6 inhibitor use. Citation Format: Yoon-Sim Yap, Yuki Kojima, Akinobu Hamada, Hirofumi Mukai, Yen-Shen Lu, Joo Hyuk Sohn, Yoshiko Umeyama, Emi Noguchi, Kazuki Sudo, Tomomi Hata, Aya Kuchiba, Taro Shibata, Shigehiro Yagishita, Masayuki Yoshida, Shinji Kohsaka, Kouya Shiraishi, Kenichi Nakamura, Kenji Tamura, Kan Yonemori. Clonal Architecture of circulating tumor DNA predicts Early Progression on Tamoxifen With or Without Palbociclib in Hormone Receptor-Positive Advanced Breast Cancer: NCCH1607/PATHWAY trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-14-01.

Implementing Standard Diagnosis and Treatment for Locally Advanced Breast Cancer Through Global Research in Latin America: Results From a Multicountry Pragmatic Trial.

Breast cancer mortality rates in Latin America (LA) are higher than those in the United States, possibly because of advanced disease presentation, health care disparities, or unfavorable molecular subtypes. The Latin American Cancer Research Network was established to address these challenges and to promote collaborative clinical research. The Molecular Profiling of Breast Cancer Study (MPBCS) aimed to evaluate the clinical characteristics and treatment outcomes of LA participants with locally advanced breast cancer (LABC). The MPBCS enrolled 1,449 participants from Argentina, Brazil, Chile, Mexico, and Uruguay. Through harmonized procedures and quality assurance measures, this study evaluated clinicopathologic characteristics, neoadjuvant chemotherapy response, and survival outcomes according to residual cancer burden (RCB) and the type of surgery. Overall, 711 and 480 participants in the primary surgery and neoadjuvant arms, respectively, completed the 5-year follow-up period. Overall survival was independently associated with RCB (worse survival for RCBIII-adjusted hazard ratio, 8.19, P < .001, and RCBII [adjusted hazard ratio, 3.69, P < .008] compared with RCB0 [pathologic complete response or pCR]) and type of surgery (worse survival in mastectomy than in breast-conserving surgery [BCS], adjusted hazard ratio, 2.97, P = .001). The hormone receptor-negative-human epidermal growth factor receptor 2-positive group had the highest proportion of pCR (48.9%). The analysis of the ASCO Quality Oncology Practice Initiative breast module revealed high compliance with pathologic standards but lower adherence to treatment administration standards. Notably, compliance with trastuzumab administration varied widely among countries (33.3%-88.7%). In LABC, we demonstrated the survival benefit of BCS and the prognostic effect of the response to available neoadjuvant treatments despite an important variability in access to key treatments. The MPBCS represents a significant step forward in understanding the real-world implementation of oncologic procedures in LA.

Cultural Adaptation of the Functional External Memory Aid Tool for Use in the United Kingdom and Australia

Purpose: The Functional External Memory Aid Tool (FEMAT) is a performance-based measure of applied cognitive-linguistic abilities and attempted use of compensatory aids and strategies (e.g., using a calendar to recall an appointment) through completion of simulated everyday living tasks. The FEMAT was originally developed in the United States (US), and a need arose from clinicians to adapt the FEMAT for use in other countries. The aim of this study is to describe the cultural adaptation process that resulted in the United Kingdom (UK) and Australian (AU) versions of the FEMAT via international clinical research partnerships. Method: The FEMAT was adapted into UK and AU cultures using established guidelines for cultural and linguistic adaptation. The adaptation was completed by researchers and clinicians from the US, UK, and AU, and we followed a six-step process: (a) preparation, (b) forward translation, (c) back translation, (d) committee review, (e) field testing, and (f) finalization. Results: The FEMAT items and materials were successfully adapted from the source culture (i.e., English-US) to the target cultures (i.e., English-UK, English-AU). Through the adaptation process, the FEMAT items were determined to be conceptually appropriate for each culture and minimal modifications were made to the FEMAT materials (e.g., voicemail recordings recorded in target dialect). The finalized FEMAT-English-UK and the FEMAT-English-AU versions are available for free on the FEMAT website. Conclusions: Through successful international clinical research collaborations, the FEMAT was successfully adapted for use in other English-speaking cultures. This work provides guidance to streamline future FEMAT cultural adaptations. Supplemental Material: https://doi.org/10.23641/asha.25564461

Current usage of explainer animations in trials: a survey of the UKCRC registered clinical trial units in the UK

BackgroundExplainer animations are a means to communicate aspects of clinical trials to participants in a more engaging and accessible way. Delivered well these have the potential to enhance recruitment and retention. The range of media technology used to deliver this material is expanding rapidly but is highly fragmented. Usage of explainer animations across the UK is unknown, the aim of this research was to determine current usage across the 52 registered UK Clinical Research Collaboration (UKCRC) Clinical Trials Units (CTUs) to understand the current landscape and any barriers that could be preventing wider uptake of this functionality.MethodsA survey link was emailed to all UKCRC CTU Directors and Trial Management Leads to ascertain current usage of explainer animations within their CTU. The survey ran between 01 February 2023 and 07 March 2023.ResultsResponses were received from 35 CTUs—representing a response rate of 67%. 24 CTUs (69%) reported that they had created/used at least one explainer animation within their unit, although the usage, cost, length and production activities varied among the units.ConclusionsThe survey showed that a high proportion of the UKCRC CTUs have used explainer animations to provide information to participants about clinical studies. For those not using the technology yet, the most common reasons cited were a lack of expertise, lack of resources and costs to produce them. One of the desired outcomes of this project is the creation of a free-to-use library of animations to encourage wider uptake and avoid duplication.

Good Statistical Practice—development of tailored Good Clinical Practice training for statisticians

BackgroundStatisticians are fundamental in ensuring clinical research, including clinical trials, are conducted with quality, transparency, reproducibility and integrity. Good Clinical Practice (GCP) is an international quality standard for the conduct of clinical trials research. Statisticians are required to undertake training on GCP but existing training is generic and, crucially, does not cover statistical activities. This results in statisticians undertaking training mostly unrelated to their role and variation in awareness and implementation of relevant regulatory requirements with regards to statistical conduct. The need for role-relevant training is recognised by the UK NHS Health Research Authority and the Medicines and Healthcare products Regulatory Agency (MHRA).MethodsThe Good Statistical Practice (GCP for Statisticians) project was instigated by the UK Clinical Research Collaboration (UKCRC) Registered Clinical Trials Unit (CTU) Statisticians Operational Group and funded by the National Institute for Health and Care Research (NIHR), to develop materials to enable role-specific GCP training tailored to statisticians. Review of current GCP training was undertaken by survey. Development of training materials were based on MHRA GCP. Critical review and piloting was conducted with UKCRC CTU and NIHR researchers with comment from MHRA. Final review was conducted through the UKCRC CTU Statistics group.ResultsThe survey confirmed the need and desire for the development of dedicated GCP training for statisticians. An accessible, comprehensive, piloted training package was developed tailored to statisticians working in clinical research, particularly the clinical trials arena. The training materials cover legislation and guidance for best practice across all clinical trial processes with statistical involvement, including exercises and real-life scenarios to bridge the gap between theory and practice. Comprehensive feedback was incorporated. The training materials are freely available for national and international adoption.ConclusionAll research staff should have training in GCP yet the training undertaken by most academic statisticians does not cover activities related to their role. The Good Statistical Practice (GCP for Statisticians) project has developed and extensively piloted new, role-specific, comprehensive, accessible GCP training tailored to statisticians working in clinical research, particularly the clinical trials arena. This role-specific training will encourage best practice, leading to transparent and reproducible statistical activity, as required by regulatory authorities and funders.

Impact of childhood 13-valent pneumococcal conjugate vaccine introduction on adult pneumonia hospitalisations in Mongolia: a time series analysis

IntroductionFew studies have assessed the potential indirect effects of childhood pneumococcal conjugate vaccine (PCV) programs on the adult pneumonia burden in resource-limited settings. We evaluated the impact of childhood PCV13 immunisation on adult all-cause pneumonia following a phased program introduction from 2016. MethodsWe conducted a time-series analysis to assess changes in pneumonia hospitalisation incidence at four district hospitals in Mongolia. Adults (≥18 years) that met the clinical case definition for all-cause pneumonia were enrolled. A negative binomial mixed-effects model was used to assess the impact of PCV13 introduction on monthly counts of pneumonia admissions from January 2015—February 2022. We also performed a restricted analysis excluding the COVID-19 pandemic period. All models were stratified by age and assessed separately. Additional analyses assessed the robustness of our findings. FindingsThe average annual incidence of all-cause pneumonia hospitalisation was highest in adults 65+ years (62·81 per 10,000 population) and declined with decreasing age. After adjusting for the COVID-19 pandemic period, we found that rates of pneumonia hospitalisation remained largely unchanged over time. We did not observe a reduction in pneumonia hospitalisations in any age group. Results from restricted and sensitivity analyses were comparable to the primary results, finding limited evidence of a reduced pneumonia burden. InterpretationWe did not find evidence of indirect protection against all-cause pneumonia in adults following childhood PCV13 introduction. Direct pneumococcal vaccination and other interventions should be considered to reduce burden of pneumonia among older adults. FundingPfizer clinical research collaboration agreement (contract number: WI236621).

Is the mechanism of synchronous cardiocerebral infarction (CCI) different from that of metachronous CCI?

Background: Cardiocerebral infarction (CCI) is the simultaneous occurrence of acute ischemic stroke (AIS) and myocardial infarction (MI) at the same time (synchronous), or one after another (metachronous). This study aimed to investigate the differences in the underlying mechanisms between synchronous and metachronous CCI. Methods: This study analyzed patients with AIS registered in the Clinical Research Collaboration for Stroke in Korea Prospective Registry at a single Stroke Center from January 2019 to December 2022. Patients with synchronous and metachronous CCI (MI within 72 hours after AIS) were included. Severity at admission and modified Rankin Scale scores 3 months after treatment were assessed.Results: Among 3,319 AIS patients, 12 (0.36%) were diagnosed with acute CCI (male: 8; mean age, 69.614.0 years). Of these, six (0.18%) had synchronous CCI, while the other six had metachronous CCI. The synchronous CCI group exhibited lower neurological severity at admission than the metachronous CCI group (median National Institutes of Health Stroke Scale, 3.5 vs. 12.5). Among the 12 patients, seven (58%) had ST-elevation myocardial infarction (STEMI), with five (83%) of the synchronous CCI cases presenting as STEMI. Two cases of new-onset atrial fibrillation occurred exclusively in patients with synchronous CCI. Also, one case with synchronous CCI had a thrombus in the left ventricle.Conclusion: Acute CCI is rare and manifests with varying degrees of severity. Our study suggests that AIS in synchronous CCI may be secondary to embolism caused by a preceding MI. In contrast, metachronous CCI exhibits diverse mechanisms, including secondary myocardial injury resulting from a preceding severe AIS.

International Collaborative Clinical Research (ICCR) Conference Abstracts

International Collaborative Clinical Research (ICCR) Conference Abstracts

Primary and secondary care collaboration in clinical research

More patients are seen in primary care than in any other part of the health system in the UK. Our NHS datasets are the envy of the world and provide us with huge opportunities to support our patients and populations. In this paper, we demonstrate the breadth of primary care research, recruitment and delivery options. We show how research can affect many different aspects of patient care and demonstrate, through the delivery and publication of game-changing research, the ability of recruitment in primary care to answer questions that are relevant to secondary care activity. Indeed, these complex and innovative study designs and their collaborative delivery across the multitude of diseases (acute and chronic) show the strength of primary care. Collaboration across boundaries, specialties and healthcare settings will provide increased opportunities for clinical research development and, most importantly, deliver the highest quality research to support our patients.

Establishment and implementation of a regional mucosal training program to facilitate multi-center collaboration in basic and clinical research in Eastern Africa

Background: The recent outbreaks of novel endemic and pandemic diseases have highlighted the importance of collaborative networks in rapid response to emerging pathogens. Over the last two decades International AIDS Vaccine Initiative (IAVI), with the support of United States Agency for International Development (USAID) and other international donors, has invested in research capacity and infrastructure in Africa. A significant portion of this support has facilitated establishing regional centers of excellence for African scientists to develop and lead a collaborative research agenda, implemented within the IAVI-led Accelerate the Development of Vaccines and New Technologies to Combat the AIDS Epidemic (ADVANCE) program. One such regional center is the University of Nairobi’s Kenya AIDS Vaccine Initiative-Institute of Clinical Research (KAVI-ICR). Objective: We designed and implemented a development program to foster inter-institutional South-South technology transfer within Africa, and address a capacity gap in mucosal research. Methods: KAVI-ICR and IAVI developed standardized mucosal sample collection, processing and technical assay methods; these were subsequently applied into several observational studies, and Phase I HIV vaccines, Varicella zoster virus vaccine, and broadly neutralizing antibodies clinical trials at KAVI-ICR. Thereafter, KAVI-ICR facilitated the technology transfer of the methods, by training staff at regional establishments in Africa. Results: Twelve standardized methodologies were developed for the collection, processing and storage of 10 mucosal sample types. Subsequently, eight regional research centers received training for a variety of clinical and laboratory methodologies; the centers later applied the techniques in follow-up collaborative research. Additionally, the training fostered collaboration while allowing the development of local networks of research groups. Conclusion: By such South-South initiatives, supported by international donors, the development of regional capacity and expertise is realizable. The established expertise can be leveraged when needed, and builds the capability for African scientists to engage at an international level, actively participating in driving internationally relevant research.

Sex-related differences in functional capacity and its implications in risk stratification before major non-cardiac surgery: a post hoc analysis of the international METS study

Poor functional capacity has been identified as an important modifiable risk factor for postoperative complications. Cardiopulmonary exercise testing (CPET) provides objective parameters of functional capacity (e.g., oxygen consumption at peak exercise, peak VO2), with significant prognostication for postoperative complications. However, sex-specific thresholds for functional capacity to predict surgical risk are yet to be established. Therefore, we performed a post hoc analysis of the international, multicentre, prospective observational METS (Measurement of Exercise Tolerance before Surgery) study to evaluate if sex-specific thresholds of peak VO2 improve risk prediction of postoperative complications. We undertook a post hoc analysis (HREC/71824/PMCC) of the METS study, which was performed between March 2013 and March 2016. We investigated whether sex-specific differences exist for CPET-derived parameters and associated thresholds for predicting postoperative complications in this large cohort of patients that had major non-cardiac surgery (n=1266). Logistic regression models were analyzed for the association of low peak VO2 with moderate-to-severe in-hospital postoperative complications. Optimal sex-specific peak VO2 thresholds were obtained by maximizing the Youden index of receiver operating characteristic (ROC) curves. Finally, multivariable logistic regression models tested the resulting sex-specific thresholds against the established non-sex-specific peak VO2 threshold (14mLkg-1 min-1) adjusted for clinically relevant features such as comorbidities and surgical complexity. Models were evaluated by bootstrapping optimism-corrected area under the ROC curve and the net reclassification improvement index (NRI). Female patients (n=480) had a lower mean (SD) peak VO2 than males (16.7 (4.9) mL kg-1 min-1 versus 21.2 (6.5) mL kg-1 min-1, p<0.001) and a lower postoperative complication rate (10.4% versus 15.3%; p=0.018) than males (n=786). The optimal peak VO2 threshold for predicting postoperative complications was 12.4mLkg-1 min-1 for females and 22.3mLkg-1 min-1 for males, respectively. In the multivariable regression model, low non-sex-specific peak VO2 did not independently predict postoperative complications. In contrast, low sex-specific peak VO2 was an independent predictor of postoperative complications (OR 2.29; 95% CI: 1.60, 3.30; p<0.001). The optimism-corrected AUC-ROC of the sex-specific model was higher compared with the non-sex-specific model (0.73 versus 0.7; DeLong's test: p=0.021). The sex-specific model classified 39% of the patients more correctly than the baseline model (NRI=0.39; 95% CI: 0.24, 0.55). In contrast, the non-sex-specific model only classified 9% of the patients more correctly when compared against the baseline model (NRI=0.09; 95% CI:-0.04, 0.22). Our data report sex-specific differences in preoperative CPET-derived functional capacity parameters. Sex-specific peak VO2 thresholds identify patients at increased risk for postoperative complications with a higher discriminatory ability than a sex-unspecific threshold. As such, sex-specific threshold values should be considered in preoperative CPET to potentially improve risk stratification and to guide surgical decision-making, including eligibility for surgery, preoperative optimization strategies (prehabilitation) or seeking non-surgical options. There was no funding for the present study. The original METS study was funded by Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research, Innovation and Science, UK National Institute of Academic Anaesthesia, UK Clinical Research Collaboration, Australian and New Zealand College of Anaesthetists, and Monash University.

Association of HbA1c with functional outcome by ischemic stroke subtypes and age.

To determine whether high HbA1c levels are related to short-and long-term functional outcomes in patients with ischemic stroke (IS) and whether this association differs according to the IS subtype and the patient's age. The data of 7,380 IS patients admitted to 16 hospitals or regional stroke centers in South-Korea, between May 2017 and December 2019, were obtained from the Clinical Research Collaboration for Stroke-Korea-National Institute of Health database and retrospectively analyzed. Among these patients, 4,598 were followed-up for one-year. The HbA1c levels were classified into three groups (<5.7, 5.7 to <6.5%, ≥6.5%). Short-and long-term poor functional outcomes were defined using the modified Rankin Scale score of 2 to 6 at three-months and one-year, respectively. IS subtypes were categorized according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. There was an association between higher HbA1c (≥6.5%) and poor functional outcomes at three-months in all patients (three-months; OR, 1.299, 95% CI 1.098, 1.535, one-year; OR, 1.181, 95% CI 0.952, 1.465). When grouped by age, the associations after both 3 months and 1 year observed in younger adult group (<65 years), but not in group aged 65 years and older (three-months; <65 years OR, 1.467, 95% CI 1.112, 1.936, ≥65 years OR, 1.220, 95% CI 0.987, 1.507, p for interaction = 0.038, one-year; <65 years OR, 1.622, 95% CI 1.101, 2.388, ≥65 years OR, 1.010, 95% CI 0.778, 1.312, p for interaction = 0.018). Among younger adult group, the higher HbA1c level was related to short-and long-term functional loss in patients with the small vessel occlusion subtype (three-months; OR, 2.337, 95%CI 1.334, 4.095, one-year; OR, 3.004, 95% CI 1.301, 6.938). However, in patients with other TOAST subtypes, a high HbA1c level did not increase the risk of poor outcomes, regardless of the age of onset. High HbA1c levels increase the risk of short-and long-term poor functional outcomes after IS onset. However, this association differs according to stroke subtype and age. Thus, pre-stroke hyperglycemia, reflected by HbA1c, may be a significant predictor for a poor prognosis after ischemic stroke, particular in young- and middle-aged adults.

Australia and New Zealand Clinical Motion Analysis Group (ANZ-CMAG) clinical practice recommendations

Clinical motion analysis involves quantitative measurement of gait patterns to identify gait anomalies that currently or have the potential to impact function, activities of daily living and participation. Clinical motion analysis services are equipped with motion capture technology and comprise specialised staff who deliver 3-dimensional motion analysis services to children and adults who present with varying levels of gait impairment. Data is then used to inform intervention recommendations to clinicians with a view to maintaining independent, functional and pain free walking (or appropriate mobility).The ANZ-CMAG (established in 2013) identified a need to establish recommendations to assist in standardising practice guidelines for both current and new clinical motion analysis services within the region. The group serves to promote collaboration between services in quality assurance processes, clinical practices, data sets and research activities. The clinical practice recommendations described in this paper cover: i) requirements for a motion analysis service (including staffing, facilities and equipment), ii) patient assessments (requirements, clinical information and data gathered, reporting and interpretation of patient data), iii) quality assurance processes (including motion capture system / biomechanical models & limitations, marker placement, data storage / record keeping, creation of normative dataset); iv) helpful resources.Better outcomes for children and adults with gait deviations is dependent upon accurate measurement and evaluation of walking and requires input from multidisciplinary clinical teams with specialist knowledge and skills. The ANZ-CMAG hopes these clinical practice recommendations are beneficial to motion analysis services with an aim to improve clinical practices, patient outcomes, and support research collaboration.

Phenotyping asthma with airflow obstruction in middle-aged and older adults: a CADSET clinical research collaboration

BackgroundThe prevalence and clinical profile of asthma with airflow obstruction (AO) remain uncertain. We aimed to phenotype AO in population- and clinic-based cohorts.MethodsThis cross-sectional multicohort study included adults ≥50 years...

Comparison of Hospital Performance in Acute Ischemic Stroke Based on Mortality and Functional Outcome in South Korea.

Recent evidence suggests a correlation between modified Rankin Scale-based measures, an outcome measure commonly used in acute stroke trials, and mortality-based measures used by health agencies in the evaluation of hospital performance. We aimed to examine whether the 2 types of measures are interchangeable in relation to evaluation of hospital performance in acute ischemic stroke. Five outcome measures, unfavorable functional outcome (3-month modified Rankin Scale score ≥2), death or dependency (3-month modified Rankin Scale score ≥3), 1-month mortality, 3-month mortality, and 1-year mortality, were collected for 8292 individuals who were hospitalized for acute ischemic stroke between January 2014 and May 2015 in 14 hospitals participating in the Clinical Research Collaboration for Stroke in Korea - National Institute of Health registry. Hierarchical regression models were used to calculate per-hospital risk-adjusted outcome rates for each measure. Hospitals were ranked and grouped based on the risk-adjusted outcome rates, and the correlations between the modified Rankin Scale-based and mortality-based ranking and their intermeasure reliability in categorizing hospital performance were analyzed. The comparison between the ranking based on the unfavorable functional outcome and that based on 1-year mortality resulted in a Spearman correlation coefficient of -0.29 and Kendall rank coefficient of -0.23, and the comparison of grouping based on these 2 types of ranks resulted in a weighted kappa of 0.123 for the grouping in the top 33%/middle 33%/bottom 33% and 0.25 for the grouping in the top 20%/middle 60%/bottom 20%, respectively. No significant correlation or similarity in grouping capacities were found between the rankings based on the functional outcome measures and those based on the mortality measures. This study shows that regardless of clinical correlation at an individual patient level, functional outcome-based measures and mortality-based measures are not interchangeable in the evaluation of hospital performance in acute ischemic stroke.

Chronic Pain Research Program—Pain Management Collaborative Clinical Research Award (DOD)

Chronic Pain Research Program—Pain Management Collaborative Clinical Research Award (DOD)

Palbociclib (P) plus tamoxifen (TAM) ± goserelin in women with hormone receptor-positive (HR+)/HER2-negative (HER2−) advanced breast cancer (ABC): Primary results of NCCH1607/PATHWAY, an Asian international double-blind randomized phase 3 trial.

LBA1068 Background: In Asian countries, BC incidence rates are rising, with a higher proportion of pre/perimenopausal (pre/peri-M) patients (pts). Data on treatment options for pre/peri-M pts are limited. Adding P to endocrine therapy (ET), such as aromatase inhibitor or fulvestrant, has improved progression-free survival (PFS) in phase 3 studies. However, the efficacy and safety of P in combination with TAM are still unclear in pts with HR+/HER2− ABC regardless of M status. This combination was investigated in PATHWAY (NCT03423199): a double-blind randomized phase 3 trial conducted in Japan, Korea, Taiwan and Singapore. The study was conducted as a Clinical Research Collaboration with the National Cancer Center Hospital being the regulatory sponsor and Pfizer providing drug and financial support. Methods: Women with HR+/HER2− ABC were randomly assigned 1:1 to receive either P (125 mg once daily, days 1-21 of a 28-day cycle) or placebo in combination with TAM (20 mg once daily, continuously) as 1st or 2nd line treatment for ABC. Pre/peri-M women received concurrent ovarian function suppression with goserelin. Pts were stratified by 1st vs 2nd line ET and M status. The primary endpoint was PFS as assessed by investigators. Secondary endpoints include overall survival (OS), objective response, safety, and patient-reported outcomes. Results: A total of 184 pts were assigned to P + TAM (91 pts) and placebo + TAM (93 pts). At data cutoff date (Sep 15, 2022), 138 PFS events had occurred. Median follow-up was 40.9 months for censored pts. Median PFS was 24.4 months (95% CI: 13.1, 32.4) with P + TAM and 11.1 months (95% CI: 7.4, 14.6) with placebo + TAM (hazard ratio [HR]: 0.602 [95% CI: 0.428, 0.848], 1-sided p-value from stratified log rank test: 0.002). The HRs for PFS of the subgroups by stratification factors were as follows: for pts with 1st line ET (HR: 0.521 [95% CI: 0.332, 0.817]) or with 2nd line ET (HR: 0.707 [95% CI: 0.421, 1.189]), and for pre/peri-M pts (HR: 0.378 [95% CI: 0.192, 0.742]) or post-M pts (HR: 0.677 [95% CI: 0.456, 1.005]). While OS data were still immature, the primary analysis showed a 27% reduction in overall risk of death (median OS: not reached in both arms, HR: 0.73 [95% CI: 0.442, 1.207]). 93.4% of pts with P + TAM vs. 20.4% of pts with placebo + TAM had grade (G) ≥3 treatment-emergent adverse events (TEAEs). The most frequently observed G ≥3 TEAE was neutropenia (89.0% in P + TAM arm and 1.1% in placebo + TAM arm). There were no G5 TEAEs in either arm. Conclusions: The study achieved its primary endpoint, demonstrating a significant and clinically meaningful improvement in PFS for P + TAM compared with placebo + TAM for pts with HR+/HER2− ABC. Early OS data with P+TAM is encouraging. TEAEs were generally consistent with the known safety profile of P and ET. Clinical trial information: NCT03423199 .

A century of retroperitoneal soft-tissue sarcoma research: From single center experience to precision oncology? A bibliometric analysis of past, present, and future perspectives

BackgroundIncreasing publication numbers in the biomedical field led to an improvement of patient care in many aspects but are challenging for scientists when integratively processing data of their fields. Using bibliometric analyses, the present study assesses the productivity and predominant topics in retroperitoneal soft-tissue sarcoma (RPS) research across the past 122 years, thereby identifying crucial questions to address in future RPS research. MethodsUsing the Web of Science Core Collection, 1018 RPS-associated publications from 1900 to 2022 were identified and analyzed regarding key bibliometric variables using the Bibliometrix R package and the VOSviewer software. ResultsA continuous increase in RPS-associated publication numbers can be noticed over the time, which is strongly pronounced from 2005 onwards, and is characterized by a multinationally driven collaborative clinical research focus. The research primarily reflects progression regarding surgical techniques, histology-based therapy, radiotherapy regimens, and identification of prognostic clinicopathological factors. This progression is accompanied with improved overall survival of RPS patients. However, a paucity of RPS-specific basic/translational research indicates that such research might be additionally needed to better understand the pathophysiology of RPS and with that to enable the development of personalized therapies and to further improve patient outcome. ConclusionIncreasing publication numbers of multinationally driven clinical RPS research are accompanied with improved overall survival of RPS patients, highlighting the importance of international collaborations to facilitate future clinical trials. However, this bibliometric analysis reveals a lack of RPS-specific basic/translational research which is needed to further improve patient outcome in the context of precision oncology.

The feasibility of utilising a cloud-based storage and analysis software in multicentre clinical electrophysiology research

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): BioSense Webster Investigator Initiated Study (IIS) Grant. Introduction The COVID-19 pandemic enforced long-term changes in healthcare towards remote working, implementing digital systems that support the safe online sharing of clinical information. A cloud-based storage and analysis software has been developed that uploads 3D mapping cases within the CARTO-3 system for remote review. In addition, it uses artificial intelligence/ machine learning to analyse large procedural datasets. We tested the feasibility of this technology as a future research tool in analysing the first 8 cases recruited to the Ripple AT PLUS study. Methods The Ripple AT PLUS trial is a planned multicentre randomised trial comparing ablation outcomes in scar based atrial tachycardia (AT) using different CARTO mapping approaches. The study recently commenced recruitment (September 2022). The CARTO files for the first 8 cases recruited into this study from different hospitals were securely transferred from CARTO 3 workstations to the Siemens teamplay gateway. Patient identifiers were removed, and anonymized datasets were successfully uploaded onto CARTONET Microsoft Azure cloud. A secure Web-site (https://eu.cartonet.net/login) was accessed for remote review by the research team. Results Uploaded study cases were readily separated from other clinical cases using a research filter. Figure 1 summarises graphical datasets for these study cases presented by CARTONET, (including total procedural duration, mapping vs ablation times, ablation lesions). Their corresponding numerical values were exportable as a Microsoft Excel spreadsheet for individualised review. More detailed mapping and ablation analytics within each case was feasible – this is exemplified in figure 2A, which presents a histogram of the proportion of acquired electrogram bipolar voltages below a modifiable cut-off (0.20mV in this example). Individual case data was easily extracted and combined from all study cases to test different hypothesis – again exemplified in figure 2B, which ascertains how tissue voltage might affect the amount of ablation delivered. Conclusion CARTONET is a secure, simple to use, and efficient cloud-based AI/machine learning system that offers access to clinically relevant data-sets from the CARTO system remotely from the hospital premises. This allows for a variety of rapid analytics, with the potential to improve the efficiency of multicentre clinical electrophysiology research collaboration.