Real-world Data Research Articles

Over a decade of experience in total knee arthroplasty with a multiradius design and fixed bearing at a single centre: Data from the Catalan Arthroplasty Registry.

Arthroplasty registers can provide feedback information on the results of arthroplasties performed by a certain institution or surgeon. The use of real-world data to achieve real-world evidence can help evaluate the performance of the implants used and help counselour patients. The main objective of our study was to determine the survivorship of the total knee implant we are currently using. A retrospective cohort study of patients who received a total knee arthroplasty from January 2009 to December 2020 in our hospital was conducted, using data from the Catalan arthroplasty registry and the Catalan health service database. Demographic and surgical data were analysed using the Kaplan-Meier method, log-rank testand Cox proportional hazards models with the R Project software (p < 0.05). A total of 1336 total knee arthroplasties were included in the study, of which992 were women. The causes for revision included aseptic loosening (17), infection (29), instability (13), patellar implantation (13), arthrofibrosis (5) and quadriceps tendon rupture (1).The cumulative risk for revision at 5 years using the Kaplan-Meier method was 6.0% and at 10 years 6.5%. Considering gender, this risk was 7.0% and 7.5% at 5 and 10 years, respectively, in womenand 3.3% in men, both at 5 and 10 years (p = 0.009). A higher risk for revision in women was seen, which is considered statistically significant (p = 0.012). Our survivorship results are comparable to those published in the literature, but with a higher revision risk in women that is only statistically significant for the whole group of reoperations and for patellar implantation, but not for the rest of the diagnoses. Level IV.

Trends in dupilumab persistence among patients with chronic rhinosinusitis with nasal polyps

Background: Establishing effective treatment algorithms for chronic rhinosinusitis with nasal polyps (CRSwNP) remains challenging, particularly concerning biologic therapies' discontinuation rates. Limited real-world data exist on the persistence of dupilumab, a biologic used in CRSwNP. We conducted a large-scale claims-based analysis to compare dupilumab discontinuation rates. Methodology: Utilizing the IBM MarketScan® Research Database, we identified CRS patients treated with dupilumab from July 2019 to December 2021. We assessed drug discontinuation rates, comorbidities, demographics, and surgical history using Kaplan-Meier curves and Cox proportional hazards models. Results: Of 1718 CRS patients on dupilumab, median age at initiation was 45 years, with 44% male. Dupilumab persistence varied by comorbidity, with patients with comorbid asthma exhibiting the longest median usage (652 days). Statistically significant differences in drug persistence were observed among comorbid conditions (p&lt;0.001). Younger patients (&lt;50 years) had higher discontinuation rates (p&lt;0.001). Conclusions: Our study reveals that many CRS patients without comorbidities discontinue dupilumab within the first year, with a median duration of 366 days. Age and comorbidities significantly influence dupilumab persistence. These findings aid clinicians in counseling CRS patients and underscore the need for further research to optimize treatment strategies.

Outcomes Analysis of 90Y Radioembolization for Tumors Other Than Metastatic Colorectal Cancer from the RESiN (Radiation-Emitting SIR-spheres in Non-resectable liver tumors) Registry

To characterize the response and survival outcomes of yttrium-90 transarterial radioembolization (90Y-TARE) for unresectable, liver-dominant metastases from primary neoplasms other than colorectal carcinoma. This study included 1474 patients enrolled in the RESiN registry who received resin 90Y-TARE as part of their oncologic management for unresectable primary or secondary liver tumors (NCT02685631). 33% (481/1474) were treated for liver metastases of non-colorectal origin (m-nonCRC), compared to 34% (497/1474) treated for colorectal liver metastases (mCRC) and 34% (496/1474) treated for hepatocellular carcinoma (HCC). Treatment response and cancer survival probabilities were computed and compared for each primary cancer type. The Kaplan-Meier method and log-rank test were used to compare survival outcomes. Radiological responses were observed in 12 unique cancer types, mostly heavily pre-treated malignancies refractory to multiple lines of systemic therapies. The overall use of resin 90Y-TARE in m-nonCRC resulted in better treatment outcomes in terms of duration of response, progression free survival, time to progression and overall survival (P = 0.04, P = 0.02, P = 0.01, P = 0.04). Analyses of cancer cell types revealed that metastatic neuroendocrine tumor, sarcoma, and ovarian, renal, prostate, and breast cancers were associated with superior treatment outcomes, whereas worse treatment outcomes were observed in metastatic lung, gastric, pancreatic and esophageal cancers. Real-world data demonstrate the use of resin 90Y-TARE in m-nonCRC refractory to standard chemotherapy. For some cell types, this expanded use achieved superior treatment outcomes relative to the reference standard of mCRC, suggesting the need for inquiry into broadened indications for 90Y-TARE.

COVID‐19 vaccine: recent advancements and future prospects

Nowadays, although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic has been handled with long-term management globally, the virus strains keep continuous evolution in an uncertain direction. The newly emerged JN.1 dominated the globally circulating variants in a short time and resulted in increasing hospitalizations. Up to 2024, variant vaccines with the composition of XBB sub-lineage were available due to the coordinated efforts of developers and regulatory agencies. The development of updated vaccines is still needed and the regular availability of coronavirus disease 2019 (COVID-19) vaccines should be timely guaranteed. The current landscape of COVID-19 vaccines and the strategies for accelerating vaccine development and approval are reviewed. Proposals to enhance variants monitoring and the establishment of the strain recommendation mechanism are made. This review provides suggestions about platform technology designation and application, real-world data leveraging and modification to regulatory pathways both for the post-pandemic era of SARS-CoV-2 and for the future unknown pathogen pandemic.

Neural likelihood surfaces for spatial processes with computationally intensive or intractable likelihoods

In spatial statistics, fast and accurate parameter estimation, coupled with a reliable means of uncertainty quantification, can be challenging when fitting a spatial process to real-world data because the likelihood function might be slow to evaluate or wholly intractable. In this work, we propose using convolutional neural networks to learn the likelihood function of a spatial process. Through a specifically designed classification task, our neural network implicitly learns the likelihood function, even in situations where the exact likelihood is not explicitly available. Once trained on the classification task, our neural network is calibrated using Platt scaling which improves the accuracy of the neural likelihood surfaces. To demonstrate our approach, we compare neural likelihood surfaces and the resulting maximum likelihood estimates and approximate confidence regions with the equivalent for exact or approximate likelihood for two different spatial processes—a Gaussian process and a Brown–Resnick process which have computationally intensive and intractable likelihoods, respectively. We conclude that our method provides fast and accurate parameter estimation with a reliable method of uncertainty quantification in situations where standard methods are either undesirably slow or inaccurate. The method is applicable to any spatial process on a grid from which fast simulations are available.

Concomitant Surgical Ablation in Paroxysmal vs Persistent Atrial Fibrillation During Mitral Surgery

Despite prospective randomized evidence supporting concomitant treatment of Atrial Fibrillation (AF) during mitral valve (MV) surgery, variation in surgical management of AF remains. We sought to assess longitudinal outcomes following surgical treatment of persistent or paroxysmal AF during MV surgery in Medicare Beneficiaries. All Medicare beneficiaries with a diagnosis of AF undergoing MV surgery (2018-2020) were evaluated. Patients were stratified by no AF treatment versus Left Atrial Appendage Obliteration (LAAO) alone versus LAAO and Surgical Ablation (SA+LAAO). Doubly robust risk-adjustment and subgroup analysis by persistent or paroxysmal AF were performed. A total of 7,517 patients with preoperative AF underwent MV surgery (32.1% no AF treatment, 23.1% LAAO alone, 44.7% SA+LAAO). After doubly robust risk-adjustment, AF treatment with SA+LAAO or LAAO alone was associated with lower 3-year readmission for stroke or bleeding. However, SA+LAAO was associated with reduced 3-year mortality, and readmission for AF or heart failure, compared to no AF treatment or LAAO alone. Compared to no AF treatment or LAAO alone, SA+LAAO was associated with lower composite endpoint of stroke or death at 3 years (HR 0.75 and HR 0.83, respectively). Subgroup analysis identified similar longitudinal benefits of SA+LAAO in patients with persistent or paroxysmal AF. In Medicare beneficiaries with AF undergoing MV surgery, SA+LAAO was associated with improved longitudinal outcomes compared to LAAO alone or no AF treatment in patients with paroxysmal or persistent AF. These contemporary real-world data further clarify the benefit of SA+LAAO during mitral valve surgery across all types of AF.

Data analysis with applications in physics and engineering using XLindley model with improved adaptive Type-II progressively censored samples

Recently, a novel improved adaptive Type-II progressive censoring strategy has been suggested in order to obtain adequate data from trials that require a lengthy amount of time. Considering this scheme, this paper focuses on various classical and Bayesian estimation challenges for parameter and some reliability metrics for the XLindley distribution. Two classical estimation methods are considered from the classical perspective to get the point and interval estimations of the model parameter as well as reliability and hazard rate functions. In addition to the usual approaches, the Bayesian methodology is looked at by leveraging the squared error loss function and the Markov chain Monte Carlo technique. The Bayes point and credible intervals are obtained based on two forms of the posterior distribution. A simulation examination is implemented adopting multiple circumstances to distinguish between the conventional and Bayesian estimations. The simulation results demonstrate that the Bayesian approach using the likelihood function is superior for estimating the model parameter when compared with the other methods. In contrast, when estimating reliability metrics, it is advisable to utilize the Bayesian method with the spacings function. Two real-world data sets are analyzed to integrate the proposed approaches into practice, and the ideal progressive censoring strategy is chosen using some optimality criteria.

Metallicities for more than 10 million stars derived from Gaia BP/RP spectra

Context. The third Gaia Data Release, which includes BP/RP spectra for 219 million sources, has opened a new window into the exploration of the chemical history and evolution of the Milky Way. The wealth of information encapsulated in these data is far greater than their low resolving power (R ~ 50) would suggest at first glance, as shown in many studies. We zeroed in on the use of these data for the purpose of the detection of “new” metal-poor stars, which are hard to find yet essential for understanding several aspects of the origin of the Galaxy, star formation, and the creation of the elements, among other topics. Aims. We strive to refine a metal-poor candidate selection method that was developed with simulated Gaia BP/RP spectra with the ultimate objective of providing the community with both a recipe to select stars for medium and high resolution observations, and a catalog of stellar metallicities. Methods. We used a dataset comprised of GALAH DR3 and SAGA database stars in order to verify and adjust our selection method to real-world data. For that purpose, we used dereddening as a means to tackle the issue of extinction, and then we applied our fine-tuned method to select metal-poor candidates, which we thereafter observed and analyzed. Results. We were able to infer metallicities for GALAH DR3 and SAGA stars with color excesses up to E(B − V) &lt; 1.5 and an uncertainty of σ[Fe/H]inf ∼ 0.36, which is good enough for the purpose of identifying new metal-poor stars. Further, we selected 26 metal-poor candidates via our method for observations. As spectral analysis showed, 100% of them had [Fe/H] &lt; −2.0, 57% had [Fe/H] &lt; −2.5, and 8% had [Fe/H] &lt; −3.0. We inferred metallicities for these stars with an uncertainty of σ[Fe/H]inf ∼ 0.31, as was proven when comparing [Fe/H]inf to the spectroscopic [Fe/H]. Finally, we assembled a catalog of metallicities for 10 861 062 stars.

Real-world outcomes of pemetrexed-platinum chemotherapy plus osimertinib after progression on first-line osimertinib in advanced EGFR-mutated NSCLC

ObjectivesFirst-line pemetrexed-platinum chemotherapy + osimertinib(Pem-Plat-Osi) improves progression-free survival as compared to osimertinib alone in advanced epidermal growth factor(EGFR)-mutated non-small cell lung cancer(NSCLC). However, many patients are hesitant to commence chemotherapy upfront. We describe outcomes to Pem-Plat-Osi after first-line osimertinib failure. Materials and methodsPatients with advanced EGFR-mutated (ex19del/L858R) NSCLC who had Pem-Plat-Osi between 1/7/2018–30/9/2023 after progression on first-line osimertinib at National Cancer Centre Singapore, Prince of Wales Hospital and Chinese University of Hong Kong were identified. Key endpoints were time to treatment failure(TTF) and overall survival(OS). ResultsA total of 60 patients were included. Median age at diagnosis was 62, 53.3 %(32/60) were male and 76.7 %(46/60) were never smokers. Ex19del comprised 56.7 %(34/60) and L858R 43.3 %(26/60). Baseline central nervous system(CNS) metastases were present in 66.7 %(40/60). Median TTF on osimertinib(TTF1) was 14.4 months(m) and median time to initiation of Pem-Plat-Osi was 41 days(d)(range 0–652) after progression on osimertinib.Partial response(PR) or stable disease to Pem-Plat-Osi was achieved in 81.7 %(49/60). Intracranial disease control was achieved in 90.6 %(29/32) of patients with measurable CNS metastases, including those who did not undergo brain radiotherapy. At median follow up of 31.2 m, median TTF on Pem-Plat-Osi(TTF2) was 6.6 m. Median TTF1 + TTF2 was 23.4 m and median OS was 34.2 m. Survival outcomes were similar comparing ex19del and L858R (median TTF1 + TTF2 21.8 m vs 23.5 m, p = 0.90; median OS 34.2 m vs 36.8 m, p = 0.37) and in patients without/with baseline CNS metastases (median TTF1 + TTF2 21.8 m vs 23.4 m, p = 0.44; median OS 36.2 m vs 31.9 m, p = 0.65).TTF1 duration was not significantly associated with TTF2 (p = 0.76). Patients who started Pem-Plat-Osi within 20d of progression on osimertinib had significantly longer TTF2 as compared to patients who started after 20d (median 8.4 m versus 6.0 months, p = 0.03) which remained statistically significant on multivariable analysis. ConclusionsOur real-world data supports the efficacy of Pem-Plat-Osi after progression on first-line osimertinib, including L858R and baseline CNS metastases. Chemotherapy initiation within 20d of Osi progression was predictive of superior TTF2.

Hilbert Curve Projection Distance for Distribution Comparison.

Distribution comparison plays a central role in many machine learning tasks like data classification and generative modeling. In this study, we propose a novel metric, called Hilbert curve projection (HCP) distance, to measure the distance between two probability distributions with low complexity. In particular, we first project two high-dimensional probability distributions using Hilbert curve to obtain a coupling between them, and then calculate the transport distance between these two distributions in the original space, according to the coupling. We show that HCP distance is a proper metric and is well-defined for probability measures with bounded supports. Furthermore, we demonstrate that the modified empirical HCP distance with the Lp cost in the d-dimensional space converges to its population counterpart at a rate of no more than O(n-1/2max{d,p}). To suppress the curse-of-dimensionality, we also develop two variants of the HCP distance using (learnable) subspace projections. Experiments on both synthetic and real-world data show that our HCP distance works as an effective surrogate of the Wasserstein distance with low complexity and overcomes the drawbacks of the sliced Wasserstein distance.

House dust mite immunotherapy: A real-world, prescription data-based analysis.

House dust mite (HDM) sensitisation can contribute to the development of allergic rhinoconjunctivitis (AR) or allergic asthma (AA). As treatment, allergen immunotherapy (AIT) is a promising approach, since it aims building immunotolerance against allergens, therewith establishing long-term efficacy. The evaluation of AIT has been investigated in many randomised controlled trials, whereas few real-world evidence studies are available. We used data from the longitudinal prescription data base IQVIA™ LRx. Data on initial AIT prescriptions against HDM from January 2009 to December 2013 was analysed regarding treatment (subcutaneous AIT with either depigmented polymerised allergen extract [dSCIT] or other allergens [oSCIT], or sublingual immunotherapy [SLIT]) and treatment duration. Treatment groups were compared with a control group of AR patients not receiving AIT. Data on symptomatic medication was collected until February 2017 and progression of AR and AA was compared. Data of 7260 patients with AIT prescriptions and of 21,780 control patients was analysed. AIT was associated with a significant decrease of AR medication intake compared with control (dSCIT: -34.0%, p<0.0001; oSCIT: -25.7%, p<0.0001; SLIT: -37.7%, p=0.0026). In asthmatics, SCIT was associated with a significant decrease of asthma medication compared with control (dSCIT: -45.2%, p<0.0001; oSCIT: -32.9%, p<0.0001). Further, a significantly reduced likelihood for onset of asthma medication was demonstrated in patients treated with SCIT compared with controls (dSCIT OR: 0.759, p=0.0476; oSCIT OR: 0.815, p=0.0339). Real-world data analyses indicate that AIT, particularly given via a subcutaneous route, reduces the need of medication against AR and AA and might delay the onset of asthma medication in patients with AR.

Identification of Influential Nodes in Social Network: Big Data - Hadoop

Software development and associated data is the most critical factor these days. Currently, people are living in an internet world where data and related artifacts are major sets of information these days. The data is correlated with real-world data. The analysis of large datasets was done as part of the experimental analysis. The dataset for online social media like Facebook and Twitter was taken for the identification of influential nodes. The analysis of the dataset provides an overview and observation of the dataset for Facebook or Twitter. Here, in the current activity, an overview of cloud computing and big data technologies are discussed along with effective methods and approaches to resolve the problem statement. Particularly, big data technologies such as Hadoop provided by Apache for processing and analysis of Gigabyte(GB) or petabyte(PB) scale datasets are discussed for processing data in distributed and parallel data fashion. Here, the processing of large datasets is done by big data technology by implementing Apache Hadoop in online social media.

Correlation analysis between driver gene mutation and clinicopathological features in lung adenocarcinoma based on real-world cumulative clinical data.

Driver genes are essential predictors of targeted therapeutic efficacy. Detecting driver gene mutations in lung adenocarcinoma (LUAD) patients can help to screen for targeted drugs and improve patient survival benefits. This study aims to investigate the mutation characterization of driver genes and their correlation with clinicopathological features in LUAD. A total of 440 LUAD patients were selected from Sir Run Run Shaw Hospital between July 2019 and September 2022. Postoperative tissue specimens were analyzed for gene mutations using next-generation sequencing technology, focusing, including epidermal growth factor receptor EGFR, ALK, ROS1, RET, KRAS, MET, BRAF, HER2, PIK3CA and NRAS. At the same time, clinicopathological data were collected and organized for multidimensional correlation analysis. Of 440 LUAD patients, driver gene mutations were not detected in 48 patients. The proportion of patients with driver gene mutations was as high as 89.09%. The top three driver genetic mutations were EGFR, KRAS, and MET. Sixty-nine types of EGFR mutations were detected and distributed in the protein tyrosine kinase catalytic domain (56, 81.16%), Furin-like cysteine-rich region (9, 13.04%), receptor binding domain (3, 4.35%), and EGFR transmembrane domain (1, 1.45%). Single gene locus mutation occurred in 343 LUAD patients, but the mutation gene types covered all tested genes. Our findings showed that EGFR mutations were more commonly observed in non-smoking and female patients (P<0.01), KRAS mutations were more prevalent in male patients and smokers (P<0.01), ROS1 mutations had larger tumor diameters (P<0.01) and RET mutations were more prevalent in smokers (P<0.05). LUAD patients exhibit diverse genetic mutations, which may co-occur simultaneously. Integrated analysis of multiple mutations is essential for accurate diagnosis and effective treatment of the disease. The use of NGS can significantly expand our understanding of gene mutations and facilitate integrated analysis of multiple gene mutations, providing critical evidence for targeted treatment methods.

A Multinational, Multi-Institutional Study Assessing the Impact of Diabetes Mellitus on the Prognosis of Patients with Non-Muscle Invasive Bladder Cancer Treated with Bacillus Calmette-Guérin

The study aimed to examine the impact of diabetes mellitus type 2 (DMII) on the oncological outcomes of non-muscle invasive bladder cancer (NMIBC) treated with Bacillus Calmette-Guérin (BCG) using comprehensive real-world data. We performed an analysis of data on NMIBC patients treated with BCG from the United States (US) National Phase II BCG/Interferon (IFN) trial database (125 centers) and pooled databases from three tertiary care institutions: France (FR), Lebanon (LB) (2000–2021), and the US (University of Iowa) (2011–2021). There were 867 patients from the Phase II trial, 1232 from the FR/LB cohort, and 233 from the US (Iowa) cohort (n = 2332). DM II was reported in 13% of the Phase II trial cohort, 14.4% of the FR/LB cohort, and 33.5% of the US (Iowa) cohort. The median follow-up was 24 months in the Phase II trial cohort, 25 months in the FR/LB cohort, and 48 months in the US (Iowa) cohort. In multivariable Cox regression analyses, DMII was not significantly associated with recurrence or progression of the tumor in any of the cohorts included in this study. DMII may not be a clinical prognostic factor for NMIBC patients treated with BCG. Prospective evaluation is needed.

A Multinational, Multi-Institutional Study Assessing the Impact of Diabetes Mellitus on the Prognosis of Patients with Non-Muscle Invasive Bladder Cancer Treated with Bacillus Calmette-Guérin

The study aimed to examine the impact of diabetes mellitus type 2 (DMII) on the oncological outcomes of non-muscle invasive bladder cancer (NMIBC) treated with Bacillus Calmette-Guérin (BCG) using comprehensive real-world data. We performed an analysis of data on NMIBC patients treated with BCG from the United States (US) National Phase II BCG/Interferon (IFN) trial database (125 centers) and pooled databases from three tertiary care institutions: France (FR), Lebanon (LB) (2000–2021), and the US (University of Iowa) (2011–2021). There were 867 patients from the Phase II trial, 1232 from the FR/LB cohort, and 233 from the US (Iowa) cohort (n = 2332). DM II was reported in 13% of the Phase II trial cohort, 14.4% of the FR/LB cohort, and 33.5% of the US (Iowa) cohort. The median follow-up was 24 months in the Phase II trial cohort, 25 months in the FR/LB cohort, and 48 months in the US (Iowa) cohort. In multivariable Cox regression analyses, DMII was not significantly associated with recurrence or progression of the tumor in any of the cohorts included in this study. DMII may not be a clinical prognostic factor for NMIBC patients treated with BCG. Prospective evaluation is needed.

Long-Term Persistence Rate of Secukinumab in Psoriatic Patients: A Six-Year Multicenter, Real-World Experience, Retrospective Study.

Background: Psoriatic disease, a chronic immune-mediated systemic inflammatory condition, significantly impairs patients' quality of life. The advent of highly targeted biological therapies has transformed treatment strategies, emphasizing the importance of selecting the most effective and cost-efficient option. Secukinumab, an IL-17A inhibitor, has demonstrated efficacy and safety in treating moderate-to-severe plaque psoriasis (PsO). However, long-term real-world data on its effectiveness and persistence rate are limited. Methods: This retrospective study, conducted across eight Italian dermatology centers, aimed to evaluate the 6-year persistence rate and effectiveness of secukinumab in patients with PsO. Additionally, the study investigated the onset of psoriatic arthritis during treatment. Results: Overall, 166 adult patients were analyzed. Their median age was 53.9 years. The mean BMI was 26.5. Of the 166 patients, 64 were bio-experienced while 102 were bio-naïve. A progressive reduction in PsO severity measured by PASI scores over 6 years of treatment was revealed: the PASI score decreased from a baseline value of 18.1 (±9.1) to 0.7 (±1.6) after 6 years of follow-up. Adverse events, including mucocutaneous fungal infections and cardiovascular disturbances, were reported in 19.9% of patients. The persistence rate was 86.8% at 24 months, decreasing to 66.4% at 72 months. Psoriatic arthritis onset during treatment was observed in 15 (9.0%) of patients. Conclusions: This study highlights the sustained effectiveness and favorable safety profile of secukinumab over 6 years, providing valuable real-world evidence. Understanding the long-term persistence rate and predictors of discontinuation could help clinicians optimize treatment decisions and improve patient outcomes in PsO management. We found that the absence of scalp PsO, no involvement of the genital area and normal weight were the best factors of persistence in secukinumab treatment in the long term.

British Photodermatology GroupOral presentationsPD01 Accelerated oral psoralen–ultraviolet A therapy in the management of polymorphic skin eruption: real-world data from a specialist centre

British Photodermatology GroupOral presentationsPD01 Accelerated oral psoralen–ultraviolet A therapy in the management of polymorphic skin eruption: real-world data from a specialist centre

Efficacy and Safety of Direct Oral Anticoagulants versus Warfarin in Obese Patients (BMI ≥ 30 kg/m2) with Atrial Fibrillation or Venous Thromboembolism: An Updated Systematic Review and Meta-Analysis.

Background: Real-world data show limited utilization of direct oral anticoagulants (DOACs) in obese patients (body mass index [BMI] ≥ 30 kg/m2) due to concerns regarding their efficacy and safety in this demographic. Aim: This review aimed to consolidate current evidence on the efficacy and safety of DOACs versus warfarin in obese patients with non-valvular atrial fibrillation (AF) or venous thromboembolism (VTE). The primary efficacy outcome assessed a composite of all-cause mortality, stroke, systemic embolism (SE), and myocardial infarction (MI). Methods: A systematic search was conducted in MEDLINE, SCOPUS, and Cochrane databases from inception to December 28, 2023. Data were synthesized using random-effects meta-analysis. Results: A total of 35 studies involving 434,320 participants were analyzed. DOAC use was associated with a significant reduction in the risk of the composite outcome (RR = 0.80, 95% CI [0.65, 0.98], I2 = 95%), hemorrhagic stroke (RR = 0.58, 95% CI [0.38, 0.88], I2 = 92%), major bleeding (RR = 0.76, 95% CI [0.63, 0.92], I2 = 94%), gastrointestinal bleeding (RR = 0.59, 95% CI [0.49, 0.72], I2 = 88%), and intracranial bleeding (RR = 0.45, 95% CI [0.34, 0.60], I2 = 44%) compared to warfarin. A non-significant benefit of DOACs was observed for all-cause mortality, MI, the composite of stroke or SE, ischemic stroke, SE, VTE, and minor bleeding compared to warfarin. Subgroup analysis indicated no significant effect modification based on the indication for anticoagulation or study design. Conclusions: DOACs demonstrated a favorable efficacy and safety profile in obese individuals compared to warfarin.

Basic Susceptibility of Patients with Psoriasis under Systemic Therapy for Respiratory Infections: Data from the German Psoriasis Registry PsoBest.

Background: Patients with psoriasis under systemic treatments are in focus regarding their susceptibility to respiratory infections. To analyse real-world data for respiratory infections in patients with psoriasis under systemic treatments. Methods: We analysed data of the prospective, non-interventional German Psoriasis Registry PsoBest and compared rates for respiratory infections of 13,823 patients on systemic treatments for psoriasis and/or psoriatic arthritis in different therapy cohorts before the COVID-19 pandemic. Results: In total, 1415 respiratory infections were observed in 970 patients. Significant differences were observed between biologics and non-biologics, but not within these groups. The highest event rates (events/100 patient years) were identified for TNF-α inhibitors, 8.1, (CI 7.4-8.9), followed by 7.0 for IL-17 inhibitors (6.2-7.9), 5.7 for IL-12/23 and IL-23 inhibitors (5.1-6.5), 4.8 for methotrexate (4.3-5.4), 3.7 for small molecules (3.3-4.2), and 2.7 for retinoids (1.2-5.1). Conclusions: Overall, the susceptibility for respiratory infections in patients under systemic therapy for psoriasis is low compared to published study data and is sufficient as comparative data for COVID-19 studies.

Real-World Effectiveness and Safety of Tixagevimab-Cilgavimab: A Target Trial Emulation Study.

Immunocompromised individuals are at high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent severe or fatal coronavirus disease 2019 (COVID-19), yet they have suboptimal responses to mRNA and inactivated COVID-19 vaccines. The efficacy of tixagevimab-cilgavimab in reducing symptomatic SARS-CoV-2 infection was demonstrated in phase III clinical trials. Nevertheless, real-world data on the effectiveness and safety of tixagevimab-cilgavimab remain limited. The aim was to evaluate the effectiveness and safety of tixagevimab-cilgavimab among immunocompromised individuals. Adults who were immunocompromised or receiving immunosuppressive therapies were included in this target trial emulation using territory-wide electronic health records in Hong Kong. A sequential trial emulation approach was adopted to compare effectiveness and safety outcomes between individuals who received tixagevimab-cilgavimab and individuals who did not. A total of 746 tixagevimab-cilgavimab recipients and 2980 controls were included from 1 May 2022 to 30 November 2022. Tixagevimab-cilgavimab significantly reduced the risk of COVID-19 infection (hazard ratio [HR] 0.708, 95% confidence interval [CI] 0.527-0.951) during a median follow-up of 60 days. No significant difference was observed in the risk of COVID-19-related hospitalisation. Zero versus eight COVID-19 mortality cases and zero versus two severe COVID-19 cases were observed in tixagevimab-cilgavimab recipients and controls, respectively. Notably, significant risk reduction in COVID-19 infection was also observed among immunocompromised individuals who had been previously vaccinated with three or more doses of COVID-19 vaccine, or had no prior COVID-19 infection history. Tixagevimab-cilgavimab was effective in reducing COVID-19 infection among immunocompromised patients during the Omicron wave. Findings were consistent among individuals who previously received three or more doses of COVID-19 vaccine, or had no previous history of COVID-19 infection.