Multinational Retrospective Cohort Study Research Articles

The prevalence of polypharmacy in older Europeans: A multi-national database study of general practitioner prescribing.

The aims of this study were to measure the prevalence of polypharmacy and describe the prescribing of selected medications known for overuse in older people with polypharmacy in primary care. This was a multinational retrospective cohort study across six countries: Belgium, France, Germany, Italy, Spain and the UK. We used anonymized longitudinal patient-level information from general practice databases hosted by IQVIA. Patients ≥65 years were included. Polypharmacy was defined as having 5-9 and ≥10 distinct drug classes (ATC Level 3) prescribed during a 6-month period. Selected medications were: opioids, antipsychotics, proton pump inhibitors (PPI), benzodiazepines (ATC Level 5). We included country experts on the healthcare context to interpret findings. Age and gender distribution was similar across the six countries (mean age 75-76 years; 54-56% female). The prevalence of polypharmacy of 5-9 drugs was 22.8% (UK) to 58.3% (Germany); ≥10 drugs from 11.3% (UK) to 28.5% (Germany). In the polypharmacy population prescribed ≥5 drugs, opioid prescribing ranged from 11.5% (France) to 27.5% (Spain). Prescribing of PPI was highest with almost half of patients receiving a PPI, 42.3% (Germany) to 65.5% (Spain). Benzodiazepine prescribing showed a marked variation between countries, 2.7% (UK) to 34.9% (Spain). The healthcare context information explained possible underreporting for selected medications. We have found a high prevalence of polypharmacy with more than half of the older population being prescribed ≥5 drugs in four of the six countries. Whilst polypharmacy may be appropriate in many patients, worryingly high usage of PPIs and benzodiazepines supports current efforts to improve polypharmacy management across Europe.

A comparison of outcomes including bile duct injury of subtotal cholecystectomy versus open total cholecystectomy as bailout procedures for severe cholecystitis: A multicenter real-world study

BackgroundDense inflammation obscuring the hepatocystic anatomy can hinder the ability to perform a safe standard laparoscopic cholecystectomy in severe cholecystitis, requiring use of a bailout procedure. We compared clinical outcomes of laparoscopic and open subtotal cholecystectomy against the traditional standard of open total cholecystectomy to identify the optimal bailout strategy for the difficult gallbladder. MethodsA multicenter, multinational retrospective cohort study of patients who underwent bailout procedures for severe cholecystitis. Procedures were compared using one-way analysis of variance/Kruskal-Wallis tests and χ2 tests with multiple pairwise comparisons, maintaining a family-wise error rate at 0.05. Multiple multivariate linear/logistical regression models were created. ResultsIn 11 centers, 727 bailout procedures were conducted: 317 laparoscopic subtotal cholecystectomies, 172 open subtotal cholecystectomies, and 238 open cholecystectomies. Baseline characteristics were similar among subgroups. Bile leak was common in laparoscopic and open fenestrating subtotal cholecystectomies, with increased intraoperative drain placements and postoperative endoscopic retrograde cholangiopancreatography(P < .05). In contrast, intraoperative bleeding (odds ratio = 3.71 [1.9, 7.22]), surgical site infection (odds ratio = 2.41 [1.09, 5.3]), intensive care unit admission (odds ratio = 2.65 [1.51, 4.63]), and length of stay (Δ = 2 days, P < .001) were higher in open procedures. Reoperation rates were higher for open reconstituting subtotal cholecystectomies (odds ratio = 3.43 [1.03, 11.44]) than other subtypes. The overall rate of bile duct injury was 1.1% and was not statistically different between groups. Laparoscopic subtotal cholecystectomy had a bile duct injury rate of 0.63%. ConclusionLaparoscopic subtotal cholecystectomy is a feasible surgical bailout procedure in cases of severe cholecystitis where standard laparoscopic cholecystectomy may carry undue risk of bile duct injury. Open cholecystectomy remains a reasonable option.

Time to Continuous Renal Replacement Therapy Initiation and 90-Day Major Adverse Kidney Events in Children and Young Adults

In clinical trials, the early or accelerated continuous renal replacement therapy (CRRT) initiation strategy among adults with acute kidney injury or volume overload has not demonstrated a survival benefit. Whether the timing of initiation of CRRT is associated with outcomes among children and young adults is unknown. To determine whether timing of CRRT initiation, with and without consideration of volume overload (VO; <10% vs ≥10%), is associated with major adverse kidney events at 90 days (MAKE-90). This multinational retrospective cohort study was conducted using data from the Worldwide Exploration of Renal Replacement Outcome Collaborative in Kidney Disease (WE-ROCK) registry from 2015 to 2021. Participants included children and young adults (birth to 25 years) receiving CRRT for acute kidney injury or VO at 32 centers across 7 countries. Statistical analysis was performed from February to July 2023. The primary exposure was time to CRRT initiation from intensive care unit admission. The primary outcome was MAKE-90 (death, dialysis dependence, or persistent kidney dysfunction [>25% decline in estimated glomerular filtration rate from baseline]). Data from 996 patients were entered into the registry. After exclusions (n = 27), 969 patients (440 [45.4%] female; 16 (1.9%) American Indian or Alaska Native, 40 (4.7%) Asian or Pacific Islander, 127 (14.9%) Black, 652 (76.4%) White, 18 (2.1%) more than 1 race; median [IQR] patient age, 8.8 [1.7-15.0] years) with data for the primary outcome (MAKE-90) were included. Median (IQR) time to CRRT initiation was 2 (1-6) days. MAKE-90 occurred in 630 patients (65.0%), of which 368 (58.4%) died. Among the 601 patients who survived, 262 (43.6%) had persistent kidney dysfunction. Of patients with persistent dysfunction, 91 (34.7%) were dependent on dialysis. Time to CRRT initiation was approximately 1 day longer among those with MAKE-90 (median [IQR], 3 [1-8] days vs 2 [1-4] days; P = .002). In the generalized propensity score-weighted regression, there were approximately 3% higher odds of MAKE-90 for each 1-day delay in CRRT initiation (odds ratio, 1.03 [95% CI, 1.02-1.04]). In this cohort study of children and young adults receiving CRRT, longer time to CRRT initiation was associated with greater risk of MAKE-90 outcomes, in particular, mortality. These findings suggest that prospective multicenter studies are needed to further delineate the appropriate time to initiate CRRT and the interaction between CRRT initiation timing and VO to continue to improve survival and reduce morbidity in this population.

Modified physiologic criteria for the field triage scheme: Efficacy of major trauma recognition in different age groups in Asia

BackgroundMajor trauma is a leading cause of unexpected death globally, with increasing age-adjusted death rates for unintentional injuries. Field triage schemes (FTSs) assist emergency medical technicians in identifying appropriate medical care facilities for patients. While full FTSs may improve sensitivity, step-by-step field triage is time-consuming. A simplified FTS (sFTS) that uses only physiological and anatomical criteria may offer a more rapid decision-making process. However, evidence for this approach is limited, and its performance in identifying all age groups requiring trauma center resources in Asia remains unclear. MethodsWe conducted a multinational retrospective cohort study involving adult trauma patients admitted to emergency departments in the included countries from 2016 to 2020. Prehospital and hospital data were reviewed from the Pan-Asia Trauma Outcomes Study database. Patients aged ≥18 years transported by emergency medical services were included. Patients lacking data regarding age, sex, physiological criteria, or injury severity scores were excluded. We examined the performance of sFTS in all age groups and fine-tuned physiological criteria to improve sFTS performance in identifying high-risk trauma patients in different age groups. ResultsThe sensitivity and specificity of the physiological and anatomical criteria for identifying major trauma (injury severity score ≥ 16) were 80.6% and 58.8%, respectively. The modified sFTS showed increased sensitivity and decreased specificity, with more pronounced changes in the young age group. Adding the shock index further increased sensitivity in both age groups. ConclusionssFTS using only physiological and anatomical criteria is suboptimal for Asian adult patients with trauma of all age groups. Adjusting the physiological criteria and adding a shock index as a triage tool can improve the sensitivity of severely injured patients, particularly in young age groups. A swift field triage process can maintain acceptable sensitivity and specificity in severely injured patients.

Abstract 374: Modified Physiologic Criteria for the Field Triage Scheme: Efficacy of Major Trauma Recognition in Different Age Groups Across Asia

Introduction: Identifying patients with major trauma in prehospital settings by Field Triage Scheme (FTS) is of paramount importance. The goal of the FTS was set with a sensitivity (Sn) of 95% and specificity (Sp) of 50% to identify patients with major trauma, although many studies showed it unachievable. A simplified FTS (sFTS) may offer a more rapid prehospital triage of patients. However, evidence of its accuracy remains unclear. Hypothesis: We examined the performance of identifying patients with major trauma by triage tools of sFTS, modified sFTS, and adding shock index (SI) in different age groups. Methods: We conducted a multinational retrospective cohort study involving a total of 51,622 adult trauma patients in the studied countries from 2016 to 2020, using data from the Pan-Asia Trauma Outcomes Study. We tested (1) sFTS comprising only physiological and anatomical criteria, (2) modified sFTS defined by fine-tuning the physiological criteria of GCS score &lt; 15, respiratory rate &lt;10 or ≥ 24 beats/minute, and systolic blood pressure &lt; 110 mmHg, and (3) sequentially added a SI of ≧0.8, to compare their performance in identifying patients with major trauma. Major trauma was defined by injury severity score ≥ 16. The cubic-spline method was used to smooth the curves of Sn/Sp across ages. Results: The overall sensitivity and specificity of the sFTS, modified sFTS, and adding SI of 0.8 to modified sFTS were, 80.6%, 82.8%, 84.3%, and 58.5%, 53.7%, 49.2%, respectively. The trade-off of Sn/Sp was illustrated in Figure 1. The top Sn/Sp of the three triage tools was constantly at patients’ age of 50, with rapidly declining in both younger and older patients. The modified sFTS showed increasing sensitivity with more pronounced changes in the younger group. Adding the shock index further increased sensitivity in both younger and older groups.

Prevalence, risk factors and outcomes of cardiac disease in cystic fibrosis: a multinational retrospective cohort study.

Although people living with cystic fibrosis (PwCF) often have some risk factors for cardiovascular disease, including diabetes and chronic inflammation, little is known about the long-term cardiac risk in this condition. We aimed to determine the characteristics, rates and outcomes for cardiac disease in CF. We looked at rates and outcomes for cardiac disease in 5649 adult PwCF in the UK CF Registry and 6265 adult PwCF in TriNetX (a global federated database of electronic healthcare record data). We used propensity matching to compare risk of major adverse cardiac events (MACE) (myocardial infarction, left-sided heart failure and atrial fibrillation) in PwCF against matched non-CF comparators in the general population and other inflammatory diseases. PwCF had a high prevalence of diabetes but low rates of hypertension and obesity. Some cardiac risk factors (age, diabetes and hypertension) were associated with MACE, but relationships between disease-specific risk factors (lung function and intravenous antibiotic days) were also observed. In propensity score-matched analyses, PwCF had higher risk of MACE than matched general population comparators (hazard ratio (HR) 1.65, 95% CI 1.40-1.95; p<0.001) and an equivalent or higher relative risk compared with other inflammatory conditions considered "high risk" for cardiovascular disease, including systemic lupus erythematosus (HR 0.95, 95% CI 0.82-1.09; p=0.44), rheumatoid arthritis (HR 1.21, 95% CI 1.00-1.48; p<0.001) and HIV (HR 0.93, 95% CI 0.82-1.06; p=0.29). PwCF are at increased risk of adverse cardiac disease events. Future work should focus on defining determinants of cardiovascular risk such that appropriate risk stratification can be employed.

Clinical outcomes by supplemental oxygen use in remdesivir-treated, hospitalised adults with COVID-19

BackgroundClinical trials show different effects of remdesivir on clinical outcomes relative to COVID-19 severity at hospital admission; in Europe, there are few real-world data. MethodsA multicentre, multinational retrospective cohort study in adult patients hospitalised with PCR-confirmed COVID-19 was conducted to understand remdesivir clinical use in different countries and to describe outcomes for patients receiving remdesivir stratified by oxygen use. Primary endpoints were all-cause mortality at day 28 and hospitalisation duration. Patients were categorised by baseline disease severity: no supplemental oxygen (NSO); low flow oxygen ≤ 6 litres (l)/minute (LFO); high flow oxygen > 6 l/minute (HFO). ResultsFour hundred and forty-eight (448) patients (72 [16.1%] HFO; 295 [65.8%] LFO; 81 (18.1%] NSO) were included; median age was 65 years and 64% were male. Mortality was higher in patients on HFO (rate 23.6%) compared to LFO (10.2%; p = 0.001) or NSO (6.2%; p = 0.002). Duration of hospitalisation was longer in patients on HFO (13 days) compared to LFO (9 days; p = 0.003) and NSO (9 days; p = 0.021). Patients who initiated remdesivir ≥ 2 days compared to within a day of hospitalisation had a 4.2 times higher risk of death, irrespective of age, sex, comorbidities, and oxygen support at baseline. Requirement for mechanical ventilation/ECMO and readmission within 28 days of discharge was similar across groups. Remdesivir use and outcomes differed by country. ConclusionsA higher mortality rate and duration of hospitalisation was seen in remdesivir-treated COVID-19 patients on HFO compared to LFO and NSO. Initiation of remdesivir upon admission as opposed to delayed initiation has a mortality benefit.Clinical Trials Registration: NCT04847622.

Clinical Characteristics of Rapid Progression in Asia-Pacific Patients With ADPKD

This study aimed to determine the utility of different methods to predict rapid progressors (RPs) and their clinical characteristics in Asia-Pacific patients with autosomal dominant polycystic kidney disease (ADPKD). This was a multinational retrospective observational cohort study of patients with ADPKD in the Asia-Pacific region. Five hospitals from Australia, China, South Korea, Taiwan, and Turkey participated in this study. RP was defined by European Renal Association-European Dialysis and Transplantation Association (ERA-EDTA) guidelines and compared to slow progressors (SPs). Among 768 patients, 426 patients were RPs. Three hundred six patients met only 1 criterion and 120 patients satisfied multiple criteria for RP. Historical estimated glomerular filtration rate (eGFR) decline fulfilled the criteria for RP in 210 patients. Five patients met the criteria for a historical increase in height-adjusted total kidney volume (TKV). The 210 patients satisfied the criteria for based on kidney volume. During the follow-up period, cyst infections, cyst hemorrhage, and proteinuria occurred more frequently in RP; and 13.9% and 2.1% of RPs and SPs, respectively, progressed to end-stage kidney disease (ESKD). RP criteria based on historical eGFR decline had the strongest correlation with eGFR change over a 2-year follow-up. Various assessment strategies should be used for identifying RPs among Asian-Pacific patients with ADPKD in real-world clinical practice during the follow-up period, cyst infections, cyst hemorrhage, and proteinuria occurred more frequently; and more patients progressed to ESKD in RPs compared with SPs.

Contextualising adverse events of special interest to characterise the baseline incidence rates in 24 million patients with COVID-19 across 26 databases: a multinational retrospective cohort study

Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population. A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases. Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism. Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term. None.

How Low Can You Go? Transfer of Low-Grade Blastocysts

Background: Low grade blastocyst (LGB) transfer results in varied live birth rates (5-39%). Only limited studies with small sample sizes (n=10-440) exist, due to LGB transfer being less desirable. Definitions of LGB and study designs are heterogenous, further confounding outcome interpretation. Aim: This study aimed to obtain sufficient LGB transfers to determine live birth rates, as well as allow subgroup analysis by blastocyst quality and maternal age. Method: This study was a multicentre, multinational retrospective cohort study across nine IVF clinics in China and New Zealand between 2012 to 2019. 6966 single blastocyst transfer cycles on days 5-7 (fresh and frozen) were collected; of these, 875 transfers were from LGBs (&lt;3BB). Blastocysts with expansion stage 1 or 2 (early blastocysts) were excluded. The main outcome was live birth rate. Blastocysts were grouped according to quality grade: good-grade blastocysts (GGBs; n=3849, AA, AB and BA), moderate-grade blastocysts (MGBs; n=2242, BB) and LGBs (n=875, AC, CA, BC, CB and CC). Live birth rates were compared using the Pearson Chi-squared test. A logistic regression analysis examined the relationship between blastocyst grade and live birth after adjustment for confounders: clinic, female age, expansion stage, and blastocyst age. Results: Live birth rates for GGBs, MGBs and LGBs were 45%, 36% and 28% respectively (p&lt;0.0001). Within the LGB group, the highest live birth rates were for grade C TE (30%) and the lowest were for grade C ICM (19%). The lowest combined grade (CC) had a 15% live birth rate (n=7/48). The odds of live birth were 2.33 (95% CI = 1.88-2.89) for GGBs compared to LGBs and 1.56 (95% CI = 1.28-1.92) for MGBs compared to LGBs following fresh and frozen blastocyst transfers (p&lt;0.0001). The odds of live birth according to ICM grade were 1.31 (A versus B; 95% CI = 1.15-1.48), 2.82 (A versus C; 95% CI = 1.91-4.18) and 2.16 (B versus C; 95% CI = 1.48-3.16; all p&lt;0.0001). The odds of live birth according to TE grade were 1.33 (A versus B; 95% CI = 1.17-1.50, p&lt;0.0001), 1.85 (A versus C; 95% CI = 1.45-2.34, p&lt;0.0001) and 1.39 (B versus C; 95% CI = 1.12-1.73, p=0.0024). Conclusion: The live birth rate for LGBs is 28%, with rates ranging between 15-31% for the different inner cell mass (ICM) and trophectoderm (TE) subgroups of LGBs. Even those in the lowest grading tier maintain modest live birth rates (15%; CC). Thus, these can be considered for transfer in women with few other options.

Treatment and Survival Outcomes of Waldenstrom Macroglobulinemia in Latin American Patients: A Multinational Retrospective Cohort Study.

PURPOSEWaldenstrom Macroglobulinemia (WM) is a rare lymphoma with distinct clinical features, and data from Latin American patients are lacking. Therefore, we aim to investigate the clinical, therapy, and outcome patterns of WM in Latin America.METHODSWe retrospectively analyzed patients with WM diagnosed between 1991 and 2019 from 24 centers in seven Latin American countries. The study outcomes were overall survival (OS) and progression-free survival (PFS).RESULTSWe identified 159 cases (median age 67 years, male 62%). Most patients (95%) were symptomatic at diagnosis. The International Prognostic Scoring System for WM (IPSSWM) at diagnosis was available in 141 (89%) patients (high-risk 40%, intermediate-risk 37%, and low-risk 23%). Twenty-seven (17%) patients were tested for MYD88L265P, with 89% (n = 24 of 27) carrying the mutation. First-line and second-line therapies were administered to 142 (89%) and 53 (33%) patients, respectively. Chemoimmunotherapy was the most commonly used first-line (66%) and second-line (45%) approach; only 18 (11%) patients received ibrutinib. With a median follow-up of 69 months, the 5-year OS rate was 81%. In treated patients, the 5-year OS and PFS rates were 78% and 59%, respectively. High-risk IPSSWM at treatment initiation was an independent risk factor for OS (adjusted hazard ratio: 4.73, 95% CI, 1.67 to 13.41, P = .003) and PFS (adjusted hazard ratio: 2.43, 95% CI, 1.31 to 4.50, P = .005).CONCLUSIONIn Latin America, the management of WM is heterogeneous, with limited access to molecular testing and novel agents. However, outcomes were similar to those reported internationally. We validated the IPSSWM score as a prognostic factor for OS and PFS. There is an unmet need to improve access to recommended diagnostic approaches and therapies in Latin America.

Comparative Treatment Persistence with Bone-Targeting Agents Among Asian Patients with Bone Metastases from Solid Tumors: A Multinational Retrospective Cohort Study.

The efficacy of bone-targeting agents has been confirmed, but the generalizabilityof results to Asia is in question. We aimed to evaluate and compare treatment persistence and re-initiation with different bone-targeting agents among patients with bone metastases from solid tumors. This population-based cohort study included patients with bone metastasis with breast, lung, or prostate cancer who initiated bone-targeting agents, including denosumab, zoledronic acid, and pamidronate in Taiwan (2013-17), Hong Kong (2013-17), and Korea (2012-16). We described the patients' persistence with bone-targeting agents, by evaluating the interruption probability, and compared risks of treatment interruption. The rates of re-initiation with index bone-targeting agents were evaluated. We included 5127 patients (denosumab: 3440, zoledronic acid: 1210, pamidronate: 477) from Taiwan, 883 patients (denosumab: 458, zoledronic acid: 357, pamidronate: 68) from Hong Kong, and 4800 patients (zoledronic acid: 4068, pamidronate: 732) from Korea. Compared with zoledronic acid, denosumab had a lower risk of interruption in Taiwan (adjusted hazard ratio: 0.44; 95% confidence interval 0.40-0.48) and Hong Kong (0.36; 0.28-0.45). However, pamidronate was more likely to be interrupted than zoledronic acid in Taiwan (1.31; 1.11-1.54) and Korea (2.06; 1.83-2.32), but not in Hong Kong (1.13; 0.71-1.78). After discontinuation, original treatments with denosumab in Taiwan and zoledronic acid in Hong Kong were more likely to be resumed, while in Korea, the rates were similar among the bisphosphonates. Denosumab was associated with a lower risk of interruption than bisphosphonates in patients with bone metastases in Taiwan and Hong Kong. Further investigations may be required to verify patients' actual reasons for discontinuation.

Bone-targeting agents in major solid tumour metastases: a multinational cohort study

ObjectiveTo describe the epidemiology, clinical characteristics and utilisation patterns of bone-targeting agents (BTAs) in patients with bone metastases from breast, prostate and lung cancer.MethodsThis is a multinational retrospective cohort study...

Transient perivascular inflammation of the carotid artery (TIPIC) syndrome.

Background: The Transient Perivascular Inflammation of the Carotid artery (TIPIC) syndrome is presumably a very rare disease characterized by a local transient inflammation of the tissue around the carotid artery. Its pathophysiology remains unknown. We performed an updated study of TIPIC syndrome cases in the setting of a multinational collaborative study. Methods: This study was conducted as an observational multinational retrospective individual patient level cohort study. Information from all known cases diagnosed with TIPIC syndrome in the literature (2005-2020) was collected after a semi-structured literature search of PubMed and Web of Science. We also collected unpublished information of patients from French, Swiss, and Italian vascular medicine or radiology departments. Results: A total of 72 patients were included and served for data analysis: 42 (58.3%) were women; the mean age was 47.9 (SD=11.4) years. Symptoms were unilateral in 92% of patients and 81.4% required pain killers. At baseline, irrespective of the imaging method used, the median thickness of the carotid lesions was 5 (Q1-Q3: 4-7; range: 2-11) mm and the median length of the lesion was 20 (Q1-Q3: 10-30; range: 3-50) mm. We found a positive linear correlation between thickness and length. At follow-up, the thickness of the carotid lesions decreased to a median of 2 (Q1-Q3: 1-3; range: 0-6) mm; the length decreased to a median 10 (Q1-Q3: 5-15; range: 0-41) mm. A linear correlation between baseline and follow-up values was observed for both thickness and length measurements. Symptoms disappeared after a median of 14 (Q1-Q3: 10-15) days. Thirteen patients experienced a recurrence after a median follow-up of 6 (Q1-Q3: 2-12) months. Conclusions: The present analysis elucidates clinical and sonographic characteristics of TIPIC syndrome, indicating the benign nature of this condition. A future international registry will study the long-term course of the disease.

Diabetes, Drug Treatment, and Mortality in COVID-19: A Multinational Retrospective Cohort Study.

Patients with type 2 diabetes mellitus (T2DM) are at increased risk of severe coronavirus disease 2019 (COVID-19) outcomes possibly because of dysregulated inflammatory responses. Glucose-regulating medications, such as glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors, and pioglitazone, are known to have anti-inflammatory effects that may improve outcomes in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In a multinational retrospective cohort study, we used the TriNetX COVID-19 Research Network of 56 large health care organizations to examine these medications in relation to the incidence of hospital admissions, respiratory complications, and mortality within 28 days after a COVID-19 diagnosis. After matching for age, sex, race, ethnicity, BMI, and significant comorbidities, use of GLP-1R agonists and/or pioglitazone was associated with significant reductions in hospital admissions (GLP-1R: 15.7% vs. 23.5%, risk ratio [RR] 0.67 [95% CI 0.57–0.79; P < 0.001]; pioglitazone: 20.0% vs. 28.2%; RR 0.71 [95% CI 0.54–0.93; P = 0.01]). Use of GLP-1R agonists was also associated with reductions in respiratory complications (15.3% vs. 24.9%, RR 0.62 [95% CI 0.52–0.73]; P < 0.001) and incidence of mortality (1.9% vs. 3.3%, RR 0.58 [95% CI 0.35–0.97]; P = 0.04). Use of DPP-4 inhibitors was associated with a reduction in respiratory complications (24.0% vs. 29.2%, RR 0.82 [95% CI 0.74–0.90]; P < 0.001), and continued use of DPP-4 inhibitors after hospitalization was associated with a decrease in mortality compared with those who discontinued use (9% vs. 19%, RR 0.45 [95% CI 0.28–0.72]; P < 0.001). In conclusion, use of glucose-regulating medications, such as GLP-1R agonists, DPP-4 inhibitors, or pioglitazone, may improve COVID-19 outcomes for patients with T2DM; randomized clinical trials are needed to further investigate this possibility.

388 TREATMENT OF ANASTOMOTIC LEAKAGE AFTER ESOPHAGECTOMY (TENTACLE—ESOPHAGUS) STUDY: FACTORS ASSOCIATED WITH ANASTOMOTIC LEAKAGE SEVERITY

Abstract Anastomotic leakage is a common and severe complication after esophagectomy. It is largely unknown which characteristics contribute to leakage severity. We aimed to investigate which factors are associated with leakage severity and to create an anastomotic leakage severity classification. Methods The TENTACLE—Esophagus is a multinational retrospective cohort study in which patients with anastomotic leakage after esophagectomy in the period 2011-2019 were included. Detailed data regarding casemix (e.g. age, sex, physical condition, comorbidity, tumor characteristics), surgical procedure (e.g. McKeown, Ivor Lewis, Orringer, anastomotic technique, omental wrap, pleural flap), leakage characteristics (e.g. contamination, drainage at leakage diagnosis, leak circumference) and treatment were collected. The primary outcome is 90-day mortality. Regression analysis will be used to analyze which leakage characteristics are associated with 90-day mortality and to compose an evidence-based anastomotic leakage severity score. The study protocol is accessible at www.tentaclestudy.com. Results Detailed data of 1407 patients with anastomotic leakage from 70 centers in 20 countries were collected. Anastomotic leakage occurred 0-43 days after surgery and 90-day mortality rate was 11.1%. The TENTACLE—Esophagus study data is currently being validated and it is awaiting full analysis. The results and the evidence based anastomotic leakage severity classification system will be ready for presentation at the ISDE meeting. Conclusion This is the largest study that investigates which factors contribute to anastomotic leakage severity after esophagectomy. The evidence-based anastomotic leakage severity classification system can be used by clinicians to grade severity of a given leak and might aid clinicians in choosing the most appropriate treatment.

952P Prognostic implication of serum alpha-fetoprotein in patients with unresectable hepatocellular carcinoma treated with regorafenib

Regorafenib is a standard therapy for patients with unresectable hepatocellular carcinoma (uHCC) after progression on sorafenib. However, there is no known reliable factor predictive of clinical outcomes for regorafenib. Serum alpha-fetoprotein (AFP) was reported as a significant predictive factor for the outcome of patients with advanced HCC on sorafenib treatment. In this multinational retrospective cohort study, implication of serum alpha-fetoprotein (AFP) in the prediction of effectiveness of regorafenib in uHCC was investigated.

Development and validation of an improved classification and risk stratification system for carotid body tumors: Multinational collaborative cohort study.

This study aims to develop and validate a new classification system that better predicts combined risk of neurological and neurovascular complications following CBT surgery, crucial for treatment decision-making. Multinational retrospective cohort study with 199 consecutive cases. A cohort of 132 CBT cases was used to develop the new classification. To undertake external validation, assessment was made between the actual complication rate and predicted risk by the model on an independent cohort (n=67). Univariate analyses showed statistically significant associations between developing a complication and the following factors: craniocaudal dimension, volume, Shamblin classification, and Mehanna types. In the multivariate prognostic model, only Mehanna type remained as a significant risk predictor. The risk of developing complications increases with increasing Mehanna type. We have developed and then validated a new classification and risk stratification system for CBTs, which demonstrated better prognostic power for the risk of developing neurovascular complications after surgery.

P–138 When is low quality really low? Should we transfer low-grade blastocysts?

Abstract Study question What is the live birth rate after single, low-grade blastocyst (LGB) transfer? Summary answer The live birth rate for LGBs is 28%, ranging between 15–31% for the different inner cell mass (ICM) and trophectoderm (TE) subgroups of LGBs. What is known already Live birth rates following LGB transfer are varied and have been reported to be in the range of 5–39%. However, these estimates are inaccurate as studies investigating live birth rates following LGB transfer are inherently limited by sample size (n = 10–440 for LGB transfers) due to LGBs being ranked last for transfer. Further, these studies are heterogenous with varied LGB definitions and design. Collating LGB live birth data from multiple clinics is warranted to obtain sufficient numbers of LGB transfers to establish reliable live birth rates, and to allow for delineation of different LGB subgroups, including blastocyst age and female age. Study design, size, duration We performed a multicentre, multinational retrospective cohort study in 9 IVF centres in China and New Zealand from 2012 to 2019. We studied the outcome of 6966 single blastocyst transfer cycles on days 5–7 (fresh and frozen) according to blastocyst grade, including 875 transfers from LGBs (&amp;lt;3bb, this being the threshold typically applied to LGB studies). Blastocysts with expansion stage 1 or 2 (early blastocysts) were excluded. Participants/materials, setting, methods The main outcome measured was live birth rate. Blastocysts were grouped according to quality grade: good-grade blastocysts (GGBs; n = 3849, aa, ab and ba), moderate-grade blastocysts (MGBs; n = 2242, bb) and LGBs (n = 875, ac, ca, bc, cb and cc) and live birth rates compared using the Pearson Chi-squared test. A logistic regression analysis explored the relationship between blastocyst grade and live birth after adjustment for the confounders: clinic, female age, expansion stage, and blastocyst age. Main results and the role of chance The live birth rates for GGBs, MGBs and LGBs were 45%, 36% and 28% respectively (p &amp;lt; 0.0001). Within the LGB group, the highest live birth rates were for grade c TE (30%) and the lowest were for grade c ICM (19%). The lowest combined grade (cc) maintained a 15% live birth rate (n = 7/48). After accounting for confounding factors, including female age and blastocyst characteristics, the odds of live birth were 2.33 (95% CI = 1.88–2.89) for GGBs compared to LGBs and 1.56 (95% CI = 1.28–1.92) for MGBs compared to LGBs following fresh and frozen blastocyst transfers (p &amp;lt; 0.0001, odds ratios confirmed in exclusively frozen blastocyst transfer cycles). When stratified by individual ICM and TE grade, the odds of live birth according to ICM grade were 1.31 (a versus b; 95% CI = 1.15–1.48), 2.82 (a versus c; 95% CI = 1.91–4.18) and 2.16 (b versus c; 95% CI = 1.48–3.16; all p &amp;lt; 0.0001). The odds of live birth according to TE grade were 1.33 (a versus b; 95% CI = 1.17–1.50, p &amp;lt; 0.0001), 1.85 (a versus c; 95% CI = 1.45–2.34, p &amp;lt; 0.0001) and 1.39 (b versus c; 95% CI = 1.12–1.73, p = 0.0024). Limitations, reasons for caution Despite the large multicentre design of the study, analyses of transfers occurring within the smallest subsets of the LGB group were limited by sample size. The study was not randomised and had a retrospective character. Wider implications of the findings: LGBs maintain satisfactory live birth rates (averaging 28%) in the general IVF population. Even those in the lowest grading tier maintain modest live birth rates (15%; cc). It is recommended that LGBs not be universally discarded, and instead considered for subsequent frozen embryo transfer to maximize cumulative live birth rates. Trial registration number Not applicable

Risk factors for enterococcal urinary tract infections: a multinational, retrospective cohort study.

Complicated urinary tract infection (cUTI) is a frequent cause of morbidity. In this multinational retrospective cohort study, we aimed to demonstrate risk factors for enterococcal UTI. Univariate and multivariate analyses of risk factors for enterococcal infection were performed. Among 791 hospitalized patients with cUTI, enterococci accounted for approximately 10% of cases (78/791). Risk factors for enterococcal UTI in multivariable analysis were male gender, age range of 55-75 years, catheter-associated UTI, and urinary retention. This information may assist treating physicians in their decision-making on prescribing empiric anti-enterococcus treatment to hospitalized patients presenting with cUTI and thus improve clinical outcomes.