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Purpose: Travel fatigue impacts cognitive and physiologic systems, but its association with elite soccer match performance is unclear. In this retrospective observational study, we aimed to explore the association between travel and match outcomes in elite North American soccer. Methods: Travel data and match outcomes (team points or goals scored and conceded) and physical performance outcomes from 26 elite professional soccer teams and their players were analyzed (148 matches [team-based data] and 1252 player matches from 297 players; age 22.7 [4.5] y). Player- and match-level correlations between performance measures and both acute and cumulated travel metrics were analyzed. Results: Cumulative travel metrics were positively associated with team (travel distance [r =.20; 95% CI,.03–.25], travel time [r =.20;.06–.37], and time away [r =.20;.06–.37]) and individual player (travel distance, [r =.14;.08–.19], travel time [r =.17–.23], and time away [r =.13;.07–.18]) high-intensity running. Cumulative time away was negatively associated with team points (r = −.14; −.28 to −.001) and positively associated with goals conceded (r =.14;.01–.27); no clear association between acute travel metrics and match outcomes or physical performance was observed. Conclusions: As travel cumulated, away teams and their players ran more but for less reward (team points), although the magnitude of these associations was small. These data are exploratory and do not imply a causal relationship; however, further research should consider cumulation of travel. [ABSTRACT FROM AUTHOR]

PURPOSE: In addition to the existing biomarkers HER2 and PD-L1, FGFR2b has become an area of interest for the development of new targeted-based treatment. Given that clinical evaluation of FGFR2 targeted therapy is underway, we sought to elucidate the genomic landscape of FGFR2amp in gastroesophageal cancer (GEC) using a circulating tumor DNA (ctDNA) platform. MATERIALS AND METHODS: We retrospectively evaluated the Guardant Health database from 2017 to 2022 for patients with GECs with Guardant360 ctDNA next-generation sequencing (NGS) performed. We assessed co-occurring genetic alterations for patients who harbored FGFR2amp versus FGFR2null. We also explored real-world evidence database with Guardant Health, publicly available genomic databases (MSK cohort using cBioPortal), and pooled clinical data from large-volume cancer centers for FGFR2amp GECs. RESULTS: Less than 4% of patients with GEC in the Guardant Health database were identified to be FGFR2amp. The most commonly co-occurring gene mutations were TP53, CTNNB1, CDH1, and RHOA. Upon interrogation of the MSK cohort, these same genes were not significant on tissue NGS in the FGFR2amp cohort of GEC. In the pooled institutional cohort, we noted that FGFR2amp tumors were most commonly involving the gastroesophageal junction (GEJ). The overall survival of these patients was noted at 13.1 months. CONCLUSION: FGFR2 is a validated target in GECs, and the contexture of FGFR2amp will be important in defining patient subgroups with responses to FGFR2-directed therapy. Using ctDNA to provide a more detailed genomic landscape in patients with GECs will allow the advancement of targeted therapy in the near future for these aggressive cancers.

INTRODUCTION: The 2021 US approval of ruxolitinib cream for treatment of atopic dermatitis (AD) in patients aged ≥ 12 years was based on the results of two pivotal phase 3 studies. Currently, real-world data to describe effectiveness of ruxolitinib cream and physician satisfaction with treatment remain limited. Our objective is to describe disease control among adults with mild to moderate AD prescribed ruxolitinib cream and physician satisfaction with treatment. METHODS: Data were from the Adelphi AD Disease Specific Programme™, a US real-world, cross-sectional survey of physician-reported data, undertaken between August 2022 and March 2023. For patients aged ≥ 18 years, physicians reported patient demographics, clinical characteristics, treatment patterns, and physician satisfaction with disease control. Descriptive analysis of data for patients with mild to moderate AD prior to the initiation of ruxolitinib cream and treated with ruxolitinib cream for ≥ 1 month was undertaken. RESULTS: Among physician-reported data from 1360 patients with AD, 149 patients had received ruxolitinib cream (in combination or as monotherapy) for ≥ 1 month, including 59 patients receiving monotherapy. Prior to treatment with ruxolitinib cream, 84.6% of patients had moderate AD (Investigators Global Assessment, IGA of 3), whereas after treatment (median duration, 26 weeks), only 21.5% had an IGA of 3, with 48.3% of patients having clear or almost clear skin (IGA of 0/1). For these patients, 81.2% were not currently experiencing a flare, and physicians were satisfied with disease control for 87.3%. Results were similar in patients receiving monotherapy. The most frequent physician-reported reasons for prescribing ruxolitinib cream included relieving itch, improving lesion redness/thickness, achieving disease control, and reducing/controlling flares. CONCLUSIONS: These real-world findings demonstrate effective disease control and physician satisfaction with ruxolitinib cream for the treatment of AD in adults in a clinical practice setting. Outcomes were similar whether ruxolitinib cream was prescribed as monotherapy or in combination regimens, suggesting a role for ruxolitinib cream across the spectrum of disease.

This article is about the two conflicting goals when teaching statistics or data science courses based on real-world data in a business school environment. We propose to look at structured socio-economic data about the Canadian economy. Canada was ranked 8th in 2017 by Open Data Watch (Government of Canada) for its data accessibility policy. Statistics Canada offers several ways to access data across its over 11,000 data tables. We built an R package to ease access to Statistics Canada's open economic data. With this package, we offer students another option to collect data about the Canadian economy.

Aim: Androgen receptor pathway inhibitors (ARPIs) prolong metastasis-free survival and overall survival in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). This study aimed to evaluate real-world treatment patterns, utilization and survival outcomes in patients with nmCRPC. Patients & methods: This retrospective cohort study used Optum database electronic health records of patients with nmCRPC from 1 January 2007 to 31 December 2020 in the US. Results: Of 1955 patients, >80% received androgen-deprivation therapy (ADT) alone or ADT + first-generation nonsteroidal antiandrogen (NSAA) as first-line treatment, while only 8.24% received ADT + ARPI. ADT + ARPI remained underutilized even among those with high-risk nmCRPC. Further, ADT + NSAA had no survival benefit compared with ADT alone. Conclusion: Practice-improvement strategies are needed for treatment intensification with ARPIs for patients with nmCRPC. Plain Language Summary Prostate cancer cells often use hormones called androgens to grow and survive. Hormone therapy is a treatment that lowers the amount of these hormones in the body to slow down the cancer's growth. It includes androgen-deprivation therapy (ADT), which can either be used alone or along with nonsteroidal antiandrogens (NSAAs) or with androgen receptor pathway inhibitors (ARPIs). Nonmetastatic castration-resistant prostate cancer (nmCRPC) is defined as prostate cancer that has not spread to other parts of the body but exhibits rising levels of serum prostate-specific antigen despite surgery or ADT to reduce androgens. Research shows that ARPIs can improve survival in patients with nmCRPC, but more data on its use are needed. This study looked at the electronic health records of patients with nmCRPC to review the treatment they had received and their survival. Between 2008 and 2020, most patients received ADT alone or with NSAA. Even though the number of patients receiving ADT with ARPI increased during this period, it remained underused, even in patients with a high risk of cancer spreading to other body parts. Post-2018, even after 2 years of these drugs being available, only about one in five patients received ADT with ARPI. Also, people who received ADT with NSAA did not have a longer survival than patients treated with ADT alone. The study indicates that ARPIs, which could improve survival of patients with nmCRPC, are not being utilized optimally. Strategies that promote early use of ARPIs are needed to improve survival of patients with nmCRPC. In this retrospective observational cohort study, treatment patterns and survival outcomes of patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) were investigated using electronic health records from the Optum clinical database. During the study period between 1 January 2007 and 31 December 2020, patients with nmCRPC defined on the basis of recorded prostate-specific antigen (PSA) values after surgical or medical castration were identified as per the inclusion and exclusion criteria. First-line (1L) regimens included ADT alone, ADT + NSAA ± glucocorticoids (ADT + NSAA), ADT + ARPI ± glucocorticoids ± NSAA (ADT + ARPI) and "other," which included all remaining regimens. Between 2008 and 2020, most patients (>80%) were treated with ADT alone or ADT + NSAA as 1L treatment, and only 8% received ADT + ARPIs, suggesting that despite ARPIs having been approved and included in treatment guidelines, they remain underutilized, even in patients at a high risk of metastasis (PSADT ≤10 months or Gleason score ≥8). Approximately, 55% of patients with nmCRPC developed metastasis during follow-up, and 70% received a new regimen (metastatic 1L treatment); ADT + ARPI was the common metastatic 1L treatment (42%), 2L (44%) and 3L (36.5%) mCRPC regimen. Time to death was shorter in the ADT + NSAA cohort (median OS: 30.87 months, 95% CI: 28.2–35.73) than the ADT-alone cohort (median OS: 41.70, 95% CI: 37.63–45.60) with statistical significance (HR: 1.33, 95% CI: 1.16–1.52), suggesting that despite ADT + NSAA appearing to be associated with worse clinical outcomes than ADT alone, it still had higher utilization than ADT + ARPI. Healthcare professionals should recognize the limited efficacy of NSAA and consider using ARPIs to treat patients with severe disease. Practice-improvement strategies are needed to ensure early treatment with ARPIs in patients with nmCRPC. [ABSTRACT FROM AUTHOR]

Purpose: To compare CDK4/6 inhibitor (CDK4/6i) with endocrine therapy (ET) in the first- versus second-line setting for treatment of hormone receptor positive (HR+), HER2 negative, metastatic breast cancer (MBC) using real-world evidence. Methods: Patients with HR+, HER2 negative MBC, diagnosed between 2/3/2015 and 11/2/2021 and having ≥ 3 months follow-up were identified from the nationwide electronic health record-derived Flatiron Health de-identified database. Treatment cohorts included: (1) first-line ET with a CDK 4/6i (1st-line CDK4/6i) versus (2) first-line ET alone followed by second-line ET with a CDK4/6i (2nd-line CDK4/6i). Differences in baseline characteristics were tested using chi-square tests and two-sample t-tests. Time to third-line therapy, time to start of chemotherapy, and overall survival were compared using Kaplan-Maier method. Results: The analysis included 2771 patients (2170 1st-line CDK4/6i and 601 2nd-line CDK4/6i). Patients receiving 1st-line CDK4/6i were younger (75% vs 68% < 75 years old, p = 0.0001), less likely uninsured or not having insurance status documented (10% vs. 13%, p = 0.04), of better performance status (50% vs 43% with ECOG 0, p = 0.03), and more likely to have de novo MBC (36% vs. 24%, p < 0.001). Time to third-line therapy (49 vs 22 months, p < 0.001) and time to chemotherapy (68 vs 41 months, p < 0.001) were longer in those receiving first-line CDK4/6i. Overall survival (54 vs 49 months, p = 0.33) was similar between groups. Conclusion: Use of CDK4/6i with first-, vs second-, line ET was associated with longer time to receipt of 3rd-line therapy and longer time to receipt of chemotherapy. [ABSTRACT FROM AUTHOR]

Aim: Characterize febrile neutropenia in the real-world and explore potentially modifiable risk factors. Patients & methods: Characteristics of patient presenting with febrile neutropenia after systemic cancer treatment were investigated, with a thorough evaluation of potential risk factors. Results: The rate of febrile neutropenia requiring hospitalization was comparable with clinical trials (mean absolute difference 2%, 95% CI: -1–4%; p = 0.29). The in-hospital mortality rate was 6%. Most cases resulted from low-risk regimens (50%) and 18.2% presented no apparent risk factors. 42.4% of patients presented modifiable factors potentially involved in the occurrence of febrile neutropenia. Conclusion: Febrile neutropenia rate in contemporary real-world evidence is comparable with clinical trials. Appropriate G-CSF administration and avoidance of potentially harmful drug-interactions represent potential areas for improvement. Even with the advance of new cancer treatment strategies, chemotherapy remain an important part of the treatment of many cancer patients. Febrile neutropenia remains one of the most common causes of cancer treatment morbidity and mortality. Other factors may come into play in the occurrence of febrile neutropenia in the real-world setting, compared with the strictly controlled environment of clinical trials. The febrile neutropenia rate in this real-world setting was comparable to rate in clinical trials. Many patients presented a modifiable factor potentially involved in the occurrence of febrile neutropenia, such as an abnormal pre-treatment laboratory value, a potentially significant drug interaction between a comedication and chemotherapy, or not receiving G-CSF in accordance with the guidelines. Despite a thorough review, we found no risk factor for 18 patients (18.2%) treated with low-risk regimen. Despite a thorough evaluation of known risk factors, febrile neutropenia remains difficult to predict for individual patients and presents an opportunity for further study. Appropriate G-CSF administration and avoidance of potentially harmful drug interactions could help reduce the burden of febrile neutropenia. [ABSTRACT FROM AUTHOR]

This paper explores the significant role of real-world data (RWD) in advancing our understanding and management of Multiple Sclerosis (MS). RWD has proven invaluable in MS research and care, offering insights from larger and diverse patient populations. A key focus of the paper is the European Health Data Space (EHDS), a significant development that promises to change how healthcare data is managed across Europe. This initiative is particularly relevant to the MS community. The paper highlights various data initiatives, discussing their importance for those affected by MS. Despite the potential benefits, there are challenges and concerns, especially about ensuring that the growth of various data platforms remains beneficial for MS patients. The paper suggests practical actions for the global MS community to consider, aimed at optimizing the use of RWD. The emphasis of this discussion is on the secondary use of health data, particularly in the European context. The content is based on the author's own experiences and interpretations, offering a personal yet informed view on using RWD to improve MS research and patient care. [ABSTRACT FROM AUTHOR]

Clinicians, researchers, regulators, and other decision-makers increasingly rely on evidence from real-world data (RWD), including data routinely accumulating in health and administrative databases. RWD studies often rely on algorithms to operationalize variable definitions. An algorithm is a combination of codes or concepts used to identify persons with a specific health condition or characteristic. Establishing the validity of algorithms is a prerequisite for generating valid study findings that can ultimately inform evidence-based health care. In this paper, we aim to systematize terminology, methods, and practical considerations relevant to the conduct of validation studies of RWD-based algorithms. We discuss measures of algorithm accuracy, gold/reference standards, study size, prioritization of accuracy measures, algorithm portability, and implications for interpretation. Information bias is common in epidemiologic studies, underscoring the importance of transparency in decisions regarding choice and prioritizing measures of algorithm validity. The validity of an algorithm should be judged in the context of a data source, and one size does not fit all. Prioritizing validity measures within a given data source depends on the role of a given variable in the analysis (eligibility criterion, exposure, outcome, or covariate). Validation work should be part of routine maintenance of RWD sources. This article is part of a Special Collection on Pharmacoepidemiology. [ABSTRACT FROM AUTHOR]

Aims/Introduction: The study aim was to investigate sulfonylurea prescription patterns in elderly patients (age ≥65 years) with type 2 diabetes mellitus in Japan. Sulfonylurea use among older adults has been insufficiently examined, despite the associated risks of hypoglycemia. Materials and Methods: This retrospective cross‐sectional survey entailed analysis of Japanese pharmacy data, extracted from the Musubi database, for patients (age 20–100 years) prescribed sulfonylureas between November 2022 and October 2023. Dose distribution, adherence to the Diabetes Treatment Guidelines for the Elderly 2023 and coprescription of other diabetes medications were investigated. Results: Of the total 91,229 patients, 80.1% were prescribed glimepiride, 16.3% gliclazide and 3.6% glibenclamide. In patients aged ≥65 years, exceeding the recommended dose (>1 mg/day for glimepiride, >40 mg/day for gliclazide) was numerically higher for glimepiride (25.0%) than for gliclazide (7.8%). The most common prescribing patterns were quadruple therapy with a sulfonylurea, a dipeptidyl peptidase‐4 inhibitor, an sodium–glucose transporter 2 inhibitor and a biguanide in patients aged 65 to <75 years, and dual therapy with a sulfonylurea and a dipeptidyl peptidase‐4 inhibitor in patients aged ≥75 years. Unfortunately, glinide was coprescribed for 338 (0.5%) of elderly patients. Insulin was coprescribed for 3,682 (5.6%) of elderly patients. Conclusions: Analysis of real‐world sulfonylurea prescription data found guideline non‐adherence, namely, excessive prescription of glimepiride, use of glibenclamide in elderly patients, and common coprescription with dipeptidyl peptidase‐4 inhibitors. These findings might provide an opportunity to reconsider the treatment of patients with type 2 diabetes mellitus who are over‐prescribed sulfonylureas to reduce residual risks, such as hypoglycemia. [ABSTRACT FROM AUTHOR]

Objectives: Biosimilars are anticipated to be widely used in the treatment of rheumatoid arthritis (RA), owing to their cost efficiency; LBEC0101 was the first etanercept (ETN) biosimilar approved in Japan. However, there are limited real-world data comparing its safety and effectiveness with those of a reference product. Methods: This study used data from the Kyoto University Rheumatoid Arthritis Management Alliance cohort, including patients with RA who received ETN therapy—ETN reference product (ETN-RP) or LBEC0101—between 2015 and 2021. Serum ETN levels were measured using liquid chromatography–tandem mass spectrometry. Results: The 1-year continuation rates of ETN-RP and LBEC0101 were 58.7% and 74.4%, respectively. Effectiveness of treatment was evaluated in 18 patients; both products significantly reduced the 28-joint RA disease activity score and erythrocyte sedimentation rate (DAS28-ESR). Moreover, to determine equivalence, we analysed 11 patients who switched from ETN-RP to LBEC0101; the DAS28-ESR and serum ETN levels before and after switching were not significantly different. Conclusions: This real-world cohort study confirmed that the biosimilar of ETN, LBEC0101, was comparable to the reference product in terms of continuation rate, effectiveness at initiation of introduction, and effect persistence before and after switching in clinical practice. [ABSTRACT FROM AUTHOR]

Computational Medicine encompasses the application of Statistical Machine Learning and Artificial Intelligence methods on several traditional medical approaches, including biochemical testing which is extremely valuable both for early disease prognosis and long-term individual monitoring, as it can provide important information about a person's health status. However, using Statistical Machine Learning and Artificial Intelligence algorithms to analyze biochemical test data from Electronic Health Records requires several preparatory steps, such as data manipulation and standardization. This study presents a novel approach for utilizing Electronic Health Records from large, real-world databases to develop predictive precision medicine models by exploiting Artificial Intelligence. Furthermore, to demonstrate the effectiveness of this approach, we compare the performance of various traditional Statistical Machine Learning and Deep Learning algorithms in predicting individuals' future biochemical test outcomes. Specifically, using data from a large real-world database, we exploit a longitudinal format of the data in order to predict the future values of 15 biochemical tests and identify individuals at high risk. The proposed approach and the extensive model comparison contribute to the personalized approach that modern medicine aims to achieve. [ABSTRACT FROM AUTHOR]

Background: The role of viral agents in the development of head and neck cancers has remained controversial. While markers of viral origin have been isolated from oral cancer tissues, a causative relationship has yet to be shown. The aim of this study was to evaluate the relationship between head and neck cancers and Herpes simplex virus, one of the most common viral infections of the oral orifice. Methods: Here, we conducted a retrospective analysis of two age‐ and gender‐matched cohorts extracted from the real‐world database TriNetX on March 10th, 2023, each consisting of 249,272 patients with and without Herpes simplex infections (ICD‐10: B00). The diagnoses C00‐C14 were analyzed, and risk analysis and Kaplan‐Meier survival statics were computed. Results: The strongest association was found for lip cancer (ICD‐10: C00) with a hazard ratio [HR (CI 95% low‐high)] of 3.08 (1.77–5.35). A significant association with HR of 1.17 (1.02–1.34) was found for the entire group of head and neck cancers. Confounders like smoking and alcohol dependence were considered using propensity score matching. Conclusion: The surprisingly strong correlation with lip, oral cavity, and pharynx neoplasms sheds new light on supposedly harmless herpes simplex infections, suggesting them as a possible new factor for risk stratification. [ABSTRACT FROM AUTHOR]

Purpose: The Observe‐and‐Plan (O&P) regimen allows for individualised treatment. In this study, we evaluated injection burden and intervals using aflibercept in an O&P regimen for eyes with neovascular age‐related macular degeneration (AMD). Methods: This was a retrospective registry‐based study of treatment‐naïve eyes with neovascular AMD. Treatment data were compiled for 3 years after commencement of intravitreal aflibercept therapy. We evaluated clinical consequences at the first follow‐up after loading dose, the proportion of patients who obtained and kept dry macula after loading dose, number of injections and intervals between injections. Results: Data were obtained for 1103 eyes. After loading dose, 0.4% were lost to follow‐up, 7.5% discontinued, 50.9% booked for further injections and 41.3% booked for monthly observations. After loading dose, the macula remained dry in 49.2% at 3 months, 34.0% at 6 months, 23.7% at 12 months and 15.2% at 24 months. For the entire population, median cumulative total number of injections was 7, 12 and 15, after 1, 2 and 3 years, respectively. After the 3rd year, the proportion of eyes in the short 4–6 weeks treatment interval was 51.1%, 8 weeks interval was kept in 14.4% and the extended treatment intervals of 10 and 12 weeks was possible in 34.4%. Conclusion: After loading dose, one in two eyes required further injections. A large proportion required therapy with shorter intervals than the label‐recommended 8 weeks. The large majority of those who obtained a dry macula after loading dose turned exudative again, mostly within the first 3 months. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy of a fixed‐ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) in people with type 2 diabetes (T2D) using derived time‐in‐range (dTIR). Methods: Participant‐level data from LixiLan‐L, LixiLan‐O and LixiLan‐G were pooled and dTIR (70‐180 mg/dL), derived time‐above‐range (> 180 mg/dL) and derived time‐below‐range (dTBR; < 70 mg/dL) were calculated from participant seven‐point self‐monitored blood glucose profiles. Results: This pooled analysis included data from 2420 participants receiving iGlarLixi (n = 1093), iGlar (n = 836), Lixi (n = 234) or a glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) (n = 257). Numerically greater improvements in least square (LS) means dTIR were seen from baseline to end of treatment (EOT) with iGlarLixi (25.7%) versus iGlar (15.8%), Lixi (11.7%) or GLP‐1 RA (16.2%). At EOT, the mean (standard deviation) dTBR was 0.71% ± 3.4%, 0.61% ± 3.2%, 0.08% ± 1.0% and 0.0% ± 0.0% for iGlarLixi, iGlar, Lixi and GLP‐1 RA, respectively. In a subgroup analysis, participants aged younger than 65 years (n = 1690) and 65 years or older (n = 713) showed numerically greater improvements in LS means dTIR from baseline to EOT with iGlarLixi versus iGlar, Lixi or GLP‐1 RA. Conclusions: iGlarLixi achieved improvements in dTIR, with low dTBR values, providing further evidence to inform clinical outcomes with the use of iGlarLixi. [ABSTRACT FROM AUTHOR]

Background: First‐line treatment in patients with acute myeloid leukemia (AML) unfit for intensive therapy is the combination of a hypomethylating agent (HMA) with venetoclax (VEN). However, retrospective data confirming the benefits of this regimen outside of clinical trials have shown conflicting results. Methods: We performed a multicenter retrospective analysis of outcomes with first‐line HMA–VEN versus HMA in AML patients unfit for intensive chemotherapy. Results: A total of 213 patients were included from three German hospitals (125 HMA–VEN, 88 HMA). Median overall survival in the HMA–VEN cohort was 7.9 months (95% confidence interval [CI], 5.1–14.7) versus 4.9 months (3.1–7.1) with HMA. After 1 year, 42% (95% CI, 33–54) and 19% (12–30) of patients were alive, respectively (hazard ratio [HR] for death, 0.64; 95% CI, 0.46–0.88). After adjusting for clinical and molecular baseline characteristics, treatment with HMA–VEN remained significantly associated with both prolonged survival (HR, 0.48; 95% CI, 0.29–0.77) and time to next treatment (HR, 0.63; 95% CI, 0.47–0.85). Patients who achieved recovery of peripheral blood counts had a favorable prognosis (HR for death, 0.52; 95% CI, 0.33–0.84). Discussion: These data align with findings from the pivotal VIALE‐A trial and support the use of HMA–VEN in patients unfit for intensive therapy. [ABSTRACT FROM AUTHOR]

The results of observational studies using real-world data, known as real-world evidence, have gradually started to be used in drug development and decision-making by policymakers. A good quality management system—a comprehensive system of process, data, and documentation to ensure quality—is important in obtaining real-world evidence. A risk-based approach is a common quality management system used in interventional studies. We used a quality management system and risk-based approach in an observational study on a designated intractable disease. Our multidisciplinary team assessed the risks of the real-world data study comprehensively and systematically. When using real-world data and evidence to support regulatory decisions, both the quality of the database and the validity of the outcome are important. We followed the seven steps of the risk-based approach for both database selection and research planning. We scored the risk of two candidate databases and chose the Japanese National Database of designated intractable diseases for this study. We also conducted a quantitative assessment of risks associated with research planning. After prioritizing the risks, we revised the research plan and outcomes to reflect the risk-based approach. We concluded that implementing a risk-based approach is feasible for an observational study using real-world data. Evaluating both database selection and research planning is important. A risk-based approach can be essential to obtain robust real-world evidence. [ABSTRACT FROM AUTHOR]

Purpose: TransCelerate BioPharma surveyed its member biopharmaceutical companies to understand current practices and identify opportunities to complement safety signal assessment with rapid real-world data (RWD) analysis. Methods: A voluntary 30-question questionnaire regarding the use of RWD in safety signal assessment was disseminated to subject matter experts at all TransCelerate member companies in July 2022. Responses were blinded, aggregated, summarized, and presented. Results: Eighteen of 20 member companies provided responses to the questionnaire. Sixteen (89%) companies reported actively leveraging RWD in their signal assessment processes. Of 18 respondent companies, 8 (44%) routinely use rapid approaches to RWD analysis, 7 (39%) utilize rapid RWD analysis non-routinely or in a pilot setting, 2 (11%) are considering using rapid RWD analysis, and 1 (6%) has no plans to use rapid RWD analysis for their signal assessment. Most companies reported that RWD adds context to and improves quality of signal assessments. To conduct RWD analysis for signal assessment, 16 of 17 (94%) respondent companies utilize or plan to utilize internally available data, 8 (47%) utilize both internal and external data, and 3 (18%) utilize data networks. Respondents identified key challenges to rapidly performing RWD analyses, including data access/availability, time for analysis execution, and uncertainties regarding acceptance of minimal or non-protocolized approaches by health authorities. Conclusion: Biopharmaceutical companies reported that they see value in the use of rapid RWD analyses for complementing signal assessments. Future work is recommended to offer a framework and process for use of rapid use of RWD analyses in signal assessment. [ABSTRACT FROM AUTHOR]

Rationale: Although recent evidence suggested that glucagon-like peptide 1 receptor agonists (GLP1RAs) might reduce the risk of asthma exacerbations, it remains unclear which subpopulations might derive the most benefit from GLP1RA treatment. Objectives: To identify characteristics of patients with asthma that predict who might benefit the most from GLP1RA treatment using real-world data. Methods: We implemented an active-comparator, new-user design analysis using commercially ensured patients 18–65 years of age from MarketScan data for 2007–2019 and identified two cohorts: GLP1RAs versus thiazolidinediones and GLP1RAs versus sulfonylureas. The outcome was acute exacerbation of asthma (hospital admission or emergency department visit for asthma) within 180 days after initiation. We applied iterative causal forest, a novel causal machine learning subgrouping algorithm, to assess heterogeneous treatment effects. In identified subgroups, we predicted propensity score, conducted propensity score trimming, and then estimated adjusted risk differences for the effect of GLP1RAs relative to comparators on asthma exacerbation using inverse probability treatment weighting in the propensity score–trimmed subpopulation. Results: Among 10,989 patients initiating GLP1RAs or thiazolidinediones and 17,088 patients initiating GLP1RAs versus sulfonylurea, GLP1RA initiators had fewer exacerbations, with adjusted risk differences of −0.5% (95% confidence interval [CI], −1.1% to 0.1%) and −1.6% (95% CI, −2.2% to −1.1%), respectively. In the GLP1RA versus sulfonylurea cohort, in which we observed a beneficial effect, our iterative causal forest analysis identified five subgroups with different treatment effects, defined by the number of emergency department visits, the number of prescriptions for short-acting β2-agonists, the number of prescriptions for inhaled steroids and long-acting β-agonists (either combination therapy or concurrent use), and age ≥ 50 years. Among these, patients with two or more emergency department visits during the 12-month baseline period had the largest absolute exacerbation risk reduction, with a decrease of 2.8% for GLP1RAs (95% CI, −4.8% to −0.9%). Conclusions: GLP1RAs demonstrated a beneficial effect on reducing asthma exacerbation relative to sulfonylureas. Patients with asthma with two or more emergency department visits (a proxy for disease severity) benefit most from GLP1RAs. Emergency department visit frequency, the number of maintenance and reliever inhalers, and age might help individualize prediction of the short-term benefit of GLP1RAs on asthma exacerbation. [ABSTRACT FROM AUTHOR]

Aim: To describe real-world biomarker testing, treatment and survival in stage IA–IIIC non-small cell lung cancer (NSCLC). Methods: Electronic records of USA-based patients in the CancerLinQ Discovery® database with stage IA–IIIC NSCLC (diagnosed between 2014 and 2018) were screened; a curated cohort of 14,452 records was identified for further analysis. Results: Of 3121 (21.6%) patients who had EGFR testing, 493 (15.8%) were EGFR-mutation positive. Of 974 patients who underwent surgical resection, 513 (52.7%) received adjuvant therapy. A quarter of patients with EGFR-mutation positive NSCLC received targeted adjuvant therapy. Conclusion: Approximately a fifth of patients underwent EGFR testing; biomarker testing is important to ensure optimal outcomes for patients with stage I–III NSCLC. Plain Language Summary A study investigating how many patients with early-stage non-small cell lung cancer (NSCLC) had mutations in a protein called EGFR and which treatments they received in routine clinical practice: The treatment recommended by medical experts for stage IA–IIIA non-small cell lung cancer (NSCLC) is surgical removal of the growth (tumor). Patients with stage II or III, and some with stage IB disease, are recommended to receive treatment with medications such as chemotherapy or oral cancer treatments after surgery (adjuvant treatment). In some lung cancers, there are mutations in a protein called EGFR. Osimertinib, a drug that blocks the activity of mutated EGFR on cancer cells, reducing their growth and spread, is recommended as an adjuvant treatment for patients with EGFR-mutated, stage IB–IIIA NSCLC. This study aimed to understand how many patients with stage I–III NSCLC have tumors with EGFR mutations, and which treatments patients received in everyday clinical practice, before new medicines such as osimertinib (that treat EGFR-mutated NSCLC) were recommended. We looked at anonymous data from 14,452 patients with stage I–III NSCLC treated at cancer clinics in the USA between 2014 and 2018. We found that 3121 (21.6%) patients had an EGFR mutation test and 493 (15.8%) had EGFR-mutation positive NSCLC. Of patients who had surgery to remove the tumor, 55% received adjuvant therapy (treatment after surgery). It is important to perform EGFR mutation testing in patients with stage IB–IIIA NSCLC so that patients with EGFR-mutation positive NSCLC can receive appropriate treatment. Article Highlights Stage I–IIIA non-small cell lung cancer (NSCLC) is typically treated surgically; adjuvant chemotherapy is recommended in patients with stage II/III, and select stage IB disease. Osimertinib, an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, is now approved for adjuvant treatment of resected EGFR-mutation positive stage IB–IIIA NSCLC. Immunotherapies have also been recently approved as neoadjuvant or adjuvant treatment in resectable NSCLC. Given these recent advancements, we assessed real-world biomarker testing patterns, and treatment and survival of patients with stage I–III NSCLC using data from the CancerLinQ Discovery® database, a health information platform that collects real-world data from oncology clinics in the USA. A cohort of 14,452 adults patients diagnosed with stage IA–IIIC NSCLC between January 2014 and December 2018 was identified. Of this cohort, 21.6% had at least one EGFR mutation test between the index date (date of diagnosis) and end of follow-up, with around two-thirds of these tests performed in the first 60 days following NSCLC diagnosis. Frequency of EGFR testing increased with increasing severity of NSCLC disease stage; female and Asian patients were more likely to receive an EGFR test. Of those with an EGFR test, 15.8% had EGFR-mutation positive (EGFRm) NSCLC; EGFRm NSCLC was more common in females, non-smokers and Asian patients. Surgical resection was the most common treatment for stage I and II NSCLC, while systemic therapy and/or radiotherapy without surgery was most common in stage III disease. Among patients who had resection, almost half did not receive a neoadjuvant or adjuvant treatment. Survival decreased with increasing disease stage; among patients with known EGFR status, median overall survival was longer in patients with EGFRm NSCLC than those with EGFRwt NSCLC. [ABSTRACT FROM AUTHOR]

Objectives Clinical Data Warehouses (CDW) are the designated infrastructures to enable access and analysis of large quantities of electronic health record data. Building and managing such systems implies extensive "data work" and coordination between multiple stakeholders. Our study focuses on the challenges these stakeholders face when designing, operating, and ensuring the durability of CDWs for research. Materials and Methods We conducted semistructured interviews with 21 professionals working with CDWs from France and Belgium. All interviews were recorded, transcribed verbatim, and coded inductively. Results Prompted by the AI boom, healthcare institutions launched initiatives to repurpose data they were generating for care without a clear vision of how to generate value. Difficulties in operating CDWs arose quickly, strengthened by the multiplicity and diversity of stakeholders involved and grand discourses on the possibilities of CDWs, disjointed from their actual capabilities. Without proper management of the information flows, stakeholders struggled to build a shared vision. This was evident in our interviewees' contrasting appreciations of what mattered most to ensure data quality. Participants explained they struggled to manage knowledge inside and across institutions, generating knowledge loss, repeated mistakes, and impeding progress locally and nationally. Discussion and conclusion Management issues strongly affect the deployment and operation of CDWs. This may stem from a simplistic linear vision of how this type of infrastructure operates. CDWs remain promising for research, and their design, implementation, and operation require careful management if they are to be successful. Building on innovation management, complex systems, and organizational learning knowledge will help. [ABSTRACT FROM AUTHOR]

Introduction: Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are chimeric antigen receptor T-cell therapies that were evaluated in third and later line (3L+) relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) in the ZUMA-1 and JULIET trials, respectively. As of October 2021, the DESCAR-T registry included 729 French patients with 3L+ r/r DLBCL who received axi-cel or tisa-cel. Using these data, propensity score matching was used to conduct an adjusted comparison between axi-cel and tisa-cel. Axi-cel was associated with statistically significant improvements in overall survival (OS) and progression-free survival (PFS), and significantly more frequent Grade ≥ 3 immune effector cell-associated neurotoxicity syndrome (ICANS), compared with tisa-cel. There was no significant difference in Grade ≥ 3 cytokine release syndrome (CRS). The current analysis assessed the cost-effectiveness of axi-cel versus tisa-cel in the treatment of 3L+ r/r DLBCL using propensity score-matched data from the DESCAR-T registry. Methods: A partitioned survival model was used to extrapolate costs and quality-adjusted life years (QALYs) over a lifetime. Survival curves for PFS and OS were based on independent mixture cure models fitted to digitized Kaplan–Meier data for the propensity score-matched DESCAR-T populations. Average duration of intensive care unit stays for each of axi-cel and tisa-cel in DESCAR-T were used to inform adverse event costs. Selected parametric survival distributions were based on clinical expert validation. Utility values were derived from ZUMA-1, and costs were obtained from French registries and published sources. List prices were used for both axi-cel and tisa-cel. Costs and outcomes were discounted at an annual rate of 2.5%. Results: Axi-cel is associated with an incremental cost-effectiveness ratio of €15,520 per QALY compared with tisa-cel. Conclusion: Based on explicit willingness-to-pay thresholds applied in Europe, axi-cel is expected to be a cost-effective use of healthcare resources in real-world clinical settings compared with tisa-cel in 3L+ r/r DLBCL. [ABSTRACT FROM AUTHOR]

Introduction: Historically, patients recently (≤ 6 months) diagnosed with pulmonary arterial hypertension (PAH; incident) have had poorer survival than those with a longer (> 6 months) time from PAH diagnosis (prevalent). Despite guideline recommendations for initial combination therapy for most patients with PAH, many are initiated and maintained on monotherapy. Real-world evidence to evaluate the benefit of early combination treatment in newly-diagnosed patients is lacking. Methods: Patients with PAH initiating combination therapy with the endothelin receptor antagonist macitentan and the phosphodiesterase-5 inhibitor tadalafil (M+T) were identified from the combined dataset of the US, multicenter OPUS (prospective, observational drug registry; NCT02126943) and OrPHeUS (retrospective, medical chart review; NCT03197688) studies (2013–2020). Descriptive analyses were performed for the incident and prevalent cohorts, as well as the subcohort of incident patients who received M+T as first-line combination therapy (incident initial combination). Results: In OPUS/OrPHeUS, 1336 patients with PAH received M+T during the observation period. For the incident [n = 453 (33.9%)], incident initial combination [n = 272 (20.4%)], and prevalent [n = 837 (62.6%)] cohorts: median (Q1, Q3) M+T exposure was 14.2 (4.2, 27.5), 12.2 (3.2, 25.5), and 14.7 (4.5, 28.0) months. 12-month Kaplan–Meier estimates (95% confidence limits) for survival were 91.2% (87.7, 93.7), 88.5% (83.2, 92.2), and 92.9% (90.6, 94.6), for patients free from hospitalization were 59.4% (54.1, 64.4), 56.3% (49.1, 62.9), and 62.3% (58.5, 65.9), and for patients persisting on combination therapy were 68.6% (63.9, 72.8), 65.0% (58.8, 70.6) and 66.9% (63.5, 70.0). Adverse events (OPUS only) were reported in 77.8%, 80.2%, and 80.3% of patients, respectively, with no unexpected adverse events observed. Conclusions: Despite a historically worse prognosis, incident patients receiving M+T, including as initial combination therapy, had similar survival and hospitalization as prevalent patients. Safety profiles were similar across cohorts. Together, these data support the use of early combination therapy with macitentan and tadalafil. Plain Language Summary: In earlier studies, patients diagnosed with pulmonary arterial hypertension (PAH) within the past 6 months (newly-diagnosed PAH, called 'incident patients' in this article) had worse health than patients diagnosed with PAH more than 6 months before (long-standing PAH, called 'prevalent patients' in this article). This is because some newly-diagnosed patients have very advanced disease and do poorly within the first 6 months. The OPUS (NCT02126943) and OrPHeUS (NCT03197688) studies collected information on patients with PAH treated in US clinics between 2013 and 2020. We identified patients that were treated with a combination of two PAH medications, macitentan and tadalafil. We then grouped them as newly-diagnosed (453 patients) or long-standing (837 patients). We also looked at the subgroup of newly-diagnosed patients who received the combination as their first treatment (272 patients, called 'incident initial combination patients' in this article). We then looked at how these patients did over time. Patients were treated with macitentan and tadalafil for an average of 12–14 months. We found that after 1 year of combination treatment, results were similar between the groups: patient survival was 91%, 89%, and 93% for those with newly-diagnosed, newly-diagnosed and previously untreated, and long-standing PAH; the proportion remaining hospitalization-free was 59%, 56%, and 62%; and the proportion remaining on combination treatment was 69%, 65%, and 67%, respectively. Side effects were in line with the known safety profiles of the medications. Despite historically having worse health outcomes, newly-diagnosed patients receiving the macitentan and tadalafil combination had similar survival and hospitalization as patients with long-standing PAH. These data suggest that there is a benefit to starting this combination of medicines early in the treatment of PAH. [ABSTRACT FROM AUTHOR]

Introduction: The substantial economic burden of acute myeloid leukemia (AML) could be reduced with post-remission maintenance therapies that delay relapse. Real-world healthcare resource utilization (HCRU) data and costs among patients with AML receiving oral azacitidine (Oral-AZA) maintenance therapy or no maintenance are not well understood. We characterize HCRU and costs among these patients in clinical practice in the USA. Methods: Data from IQVIA PharMetrics® Plus (January 1, 2016–June 30, 2022) were used. Patients ≥ 18 years who were newly diagnosed with AML, received first-line systemic induction therapy, and attained disease remission were eligible. Patients receiving Oral-AZA maintenance and those receiving no maintenance ("watch and wait" [W&W]) were matched 1:3 on baseline characteristics using propensity score matching (PSM) and followed until hematopoietic stem cell transplantation or end of continuous insurance enrollment, whichever occurred first. Outcomes included treatment patterns, inpatient and outpatient visits, and costs. Results: After PSM, the Oral-AZA cohort included 43 patients and the W&W cohort 129. Of the 43 patients receiving Oral-AZA, 88.4% started at the recommended dose of 300 mg and 11.6% at 200 mg. The Oral-AZA cohort had significantly (p = 0.0025) longer median (95% CI) time to relapse from the index maintenance date (median not reached [NR; 9.0 months–NR] vs 3.3 months [0.8 months–NR]), and fewer per person per month (PPPM) hospitalizations (0.23 vs 0.61; p = 0.0005) and overall outpatient visits (5.77 vs 7.58; p = 0.0391) than the W&W cohort. Despite higher AML drug costs PPPM in the Oral-AZA cohort ($16,401 vs $10,651 for W&W), total healthcare costs PPPM were lower ($25,786 vs $38,530 for W&W; p < 0.0001). Conclusions: Patients with newly diagnosed AML treated with Oral-AZA maintenance in clinical practice had prolonged remission and lower HCRU and costs than patients receiving no maintenance therapy. These findings underscore the clinical and economic value of Oral-AZA in clinical practice. [ABSTRACT FROM AUTHOR]

Conducting randomized controlled trials for medications targeting rare diseases presents significant challenges, due to the scarcity of participants and ethical considerations. Under such circumstances, leveraging real-world data (RWD) to generate supporting evidence may be accepted by the regulatory agency. Constructing an external control arm (ECA) from RWD for a single-arm trial has been conducted occasionally. A complication in this design is that patients from RWD may be eligible at multiple time points. Most studies approach this by selecting one time point as the index date for ECA patients. Here, we propose a novel design for externally controlled trials that permits the inclusion of ECA patients at various entry points. Accompanying this design, we make recommendations for statistical methods to account for measured confounders, limited sample size, within-subject correlation, and potential overdispersion inherent in count data. Furthermore, we present an idea for the blinding process for this type of study. We have conducted a series of simulations to assess the performance of the design and statistical methods in terms of bias, type I error, and efficiency, as compared to the approach of selecting only one entry per ECA patient. The study and parameter setup were based on a hypothetical case inspired by a rare disease study. The results indicate that allowing multiple entries for ECA patients can lead to enhanced performance in many aspects. It provides a controlled type I error, robustness against certain model misspecifications, and a moderate power improvement compared with selecting a single entry per ECA patient. [ABSTRACT FROM AUTHOR]

Globally, breast cancer is the most prevalent cancer and one of the leading causes of cancer-related death among women. HER2-low breast cancer represents a recently identified molecular category within breast cancer characterized by tumors displaying only slight overexpression of HER2 or lacking gene amplification. To illustrate, HER2-low tumors typically have an IHC (immune histochemistry) score of 1+ or 2+ with negative amplification. Nonetheless, recent findings indicate that even a slight amplification of HER2 could notably influence both therapeutic responses and prognostic outcomes. Our study aims to unveil the impact of HER2-low expression on the response to anthracycline and taxane-based neoadjuvant chemotherapy (NACT) in comparison to the HER2-negative group in non-metastatic breast cancer. This is a retrospective cohort study. All patients’ profiles with non-metastatic, HER2- low, and HER2-negative breast cancers who were administered neo-adjuvant chemotherapy and had surgery performed within the period spanning from 1 January 2018 to 30 August 2022 were enrolled. HER2-positive breast cancer patients were excluded. The evaluation of patients’ responses was conducted through the examination of surgical pathology reports to compare the two study groups (HER2-low and HER2-negative). The primary objective was evaluating the response to NACT comparing the objective response rate (ORR) in each of the two groups of HER2-low and HER2-negative patients. The total number of patients included was 262 patients; the majority were HER2-low 89% (233/ 262) vs. 11% (29/262) HER2-negative. An ORR (complete and partial response) to NACT was shown in 71% (185/262) of all patients. The ORR was similar in both groups, 70% (164/233) in the HER2-low group vs. 73% (21/29) in the HER2- negative group, with a statistical difference, OR: 1 (95% CI: 0.8–1), p-value 0.8. Similarly, the pathological complete response (pCR) rate was the same in both study groups at 14%, OR: 0.7 (95% CI: 0.2–3), p-value: 0.6. Interestingly, patients with hormone-positive tumors across both study groups had a higher response rate compared to hormone-negative patients. In the HER2-low cohort, the ORR was higher in patients with hormone-positive tumors in comparison with those with hormone-negative tumors [73% vs. 27%, OR: 0.8 (95% CI:0.8–1), p-value: 0.001]. Comparatively, in the HER2-negative cohort, ORR was also higher in patients with hormone-positive tumors compared to hormone-negative tumors [52% vs. 48%, OR: 2 (95% CI: 1–5), p-value: 0.05]. Subsequently, the ORR of all hormone-positive tumors with a positive outcome (CR or PR) was assessed categorizing the patients based on their HER2 expression. Concerning patients who expressed partial response (N = 115), a statistically significant difference was observed in HER2- low hormone-positive tumors as opposed to HER2-negative hormone-positive tumors [90% vs. 10%, OR: 0.7 (95% CI: 0.5–0.9), p-value: 0.001]. Remarkably, all patients with complete responses were from the HER2- low cohort. Our findings demonstrated a significant influence of HER2-low expression on the response to neoadjuvant chemotherapy among patients with hormone-positive HER2-low breast cancer within the studied cohort. Further studies are needed to evaluate the influence of hormonal expression on the response rate to NACT in the HER2-low patients in our population. [ABSTRACT FROM AUTHOR]

Background: Alemtuzumab (ALEM) is a humanised monoclonal antibody that depletes circulating lymphocytes by selectively targeting CD52, which is expressed in high levels on T- and B-lymphocytes. This depletion is followed by lymphocyte repopulation and a cytokine expression shift towards a lesser inflammatory profile, both of which may contribute to prolonged efficacy. National recommendations for enrolling and treating multiple sclerosis (MS) patients with ALEM have been established. However, there are no recommendations in place for the treatment of MS reactivation after the ALEM treatment. Objectives: To evaluate the effectiveness and safety of the use of ALEM and to analyse subsequent disease-modifying treatments (DMTs). A multidimensional prediction model was developed to make a patient-specific prognosis regarding the response to ALEM. Design: A multicentre, prospective, non-controlled, non-interventional, observational cohort study. Methods: Relapsing multiple sclerosis patients (RMSp) who received ⩾1 dose of ALEM were enrolled. In each treatment year, the following baseline and prospective data were collected: age, MS history, number, type and duration of previous disease-modifying treatment (PDMT), relapse rate (REL), expanded disability status scale (EDSS), magnetic resonance imaging and serious adverse events (AE). In cases of reactivation of MS, all data about the subsequent DMT were collected. Results: A total of 142 RMSp from 10 MS Slovak Centres fulfilled the inclusion criteria. The average age was 35 years (standard error 8.56). The overall average EDSS was 3.87 (1.46) when ALEM was started. The average duration of PDMT was 6.0 (4.04) years, and the median number of PDMTs was 3 (0–5), while the patients were mostly treated with 2 or 3 DMTs (>65.00%). Post-ALEM treatment was needed in 39 cases (27.46%). The most frequent post-ALEM treatment indicated was ocrelizumab, followed by natalizumab (NAT), siponimod and cladribine. The ocrelizumab and NAT treatment bring little benefit to patients. Siponimod showed less EDSS increase in contrast to ocrelizumab and NAT. Another repopulation therapy, cladribine, may also be an effective option. Statistically significant predictors for the expected EDSS are age (p -value <0.0001), number of ALEM cycles (0.0066), high number of PDMT (0.0459) and the occurrence of relapses (<0.0001). There was no statistically significant effect on the patient's gender (0.6038), duration of disease-modifying treatment before alemtuzumab (0.4466), or the occurrence of AE (0.6668). Conclusion: The study confirms the positive effect of ALEM on clinical and radiological outcomes. We need more data from long-term sequencing studies. [ABSTRACT FROM AUTHOR]

Aim: To assess treatment patterns and outcomes in patients with non-del(5q) lower-risk myelodysplastic syndromes. Methods: Patient medical records were reviewed in the USA, Canada (CAN), UK and the EU. Results: Analysis included 119 patients in the USA/CAN (median age, 61.5 years) and 245 patients in the UK/EU (median age, 67.3 years). Most patients received erythropoiesis-stimulating agents (ESAs) as first-line (1L) therapy (USA/CAN: 89.0%; UK/EU: 90.2%). A substantial proportion of 1L erythropoiesis-stimulating agent-treated patients were transfusion dependent before 1L (USA/CAN: 37.1%; UK/EU: 51.2%); a small percentage of these patients achieved transfusion independence during 1L therapy (USA/CAN: 2.8%; UK/EU: 14.4%). Conclusion: These findings highlight an unmet need for more effective treatments among patients with non-del(5q) lower-risk myelodysplastic syndromes. Article highlights Patients with lower-risk myelodysplastic syndromes (LR-MDS) often present with anemia and frequently require red blood cell transfusions (RBCTs). Transfusion dependence is associated with reduced survival and poor quality of life. Therefore, the goal of LR-MDS treatment is to manage anemia and reduce transfusion burden. In patients with non-del(5q) LR-MDS, erythropoiesis-stimulating agents (ESAs), with or without granulocyte colony-stimulating factor, are an established treatment for anemia in patients who are ESA-naive. Treatment options are limited for patients who are unresponsive to ESAs. Currently, little is known about the real-world treatment patterns and clinical outcomes of patients with non-del(5q) LR-MDS. This retrospective medical record review aimed to describe patient characteristics, treatment patterns and hematologic outcomes among patients with non-del(5q) LR-MDS in the USA, Canada (CAN), UK and EU (France, Germany, Spain). Data were abstracted for 119 patients with non-del(5q) LR-MDS in the USA/CAN and 245 patients in the UK/EU. Most patients initiated first-line (1L) therapy (USA/CAN: 109 [91.6%]; UK/EU: 225 [91.8%]) with a mean time from MDS diagnosis to initiation of 1L treatment of 10.1 months in the USA/CAN and 9.6 months in the UK/EU. The majority of patients received ESAs as 1L therapy (USA/CAN: 97 [89.0%]; UK/EU: 203 [90.2%]) and the median duration of 1L ESA treatment was 25.8 months in the USA/CAN and 31.8 months in the UK/EU. Prior to 1L treatment, 36 patients (37.1%) treated with 1L ESA-containing regimens were transfusion dependent (TD) in the USA/CAN, while 104 patients (51.2%) were TD in the UK/EU. Among these patients who were TD before 1L, only a small proportion (2.8% USA/CAN; 14.4% UK/EU) achieved transfusion independence during 1L. An RBCT reduction was achieved by 41.7% and 52.9% of 1L ESA-treated patients who were TD at treatment initiation in the USA/CAN and UK/EU, respectively. A hemoglobin improvement was achieved by 32.1% of 1L ESA-treated patients in the USA/CAN and 44.8% in the UK/EU. These findings highlight an unmet need in anemia management among patients with non-del(5q) LR-MDS and a requirement for new and more effective treatment options. [ABSTRACT FROM AUTHOR]

Summary Management of chemotherapy‐induced thrombocytopenia (CIT) is challenging, often resulting in chemotherapy treatment delays, dose reduction, and treatment interruption. Randomized trials support the potential efficacy and safety of thrombopoietin receptor agonists in CIT management. A phase III trial of avatrombopag (AVA) demonstrated increased platelet counts (PC) in patients with solid tumours experiencing CIT. To complement those findings, this case series of six patients with solid tumours and CIT is presented. Results from these cases support the clinical benefit of AVA in improving PC and reducing the impact of CIT on tumour treatment, allowing continued therapy without dose reduction or treatment interruption. [ABSTRACT FROM AUTHOR]

Background: Best supportive care (BSC) measures are an essential component for the management of primary progressive multiple sclerosis (PPMS). Objectives: RETRO PPMS (ML39631) is the first study to systematically analyze the therapeutic journey and standard of BSC of patients with PPMS in Germany. Design: This multicenter, non-interventional study retrospectively analyzed patient charts. Methods: Data were recorded up until the first infusion of ocrelizumab (July 2018 to October 2021). Medical history, disease status, disease activity and treatments were assessed from 12 months before PPMS diagnosis until study start. Acute interventions, BSC parameters and rehabilitation measures from the past 27 months were assessed. Results: The core analysis population (N = 462) had a mean age (range) of 57.4 (27–85) years and mean disease duration of 13.7 (0.3–55.2) years. The most frequently reported symptoms were muscle spasticity, bladder disorder, ataxia, gait disturbance and fatigue. The most commonly used treatment was physical/occupational therapy (66.5% of patients); 47.2% received off-label treatment with corticosteroids/disease-modifying therapies. BSC measures for many symptoms were strikingly rare – especially for fatigue and cognitive impairment. Conclusion: This analysis uncovers severe BSC deficits for many debilitating PPMS symptoms. There is still a large unmet need for innovative multidisciplinary care concepts and improvements in neurological primary and secondary care. [ABSTRACT FROM AUTHOR]

Summary: We aimed to investigate the risk of hip fracture associated with zoledronic acid treatment compared to alendronate on a population level. The risk of hip fracture was lower in women using zoledronic acid and higher in women who had discontinued treatment. The findings support the effectiveness of intravenous bisphosphonate. Purpose: To investigate whether zoledronic acid (ZOL) was associated with a lower risk of the first hip fracture than alendronate (ALN) in Norway using real-world data. Methods: Nationwide data on drugs dispensed in outpatient pharmacies were individually linked with all hospital-treated hip fractures. Individuals aged 50–89 years without previous hip fracture were included at their first filling of a prescription for ALN or ZOL during 2005–2016. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) for first hip fracture by time-varying exposure to ZOL versus ALN were estimated in sex-stratified flexible parametric survival analyses. Covariates included time-varying accumulated ALN exposure and comorbidity level expressed by the prescription-based Rx-Risk Comorbidity Index, marital status, education, and residential urbanity. Results: Of 75,250 women who initiated treatment, 72,614 (96.5%) were exposed to ALN and 6366 (8.5%) to ZOL. Of 12,739 men who initiated treatment, 12,311 (96.6%) were exposed to ALN and 784 (6.2%) to ZOL. In women, the HR for first hip fracture was 0.75 (95% CI: 0.61–0.91) for ZOL versus ALN. In men, the corresponding HR was 0.59 (95% CI: 0.32–1.07). Discontinued treatment was associated with increased risk compared with current ALN treatment in women (HR: 1.33; 95% CI: 1.24–1.42, men: HR 1.13 (95% CI: 0.95–1.35)). Conclusions: In women, the risk of first hip fracture when treated with ZOL was 25% lower than when treated with ALN. Discontinued treatment was associated with a 33% increase in hip fracture risk. Similar, albeit statistically non-significant, results were observed in men. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explored the current practices in the real world for grade 2 glioma, an uncommon primary brain cancer. Leveraging the prospective BRAIN registry, this study demonstrates that whilst sequential radiotherapy and chemotherapy improve progression-free survival in high-risk grade 2 glioma, the majority of patients are observed following surgery. In high-risk patients who are observed, 61% remain progression-free at 12 months, with 10% being progression-free at 5 years. This clinically meaningful progression-free survival suggests that validated biomarkers beyond the usual definition of high-risk are required to better inform patient management. Factors contributing to decision-making are underway. Background: Grade-2 gliomas (G2-glioma) are uncommon. In 2016, RTOG9802 established the addition of chemotherapy after radiation (CRT) as a new standard of care for patients with high-risk G2-glioma, defined as subtotal resection or age ≥40 yrs. Here, we report current practices using real-world data. Methods: Patients diagnosed with G2-glioma from 1 January 2016 to 31 December 2022 were identified in BRAIN, a prospective clinical registry collecting data on patients with brain tumours. High- and low-risk were defined as per RTOG9802. Two time periods, January 2016–December 2019 (TP1) and January 2020–December 2022 (TP2), were defined. Survival was estimated using the Kaplan–Meier method. Results: 224 patients were identified. Overall, 38 (17%) were low-risk, with 35 (91%) observed without further treatment. A total of 186 (83%) were high-risk, with 96 (52%) observed, 63 (34%) receiving CRT, and 19 (10%) receiving radiation. Over time, CRT use increased (TP1 vs. TP2: 22% vs. 36%, p = 0.004), and the rate of biopsy (TP1 vs. TP2: 35% vs. 20%, p = 0.02) and radiotherapy alone (TP1 vs. TP2: 14% vs. 4%, p = 0.01) decreased. Median progression-free survival (PFS) was significantly longer in high-risk patients who received CRT (NR) over observation (39 months) (HR 0.49, p = 0.007). In high-risk patients who were observed, 59 (61%) were progression-free at 12 months and 10 (10%) at 5 years. OS data remains immature. Conclusion: Congruent with RTOG9802, real-world BRAIN data shows CRT is associated with improved PFS compared to observation in high-risk G2-glioma. Whilst CRT use has increased over time, observation after surgery remains the most common strategy, with some high-risk patients achieving clinically meaningful PFS. Validated biomarkers are urgently required to better inform patient management. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explores the effectiveness and safety of a common breast cancer treatment in elderly patients, a group often overlooked in clinical trials. Specifically, it focuses on using CDK4/6 inhibitors with hormone therapy for treating metastatic HR+/HER2- breast cancer in patients aged 70 and older. This research aims to understand how well this treatment works and how tolerable it is for this vulnerable population, which faces unique challenges due to age and other health conditions. The results of this study may provide valuable insights for clinicians, enabling more informed treatment decisions which optimize therapeutic outcomes and enhance the quality of life for elderly patients with breast cancer. Background: Metastatic HR+/HER2- breast cancer is commonly treated with CDK4/6 inhibitors in combination with endocrine therapy. However, the efficacy and safety of this approach in elderly patients (≥70 years) remain unclear, particularly in the context of real-world clinical practice. This study aims to evaluate the clinical outcomes and tolerability of CDK4/6 inhibitor treatments in this fragile population, which is often under-represented in randomized clinical trials. Patients and methods: This retrospective multicenter study included elderly patients with metastatic HR+/HER2-negative breast cancer receiving first-line CDK4/6 inhibitors. The primary endpoint was progression-free survival (PFS). The secondary endpoints focused on the overall survival (OS), safety, and tolerability, considering variables such as tumor subtype, age, comorbidities, and treatment specifics. Results: The median PFS and OS were slightly lower than those reported in clinical trials, reflecting the inclusion of a more fragile population. The luminal B subtype was linked to a poorer PFS, while other factors like age, BMI, and ECOG status did not significantly affect the outcomes. A safety analysis indicated a higher incidence of grade 3 or higher toxicities, especially in frail patients, leading to dose reductions. Despite these challenges, CDK4/6 inhibitors were generally well-tolerated, allowing most patients to continue therapy. Conclusions: CDK4/6 inhibitors with endocrine therapy are effective in elderly patients with metastatic HR+/HER2- breast cancer, though careful management is crucial to balance efficacy and minimize adverse events. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion To analyse the impact on cost if faricimab is used as the first‐line treatment for neovascular age‐related macular degeneration (nAMD) compared to standard treatment with bevacizumab.Retrospective registry study including real‐world data from the Swedish Macula Registry between 2017 and 2022. The observed number of injections and visits for bevacizumab during the first two years of treatment was used (n = 437 patients). Number of faricimab injections was obtained from published clinical trial data and unit costs mostly from publicly available Swedish sources. The provider cost included medication and visit cost and societal cost included additionally patient travel cost. Costs are presented in 2023 EUR.The incremental societal cost of faricimab was 277 EUR per patient compared to bevacizumab in the base case. Medication cost was higher (1516 EUR) while visit cost (−1183 EUR) and patient travel cost (−56 EUR) were lower due to longer injection intervals. Faricimab was of similar cost as bevacizumab for patients residing far from the clinic. The faricimab injection interval and the number of bevacizumab injections were major drivers of uncertainty in the results.Faricimab represents a cost‐effective alternative to bevacizumab for patients with nAMD in Sweden. Its extended treatment interval is particularly beneficial for patients living far from clinics, and if the real‐life faricimab injection interval extends beyond 12 weeks. Our findings emphasize faricimab's potential to free up healthcare staff to treat a larger patient population with existing clinic resources. [ABSTRACT FROM AUTHOR]

Background: For patients with interstitial lung diseases (ILDs) presenting with a progressive pulmonary fibrosis (PPF) phenotype, current knowledge of disease characteristics at diagnosis, patient journey, and treatment is limited. This study aimed to describe demographics and clinical experiences of patients presenting with PPF in a European real-world setting. Methods: Data were analysed from the Adelphi Real World PPF-ILD Disease Specific Programme™, a cross-sectional survey of pulmonologists and rheumatologists in five European countries (France, Germany, Italy, Spain, United Kingdom) and internal medicine specialists (France) from April to October 2022. Physicians provided data for up to 12 consecutive patients with physician-confirmed ILD with a progressive phenotype other than idiopathic pulmonary fibrosis. Analyses were descriptive. Results: Overall, 265 physicians reported on 1,335 patients. Mean (standard deviation) age at survey date was 60.4 (11.6) years, 91.2% were white, 58.1% female, 44.0% non-smokers. Most patients (63.3%) first consulted a primary care physician. There was a mean delay of 7.8 (22.7) months between first ILD symptom and healthcare professional visit, and another 7.7 (12.8) months to ILD diagnosis. At survey date, 47.7% of patients had physician-reported moderate ILD, 42.3% had mild ILD and 10.0% had severe ILD. Disease progression was reported in the 12 months prior to the survey for 19.5% of patients; of these, progression was based on worsening symptom in 27.3% and lung function decline in 25.8%. For patients experiencing symptoms prior to ILD diagnosis (72.8%), the most common symptoms were dyspnoea on exertion (80.5%) and cough (57.8%). Overall, 17.4% of patients were misdiagnosed prior to ILD diagnosis, with chronic obstructive pulmonary disease suspected in 39.2% of them. The most frequent comorbidities were anxiety (16.9%) and gastroesophageal reflux (15.5%). Although 77.8% of patients were receiving treatment for ILD at survey date, 15.6% of patients had never been prescribed treatment for ILD. Conclusions: This real-world study expands our understanding of patients, diagnostic delays and treatment gaps experienced by patients diagnosed with PPF in Europe. There was a mean delay of 15.5 months between first ILD symptoms and ILD diagnosis. Given the progressive nature of PPF, diagnostic delay may lead to poor outcomes, including shorter survival. Trial registration: N/a. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusions The reliability of data‐driven predictions in real‐world scenarios remains uncertain. This study aimed to develop and validate a machine‐learning‐based model for predicting clinical outcomes using real‐world data from an electronic clinical pathway (ePath) system.All available data were collected from patients with lung cancer who underwent video‐assisted thoracoscopic surgery at two independent hospitals utilizing the ePath system. The primary clinical outcome of interest was prolonged air leak (PAL), defined as drainage removal more than 2 days post‐surgery. Data‐driven prediction models were developed in a cohort of 314 patients from a university hospital applying sparse linear regression models (least absolute shrinkage and selection operator, ridge, and elastic net) and decision tree ensemble models (random forest and extreme gradient boosting). Model performance was then validated in a cohort of 154 patients from a tertiary hospital using the area under the receiver operating characteristic curve (AUROC) and calibration plots.To mitigate bias, variables with missing data related to PAL or those with high rates of missing data were excluded from the dataset. Fivefold cross‐validation indicated improved AUROCs when utilizing key variables, even post‐imputation of missing data. Dichotomizing continuous variables enhanced performance, particularly when fewer variables were employed in the decision tree ensemble models. Consequently, regression models incorporating seven key variables in complete case analysis demonstrated superior discriminatory ability for both internal (AUROCs: 0.77–0.84) and external cohorts (AUROCs: 0.75–0.84). These models exhibited satisfactory calibration in both cohorts.The data‐driven prediction model implementing the ePath system exhibited adequate performance in predicting PAL post‐video‐assisted thoracoscopic surgery, optimizing variables and considering population characteristics in a real‐world setting. [ABSTRACT FROM AUTHOR]

Background: Radical prostatectomies can be performed using open retropubic, laparoscopic, or robot-assisted laparoscopic surgery. The literature shows that short-term outcomes (in particular, inpatient complications) differ depending on the type of procedure. To date, these differences have only been examined and confirmed in isolated cases based on national routine data. Methods: The data was based on the Swiss Medical Statistics from 2016 to 2018 from a national survey of administrative data from all Swiss hospitals. Cases with the coded main diseases neoplasm of the prostate (ICD C61) and the main treatments of laparoscopic (CHOP 60.5X.20) or retropubic (CHOP 60.5X.30) radical prostatectomies were included, resulting in a total sample size of 8,593 cases. Results: A procedure-related complication occurred in 998 cases (11.6%). By surgical procedure, complication rates were 10.1% for robotic-assisted laparoscopic radical prostatectomy 9.0% for conventional laparoscopic radical prostatectomy and 17.1% for open retropubic radical prostatectomy (p < 0.001). Conventional and robotic-assisted laparoscopic radical prostatectomies had a significantly lower risk of complications than retropubic procedures. Moreover, the risk of a procedure-related complication was almost twice as high in cases operated on retropubically; however, no significant difference was found between conventional and robotic-assisted laparoscopic cases. Discussion: The use of a surgical robot showed no advantages in radical prostatectomies regarding procedure-related during the hospital stay. However, both conventional and robotic-assisted laparoscopically operated radical prostatectomies show better results than open retropubic procedures. Further studies on the long-term course of patients based on claims data are needed to confirm the inherent benefits of surgical robots in tandem with them being increasingly employed in hospitals. [ABSTRACT FROM AUTHOR]

The article discusses the real-world effectiveness and drug survival of guselkumab over a 3-year period in treating moderate-to-severe plaque psoriasis, including difficult-to-treat areas. Guselkumab, an anti-IL23 biologic, has shown superior efficacy compared to adalimumab in clinical trials, with sustained high levels of clinical response over 5 years of treatment. Real-life studies have confirmed the effectiveness and safety of guselkumab, particularly in difficult-to-treat areas like scalp, palmoplantar, and genital psoriasis. The study emphasizes the importance of being treatment-naive for achieving complete or almost complete clinical clearance at Week 52. [Extracted from the article]

Background and Aims: Acute porphyria is a chronic recurrent disease with late diagnosis, heterogeneous clinical presentations and potentially devastating complications. The study aimed at providing real‐world evidence on the natural course of acute porphyria, patient characteristics, disease burden, and healthcare utilization before diagnosis. Methods: This observational study used anonymized claims data covering 8 365 867 persons from German statutory health insurance, spanning 6 years (2015–2020). Patients with at least one diagnosis of acute porphyria during the index period (2019–2020) were classified into three groups by attack frequency. These findings were compared with two age‐ and sex‐adjusted reference groups: the general population and fibromyalgia patients. Prevalence over the index period was calculated for all porphyria patients and those with active acute porphyria. Results: We revealed a prevalence of 79.8 per 1 000 000 for acute porphyria, with 12.9 per 1 000 000 being active cases. Acute porphyria patients, particularly with frequent attacks, demonstrated a higher comorbidity burden compared to the general population. Within the year before the recorded diagnosis, patients with acute porphyria required a median of 23.0 physician visits, significantly higher than the general population's 16.0. Additionally, 33.8% were hospitalized at least once during this period, a notably higher proportion than the general population (19.3%). Conclusions: This study's findings, collected before the introduction of givosiran, as the first approved preventive therapy for acute porphyria in Europe, highlight the need for healthcare strategies and policies tailored to the complex needs of acute porphyria patients. The significant healthcare demands, heightened comorbidity burden, and increased healthcare system utilization emphasize the urgency of developing a comprehensive support infrastructure for these patients. Also, these acute porphyria real‐world findings provide additional insights on disease characteristics in Germany. [ABSTRACT FROM AUTHOR]

Since 1980's, the established/standard treatment of acute myeloid leukemia (AML) is cytarabine infusion with anthracycline (7 + 3 regimen). We compared the 7 + 3 regimen in older secondary/high-risk AML patients from a clinical trial with a matched population from the Swedish AML Registry treated with an increased cytarabine dose in induction and consolidation as recommended in the Swedish National Guidelines since 2005. After successful propensity score matching, 104 patients per group were included. The primary outcome was overall survival (OS), and standard dosed patients had a median OS of 6.4 versus 10.7 months with increased dose intensity (hazard ratio: 0.69, p = 0.012), with 5-year OS of 8.7% and 18.1%, and remission rates of 36% and 60%, respectively (p < 0.001). Median OS after allogeneic hematopoietic cell transplantation (in 27.9% per group) was 10.4 and 20.7 months, respectively. We conclude that the more intensive cytarabine schedule seems to provide improved outcomes inthe investigated AML patient group. [ABSTRACT FROM AUTHOR]

Aims/Introduction: History of coronary artery disease (CAD), cerebrovascular disease (CeVD), type 2 diabetes and their combined effect on cardiovascular disease are essential for cardiovascular risk management. We investigated the association of prior CAD, prior CeVD, type 2 diabetes and their combination with the risk of cardiovascular disease. Materials and Methods: This is a historical cohort study including 342,033 participants (aged 18–72 years) followed up for ≥5 years between 2008 and 2016. Participants were classified into eight groups (with or without prior CAD, prior CeVD and type 2 diabetes). Type 2 Diabetes was defined by fasting plasma glucose and glycated hemoglobin levels, and antidiabetic drug prescription. Prior and subsequent CAD and CeVD were identified according to claims using International Classification of Diseases 10th Revision codes, medical procedures and questionnaires. Cox regression models were used to evaluate the risk of cardiovascular events. Results: The median follow‐up period was 6.4 years. The incidence of composite cardiovascular events of CAD and CeVD in the CAD−/CeVD−, CAD+/CeVD−, CAD−/CeVD+ and CAD+/CeVD+ groups were 1.92 and 6.94, 25.14 and 31.98 per 1,000 person‐years in non‐diabetes participants, and 8.66, 18.04, 39.98 and 60.72 in type 2 diabetes patients, respectively. Hazard ratios of cardiovascular events compared with CAD−/CeVD−/non‐diabetes were 1.66 (95% confidence interval 1.55–1.78) in CAD−/CeVD−/type 2 diabetes and 1.84 (1.56–2.18) in CAD+/CeVD−/non‐diabetes. CeVD+ was linked to a 4‐7‐fold increase in the risk of cardiovascular events regardless of CAD+ or type 2 diabetes. Conclusions: Type 2 diabetes increased the risk of cardiovascular disease as high as a history of CAD, whereas prior CeVD alone increased the risk of future CeVD without additional effects by type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Real-world evidence (RWE) plays a key role in regulatory and healthcare decision-making, but the potentially fragmentated nature of generated evidence may limit its utility for clinical decision-making. Heterogeneity and a lack of reproducibility in RWE resulting from inconsistent application of methodologies across data sources should be minimized through harmonization. Methods: This paper's aim is to describe and reflect upon a multidisciplinary research platform (FOUNTAIN; FinerenOne mUlti-database NeTwork for evidence generAtIoN) with coordinated studies using diverse RWE generation approaches and explore the platform's strengths and limitations. With guidance from an executive advisory committee of multidisciplinary experts and patient representatives, the goal of the FOUNTAIN platform is to harmonize RWE generation across a portfolio of research projects, including research partner collaborations and a common data model (CDM)–based program. FOUNTAIN's overarching objectives as a research platform are to establish long-term collaborations among pharmacoepidemiology research partners and experts and to integrate diverse approaches for RWE generation, including global protocol execution by research partners in local data sources and common protocol execution in multiple data sources through federated data networks, while ensuring harmonization of medical definitions, methodology, and reproducible artifacts across all studies. Specifically, the aim of the multiple studies run within the frame of FOUNTAIN is to provide insight into the real-world utilization, effectiveness, and safety of finerenone across its life-cycle. Results: Currently, the FOUNTAIN platform includes 9 research partner collaborations and 8 CDM-mapped data sources from 7 countries (United States, United Kingdom, China, Japan, The Netherlands, Spain, and Denmark). These databases and research partners were selected after a feasibility fit-for-purpose evaluation. Six multicountry, multidatabase, cohort studies are ongoing to describe patient populations, current standard of care, comorbidity profiles, healthcare resource use, and treatment effectiveness and safety in different patient populations with chronic kidney disease and type 2 diabetes. Strengths and potential limitations of FOUNTAIN are described in the context of valid RWE generation. Conclusion: The establishment of the FOUNTAIN platform has allowed harmonized execution of multiple studies, promoting consistency both within individual studies that employ multiple data sources and across all studies run within the platform's framework. FOUNTAIN presents a proposal to efficiently improve the consistency and generalizability of RWE on finerenone. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to analyse the initiation adherence phase to lipid‐lowering therapy for primary prevention of cardiovascular disease in a Spanish population aged 70 years or older. The secondary objective was to identify the determinants of initiation and early discontinuation. Methods: This was an observational study conducted in the CArdiovascular Risk factors for HEalth Service research (CARhES) cohort. People aged 70 and older with a first prescription of a lipid‐lowering drug and without a previous major adverse cardiovascular event (MACE) were selected (2018–2021). Data on sociodemographics, clinical conditions, drugs and use of health services were collected from clinical and administrative electronic databases. The study population was classified into: non‐initiation, early discontinuation (i.e., discontinuation after the first dispensing) and initiation with more than one dispensing. Their characteristics were compared. Determinants of initiation and early discontinuation were explored. Results: Among the 15 019 people studied, 80.2% initiated the medication, 11.2% showed an early discontinuation and 8.6% were non‐initiators. An older age or conditions such as dementia, diabetes or depression reduced the likelihood of initiation, while obesity and a high pharmacological burden increased it. People over 90 years of age or those prescribed a statin in combination were more likely to have an early discontinuation. Conclusions: Non‐initiation and early discontinuation are common among older people prescribed lipid‐lowering drugs as primary prevention of cardiovascular disease for the first time. The presence of chronic pathologies other than cardiovascular ones should be considered when assessing whether or not to prescribe these drugs in the elderly. [ABSTRACT FROM AUTHOR]

Background: Vitamin‐K antagonists (VKAs) have widely been replaced by non‐VKA oral anticoagulants (NOACs). This includes Austria, Germany and Switzerland, where as VKA, instead of warfarin, the much longer‐acting phenprocoumon is used, which was not compared to NOACs in clinical trials. Methods: Using administrative data from a large German health insurance, we included all anticoagulation‐naïve patients with a first prescription of a NOAC or VKA between 2012 and 2020. We analysed overall survival, major adverse cardiac and cerebrovascular events, major thromboembolic events and major bleeding. Results: Overall, 570,137 patients were included (apixaban: 26.9%, dabigatran: 4.6%, edoxaban: 8.8%, rivaroxaban: 39.1% and VKA: 20.7% of these 99.4% phenprocoumon). In the primary analysis using a 1:1 propensity score matching‐cohort (PSM‐cohort), a significantly higher overall mortality was found for apixaban, edoxaban and rivaroxaban (all p < 0.001) but not for dabigatran (p = 0.13) compared to VKA. In this PSM‐cohort, 5‐year mortality was 22.7% for apixaban versus 12.7% for VKA, 19.5% for edoxaban versus 11.4% for VKA, 16.0% for rivaroxaban versus 12.3% for VKA (all p < 0.001) and 13.0% for dabigatran versus 12.8% for VKA (p = 0.06). The observed effect was confirmed in sensitivity analyses using un‐weighted and three different weighted Fine–Gray regression models on the basis of the entire cohort. Conclusions: In this large real‐world analysis, apixaban, edoxaban and rivaroxaban, but not dabigatran, were associated with worse survival compared to VKA. These findings, consistent with a few other studies including phenprocoumon, cast profound doubts on the unreflected, general use of NOACs. Randomized trials should assess whether phenprocoumon might actually be superior to NOACs. [ABSTRACT FROM AUTHOR]

Effective healthcare planning, resource allocation, and budgeting require accurate predictions of the number of patients needing treatment at specific cancer stages and treatment lines. The Predicting the Population Health Economic Impact of Current and New Cancer Treatments (PRIMCAT) for Colorectal Cancer (CRC) simulation model (PRIMCAT-CRC) was developed to meet this requirement for all CRC stages and relevant molecular profiles in Australia. Real-world data were used to estimate treatment utilization and time-to-event distributions. This populated a discrete-event simulation, projecting the number of patients receiving treatment across all disease stages and treatment lines for CRC and forecasting the number of patients likely to utilize future treatments. Illustrative analyses were undertaken, estimating treatments across disease stages and treatment lines over a 5-year period (2022-2026). We demonstrated the model's applicability through a case study introducing pembrolizumab as a first-line treatment for mismatch-repair-deficient stage IV. Clinical registry data from 7163 patients informed the model. The model forecasts 15 738 incident and 2821 prevalent cases requiring treatment in 2022, rising to 15 921 and 2871, respectively, by 2026. Projections show that over 2022 to 2026, there will be a total of 116 752 treatments initiated, with 43% intended for stage IV disease. The introduction of pembrolizumab is projected for 706 patients annually, totaling 3530 individuals starting treatment with pembrolizumab over the forecasted period, without significantly altering downstream utilization of subsequent treatments. PRIMCAT-CRC is a versatile tool that can be used to estimate the eligible patient populations for novel cancer therapies, thereby reducing uncertainty for policymakers in decisions to publicly reimburse new treatments. • Accurate forecasting of patient numbers at specific cancer stages and treatment lines is vital for efficient healthcare planning and resource distribution. However, current predictions are typically limited to overall and stage-specific incidence forecasting. To ensure effective healthcare planning, novel tools are needed for Australia's colorectal cancer (CRC) landscape. • The Predicting the Population Health Economic Impact of Current and New Cancer Treatments-CRC model, grounded in real-world Australian data, offers unparalleled granularity in predicting CRC patient counts segmented by disease stage, cancer type, and treatment utilization. The model's ability to simulate the introduction of new treatments, exemplified through the pembrolizumab case study, demonstrates its adaptability and relevance for both present and future healthcare scenarios. • The Predicting the Population Health Economic Impact of Current and New Cancer Treatments-CRC model sheds light on Australia's current CRC treatment trajectory. As a dynamic tool, it may assist policymakers in assessing the impact of introducing new cancer treatments by forecasting potential patient populations. Its adaptability ensures proactive healthcare planning, for various interventions throughout the patient pathway. [ABSTRACT FROM AUTHOR]

Aim: To investigate, through post hoc analysis of nine studies from the SemaglUtide Real‐world Evidence (SURE) programme, the safety of once‐weekly (OW) semaglutide in adults with type 2 diabetes (T2D) and in subpopulations in routine clinical practice, complementing findings from the phase 3 randomized clinical trial (RCT) SUSTAIN programme. Methods: The SURE studies had a duration of ~30 weeks and included adults with diagnosed T2D treated with OW semaglutide. Safety information, including hypoglycaemic events, were collected and analysed for the total study population and for patient subgroups based on baseline patient characteristics, baseline co‐medication and prescriber specialty. Results: Of the total 3505 patients, 24.3% reported adverse events (AEs), with most patients reporting non‐serious (22.3%) and mild (17.1%) AEs. AEs mainly belonged to the gastrointestinal disorders system organ class (16.3% of patients). In total, 5.1% of patients reported AEs that led to treatment discontinuation, 0.5% reported serious adverse drug reactions and 0.2% had an AE with a fatal outcome, reported as unrelated to treatment. Overall, 1.1% and 0.1% of patients reported level 2 and 3 hypoglycaemic events, respectively. A higher rate of level 2 hypoglycaemia was observed in patients with baseline microvascular complications treated with insulin versus those on insulin without these complications. Conclusions: Safety data reported in the real‐world SURE studies were generally consistent with observations in phase 3 OW semaglutide RCTs. No new safety concerns were identified, highlighting that OW semaglutide is well tolerated by adults with T2D and in subpopulations in routine clinical practice. [ABSTRACT FROM AUTHOR]

The bidirectional relationships between metabolic syndrome (MetS) and major depressive disorder (MDD) were discovered, but the influencing factors of the comorbidity were barely investigated. We aimed to fully explore the factors and their associations with MetS in MDD patients. The data were retrieved from the electronic medical records of a tertiary psychiatric hospital in Beijing from 2016 to 2021. The influencing factors were firstly explored by univariate analysis and multivariate logistic regressions. The propensity score matching was used to reduce the selection bias of participants. Then, the Bayesian networks (BNs) with hill-climbing algorithm and maximum likelihood estimation were preformed to explore the relationships between influencing factors with MetS in MDD patients. Totally, 4126 eligible subjects were included in the data analysis. The proportion rate of MetS was 32.6 % (95 % CI: 31.2 %–34.1 %). The multivariate logistic regression suggested that recurrent depression, uric acid, duration of depression, marriage, education, number of hospitalizations were significantly associated with MetS. In the BNs, number of hospitalizations and uric acid were directly connected with MetS. Recurrent depression and family history psychiatric diseases were indirectly connected with MetS. The conditional probability of MetS in MDD patients with family history of psychiatric diseases, recurrent depression and two or more times of hospitalizations was 37.6 %. Using the BNs, we found that number of hospitalizations, recurrent depression and family history of psychiatric diseases contributed to the probability of MetS, which could help to make health strategies for specific MDD patients. • The proportion rate of metabolism syndrome (MetS) was 32.6% in major depressive disorder (MDD) patients. • The number of hospitalizations and uric acid were directly connected with MetS. • Recurrent depression and family history psychiatric diseases were indirectly connected with MetS. • The conditional probability of MetS in MDD patients with family history, recurrent and hospitalization times ≥2 was 37.6%. [ABSTRACT FROM AUTHOR]

Precision medicine has the ambition to improve treatment response and clinical outcomes through patient stratification and holds great potential for the treatment of mental disorders. However, several important factors are needed to transform current practice into a precision psychiatry framework. Most important are 1) the generation of accessible large real-world training and test data including genomic data integrated from multiple sources, 2) the development and validation of advanced analytical tools for stratification and prediction, and 3) the development of clinically useful management platforms for patient monitoring that can be integrated into health care systems in real-life settings. This narrative review summarizes strategies for obtaining the key elements—well-powered samples from large biobanks integrated with electronic health records and health registry data using novel artificial intelligence algorithms—to predict outcomes in severe mental disorders and translate these models into clinical management and treatment approaches. Key elements are massive mental health data and novel artificial intelligence algorithms. For the clinical translation of these strategies, we discuss a precision medicine platform for improved management of mental disorders. We use cases to illustrate how precision medicine interventions could be brought into psychiatry to improve the clinical outcomes of mental disorders. [ABSTRACT FROM AUTHOR]

Background and Objectives: Recent studies suggest that the binary categorization of first-generation antipsychotics (FGAs) as being primarily responsible for extrapyramidal symptoms (EPSs) and second-generation antipsychotics (SGAs) for cardiometabolic abnormalities is an oversimplification. SGAs also demonstrate antagonistic affinity for D2 receptors, indicating their potential to induce EPSs. This study utilized the Korea Adverse Event Reporting System (KAERS) database to explore adverse drug event (ADE) signals related to both FGAs and SGAs. Materials and Methods: Relevant ADE reports from January 2013 to December 2022 were extracted from the KAERS database and analyzed using disproportionality analysis, employing the proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) with its 95% lower confidence interval (LCI) indices. Results: Of the initial dataset of 2,890,702 ADE reports, those with insufficient data and duplicates were removed, resulting in a final dataset of 5249 reports for analysis. Aripiprazole, an SGA, showed signals for movement disorders, including EPSs (PRR 4.7, ROR 4.8, IC 2.2), tremors (PRR 5.3, ROR 5.4, IC 2.4), and akathisia (PRR 18.6, ROR 19.3, IC 3.5). Notably, for quetiapine, cardiovascular signals were detected, including increased blood pressure (PRR 2.1, ROR 2.3, IC 0.5), and tachyarrhythmia (PRR 13.9, ROR 14.1, IC 1.8), along with peripheral edema (PRR 2.5, ROR 2.5, IC 0.2). Metabolic abnormalities, such as weight gain and increased appetite, were identified for four SGAs: aripiprazole, olanzapine, quetiapine, and risperidone. Safety signals related to movement disorders were not detectable for FGAs, likely due to the limited number of ADE reports available for analysis. Conclusions: Our study findings support that the distribution of ADEs between FGAs and SGAs is not strictly binary. Aripiprazole, despite being an SGA, showed signals for extrapyramidal movement disorders. Four SGAs (aripiprazole, olanzapine, quetiapine, and risperidone) were linked to metabolic side effects, while quetiapine was associated with cardiovascular safety signals. [ABSTRACT FROM AUTHOR]

Upper tract urothelial carcinoma (UTUC) accounts for the 5–10% of all urothelial carcinomas (UCs). In this analysis, we reported the real-world data from the ARON-2 study (NCT05290038) on the efficacy of pembrolizumab in patients with UTUC who recurred or progressed after platinum-based chemotherapy. Medical records of patients with metastatic UTUC treated with pembrolizumab as second-line therapy were reviewed from 34 institutions in 14 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. 235 patients were included in our analysis. Median OS was 8.6 months (95% CI 6.6–12.1), the 1 year OS rate was 43% while the 2 years OS rate 29%. The median PFS was 5.1 months (95% CI 3.9–6.9); 46% of patients were alive at 6 months, 34% at 12 months and 25% at 24 months. According to RECIST 1.1, 18 patients (8%) experienced complete response (CR), 57 (24%) partial response (PR), 44 (19%) stable disease (SD), and 116 (49%) progressive disease (PD), with an ORR of 32%. Our study confirms the effectiveness of pembrolizumab in patients pretreated with a platinum-based combination, irrespective of their sensitivity to the first-line treatment and of their histology. In addition, we emphasized the limited benefit of the treatment with pembrolizumab in patients with hepatic metastases and poor ECOG performance status. [ABSTRACT FROM AUTHOR]