Association Between PD-L1 Score and the Outcomes of Consolidation Durvalumab in a Large Nationwide Series of Patients With Stage III NSCLC Treated With Chemoradiotherapy.

BACKGROUND: The Pacific trial reported improved outcomes when durvalumab was administered following concurrent chemoradiotherapy (CRT) for stage III NSCLC. Post-hoc subgroup analysis did not show favorable results for PD-L1 negative cases. We compared nationwide survival data with the trial outcomes, and evaluated the influence of PD-L1. PATIENTS AND METHODS: Data from the Netherlands Cancer Registry were queried regarding patients with clinical stage III who underwent CRT, either by concurrent or sequential administration. Predictors for the use of consolidation treatment with durvalumab were evaluated by tabulations and logistic regression analysis. Overall survival (OS) was calculated from start of radiation or start of durvalumab and was stratified by PD-L1 score. RESULTS: Between 2017 and 2021, application of consolidation durvalumab increased from 2% to 21%, 40%, 57%, 62%, respectively. In the period 2020-2021, durvalumab use was more frequent among patients with younger age, concurrent CRT, better performance score and proton radiation, but was irrespective of PD-L1 score. For patients receiving durvalumab (n = 1639), the 4-year OS was 53% overall (95%CI 50-57), and it was 56% (95%CI 52-60) after concurrent CRT. Four-year OS was considerably better for the PD-L1 subgroup ≧50% at 67% (95%CI 59-73), and it was similar for PD-L1 subgroups 0 and 1-49, at 51% (95%CI 42-58) and 46% (95%CI 39-54), respectively. CONCLUSION: In real-world clinical practice, survival outcomes were equivalent to results from trial series. Overall survival in patients with negative PD-L1 was similar to the survival in patients with PD-L1 1-49, questioning the restrictions imposed by the European Medicines Agency.

Real-world outcomes of long-term use of silexan in patients with anxiety disorders: a single-centre experience.

OBJECTIVE: To evaluate the effectiveness and safety of long-term use of silexan in patients with a wide range of anxiety disorders. METHODS: A retrospective chart review was conducted on 50 patients diagnosed with various anxiety disorders who were prescribed silexan. The primary outcomes measured included the resolution of anxiety symptoms, changes in Generalized Anxiety Disorder-7 (GAD-7) scores, and Clinical Global Impressions-Improvement (CGI-I) scores. The duration of silexan use and any reported adverse events were also recorded. RESULTS: Silexan effectively resolved anxiety symptoms in 35 patients, with 24 out of 25 patients who received silexan for more than 12 weeks showing significant improvement. Median GAD-7 and CGI-I scores decreased significantly (p<0.001). By the end of the follow-up period, 46% of patients had minimal anxiety and 24% had mild anxiety. No adverse events were reported during the study period. CONCLUSIONS: Long-term use of silexan is feasible, safe, and effective in managing a wide range of anxiety disorders in real-world clinical settings.

While silexan has shown promising results in the treatment of anxiety disorders in various clinical trials, there is a significant gap in our understanding of its effects in long-term use.The present study supports the long-term use of silexan as a safe and effective alternative or adjunct to conventional anxiolytics.Using silexan as an alternative or adjunct to traditional anxiolytics may provide additional treatment options, potentially reducing the burden of these prevalent and disabling conditions.Silexan may be an appropriate choice for patients seeking natural or complementary treatments for anxiety.

The future of medicine: an outline attempt using state-of-the-art business and scientific trends.

Introduction: Currently, there is a lot of discussion about the future of medicine. From research and development to regulatory approval and access to patients until the withdrawal of a medicinal product from the market, there have been many challenges and a lot of barriers to overcome. In parallel, the business environment changes rapidly. So, the big question is how the pharma ecosystem will evolve in the future. Methods: The current literature about the latest business and scientific evolutions and trends was reviewed. Results: In the business environment, vast changes have taken place via the development of the internet as well as the Internet of Things. A new approach to production has emerged in a frame called Creative Commons; producer and consumer may be gradually identified in the context of the same process. As technology rapidly evolves, it is dominated by Artificial Intelligence (AI), its subset, Machine Learning, and the use of Big Data and Real-World Data (RWD) to produce Real-World Evidence (RWE). Nanotechnology is an inter-science field that gives new opportunities for the manufacturing of devices and products that have dimensions of a billionth of a meter. Artificial Neural Networks and Deep Learning (DL) are mimicking the use of the human brain, combining computer science with new theoretical foundations for complex systems. The implementation of these evolutions has already been initiated in the medicinal products' lifecycle, including screening of drug candidates, clinical trials, pharmacovigilance (PV), marketing authorization, manufacturing, and the supply chain. This has emerged as a new ecosystem which features characteristics such as free online tools and free data available online. Personalized medicine is a breakthrough field where tailor-made therapeutic solutions can be provided customized to the genome of each patient. Conclusion: Various interactions take place as the pharma ecosystem and technology rapidly evolve. This can lead to better, safer, and more effective treatments that are developed faster and with a more solid, data-driven and evidence-concrete approach, which will drive the benefit for the patient.

Analysis of thromboembolism and prognosis in metastatic pancreatic cancer from the Tokushukai REAl­world data project.

Cancer-associated thromboembolism (CAT), including venous thromboembolism (VTE) and arterial thromboembolism (ATE), is a frequent complication of advanced pancreatic cancer. However, reports on its incidence and clinical outcomes, especially on ATE, are limited. The present study aimed to investigate the incidence of CAT and its effects on overall survival in patients with metastatic pancreatic cancer. As part of the Tokushukai REAl-world data project in Japan, 846 eligible patients with metastatic pancreatic cancer treated with first-line chemotherapy were identified between April 2010 and March 2020. Using diagnosis procedure combination data from these patients, the present study investigated the incidence of VTE, ATE and cerebral and gastrointestinal bleeding requiring hospitalization. Blood laboratory data were collected within 14 days of the start of first-line treatment, and Khorana scores were calculated. The associations between CAT complications and comorbidities, concomitant medications and prognosis were examined. Among the 846 patients, 21 (2.5) and 70 (8.3%) had VTE and ATE, respectively (including five with overlapping VTE and ATE). CAT-positive patients had a significantly higher rate of gastrointestinal bleeding events compared with CAT-negative patients [13 of 86 (15.2%) vs. 46 of 760 (6.1%); P=0.01]. CAT-positive patients had a poorer prognosis [hazard ratio (HR), 1.28; 95% confidence interval (CI), 1.01-1.62] compared with CAT-negative patients, even after adjusting for background factors (HR, 1.20; 95% CI, 0.95-1.52). Cox regression analyses showed that higher Khorana scores were associated with significantly worse prognosis. This real-world data demonstrated that the incidence rate of CAT in patients with metastatic pancreatic cancer was 10.2%, and no statistically significant differences were observed, although there was a trend toward an adverse prognosis. The Khorana score may also be useful for predicting prognosis, even in the absence of CAT. This study was registered in the UMIN Clinical Trial Registry (http://www.umin.ac.jp/ctr/index.htm; clinical trial no. UMIN000050590).

Treating chronic atrophic gastritis: identifying sub-population based on real-world TCM electronic medical records.

Background and Objective: Chronic atrophic gastritis (CAG) is a complex chronic disease caused by multiple factors that frequently occurs disease in the clinic. The worldwide prevalence of CAG is high. Interestingly, clinical CAG patients often present with a variety of symptom phenotypes, which makes it more difficult for clinicians to treat. Therefore, there is an urgent need to improve our understanding of the complexity of the clinical CAG population, obtain more accurate disease subtypes, and explore the relationship between clinical symptoms and medication. Therefore, based on the integrated platform of complex networks and clinical research, we classified the collected patients with CAG according to their different clinical characteristics and conducted correlation analysis on the classification results to identify more accurate disease subtypes to aid in personalized clinical treatment. Method: Traditional Chinese medicine (TCM) offers an empirical understanding of the clinical subtypes of complicated disorders since TCM therapy is tailored to the patient's symptom profile. We gathered 6,253 TCM clinical electronic medical records (EMRs) from CAG patients and manually annotated, extracted, and preprocessed the data. A shared symptom-patient similarity network (PSN) was created. CAG patient subgroups were established, and their clinical features were determined through enrichment analysis employing community identification methods. Different clinical features of relevant subgroups were correlated based on effectiveness to identify symptom-botanical botanical drugs correspondence. Moreover, network pharmacology was employed to identify possible biological relationships between screened symptoms and medications and to identify various clinical and molecular aspects of the key subtypes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results: 5,132 patients were included in the study: 2,699 males (52.60%) and 2,433 females (47.41%). The population was divided into 176 modules. We selected the first 3 modules (M29, M3, and M0) to illustrate the characteristic phenotypes and genotypes of CAG disease subtypes. The M29 subgroup was characterized by gastric fullness disease and internal syndrome of turbidity and poison. The M3 subgroup was characterized by epigastric pain and disharmony between the liver and stomach. The M0 subgroup was characterized by epigastric pain and dampness-heat syndrome. In symptom analysis, The top symptoms for symptom improvement in all three subgroups were stomach pain, bloating, insomnia, poor appetite, and heartburn. However, the three groups were different. The M29 subgroup was more likely to have stomach distention, anorexia, and palpitations. Citrus medica, Solanum nigrum, Jiangcan, Shan ci mushrooms, and Dillon were the most popular botanical drugs. The M3 subgroup has a higher incidence of yellow urine, a bitter tongue, and stomachaches. Smilax glabra, Cyperus rotundus, Angelica sinensis, Conioselinum anthriscoides, and Paeonia lactiflora were the botanical drugs used. Vomiting, nausea, stomach pain, and appetite loss are common in the M0 subgroup. The primary medications are Scutellaria baicalensis, Smilax glabra, Picrorhiza kurroa, Lilium lancifolium, and Artemisia scoparia. Through GO and KEGG pathway analysis, We found that in the M29 subgroup, Citrus medica, Solanum nigrum, Jiangcan, Shan ci mushrooms, and Dillon may exert their therapeutic effects on the symptoms of gastric distension, anorexia, and palpitations by modulating apoptosis and NF-κB signaling pathways. In the M3 subgroup, Smilax glabra, Cyperus rotundus, Angelica sinensis, Conioselinum anthriscoides, and Paeonia lactiflora may be treated by NF-κB and JAK-STAT signaling pathway for the treatment of stomach pain, bitter mouth, and yellow urine. In the M0 subgroup, Scutellaria baicalensis, Smilax glabra, Picrorhiza kurroa, Lilium lancifolium, and Artemisia scoparia may exert their therapeutic effects on poor appetite, stomach pain, vomiting, and nausea through the PI3K-Akt signaling pathway. Conclusion: Based on PSN identification and community detection analysis, CAG population division can provide useful recommendations for clinical CAG treatment. This method is useful for CAG illness classification and genotyping investigations and can be used for other complicated chronic diseases.

Jin-Gu-Lian Capsule Did Not Significantly Improve Clinical Value in Rheumatoid Arthritis Therapy: A Real-World Study.

Purpose: To investigate the clinical value of adding Jin-gu-lian (JGL) capsules into rheumatoid arthritis (RA) treatment by examining its impact on disease activity and quality of life (QoL) through a real-world study (RWS). Patients and methods: RWS was conducted to compare the inflammatory markers, including IgM-RF, ESR, and CRP, between RA patients treated with only Western medicine (reference group) and Western medicine plus JGL (study group) during one-year follow-up. The clinical data was acquired from the hospital information system (HIS). Telephone call-based follow-up on QoL (SF-36) and accompanying symptoms, including gastrointestinal complaints, attacks of pneumonia, herpes zoster, URTIs, UTIs, and LTBIs. Finally, the anti-rheumatic drugs given to both groups were also compared. RWS was further validated for its feasibility by performing studies with hydroxychloroquine (HCQ) treatment, which is a commonly used anti-rheumatic drug for RA with mild effect. Results: The study group failed to show a significant effect on inflammatory markers, especially on the CRP levels, indicating no additional clinical value of supplementing with JGL. Similarly, at the endpoint, no significant differences between the two groups on QoL and related symptoms were observed. Our study suggests that the patients in the study group might need more anti-rheumatic drugs to fill the treatment insufficiency, and the application ratio of NSAIDs would be significantly higher than the reference group. By conducting this study on HCQ treatment, the positive aspects of controlling disease activity and reducing NSAIDs application were found, which demonstrates the utility of performing the RWS to evaluate the effect of JGL. Conclusion: Adding JGL did not significantly improve the clinical efficacy of RA treatment by this RWS. Folk herbal prescriptions such as JGL are suggested to underwent strict clinical trials before application.

Real-world use of pemigatinib for the treatment of cholangiocarcinoma in the US.

BACKGROUND: Pemigatinib demonstrated efficacy in fibroblast growth factor receptor (FGFR)-altered cholangiocarcinoma (CCA) in the FIGHT-202 trial. However, limited real-world evidence exists on treatment patterns and outcomes in this setting. PATIENTS AND METHODS: Patient characteristics, treatment patterns, and outcomes of US adults who received pemigatinib for unresectable, locally advanced or metastatic CCA were collected via retrospective physician-abstracted chart review. Results were summarized using descriptive statistics. RESULTS: Data from 120 patients (49.2% male; 55.0% White; 19.2% Hispanic; median age at initial pemigatinib prescription, 64.5 years) were collected from 18 physicians/practices. At the time of prescribing, 90.0% of patients had metastatic disease. FGFR2 testing was completed for 92.5% of patients; of those, all but one (result unknown) tested positive, and 95.5% were tested using next-generation sequencing. Pemigatinib was prescribed as second- and third-line therapy among 94.2% and 5.8% of patients, respectively. The most common starting dosage was 13.5 mg daily for 14 days of 21-day cycles (87.5% of patients). Among 60 patients (50.0% of the full cohort) who discontinued pemigatinib during the 6.5-month median study follow-up period, 68.3% discontinued due to disease progression. The median real-world progression-free survival (rwPFS) from the date of pemigatinib initiation was 7.4 months (95% CI: 6.4-8.6), and the real-world overall response rate (rwORR) was 59.2% (95% CI: 50.0%-68.4%). CONCLUSION: This study complements the FIGHT-202 clinical trial by assessing the use of pemigatinib among a diverse population of patients with CCA under real-world conditions. Findings support the clinical benefit of pemigatinib demonstrated in FIGHT-202.

Data Quality-Driven Improvement in Health Care: Systematic Literature Review.

BACKGROUND: The promise of real-world evidence and the learning health care system primarily depends on access to high-quality data. Despite widespread awareness of the prevalence and potential impacts of poor data quality (DQ), best practices for its assessment and improvement are unknown. OBJECTIVE: This review aims to investigate how existing research studies define, assess, and improve the quality of structured real-world health care data. METHODS: A systematic literature search of studies in the English language was implemented in the Embase and PubMed databases to select studies that specifically aimed to measure and improve the quality of structured real-world data within any clinical setting. The time frame for the analysis was from January 1945 to June 2023. We standardized DQ concepts according to the Data Management Association (DAMA) DQ framework to enable comparison between studies. After screening and filtering by 2 independent authors, we identified 39 relevant articles reporting DQ improvement initiatives. RESULTS: The studies were characterized by considerable heterogeneity in settings and approaches to DQ assessment and improvement. Affiliated institutions were from 18 different countries and 18 different health domains. DQ assessment methods were largely manual and targeted completeness and 1 other DQ dimension. Use of DQ frameworks was limited to the Weiskopf and Weng (3/6, 50%) or Kahn harmonized model (3/6, 50%). Use of standardized methodologies to design and implement quality improvement was lacking, but mainly included plan-do-study-act (PDSA) or define-measure-analyze-improve-control (DMAIC) cycles. Most studies reported DQ improvements using multiple interventions, which included either DQ reporting and personalized feedback (24/39, 61%), IT-related solutions (21/39, 54%), training (17/39, 44%), improvements in workflows (5/39, 13%), or data cleaning (3/39, 8%). Most studies reported improvements in DQ through a combination of these interventions. Statistical methods were used to determine significance of treatment effect (22/39, 56% times), but only 1 study implemented a randomized controlled study design. Variability in study designs, approaches to delivering interventions, and reporting DQ changes hindered a robust meta-analysis of treatment effects. CONCLUSIONS: There is an urgent need for standardized guidelines in DQ improvement research to enable comparison and effective synthesis of lessons learned. Frameworks such as PDSA learning cycles and the DAMA DQ framework can facilitate this unmet need. In addition, DQ improvement studies can also benefit from prioritizing root cause analysis of DQ issues to ensure the most appropriate intervention is implemented, thereby ensuring long-term, sustainable improvement. Despite the rise in DQ improvement studies in the last decade, significant heterogeneity in methodologies and reporting remains a challenge. Adopting standardized frameworks for DQ assessment, analysis, and improvement can enhance the effectiveness, comparability, and generalizability of DQ improvement initiatives.

Exploring emission spatiotemporal pattern and potential reduction capacity in China's aviation sector: Flight trajectory optimization perspective.

China's rapid expansion of civil aviation has led to an increase in pollution-related issues, causing adverse health effects on populations near airports and downwind. Accurately quantifying aviation emissions is essential for effective emission management. Here, we developed a high-resolution aviation emissions inventory for China by employing a bottom-up approach that relied on daily flight schedules. By using the Aeronautical Information Publication (AIP) to reproduce real-world flight routes rather than conventional great-circle routes, we improved the accuracy of emissions and investigated the potential for reducing these emissions. Our findings demonstrated substantial variations in domestic civil aviation emissions both spatially and temporally. Emissions peaked in most provinces during Chinese holidays, particularly the Chinese Lunar New Year and summer holidays, highlighting the importance of detailed activity data for accurate emissions calculations. Therefore, we recommend extensive utilization of real-world flight routes, particularly in areas with limited Automatic Dependent Surveillance-Broadcast (ADS-B) coverage since they provide more accurate representations of actual flight trajectories. Our study also identified regions like Shaanxi, Sichuan, Beijing, and their surroundings having considerable potential for emission reduction due to substantial deviations from great-circle routes. This approach can enhance the accuracy and spatiotemporal resolution of aviation emissions at national and global scales throughout the year, without relying on extensive, long-term real-time flight trajectories. Additionally, it provides a unique way to quantify the potential for emission reductions across provinces in civil aviation, ultimately contributing to mitigating pollution-related health impacts from aviation emissions and promoting a more sustainable aviation industry.

Real-World Healthcare Resource Use Associated with Recurrent or Metastatic Head and Neck Cancer Patients Care in Portugal-TRACE Study.

Recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a challenging disease, requiring personalized management by a multidisciplinary team. The aim of this retrospective multicentric study was to characterize real-world healthcare resource use and patient care for R/M HNSCC in Portugal during the first year after diagnosis. A total of 377 patients ineligible for curative treatment were included, mostly male (92.8%), aged 50-69 years (74.5%), with heavy alcohol (72.7%) or smoking habits (89.3%). Oropharynx (33.2%) and oral cavity (28.7%) were primary tumor locations, with lung metastases being the most common (61.4%). Eligible patients for systemic treatment with palliative intent (80.6%) received up to four treatment lines, with varied regimens. Platinum-based combination chemotherapy dominated first-line treatment (>70%), while single-agent chemotherapy and anti-PD1 immunotherapy were prevalent in later lines. Treatment approaches were uniform across disease stages and primary tumor locations but varied geographically. Treated patients received more multidisciplinary support than those who were ineligible. This study provides the first Portuguese real-world description of R/M HNSCC patient characteristics, treatment patterns, and supportive care during the year after diagnosis, highlighting population heterogeneity and aiming to improve patient management.

Non-Small-Cell Lung Cancer Patients Harboring ROS1 Rearrangement: Real World Testing Practices, Characteristics and Treatment Patterns (ROS1REAL Study).

ROS1 rearrangements are considered rare in non-small-cell lung cancer (NSCLC). This retrospective real-world study aimed to evaluate first-line treatment with crizotinib, a tyrosine kinase inhibitor (TKI) standard of care vs. new generation ROS1 anti-cancer agents. Forty-nine ROS1-expressing NSCLC patients, diagnosed with advanced metastatic disease, were included. Molecular profiling using either FISH/CISH or NGS was performed on tissue samples. Twenty-eight patients were treated with crizotinib, while fourteen patients were administered newer drugs (entrectinib, repotrectinib) and seven patients received platinum-doublet chemotherapy in a first-line setting. Overall response rate and disease control rate for the crizotinib and entrectinb/repotrectinib cohort were 68% and 82% vs. 86% and 93%, respectively. Median progression free survival was 1.6 years (95% CI 1.15-2.215) for the crizotinib treatment vs. 2.35 years for the entrectinib/repotrectinib cohort (95% CI 1.19-3.52). Central nervous system progression was noted in 20% and 25% of the crizotinib and entrectinib/repotrectinib cohorts, respectively. This multi-center study presents real-world treatment patterns of ROS1 NSCLC population, indicating that crizotinib exhibited comparable results to entrectinib/repotrectinib in a first-line setting, although both response rate and survival was numerically longer with treatment with newer agents.

Impact of Timing of Immunotherapy and Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma: Real-World Data on Survival Outcomes from the CKCis Database.

Immunotherapy-based systemic treatment (ST) is the standard of care for most patients diagnosed with metastatic renal cell carcinoma (mRCC). Cytoreductive nephrectomy (CN) has historically shown benefit for select patients with mRCC, but its role and timing are not well understood in the era of immunotherapy. The primary objective of this study is to assess outcomes in patients who received ST only, CN followed by ST (CN-ST), and ST followed by CN (ST-CN). The Canadian Kidney Cancer information system (CKCis) database was queried to identify patients with de novo mRCC who received immunotherapy-based ST between January 2014 and June 2023. These patients were classified into three categories as described above. Cox proportional hazards models were used to assess the impact of the timing of ST and CN on overall survival (OS) and progression-free survival (PFS), after adjusting for the International Metastatic RCC Database Consortium (IMDC) risk group, age, and comorbidities. Best overall response and complications of ST and CN for these cohorts were collected. A total of 588 patients were included in this study: 331 patients received ST only, 215 patients received CN-ST, and 42 patients received ST-CN. Patient and disease characteristics including age, gender, performance status, IMDC risk category, comorbidity, histology, type of ST, and metastatic sites are reported. OS analysis favored patients who received ST-CN (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.13-0.68) and CN-ST (HR 0.68, CI 0.47-0.97) over patients who received ST only. PFS analysis showed a similar trend for ST-CN (HR 0.45, CI 0.26-0.77) and CN-ST (HR 0.9, CI 0.68-1.17). This study examined baseline features and outcomes associated with the use and timing of CN and ST using real-world data via a large Canadian real-world cohort. Patients selected to receive CN after ST demonstrated improved outcomes. There were no appreciable differences in perioperative complications across groups. Limitations include the small number of patients in the ST-CN group and residual confounding and selection biases that may influence the outcomes in patients undergoing CN.

The Impact of a Gamified Intervention on Daily Steps in Real-Life Conditions: Retrospective Analysis of 4800 Individuals.

BACKGROUND: Digital interventions integrating gamification features hold promise to promote daily steps. However, results regarding the effectiveness of this type of intervention are heterogeneous and not yet confirmed in real-life contexts. OBJECTIVE: This study aims to examine the effectiveness of a gamified intervention and its potential moderators in a large sample using real-world data. Specifically, we tested (1) whether a gamified intervention enhanced daily steps during the intervention and follow-up periods compared to baseline, (2) whether this enhancement was higher in participants in the intervention than in nonparticipants, and (3) what participant characteristics or intervention parameters moderated the effect of the program. METHODS: Data from 4819 individuals who registered for a mobile health Kiplin program between 2019 and 2022 were retrospectively analyzed. In this intervention, participants could take part in one or several games in which their daily step count was tracked, allowing individuals to play with their overall activity. Nonparticipants were people who registered for the program but did not take part in the intervention and were considered as a control group. Daily step counts were measured via accelerometers embedded in either commercial wearables or smartphones of the participants. Exposure to the intervention, the intervention content, and participants' characteristics were included in multilevel models to test the study objectives. RESULTS: Participants in the intervention group demonstrated a significantly greater increase in mean daily steps from baseline than nonparticipants (P<.001). However, intervention effectiveness depended on participants' initial physical activity. The daily steps of participants with <7500 baseline daily steps significantly improved from baseline both during the Kiplin intervention (+3291 daily steps) and the follow-up period (+945 daily steps), whereas participants with a higher baseline had no improvement or significant decreases in daily steps after the intervention. Age (P<.001) and exposure (P<.001) positively moderated the intervention effect. CONCLUSIONS: In real-world settings and among a large sample, the Kiplin intervention was significantly effective in increasing the daily steps of participants from baseline during intervention and follow-up periods compared to nonparticipants. Interestingly, responses to the intervention differed based on participants' initial steps, with the existence of a plateau effect. Drawing on the insights of self-determination theory, we can assume that the effect of gamification could depend of the initial motivation and activity of participants.

The LOD paradox: When lower isn't always better in biosensor research and development.

Biosensor research has long focused on achieving the lowest possible Limits of Detection (LOD), driving significant advances in sensitivity and opening up new possibilities in analysis. However, this intense focus on low LODs may not always meet the practical needs or suit the actual uses of these devices. While technological improvements are impressive, they can sometimes overlook important factors such as detection range, ease of use, and market readiness, which are vital for biosensors to be effective in real-world applications. This review advocates for a balanced approach to biosensor development, emphasizing the need to align technological advancements with practical utility. We delve into various applications, including the detection of cancer biomarkers, pathology-related biomarkers, and illicit drugs, illustrating the critical role of LOD within these contexts. By considering clinical needs and broader design aspects like cost-effectiveness, sustainability, and regulatory compliance, we argue that integrating technical progress with practicality will enhance the impact of biosensors. Such an approach ensures that biosensors are not only technically sound but also widely useable and beneficial in real-world applications. Addressing the diverse analytical parameters alongside user expectations and market demands will likely maximize the real-world impact of biosensors.

The Efficacy and Safety of Apatinib and Anlotinib in Advanced Non-Small Cell Lung Cancer.

Background: Anlotinib and apatinib, both vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs), are clinically established in the treatment of advanced non-small cell lung cancer (NSCLC) in China, with anlotinib emerging as a standard treatment strategy. This study was conducted to evaluate the efficacy and safety of apatinib and anlotinib, and to compare their differences in treating patients with advanced NSCLC. Patients and Methods: We retrospectively analyzed the data of patients with advanced NSCLC treated with apatinib or anlotinib at a hospital in Eastern China from January 2017 to December 2021. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profile. Results: A total of 145 patients were included in this study. Median PFS (mPFS) was 3.53 months for the apatinib group and 5.3 months for the anlotinib group (HR = 0.59, 95% CI: 0.41-0.84; P = 0.004), and median OS (mOS) was 7.6 months versus 15.6 months (HR = 0.68, 95% CI: 0.46-1.00; P = 0.048), which all showed significant differences after adjusting for confounders (P < 0.05). Subgroup analysis revealed that the presence or absence of bone metastases significantly influenced PFS in both treatment groups. The ORR was 3.03% in the anlotinib group versus 10.13% in the apatinib group (P = 0.12), the DCR was 72.73% versus 51.90% (P = 0.21). No unanticipated adverse events (AEs) were observed. The incidence of grade 3-4 AEs was significantly higher in the apatinib group (31.65% vs 13.64%, P < 0.05). Conclusion: Anlotinib demonstrated greater efficacy and safety compared to apatinib in the treatment of advanced NSCLC, particularly in patients with bone metastases and EGFR(-).

Treatment of systemic lupus erythematosus: Analysis of treatment patterns in adult and paediatric patients across four European countries.

OBJECTIVE: Multiple treatment options are recommended for Systemic Lupus Erythematosus (SLE) by clinical guidelines. This study aimed to explore SLE treatment patterns as there is limited real-world data of SLE medication utilisation, especially in childhood-onset SLE (cSLE). METHODS: We conducted a longitudinal cohort study using five routinely collected healthcare databases from four European countries (United Kingdom, France, Germany, and Spain). We described the characteristics of adult and paediatric patients at time of SLE diagnosis. We calculated the percentage of patients commencing SLE treatments in the first month and year after diagnosis, reported number of prescriptions, starting dose, cumulative dose, and duration of each treatment, and characterised the line of therapy. RESULTS: We characterised 11,255 patients with a first diagnosis of SLE and included 5718 in our medication utilisation analyses. The majority of adult SLE patients were female (range 80-88 %), with median age of 49 to 54 years at diagnosis. In the paediatric cohort (n = 378), 66-83 % of SLE patients were female, with median age of 12 to 16 years at diagnosis. Hydroxychloroquine and glucocorticoids were common first-line treatments in both adults and children, with second-line treatments including mycophenolate mofetil and methotrexate. Few cases of monoclonal antibody use were seen in either cohort. Initial glucocorticoid dosing in paediatric patients was often higher than in adults. CONCLUSION: Treatment choices for adult SLE patients across four European countries were in line with recent therapeutic consensus guidelines. High glucocorticoid prescriptions in paediatric patients suggests the need for steroid-sparing treatment alternatives and paediatric specific guidelines.

Trends in the Completeness and Validity of Sources of Death Data Against the National Death Index From 2010 to 2018.

PURPOSE: We investigated time trends in validation performance characteristics for six sources of death data available within the Healthcare Integrated Research Database (HIRD) over 8 years. METHODS: We conducted a secondary analysis of a cohort of advanced cancer patients with linked National Death Index (NDI) data identified in the HIRD between 2010 and 2018. We calculated sensitivity, specificity, positive predictive value, and negative predictive value for six sources of death status data and an algorithm combining data from available sources using NDI data as the reference standard. Measures were calculated for each year of the study including all members in the cohort for at least 1 day in that year. RESULTS: We identified 27 396 deaths from any source among 40 692 cohort members. Between 2010 and 2018, the sensitivity of the Death Master File (DMF) decreased from 0.77 (95% CI = 0.76, 0.79) to 0.12 (95% CI = 0.11, 0.14). In contrast, the sensitivity of online obituary data increased from 0.43 (95% CI = 0.41, 0.45) in 2012 to 0.71 (95% CI = 0.68, 0.73) in 2018. The sensitivity of the composite algorithm remained above 0.83 throughout the study period. PPV was observed to be high from 2010 to 2016 and decrease thereafter for all sources. Specificity and NPV remained at high levels throughout the study. CONCLUSIONS: We observed that the sensitivity of mortality data sources compared with the NDI could change substantially between 2010 and 2018. Other validation characteristics were less variable. Combining multiple sources of mortality data may be necessary to achieve adequate performance particularly for multiyear studies.

PCSK9 inhibitors in real life-Cardiometabolic risk management in dyslipidemic patients in Vienna.

BACKGROUND: Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors have emerged as important therapeutic options for patients unable to achieve the low-density lipoprotein cholesterol (LDL­C) target or to tolerate alternative lipid-lowering agents. The aim of this study was to investigate the efficacy of PCSK9 inhibitor treatment in tertiary routine care, by determining the percentage of patients reaching individual LDL­C target levels 1 year after treatment initiation. PATIENTS AND METHODS: Patients routinely started on PCSK9 inhibitors at our lipid clinic between 2017 and 2020 were retrospectively analyzed. Attainment of the LDL­C target, utilization of follow-ups, cardiovascular events and effects on laboratory parameters were investigated. RESULTS: In this study 347 patients were included, with the majority managed in secondary prevention (94.5%). The LDL­C target was achieved by 44.9% after ca. 14 months, with differences between statin users and non-users (51.0% vs. 22.7%; p < 0.001). The median LDL­C decreased from 126.00 mg/dL at baseline to 48 mg/dL (-61.6%; -77.00 mg/dL; p < 0.001) after ~2 months and to 60 mg/dL (-52.9%; -59.00 mg/dL; p < 0.001) after ~14 months. Median lipoprotein(a) levels decreased significantly from 184.0 nmol/L to 165.5 nmol/L (-25.9%; -25.5 nmol/L; p = 0.001) after ~2 months, whereas no effects on creatine kinase, amylase and lipase were detectable. Of the patients 15% utilized 4 follow-ups. The PCSK9 inhibitor intolerance occurred in 3.5% of patients. CONCLUSION: With the effect of LDL-lowering remaining constant over 14 months, PCSK9 inhibitor treatment showed effective and sustainable LDL­C lowering in a majority of patients in secondary prevention, bringing them closer to the recommended LDL­C goal, particularly those under concomitant statin medication. Treatment with PCSK9 inhibitors appears to be well-tolerated, confirming data from clinical trials in real life.

Endometrial cancer treatment and outcomes in Argentina: ECHOS-A real-world study.

Objective: Real-world data for patients with endometrial cancer (EC) are limited, particularly in Latin America. We present treatment pattern findings from ECHOS-A - Endometrial Cancer Health Outcomes Study in Argentina. Materials and methods: A retrospective study using clinical data from privately insured patients with EC diagnosed from 2010 to 2019. Index (diagnosis proxy) was first date of an EC-related health term or treatment. Demographics, clinical characteristics, and FIGO staging were described. Disease progression and survival were assessed until study end, loss to follow-up, or death. Results: Of 805 patients with EC, 77.4 % (n = 623/805) received any treatment and 22.6 % (n = 182/805) received none. Among those treated, 31.8 % (n = 198/623) had first-line (1L) systemic therapy, and 45.5 % (n = 90/198) proceeded to second-line (2L) therapy. Mean follow-up was 33.6 (SD 31.8) months. Of those receiving any treatment, 87.3 % (n = 544/623) had FIGO stage data (I, 62.9 %; II, 18.6 %; III, 13.6 %; IV, 5.0 %). Treatment by class in 1L and 2L, respectively, were platinum chemotherapy, 73.7 %, 36.7 %; non-platinum chemotherapy, 73.7 %, 62.2 %; immunotherapy, 1.0 %, 11.1 %; hormone therapy, 17.7 %, 26.7 %. Carboplatin/paclitaxel was the most frequent 1L (52.5 %) and 2L (14.4 %) regimen. Mean time to progression was 14.1 (SD 16.3) and 8.8 (SD 8.3) months in 1L and 2L, respectively. Adjusted 1- to 5-year risk of progression/death was 46.5-77.5 % and 65.0-86.2 % in 1L and 2L, respectively. Conclusions: Approximately one-quarter of patients with EC received no treatment, and approximately two-thirds were not treated with 1L systemic therapy. Efforts to better understand the reasons for these treatment patterns are crucial for improving patient outcomes.

Real-world safety profile of once-weekly semaglutide in people with type 2 diabetes: Analysis of pooled data from the SemaglUtide Real-world Evidence (SURE) programme.

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.