Real-world Analysis Research Articles

Renal injury in NSAIDs: a real-world analysis based on the FAERS database.

This study aims to evaluate the reporting risk of renal injury associated with non-steroidal anti-inflammatory drugs (NSAIDs), with a particular focus on the reporting risk levels and onset times of different NSAIDs. A pharmacovigilance study was conducted using data from the FAERS database from January 2004 to December 2023. Reports of renal injury were identified, and signal detection was performed using reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) methods. The study compared the incidence, mortality rates, and onset times of renal injury across five NSAIDs. Among the 7436 cases of NSAID-associated renal injury analyzed, elderly patients are at an increased risk of renal injury associated with NSAID usage. Ibuprofen had the highest number of reports (3475 cases, 46.7%), while celecoxib had the lowest (542 cases, 7.3%). Ibuprofen showed the highest signal with renal injury (ROR 3.3, IC025 1.7), whereas celecoxib exhibited the lowest (ROR 1.4, IC025 0.4). Aspirin had the highest mortality rate associated with renal injury (18.7%), while ibuprofen had the lowest (3.8%). The median onset time for renal injury was 6days, with 79.3% of adverse events occurring within the first 30days of use. The study indicates that ibuprofen presents the highest signal of renal injury, while celecoxib shows the lowest signal. The likelihood of NSAID-associated renal injury is heightened in elderly patients, and all five studied NSAIDs are linked to an increased likelihood of acute renal injury. NSAID-related renal damage tends to occur early in the treatment process, potentially leading to serious consequences. Due to the inherent limitations of pharmacovigilance studies, certain findings require additional validation like cohort studies. Nonetheless, the potential for an increased risk of renal injury must be taken into account in patient care.

BRCA and homologous recombination repair deficiency testing in advanced ovarian cancer: A real-world data analysis

BRCA and homologous recombination repair deficiency testing in advanced ovarian cancer: A real-world data analysis

Patterns in maintenance therapy use in advanced ovarian cancer patients: Real-world data analysis

Patterns in maintenance therapy use in advanced ovarian cancer patients: Real-world data analysis

Patient-reported disability progression outcomes among patients with multiple sclerosis: Results of an outcomes-based agreement.

Outcomes-based agreements (OBAs) are agreements between payers and manufacturers in which payment for medications is tied to patient outcomes. These contracts aim to measure the value of prescription medications on predefined clinical indicators in real-world patient populations. OBAs are gaining traction in the United States as the health care industry shifts from volume-based to value-based care. Multiple sclerosis (MS) is an appealing therapeutic area for OBAs because of its prevalence, high cost of medications, and multiple effective therapeutic options. To describe findings from an OBA that was prospectively conducted in a large regional health system for patients with MS taking interferon β-1a or dimethyl fumarate. In this prospective real-world analysis, commercial or health insurance exchange members were included based on the parameters of the OBA. Disability progression was assessed using a patient-reported outcome, patient-determined disease steps (PDDS). In the OBA, members aged 18 years or older with an MS diagnosis were included in the contract. A baseline score was collected for eligible members, with follow-up scores occurring between a 90-day and 180-day postbaseline score. If a follow-up score was greater than the baseline score, a subsequent PDDS score was collected between 90-days and 120-days to determine if the PDDS score remained elevated, indicating that the member had disability progression. During the contract period, 410 patients were eligible for PDDS collection, with 241 and 169 patients in the dimethyl fumarate and interferon β-1a cohorts, respectively. There were 162 patients who were lost to follow-up, and 64 patients who were ineligible per contract parameters. Of the remaining 184 eligible patients (107 on dimethyl fumarate and 77 on interferon β-1a), 21 (11%) patients had confirmed disability progression (6 on dimethyl fumarate [5.6%] and 15 on interferon β-1a [19.5%]). Our findings suggest that meaningful patient-reported outcomes, such as disability progression, can be operationalized in an innovative OBA.

Safety and Efficacy of 177Lu-PSMA Therapy Following 223Radium Treatment: A Retrospective Multinational Real-World Analysis

Safety and Efficacy of 177Lu-PSMA Therapy Following 223Radium Treatment: A Retrospective Multinational Real-World Analysis

Comment on “Impact of Back-to-Base Normothermic Machine Perfusion on Complications and Costs: A Multi-Center, Real-World Risk-Matched Analysis”

Comment on “Impact of Back-to-Base Normothermic Machine Perfusion on Complications and Costs: A Multi-Center, Real-World Risk-Matched Analysis”

Efficacy of integrated traditional Chinese and western medicine in managing mild-moderate acute pancreatitis: a real-world clinical perspective analysis

BackgroundGiven the prevalent utilization of integrated traditional Chinese and western medicine (ITCWM) in the management of acute pancreatitis, the majority of studies have concentrated on severe cases, lacking robust evidence-based medical research. Real-world investigations can provide an objective assessment of the clinical effectiveness of combining traditional Chinese medicine with western medicine. Consequently, relying on real-world research, we intend to evaluate the clinical efficacy and safety of the combined approach in treating mild to moderate acute pancreatitis.MethodsA total of 563 AP patients from Henan Central Hospital were collected from January 2019 to October 2023. A propensity score matching (PSM) analysis was conducted to evaluate the clinical efficacy of traditional Chinese medicine (TCM) in treating mild to moderate acute pancreatitis. Patients were divided into a control group (61 cases) and an integrated traditional Chinese and Western medicine (ITCWM) group (120 cases). To further assess the clinical efficacy of TCM enema in the treatment of mild to moderate acute pancreatitis, PSM analysis was conducted across three groups. The patients were categorized into a control group (n = 49), an oral TCM treatment group (OCM group, n = 274), and an oral TCM plus enema treatment group (OCM+E group, n = 131). Logistic regression was used to analyze factors after treatment in each group, and the Kaplan-Meier method compared symptom duration in each group.ResultsCompared with the control group, the ITCWM group significantly decreased C-reactive protein (CRP, mg/L) (17.8 [1.2–59.5] vs. 8.0 [3.3–33.5], P = 0.022), shortened the duration of abdominal distension, abdominal pain, nausea and bitter taste symptoms (P < 0.05), and shortened the length of hospital stay (median 19.0 and 11.5 days, respectively, P = 0.001); Compared with the other two groups, the neutrophil percentage (NEUT%) was lower (74.1 vs. 61.9 vs. 59.5, P < 0.05) and serum prealbumin (PA, mg/L) was higher (116.0 vs. 184.4 vs. 220.0, P < 0.05), the length of hospitalization (days) was shortened (19.0 vs.12.0 vs.10.0, P < 0.05) in the OCM+E group.ConclusionThe combination of traditional Chinese medicine and modern medicine has been shown to effectively decrease inflammatory indicators in patients with mild to moderate acute pancreatitis, leading to a reduction in symptom duration and hospitalization period, as well as promoting disease recovery. Notably, the use of traditional Chinese medicine in conjunction with enema therapy yields more pronounced benefits.

Twelve-month analysis of real-world evidence from a telehealth obesity-treatment provider using antiobesity medications.

The objective of this study was to describe weight changes in members of a large-scale telehealth obesity-treatment provider who were using antiobesity medications (AOMs). This retrospective observational study analyzed real-world data from adults who initiated AOM treatment with the WW International, Inc. (formerly Weight Watchers) Clinic telehealth program between January 2022 and July 2023 (n = 53,590). The main outcomes were changes in body weight over 12 months, side effects over follow-up, and medication usage patterns. The 53,590 patients who initiated treatment were predominantly female (88.6%), with a mean BMI of 36.9 kg/m2. Mean (SD) treatment duration was 5.3 (4.3) months. Program retention rates based on the number of patients whose time from enrollment was at least 3, 6, 9, and 12 months were 78% (n = 39,907/51,247), 63% (n = 25,515/40,203), 58% (n = 15,472/26,794), and 77% (n = 6459/8394), respectively. Average weight loss was 8.9% at 3 months (n = 37,565), 14.1% at 6 months (n = 24,140), 17.7% at 9 months (n = 15,169), and 19.4% at 12 months (n = 6089). Glucagon-like peptide-1 receptor agonist (GLP-1-RA)-based treatments were predominant. Side effects were consistent with the classes of medications used, and frequency declined over time. This real-world analysis of a telehealth-delivered obesity-treatment program demonstrated outcomes consistent with recent phase 3 clinical trials of AOMs, suggesting generalizability beyond clinical trial and in-person settings.

Prediction of incident major adverse cardiac events in patients starting haemodialysis for end stage kidney disease, using clinical laboratory cardiac biomarkers - a real world analysis.

Abstract Background and Aims Despite its many advantages, haemodialysis (HD) is associated with increased cardiovascular mortality and morbidity, with some studies reporting 48% higher mortality within 2 years of starting HD. Cardiac biomarkers provide insight into cardiac structure and function, including myocyte stress, inflammation and fibrosis. We aimed to investigate the prognostic significance of routine cardiac biomarkers (troponin and natriuretic peptides) in the prediction of incident major adverse cardiac events (MACE) within 5 years if commencing HD. Methods A retrospective cohort study was performed using electronic medical records from a global federated research network from the US. The network was searched on 26th February 2023. The cohorts commenced HD post-diagnosis of end-stage kidney disease. Data censoring for MACE was invoked prior to the index event of HD. Cardiac biomarkers were the first reported result within 3 months of starting HD. Cohorts were grouped according to biomarker-specific thresholds and 1:1 propensity-score matched for age, gender and co-morbidities (hypertension, diabetes mellitus and smoking status). Logistical regression produced odds ratios with 95%CI for 5-year incident MACE. MACE was defined, a priori, as a composite of ischaemic heart disease, angina pectoris, acute myocardial infarction, heart failure, AF, stroke and all-cause mortality. All statistical analysis was performed on the online platform. Results The results are shown Tables 1(Troponin I and BNP alone) and 2 (Combined Troponin I and BNP). Results that reached statistical significance (p<0.05) are shown. Conclusion Routinely available cardiac biomarkers can predict MACE and cardiac outcomes in incident HD, although results differ between markers of myocyte injury (troponin) and stress (BNP). A combined approach may prove most beneficial. The results suggest the clinical need for CV mortality and morbidity risk profiling in incident dialysis using a combination of clinical and laboratory variables and the need for prospective validation.Table 1Table 2

Comparative outcomes of drug-coated balloon angioplasty versus second-generation drug-eluting stent for in-stent restenosis: a real-world data analysis

Abstract Background Coronary in-stent restenosis (ISR) poses a significant challenge in interventional cardiology, with optimal treatment strategies being the subject of ongoing debate. Current clinical guidelines offer a choice between drug-coated balloon angioplasty (DCB) and repeat stenting with second-generation drug-eluting stents (DES), each with distinct implications for long-term patient outcomes. Purpose The aim of this study is to compare 1-year outcomes between DCB angioplasty and second-generation DES in the treatment of ISR. Longitudinal real-world data are used from the OBSERVABLE database, which comprises German health claims data between 2012 and 2021. Methods A total of 10,440 ISR individuals undergoing DCB or DES intervention were identified. After exclusion of bare-metal stents, first generation stents and non-DCBs, 3,810 propensity score-matched individuals remained. The primary outcome was the composite of all-cause mortality and myocardial infraction (MI). Secondary outcomes included all-cause death, MI, and bleeding as a safety outcome. Results At 1-year follow-up, the primary outcome of all-cause mortality and MI was observed in 246 individuals (12.9%) in the DES group, compared with 201 individuals (10.6%) in the DCB group (HR, 1.27; 95% CI, 1.06-1.53). Sensitivity analysis confirmed the robustness of these findings. Secondary outcomes revealed higher all-cause mortality in the DES group (7.9%) compared to the DCB group (6.3%) (HR, 1.31; 95% CI, 1.03-1.66), with no difference in MI. Bleeding events were comparable between the two treatments, with 244 individuals (12.8%) in the DES group and 206 individuals (10.8%) in the DCB group (HR, 1.17; 95% CI, 0.89-1.53). Conclusion This real-world data analysis demonstrated a higher incidence of the primary composite endpoint of all-cause mortality and MI within one year, after treatment with DES compared to DCB. Our results support prior findings about the safety profile of repeated DES implantation and strengthen DCB as a potential superior alternative to DES in ISR management.

Real-world analysis of transcatheter aortic valve replacement in patients with prostate cancer and severe aortic stenosis

Abstract Background Patients with prostate cancer have a high prevalence of cardiovascular disease, including degenerative heart valve diseases such as aortic stenosis. It is not uncommon in clinical practice to perform transcatheter aortic valve replacement (TAVR) in patients with severe aortic stenosis and active prostate cancer. Still, the prognosis after this procedure in this population is not well known. Purpose To evaluate 1-year and 3-year survival rates after TAVR in patients with prostate cancer who have undergone TAVR when compared with patients without active cancer. Methods Data were extracted from electronic medical records of a large multinational collaborative network (TriNetX) that currently englobes 113 healthcare organizations worldwide with more than 100 million patients. Patients aged 18 years or older with prostate cancer documented up to 12 months before TAVR as well as controls undergoing TAVR without oncologic history before the proceeding were included. The survival analysis for 1 year and 3 years was performed with Kaplan Meier survival plots and log-rank test. Propensity score matching, using clinical and demographic variables, was performed to pair the cohorts. Results From a cohort of 26,656 men who had undergone TAVR, we identified 1,040 with prostate cancer diagnosed up to 1 year before TAVR ( prostate cancer group) and 20,231 patients without oncologic history before TAVI (control group). After propensity score matching, analyzing 1,040 patients in each group, the 1-year and 3-year survival probabilities were not different between the prostate cancer group versus the control group ( 89.5% vs 88.9%, log-rank test P=0.70 and 72.6% vs 68.7%, log-rank test P=0.22, respectively). Considering a subgroup of patients with metastatic prostate cancer ( n=229) under androgen deprivation therapy vs the control group ( n =229), we have also not observed a survival difference between the two groups at 1-year and 3-year follow-up ( 88.1 vs 89.1%, log-rank test P=0.69 and 58.7% vs 67.4%, log-rank test P=0.25). Conclusions In this real-world analysis, patients with prostate cancer and severe aortic stenosis who underwent TAVR, including patients with metastatic disease, the 1-year and 3-year survival rates were not significantly different when compared to patients without oncologic hystory who underwent TAVR.

Adherence to anti-hypertensive therapy with perindopril-based single-pill versus free-pill combinations: a 10-year real-world analysis in Italy

Abstract Background/Introduction Despite the growing availability of blood pressure-lowering drugs, hypertension remains poorly controlled and a significant mortality cause worldwide. The silent course of the disease, suboptimal adherence, and complexity of therapeutic schedules are important factors in reducing the effectiveness of anti-hypertensive treatments at the population level. With the purpose of simplifying patients’ medication self-management, guidelines have strongly endorsed the use of anti-hypertensive therapy with single-pill combinations (SPCs). Perindopril (PER)-based SPCs, including both two- and three-drug combinations, have been available since 2008. Purpose We explored treatment adherence over 10 years in patients receiving PER-based regimens (SPC or free-pill combination) in Italy. Methods A retrospective real-world analysis was conducted on administrative databases covering 6.7 million Italian health-assisted residents. Among adults with hospitalization discharge diagnosis or exemption code for hypertension between 2010 and 2021, those with PER-based prescriptions were identified, considering combinations with amlodipine (AML) and/or indapamide (IND), either as SPC or free-pill or mixed (SPC+separate pill). The index-date (ID) was that of the first prescription of a PER-based regimen throughout the inclusion period. All patients with at least 12 months of available data before and after the ID were included. A cross-sectional analysis evaluated the yearly adherence for the period 2012-2021, calculating the proportion of days covered (PDC) by drug prescriptions on 1-year follow-up (PDC≥80% indicated high-adherence). Results Over 2012-2021, of 121,397 patients on a PER-based therapy, those treated with SPC ranged from 87% (during 2012) to 94.4% (during 2021), while free-pill and SPC+separate pill cohorts represented, respectively, 10.6-3.5% and 2.4-2.1% of all hypertensive patients. Over the decade, the proportion of adherent patients in SPC users was markedly higher than in free-pill and SPC+separate pill cohorts (Fig. 1). The sudden reduction of adherent patients during 2018-2019 was possibly due to a temporary shortage of PER/AML/IND as SPC in Italy from Nov-2018 to Mar-2019. Multivariate analysis showed that over 2012-2021 decade, free-pill and SPC+separate pill regimens resulted in significantly lower adherence (more than 80% reduction) than SPC formulation, while male gender and older age were predictive of better adherence (Table 1). Conclusions These findings from real clinical practice in Italy highlighted a growing attitude from clinicians to prescribe more manageable anti-hypertensive schemes based on SPC formulations, in line with current guidelines. The higher proportion of adherent patients among the users of PER-based SPCs corroborates the importance of alleviating pill burden, that is a key component in blood pressure control, and so in the reduction of hypertensive complications and cardiovascular risk.

Cardiovascular and non-cardiovascular adverse events in patients with hematologic malignacies treated with BTK inhibitors: a real-world analysis

Abstract Background Bruton tyrosine kinase (BTK) inhibitors play an important role in targeted treatment of B-cell lymphoproliferative disorders. However, adverse events may limit the proper course of treatment in many patients. Purpose To compare the risk of cardiovascular and non-cardiovascular adverse events in patients with chronic lymphocytic leukemia (CLL) or small cell lymphocytic lymphoma (SLL) treated with first-generation BTK inhibitor ibrutinib versus second-generation acalabrutinib, using real-world data from electronic medical records. Methods We used data from a large collaborative multinational network ( TriNetX), that emcompasses more than 100 healthcare organizations worldwide. We queried the databank for patients aged ≥ 18 years with chronic lymphocytic leukemia or small-cell lymphomas treated with ibrutinib or acalabrutinib in the past 10 years before the analysis. We used propensity score matching to balance the cohorts. The 3-year cumulative incidences and hazard ratios for the following outcomes were calculated: atrial flutter or fibrillation, other arrhythmias, heart failure, ischemic stroke or peripheral embolism, acute coronary syndrome, bleeding, and sepsis. Results We compared 2,107 patients in each group. The 3-year incidences of atrial fibrillation or flutter in the acalabrutinib and ibrutinib groups were 7.11% and 14.78% respectively, with a lower ratio in patients treated with acalabrutinib than those treated with ibrutinib (hazard ratio, HR 0.68, 95% CI 0.55-0.84). New-onset hypertension occurred during the 3-year follow-up in 16.29% patients in the acalabrutinib group versus 27.8% patients in the ibrutinib group (HR 0,81, 95% CI 0.66-0.98). The incidence of sepsis was 6.49% in patients treated with acalabrutinib versus 11.37% in those treated with ibrutinib group (HR 0.77, 95% CI 0.60-0.98). Concerning the other adverse events, there were no significant differences between the two groups. Conclusions In this large real-world analysis, patients with CLL or SLL treated with acalabrutinib had a better cardiovascular and non-cardiovascular safety profile than those treated with ibrutinib, with lower incidence of atrial flutter or fibrillation, new-onset arterial hypertension, and sepsis.Figure 1.Cardiovascular outcomesFigure 2.Non-cardiovascular outcomes

The impact of comorbidities on therapy-optimization and their prognostics role among hospitalized patients with heart failure with reduced ejection fraction

Abstract Background The early, accurate diagnosis and proper treatment of comorbidities (CMs) are of strategic importance in heart failure (HF), as stated in the current ESC HF Guidelines. Unquestionably, the presence of CMs is associated with worse prognosis. Moreover, CMs can unfavourably affect the implementation of the guideline-directed medical therapy (GDMT) in heart failure with reduced ejection fraction (HFrEF). Aim To assess the prevalence of the relevant prognosis-modifying CMs among patients requiring hospitalization due to HFrEF, investigate their effect on the implementation and optimization of GDMT, and examine the impact of the presence of CMs on the prognosis in HFrEF. Patients and methods The data of 313 patients requiring hospitalization at our Institution due to HFrEF between 2021-2023 (male: 77%, age: 60[50-70]years, coronary artery disease: 46%, diabetes: 36%, hypertension: 65%, atrial fibrillation: 42%, LVEF: 24[20-30]%, eGFR at admission: 57[46-74]mL/min/1.73m², NT-proBNP at admission: 5035[2376-9369]pg/mL, SBP: 121[110-140]mmHg; GDMT at admission - RASi[ACEi/ARB/ARNI]: 60%, βB: 59%, MRA: 44%, SGLT2i: 14%) were analyzed retrospectively. Based on the number of diagnosed CMs, patients were divided into 3 categories: 0-1 vs. 2-3 vs. ≥4 CMs. The implemented GDMT at discharge was compared among CM categories with Chi-square test, while all-cause mortality (ACM) rates were investigated with Kaplan-Meier method and multivariate Cox-regression analysis. Results During the hospitalization in the total cohort the proportion of patients on GDMT increased significantly (RASi: 91%, βB: 85%, MRA: 96%, SGLT2i: 57%; patients on triple [TT] therapy [RASi+βB+MRA]: 83%, patients on quadruple therapy [TT+SGLT2i]: 52%; p＜0.05). However, among patients with higher rates of CMs, the application of GDMT was less favourable (RASi: 97% vs. 94% vs. 82%; βB: 93% vs. 89% vs. 75%; p＜0.05; 0-1 vs. 2-3 vs. ≥4 CMs), the proportion of patients on TT and QT remained remarkably high even among those with ≥4 CMs (TT: 93% vs. 87% vs. 71%; QT: 65% vs. 52% vs. 45%; p＜0.05). During the median follow-up period of 1.3 year, the ACM of patients with increased burden of CMs was higher (12% vs. 18% vs. 37%, p＜0.001). According to the results of the multivariate Cox-regression analysis, more advanced left ventricular systolic dysfunction (/1%), previously confirmed diagnosis of HFrEF, the growing number of CMs proved to be negative independent predictors of ACM, while the application of TT or QT reduced the risk of ACM significantly (HR: 0.471, 95% CI: 0.271-0.819, p=0.008). Conclusions According to our real-world analysis, although among HFrEF patients with an increased burden of CMs, less favourable prognosis can be expected, the application of modern GDMT is even possible among them, resulting in a significantly improved prognosis. Thus, clinicians should insist on the early, conscious implementation of GDMT among these patients as well.

External validation of the CA-AKI score in patients with acute coronary syndrome: A real-world cohort analysis from Asia

Abstract Background Contrast-associated acute kidney injury (CA-AKI) is associated with long-term impairment of kidney function, the need for renal replacement therapy, and subsequent all-cause deaths. A practical risk score, the CA-AKI risk score is derived for the prediction of contrast-associated acute kidney injury. However, this novel score has not received sufficient evidence of external validation in real-world studies, especially in Asian individuals. Methods Short-term endpoints and long-term endpoints were assessed in 8,816 patients with acute coronary syndrome enrolled in a large Asia registry. Discrimination was assessed by Harrell’s C statistic, and calibration was assessed by calibration plots. The ability of the CA-AKI score to predict short-term and long-term prognosis was assessed. Results CA-AKI occurred in 5.3% of the patients, with a stepwise increase of CA-AKI rates from the lowest to the highest of the 4 risk categories. When predicting the risk of CA-AKI, both discrimination and calibration were helpful in model 2 (C-index: 0.72; slope: 0.97) and in model 1(C-index: 0.69; slope: 1.02). The risks of 1-year all-cause mortality and 1-year bleeding were higher in CA-AKI patients (HR: 2.70 [95% CI: 2.22-3.30] and HR: 1.76 [95% CI: 1.41-2.46]; respectively). Conclusion The updated CA-AKI risk score could accurately identify patients with contrast-associated acute kidney injury, the occurrence of which is strongly associated with long-term mortality and bleeding.

Safety Profile of Statins for Post-Marketing Adverse Cardiovascular Events: A Real-World Pharmacovigilance Analysis.

The purpose of this study was to comprehensively evaluate the association of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) with neurological adverse events using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, with the aim of guiding the rational use of statins. The number and clinical characteristics of adverse events (AEs) to statins in the FAERS database between 2012 and March, 2023, were extracted. Neurological AEs were defined by the system organ classes (SOCs) of "Nervous System Disorders (10029205)" and the corresponding PT. Disproportionality was calculated using the reporting dominance ratio (ROR), proportional reporting ratio (PRR), and information component (IC025). Between January, 2012 and March, 2023, a total of 90,357 AEs were reported for the three statins (atorvastatin, resuvastatin, and simvastatin). The majority of reports on AEs came from the United States (n = 7284). A total of 8409 reports described neurological AEs following the use of the three statins, with atorvastatin accounting for more than half of the reports (n = 4430). The mean age of patients who developed neurological AEs was 55 years and older. The prevalence was similar in female patients (2230/4480) and male patients (1999/4480). Disproportionate analyses showed that at the SOC level, only the correlation between atorvastatin and neurological AEs suggested a positive signal (ROR: 9.77 (9.56-9.99); IC025: 3.28; PRR (χ2): 9.76 (16.07)) and in total, there were 32 PTs with a positive signal. The median time for neurological AEs was 71 days (IQR: 14-559 days), and the most common AEs were other serious effects (important medical event) (OT) (n = 2283) and hospitalization (HO) (n = 715). This study suggests that atorvastatin may be associated with an increased risk of neurological AEs. This study provides realistic evidence of the potential risk of statin-related adverse events.

Machine learning methods for propensity and disease risk score estimation in high-dimensional data: a plasmode simulation and real-world data cohort analysis

IntroductionMachine learning (ML) methods are promising and scalable alternatives for propensity score (PS) estimation, but their comparative performance in disease risk score (DRS) estimation remains unexplored.MethodsWe used real-world data comparing antihypertensive users to non-users with 69 negative control outcomes, and plasmode simulations to study the performance of ML methods in PS and DRS estimation. We conducted a cohort study using UK primary care records. Further, we conducted a plasmode simulation with synthetic treatment and outcome mimicking empirical data distributions. We compared four PS and DRS estimation methods: 1. Reference: Logistic regression including clinically chosen confounders. 2. Logistic regression with L1 regularisation (LASSO). 3. Multi-layer perceptron (MLP). 4. Extreme Gradient Boosting (XgBoost). Covariate balance, coverage of the null effect of negative control outcomes (real-world data) and bias based on the absolute difference between observed and true effects (for plasmode) were estimated. 632,201 antihypertensive users and nonusers were included.ResultsML methods outperformed the reference method for PS estimation in some scenarios, both in terms of covariate balance and coverage/bias. Specifically, XgBoost achieved the best performance. DRS-based methods performed worse than PS in all tested scenarios.DiscussionWe found that ML methods could be reliable alternatives for PS estimation. ML-based DRS methods performed worse than PS ones, likely given the rarity of outcomes.

Adverse event profile of albumin-bound paclitaxel: a real-world pharmacovigilance analysis

BackgroundAbraxane plays a crucial role in the treatment of various types of cancer, despite the considerable attention it has garnered for its adverse drug events (ADEs). Nevertheless, there is currently a significant lack of comprehensive real-world pharmacovigilance studies on the ADEs associated with Abraxane.MethodsWe conducted a retrospective analysis of ADEs associated with Abraxane using data mining from the FAERS database, analyzing data from 2005 to 2023. In a real-world setting, we quantified and visualized the signals of these ADEs using four pharmacovigilance algorithms.ResultsThe FAERS database identified a total of 10,230 adverse event reports associated with Abraxane. The study revealed that Abraxane-related adverse drug events involved 27 system organ classes (SOC), with the strongest signals associated with the lymphatic and hematological systems and hepatobiliary disorders. Additionally, we identified 70 significant Preferred Terms (PT) signals, which included some critical adverse events not highlighted in the product labeling, such as cystoid macular edema. Further analysis of the timing of adverse reactions showed a median onset time of 41 days. Most adverse events (AEs) occurred within the first month of using Abraxane (43.5%), although some were still possible 1 year after treatment (3.5%). Gender-specific analysis indicated that high-risk AEs differed between females (nausea, vomiting, and erythema) and males (febrile neutropenia, disseminated intravascular coagulation, and upper gastrointestinal bleeding).ConclusionThe examined results provide crucial recommendations for optimizing the administration of Abraxane, enhancing its effectiveness, and mitigating potential adverse effects. This knowledge will substantially facilitate the implementation of the substance in clinical settings.

Delays in diagnosis and treatment initiation of ATTR cardiac amyloidosis: a real-world data analysis

Abstract Introduction Cardiac amyloidosis (CA) is a serious condition characterized by the accumulation of abnormal protein deposits in the heart muscle, leading to functional impairments and, ultimately, heart failure. Transthyretin amyloid cardiomyopathy (ATTR-CM) is the most common form encountered in CA diagnosis with previously underestimated prevalence. ATTR-CM poses a diagnostic challenge, with a substantial number of cases diagnosed late and at advanced stages. The availability of specific pharmacological treatment using the transthyretin-stabilizer tafamidis further emphasizes the need for timely diagnosis. Here, we aim to assess delays in diagnosis and initiation of therapy in a real-world collective of patients with ATTR-CM. Methods All individuals diagnosed from 01/2018 to 05/2023 with ATTR-CM at our university hospital, Germany, were systematically assessed for eligibility in this study. Specifically, we enrolled patients who were undergoing transthyretin stabilizer therapy. The investigation aimed to determine the duration, in days, from the initial suspicion of heart disease to the definitive diagnosis of ATTR-CM. It was also investigated whether the diagnosis of ATTR-CM was made more quickly over time as awareness increased. Additionally, the study assessed the time elapsed until patients received pharmacological therapy following the confirmed diagnosis. The study was approved by the local ethics committee (23-11500-BO). Results After screening of 194 consecutive patients, 154 were included in the analysis, while 40 patients were excluded due to insufficient records. The results of this study reveal that a median of 300 (113-962) days elapsed from the initial suspicion of amyloidosis to the final confirmation. Initial indications of CA often presented as nonspecific symptoms such as unclear dyspnea (16.2% n=25), abnormal echocardiography (75.3% n=116), or, in rare cases, incidental findings (8.4% n=13). Following the diagnosis, an additional median of 84 (46-163.5) days passed before the first prescription of a transthyretin stabilizer. To assess an improvement of ATTR-CM diagnosis over time, we stratified the data into tertiles by date of first diagnosis. The results showed a gradually decrease in medium time to diagnosis of 466 (181-1035) days in the earliest tertile (2018-2019) to 389 (141-1508) days in the most recent tertile (2022-2023) (p<0.001). Conclusion This study shows a major healthcare deficit and underscores the medical need for improved screening procedures and diagnostic modalities to expedite the timely diagnosis of CA, as early identification of the condition is crucial for enhancing the quality of life for patients and preventing life-threatening complications.

Prevalence and incidence of chronic wounds in Austria - a population-based real-world data analysis

Abstract Background Chronic wounds are associated with pain, odor, loss of mobility, an increased risk for infection and sepsis and a reduced quality of life. Treatment costs are rising due to the longevity of the population and increasing number of diabetes cases. For service planning in healthcare, it is thus necessary to describe patient characteristics and estimate the prevalence and incidence of chronic wounds. Currently, no data exists on this subject broken down by age group, gender, and province in Austria. Methods A retrospective analysis of real-world data was conducted using two merged datasets from an outpatient wound centre and the Austrian Health Insurance Fund. The study population consisted of people who resided in Austria and were covered by statutory health insurance from 2018 to 2022. We performed a descriptive, socio-demographic analysis of the data of patients, followed by a set of cluster analyses using the unsupervised K-means algorithm. From these clusters, we derived subgroup characteristics and patient trajectories and calculated prevalence and incidence rates for chronic wounds according to diagnoses, different age groups, gender, and different regions. Results Gender was almost evenly distributed in the wound centre’s data set (n = 4963; 49.6% female). The age distribution revealed the age group from 71-80 years being the largest group. In general, more women than men are affected by chronic wounds from the age of 81 onwards. 31% of chronic wound patients had diabetes as an underlying condition. More men were affected by peripheral arterial occlusive disease and diabetic foot syndrome and, conversely, more women by chronic venous insufficiency. These are preliminary results of the analyses. Conclusions Chronic wound patients were characterised by older age and multi-morbidity. Interestingly, gender differences appeared in the occurrence of comorbidities. Key messages • This study makes a crucial contribution in making routine data usable for the epidemiological study of chronic wounds, a cluster of diseases of complex aetiology. • It thus contributes to filling a knowledge gap. The prevalence estimate serves as a basis of knowledge for health care planning and a basis for the health economic assessment of the problem.