Real-world Clinical Setting Research Articles

Clinical applicability of signal heterogeneity and tumor border assessment on T2-weighted MR images to distinguish astrocytic from oligodendroglial origin of gliomas

Background and purposeRadiological features on magnetic resonance imaging (MRI) were attributed to oligodendroglioma, although the diagnostic accuracy in a real-world clinical setting remains partially elusive. This study investigated the accuracy and robustness of tumor heterogeneity and tumor border delineation on T2-weighted MRI to distinguish oligodendroglioma from astrocytoma. Materials and methodsEight readers from three different specialties (radiology, neurology, neurosurgery) with varying levels of experience blindly rated 79 T2-weighted MR images of patients with either oligodendroglioma or astrocytoma. After the first reading session, all readers were re-invited for a second reading session within three weeks. Diagnostic accuracy, including area under the receiver operator characteristics curve (AUC), and intra-observer variability and inter-observer variability were used as outcome measures. ResultsPooled sensitivity and specificity to distinguish oligodendroglioma from astrocytoma for the use of tumor heterogeneity were 59.9 % respectively 74.5 %, and 85.7 % respectively 40.1 % for tumor border. A second reading session did not result in a significant change in sensitivity or specificity for tumor heterogeneity (P = 0.752 and P = 0.733, respectively) or tumor border (P = 0.309 and P = 0.271, respectively). An AUC of 0.825 was achieved with regard to predicting oligodendroglial origin of gliomas. Intra-observer agreement ranged from moderate to very good for tumor heterogeneity (kappa-value 0.43–0.87) and tumor border (0.40–0.84). A moderate inter-oberserver agreement was achieved for tumor heterogeneity and tumor border (kappa-value of 0.50 and 0.45, respectively). ConclusionThis study demonstrates that tumor heterogeneity and tumor borders on T2-weighted MRI could be used with moderate Finter-observer agreement to non-invasively distinguish oligodendroglioma from astrocytoma.

Breast Cancer Screening With Automated Breast US and Mammography vs Handheld US and Mammography in Women With Dense Breasts in a Real-World Clinical Setting.

We compared the performance of 2 breast cancer screening approaches, automated breast US (ABUS) with same-day mammography (ABUS/MG) and handheld US (HHUS) with same-day mammography (HHUS/MG), in women with dense breasts to better understand the relative usefulness of ABUS and HHUS in a real-world clinical setting. In this institutional review board-approved, retrospective observational study, we evaluated all ABUS/MG and HHUS/MG screening examinations performed at our institution from May 2013 to September 2021. BI-RADS categories, biopsy pathology results, and diagnostic test characteristics (eg, sensitivity, specificity) were compared between the 2 screening approaches using Fisher's exact test. A total of 1120 women with dense breasts were included in this study, with 852 undergoing ABUS/MG and 268 undergoing HHUS/MG. The sensitivities of ABUS/MG and HHUS/MG were 100% (5/5) and 75.0% (3/4), respectively, which was not a statistically significant difference (P = .444). The ABUS/MG approach demonstrated a slightly higher specificity (97.4% [825/847] vs 94.3% [249/264]; P = .028), higher accuracy (97.4% [830/852] vs 94.0% [252/268]; P = .011), and lower biopsy recommendation rate (3.2% [27/852] vs 6.7% [18/268]; P = .019) than the HHUS/MG approach in our patient population. Our findings suggest that ABUS/MG performs comparably with HHUS/MG as a breast cancer screening approach in women with dense breasts in a real-world clinical setting, with the ABUS/MG approach demonstrating a similar sensitivity and slightly higher specificity than the HHUS/MG approach. Additional variables, such as patient experience and physician time, may help determine which imaging approach to employ in specific clinical settings.

The Efficiency of an Advanced Hybrid Closed Insulin Pump in Patients with Type 1 Diabetes for Improved Blood Glucose Control

Abstract Background Diabetes technology, especially advanced hybrid closed-loop (AHCL) systems, is rapidly advancing, offering improved glycemic control, reduced hypoglycemia, and reduced treatment burden for patients with type 1 diabetes (T1D). This study aimed to evaluate the clinical efficiency of an AHCL system—the Medtronic MiniMed 780G insulin pump combined with continuous glucose monitoring—among individuals with T1D in real-world clinical settings. Methods In an observational retrospective study, we identified a cohort of 41 patients (mean age, 47.1 ± 13.7 years; T1D duration, 23.6 ± 13 years; 73.2% female) previously using an insulin pump or those on multiple daily insulin injections, currently using the AHCL system for at least 6 months. Primary outcomes were the changes of the following parameters, before AHCL initiation and at 6 months after treatment; (1) time in range (TIR): time with glucose levels in the range of 70 to 180 mg/dL, (2) time below range (TBR): time with glucose levels below 70 mg/dL, and (3) time above range (TAR): time with glucose levels above 180 mg/dL. Results Data analysis from 41 patients showed a significant 16.5% ± 13.8% increase in TIR (from 56.6 ± 17.9 to 73.1 ± 10.6%, p < 0.001). Both TBR and TAR decreased by 2.9 ± 4.8% (p = 0.004) and 13.6 ± 16.4% (p < 0.001), respectively. Mean glucose concentration, coefficient of variation, and glucose management indicator significantly improved. Conclusion The AHCL system effectively improved glucose control regarding TIR, TBR, and TAR. Enhanced glycemic control metrics highlight the potential for wider adoption of AHCL technology.

Real world community-based HIV Rapid Start Antiretroviral with B/F/TAF versus prior models of antiretroviral therapy start – the RoCHaCHa study, a pilot study

BackgroundThe rapid start of antiretroviral therapy (RSA) model initiates antiretroviral therapy (ART) as soon as possible after a new or preliminary diagnosis of HIV, in advance of HIV-1 RNA and other baseline laboratory testing. This observational study aims to determine if RSA with a single tablet regimen of bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) is an effective regimen for achieving viral suppression and accepted by patients at the time of diagnosis.MethodsAdults newly or preliminarily diagnosed with HIV were enrolled from October 2018 through September 2021. Real world advantage, measured in days between clinical milestones and time to virologic suppression, associated with B/F/TAF RSA was compared to historical controls.ResultsAll Study RSA participants (n = 45) accepted treatment at their first visit and 43(95.6%) achieved virologic suppression by week 48. Study RSA participants had a significantly shorter time (median 32 days) from diagnosis to ART initiation and virologic suppression, in comparison to historical controls (median 181 days) (n = 42). Qualitative feedback from study RSA participants showed high acceptance positive response to RSA.ConclusionsRSA is feasible and well accepted by patients in a real-world community-based clinic setting. Promoting RSA in community-based clinics is an important tool in ending the HIV epidemic.

Meaningful changes in motor function in Duchenne muscular dystrophy (DMD): A multi-center study.

Evaluations of treatment efficacy in Duchenne muscular dystrophy (DMD), a rare genetic disease that results in progressive muscle wasting, require an understanding of the 'meaningfulness' of changes in functional measures. We estimated the minimal detectable change (MDC) for selected motor function measures in ambulatory DMD, i.e., the minimal degree of measured change needed to be confident that true underlying change has occurred rather than transient variation or measurement error. MDC estimates were compared across multiple data sources, representing >1000 DMD patients in clinical trials and real-world clinical practice settings. Included patients were ambulatory, aged ≥4 to <18 years and receiving steroids. Minimal clinically important differences (MCIDs) for worsening were also estimated. Estimated MDC thresholds for >80% confidence in true change were 2.8 units for the North Star Ambulatory Assessment (NSAA) total score, 1.3 seconds for the 4-stair climb (4SC) completion time, 0.36 stairs/second for 4SC velocity and 36.3 meters for the 6-minute walk distance (6MWD). MDC estimates were similar across clinical trial and real-world data sources, and tended to be slightly larger than MCIDs for these measures. The identified thresholds can be used to inform endpoint definitions, or as benchmarks for monitoring individual changes in motor function in ambulatory DMD.

The development and initial evaluation of conversation cards for optimizing consultations for patients with atopic dermatitis

Purpose: Patients with atopic dermatitis (AD) require both skills and support to effectively manage life with the disease. Here, we developed an agenda-setting tool for consultations with patients with AD to establish a collaborative agenda that enhances patient involvement and prioritizes on self-management support. Materials and methods: Using the design thinking process, we included 64 end-users (patients and healthcare professionals (HCPs)) across the different phases of design thinking. We identified seven overall categories that patients find important to discuss during consultations, which informed the development of a tool for co-creating a consultation agenda (conversation cards, CCs). Results: Through iterative user testing of the CCs, patients perceived the cards as both inspiring and an invitation from HCPs to openly discuss their needs during consultations. Healthcare professionals have found the CCs easy to use, despite the disruption to the typical consultation process. Conclusion: In summary, the CCs provide a first-of-its-kind agenda-setting tool for patients with AD. They offer a simple and practical method to establishing a shared agenda that focuses on the patients’ needs and are applicable within real-world clinical settings.

Effect of concomitant use of yokukansan on steady-state blood concentrations of donepezil and risperidone in real-world clinical practice.

Yokukansan is one of the most frequently used herbal medicines that can improve the behavioral and psychological symptoms of dementia. In this exploratory study, we investigated whether yokukansan affects the steady-state blood concentrations of donepezil, risperidone, and the major metabolites of both drugs in a real-world clinical setting. A non-randomized, open-label, single-arm study examining drug-drug interactions was conducted. Fifteen dementia patients taking donepezil for at least 4 weeks and eight schizophrenia patients taking risperidone for at least 2 weeks were orally administered 2.5 g of yokukansan three times a day before or between meals, and blood samples were collected before and 8 weeks after starting co-treatment with yokukansan. Plasma concentrations of donepezil, risperidone, and each metabolite were measured using high-performance liquid chromatography-tandem mass spectrometry and compared before and after the 8-week administration of yokukansan. The plasma concentrations of donepezil and its metabolites (6-O-desmethyl-donepezil, 5-O-desmethyl-donepezil, and donepezil-N-oxide), risperidone, and its metabolite paliperidone did not differ before and after the 8-week treatment with yokukansan. The findings of this study show that the concomitant use of yokukansan may have little clinical impact on the steady-state blood levels of donepezil and risperidone in patients with dementia or schizophrenia.

Enhancing team communication to improve implementation of a supervised walking program for hospitalized veterans: Evidence from a multi-site trial in the Veterans Health Administration.

The timely translation of evidence-based programs into real-world clinical settings is a persistent challenge due to complexities related to organizational context and team function, particularly in inpatient settings. Strategies are needed to promote quality improvement efforts and implementation of new clinical programs. This study examines the role of CONNECT, a complexity science-based implementation intervention to promote team readiness, for enhancing implementation of the 'Assisted Early Mobility for Hospitalized Older Veterans' program (STRIDE), an inpatient, supervised walking program. We conducted a stepped-wedge cluster randomized trial using a convergent mixed-methods design. Within each randomly assigned stepped-wedge sequence, Veterans Affairs Medical Centers (VAMCs) were randomized to receive standardized implementation support only or additional training via the CONNECT intervention. Data for the study were obtained from hospital administrative and electronic health records, surveys, and semi-structured interviews with clinicians before and after implementation of STRIDE. Eight U.S. VAMCs. Three hundred fifty-three survey participants before STRIDE implementation and 294 surveys after STRIDE implementation. Ninety-two interview participants. CONNECT, a complexity-science-based intervention to improve team function. The implementation outcomes included STRIDE reach and fidelity. Secondary outcomes included validated measures of team function (i.e., team communication, coordination, role clarity). At four VAMCs randomized to CONNECT, reach was higher (mean 12.4% vs. 3.8%), and fidelity was similar to four non-CONNECT VAMCs. VAMC STRIDE delivery teams receiving CONNECT reported improvements in team function domains, similar to non-CONNECT VAMCs. Qualitative findings highlight CONNECT's impact and the influence of team characteristics and contextual factors, including team cohesion, leadership support, and role clarity, on reach and fidelity. CONNECT may promote greater reach of STRIDE, but improvement in team function among CONNECT VAMCs was similar to improvement among non-CONNECT VAMCs. Qualitative findings suggest that CONNECT may improve team function and implementation outcomes but may not be sufficient to overcome structural barriers related to implementation capacity.

The impact of simulation-based training in medical education: A review.

Simulation-based training (SBT) has emerged as a transformative approach in medical education, significantly enhancing healthcare professionals' learning experience and clinical competency. This article explores the impact of SBT, tracing its historical development and examining the various types of simulations utilized today, including high-fidelity mannequins, virtual reality environments, standardized patients, and hybrid simulations. These methods offer a safe and controlled environment for students to practice and hone technical and non-technical skills, ultimately improving patient safety and clinical outcomes. The benefits of SBT are manifold, including enhanced skill acquisition, error reduction, and the opportunity for repeated practice without risk to actual patients. Immediate feedback and structured debriefing further solidify learning, making Simulation an invaluable tool in medical education. However, the implementation of SBT is challenging. It requires substantial financial investment, specialized equipment, and trained faculty. Additionally, there are concerns about the realism of simulations and the transferability of skills to real-world clinical settings. Despite these challenges, numerous case studies and empirical research underscore the effectiveness of SBT compared to traditional methods. Looking ahead, advancements in technology, such as artificial intelligence and improved virtual reality applications, promise to enhance the efficacy and accessibility of simulation training. The integration of Simulation with other training modalities and its adoption in diverse global contexts highlight its potential to revolutionize medical education worldwide. This article affirms the crucial role of SBT in preparing the next generation of healthcare professionals and its ongoing evolution driven by technological innovations.

Clinical Application of ISO and CEN/TS Standards for Liquid Biopsies-Information Everybody Wants but Nobody Wants to Pay For.

Liquid biopsies are emerging as valuable clinical biomarkers for cancer monitoring. Although International Organization for Standards (ISO) and Technical Specifications from the European Committee for Standardization (CEN/TS) standardized workflows exist, their implementation in clinical practice is underdeveloped. We aimed to assess the applicability of ISO and CEN/TS standards in a real-world clinical setting, with a particular focus on evaluating the impact of preanalytical parameters and hemolysis on liquid biopsy analysis. We evaluated 659 peripheral blood samples from advanced prostate cancer patients against ISO and CEN/TS standards and documented all essential criteria, including tube draw order, filling level, temperature, and time tracking from blood draw to storage. We assessed hemolysis and its effect on circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) analysis. Our results demonstrated a high compliance rate, with 96.2% (634/659) of samples meeting essential ISO and CEN/TS criteria. We did not observe a significant impact on ctDNA or CTC detection rates between hemolytic and nonhemolytic samples. Hemolysis was identified in 12.9% (40/311) of plasma samples from our advanced prostate cancer cohort, and within the draw order of 5 blood collection tubes, hemolysis did not significantly increase from tube 1 to 5. In total, 83.8% (552/659) of blood collection tubes had high fill levels above 80% of nominal filling level. Our study demonstrates the feasibility and benefits of adhering to ISO and CEN/TS standards in a clinical liquid biopsy study. The standards revealed that hemolysis occurred frequently but did not impair downstream ctDNA and CTC analysis in our cohort of advanced prostate cancer patients.

Bundle Implementation to Prevent Surgical Site Infections - A Study of SRN Hospitals

Background: Guidelines recommend bundles with multiple infection control elements to prevent surgical site infections (SSI). Although effective in multiple research studies, little is known about the implementation of such complex bundles in the real-world clinical setting. Methods: A survey was distributed to the SHEA Research Network (SRN) hospitals during November 2022 – December 2023, to assess processes related to the implementation of SSI prevention bundles in colorectal surgery. Results: Of the 93 US and international hospitals within SRN, 49 completed the survey (53% response rate). The mean volume of colorectal surgeries per year was 377 (median 400). Figure 1 shows the individual elements of SSI prevention bundle reported as consistently used in most surgeries. There were no significant differences between hospitals with high vs. low volume (cut-off 400 surgeries), except for wound protectors or retractors, more likely to be used in high-volume hospitals (P = 0.047). A formal process for auditing adherence was reported by 71% of respondents for antibiotic prophylaxis, and 51% for skin prep, with the remaining elements audited &lt; 50% of the time. Feedback of audited adherence to surgeons occurred &lt; 50% of the time for all bundle elements, except antibiotic prophylaxis (59%). Table 1 shows the most common barriers reported as either successfully mitigated or still persistent at the time of the survey. High-volume hospitals were more likely to report persistent clinicians’ low bundle adherence (P = 0.016) and inadequate bundle adherence audit and feedback (P = 0.0016). Conclusion: Implementation of guideline-recommended colorectal SSI Prevention bundles remains highly variable. Further research aiming to develop strategies that optimize implementation and adherence is needed.

Real-world Safety and Effectiveness of Edoxaban in Patients with Venous Thromboembolism with or without Preceding Parenteral Anticoagulants: A Single-center Retrospective Study.

Objective Edoxaban is an anticoagulant used for venous thromboembolism (VTE) treatment and requires pretreatment with parenteral anticoagulants. However, pretreatment is not always performed in the clinical setting. In this study, we investigated the safety and effectiveness of edoxaban treatment in patients with VTE with or without pretreatment. Methods We retrospectively enrolled 364 patients who received edoxaban for VTE treatment between September 2014 and March 2020 and investigated patient demographics, VTE recurrence, and major bleeding as clinical outcomes in patients with or without pretreatment. Furthermore, the factors contributing to pretreatment decisions were assessed. Results Patients without pretreatment (n=208) had more active cancer cases and fewer pulmonary embolism complications than those with pretreatment (n=156). Lower levels of hemoglobin and higher levels of white blood cell counts, C-reactive protein, and D-dimer at the diagnosis were found in patients who received pretreatment than in those without pretreatment. No symptomatic VTE recurrence was observed. After propensity score matching, the cumulative incidence of major bleeding was not significantly higher in patients with pretreatment than in those without it (log-rank test, p=0.136). The incidence of deteriorated VTE on imaging did not significantly differ between patients with and without pretreatment, even after propensity matching (log-rank test, p=0.414). Conclusion In a real-world clinical setting, where physicians determined the use of parenteral anticoagulant lead-in according to their experience, patient demographics, and VTE characteristics, no significant differences were found regarding safety and effectiveness in edoxaban-treated VTE patients with or without pretreatment with parenteral anticoagulants.

Artificial intelligence in shoulder arthroplasty: how smart is it?

BackgroundThe application of artificial intelligence (AI) is growing rapidly in many fields, and the medical field is no exception. The amount of information we collect before, during, and after surgery is growing exponentially, making the opportunity for AI applications to be integrated into our daily practice more and more apparent. MethodsA literature search was conducted in January 2024 using PubMed (MEDLINE), SCOPUS, and EMBASE databases. A critical analysis of the relevant literature on AI technology in shoulder arthroplasty was conducted. ResultsIn the field of shoulder arthroplasty, recent literature reports the predictive value of AI models in predicting length of stay and healthcare costs, predicting clinical outcomes and complications, and identifying implants. By leveraging ML before, during, and after surgery, surgeons can make clinical decisions, predict possible problems, estimate resources needed and clinical outcomes, and ultimately personalize care for each patient. ConclusionsAI technology is becoming more and more advanced, especially in the medical field. By leveraging ML before, during, and after surgery, surgeons can make clinical decisions, predict possible problems, estimate resources needed and clinical outcomes, and ultimately personalize treatment for each patient. Because this technology is still in its infancy, there are several limitations to bringing it into the real-world clinical setting. However, it is advancing at a rapid pace, and therefore, as a shoulder surgeon, you need to understand and be interested in AI technology.

Ultrahypofractionation in postoperative radiotherapy for breast cancer: A single-institution retrospective cohort series.

The 'FAST-forward', study published in April 2020, demonstrated the effectiveness of an extremely hypofractionated radiotherapy schedule, delivering the total radiation dose in five sessions over the course of 1 week. We share our department's experience regarding patients treated with this regimen in real-world clinical settings, detailing outcomes related to short-term toxicity and efficacy. A descriptive observational study was conducted on 160 patients diagnosed with breast cancer. Between July 2020 and December 2021, patients underwent conservative surgery followed by a regimen of 26 Gy administered in five daily fractions. The median age was 64 years (range: 43-83), with 82 patients (51.3%) treated for left-sided breast cancer, 77 patients (48.1%) for right-sided breast cancer, and 1 instance (0.6%) of bilateral breast cancer. Of these, 66 patients had pT1c (41.3%), 70.6% were infiltrative ductal carcinomas, and 11.3% were ductal carcinoma insitu. Most tumours exhibited intermediate grade (41.9%), were hormone receptor positive (81.3%), had low Ki-67 (Ki-67 < 20%; 51.9%) and were Her 2 negative (85%). The majority of surgical margins were negative (99.4%). Among the patients, 72.5% received hormonotherapy, and 23.8% received chemotherapy. Additionally, 26 patients (16.3%) received an additional tumour boost following whole breast irradiation (WHBI) of 10 Gy administered in five sessions of 2 Gy over a week. The median planning target volume (PTV) was 899 cm3 (range: 110-2509 cm3). Early toxicity was primarily grade I radiodermatitis, affecting 117 patients (73.1%). During a median follow-up of 15 months (range: 3.9-28.77), only one patient experienced a local relapse, which required mastectomy. The implementation of this highly hypofractionated regimen in early-stage breast cancer appears feasible and demonstrates minimal early toxicity. However, a more extended follow-up duration would be required to evaluate long-term toxicity and efficacy accurately.

Artificial Intelligence Applications for Thoracic Surgeons: "The Phenomenal Cosmic Powers of the Magic Lamp".

In the digital age, artificial intelligence (AI) is emerging as a transformative force in various sectors, including medicine. This article explores the potential of AI, which is akin to the magical genie of Aladdin's lamp, particularly within thoracic surgery and lung cancer management. It examines AI applications like machine learning and deep learning in achieving more precise diagnoses, preoperative risk assessment, and improved surgical outcomes. The challenges and advancements in AI integration, especially in computer vision and multi-modal models, are discussed alongside their impact on robotic surgery and operating room management. Despite its transformative potential, implementing AI in medicine faces challenges regarding data scarcity, interpretability issues, and ethical concerns. Collaboration between AI and medical communities is essential to address these challenges and unlock the full potential of AI in revolutionizing clinical practice. This article underscores the importance of further research and interdisciplinary collaboration to ensure the safe and effective deployment of AI in real-world clinical settings.

Clinical Association Between Immune-related Adverse Events and Treatment Efficacy in Patients With Non-small-cell Lung Cancer Treated With Nivolumab-Ipilimumab-based Therapy.

Nivolumab and ipilimumab combination therapy has been extensively explored for the treatment of advanced non-small-cell lung cancer (NSCLC) through the pivotal phase III trials CheckMate 227 and CheckMate 9LA. However, the relationship between immune-related adverse events (irAEs) and the effectiveness of nivolumab plus ipilimumab-based therapy in a real-world clinical setting remains uncertain. We performed a retrospective analysis of 28 patients with advanced or recurrent NSCLC who underwent treatment with nivolumab plus ipilimumab, with or without platinum-doublet chemotherapy, from February 2021 to January 2023. The primary objective was to elucidate the clinical association between irAEs and treatment efficacy associated with nivolumab plus ipilimumab-based therapy. Among the 28 patients, 22 (78.6%) experienced irAEs. The median progression-free survival (PFS) was significantly longer for patients with irAEs than for those without (p=0.0158), as was overall survival (OS) (p=0.000394). The severity of irAEs had no significant influence on PFS or OS. The objective response rate tended to be higher in patients with irAEs than in those without (50.0% versus 0.0%, respectively; p=0.0549). Multivariate analysis indicated that irAE occurrence was an independent factor for improved PFS (hazard ratio=0.2084, p=0.01383) and OS (hazard ratio=0.0857, p=0.001588). Interstitial lung disease was inferior to other irAE profiles for both PFS and OS. Patients with advanced NSCLC experiencing irAEs demonstrated superior clinical outcomes when treated with nivolumab plus ipilimumab-based therapy compared with those without irAEs. However, immune-related interstitial lung disease may be less linked with PFS and OS than other irAE profiles.

A PrOsPective Cohort Study on Interstitial Lung Disease-Associated Pulmonary Hypertension with a ParticulaR Focus on the Subset with Pulmonary Arterial Hypertension Features (POPLAR Study).

The pathogenesis and clinical profiles of patients with pulmonary hypertension (PH) associated with interstitial lung disease (ILD-PH) are poorly understood. Whether and to what extent pulmonary arterial hypertension (PAH)-specific therapy improves hemodynamic and outcome in ILD-PH are also unknown. This study aims to clarify the characteristics, clinical course and response to PAH-specific therapy of ILD and/or PH by enrolling three unique subsets: PAH, ILD-PH, and ILD. The proposed study is a retrospective and prospective, multi-centre, observational cohort study of patients treated at any of three university hospitals in the Hokkaido region of Japan who have any one of the following: PAH; ILD-PH with or without PAH features; or ILD without PH. We aim to enrol 250 patients in total. For the retrospective observation period, data obtained after 1 January 2010, will be analysed, and the prospective observation period will be 1year. We will compare the clinical data of patients with ILD-PH with those of patients with PAH and those of patients with ILD without PH in the real-world clinical setting. In addition, within the cohort of patients with ILD-PH, we will explore the subset with "ILD-PH with PAH features" and compare the response to PAH-specific therapy with that of PAH. The primary outcome will be the change in pulmonary vascular resistance from first treatment to follow-up in patients with PAH and ILD-PH with PAH features (excluding ILD-PH without PAH feature and ILD-no-PH for the primary outcome). The exploratory outcomes will include analyses of PH-associated biomarkers, right ventricular function and patient-reported outcomes. This is a protocol article and the results will be presented after data collection is completed. The POPLAR study will provide data that help better understand the pathophysiology of ILD-PH and improve the quality of life and outcome of patients with PH and/or ILD. Japan Registry of Clinical Trials: jRCT1010230018.

Evaluating the effect of dimethyl fumarate on subclinical biomarkers in a real-world patient cohort

ObjectiveEvaluate the real-world effect of dimethyl fumarate (DMF) on subclinical biomarkers in patients with relapsing-remitting multiple sclerosis (RRMS) and compare with results from clinical trials. MethodsMagnetic resonance imaging (MRI) data from 102 RRMS patients were retrospectively collected and processed using icobrain to assess brain atrophy and to assist semi-manual lesion count. ResultsMean (±SD) annualized percent brain volume change in the first 3 years after DMF-initiation were: −0.33 ± 0.68, −0.10 ± 0.60, and − 0.35 ± 0.71%/year, respectively. No new FLAIR lesions were detected in 73.7%, 77.3%, and 73.3% of the patients during years 1, 2, and 3. ConclusionsResults of this real-world study were consistent with previous DMF phase III clinical trials, supporting the generalizability of the effects observed in clinical trials to the real-world clinical setting.

Real-world effectiveness of imeglimin in patients with type 2 diabetes: A retrospective longitudinal study in Japan

ObjectiveTo examine the real-world effects of imeglimin on glycemic control and other metabolic factors in patients with type 2 diabetes (T2DM). MethodsA retrospective longitudinal study was conducted based on a chart review. We recruited patients with T2DM who took imeglimin continuously for at least 3 months. Data on various metabolic parameters were collected at the first prescription of imeglimin and at 3, 6 and 12 months after the initiation of imeglimin. Statistical comparisons were performed using paired t-tests. Results68 patients were eligible for this study. HbA1c decreased by 0.7 % at 3 months, 1.1 % at 6 months and 1.0 % by 12 months after the initiation of imeglimin. The decreases in HbA1c were observed regardless of age, gender, body mass index, duration of diabetes, renal function and concomitant use of hypoglycemic agents. There were also significant decreases in body weight, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and non-HDL-C during imeglimin treatment. ConclusionsThis is the first report showing the long-term effects of imeglimin in a real-world setting. We confirmed the glucose-lowering effects of imeglimin. Furthermore, favorable effects of imeglimin on body weight and serum lipids were also suggested.

Zero-shot learning to extract assessment criteria and medical services from the preventive healthcare guidelines using large language models.

The integration of these preventive guidelines with Electronic Health Records (EHRs) systems, coupled with the generation of personalized preventive care recommendations, holds significant potential for improving healthcare outcomes. Our study investigates the feasibility of using Large Language Models (LLMs) to automate the assessment criteria and risk factors from the guidelines for future analysis against medical records in EHR. We annotated the criteria, risk factors, and preventive medical services described in the adult guidelines published by United States Preventive Services Taskforce and evaluated 3 state-of-the-art LLMs on extracting information in these categories from the guidelines automatically. We included 24 guidelines in this study. The LLMs can automate the extraction of all criteria, risk factors, and medical services from 9 guidelines. All 3 LLMs perform well on extracting information regarding the demographic criteria or risk factors. Some LLMs perform better on extracting the social determinants of health, family history, and preventive counseling services than the others. While LLMs demonstrate the capability to handle lengthy preventive care guidelines, several challenges persist, including constraints related to the maximum length of input tokens and the tendency to generate content rather than adhering strictly to the original input. Moreover, the utilization of LLMs in real-world clinical settings necessitates careful ethical consideration. It is imperative that healthcare professionals meticulously validate the extracted information to mitigate biases, ensure completeness, and maintain accuracy. We developed a data structure to store the annotated preventive guidelines and make it publicly available. Employing state-of-the-art LLMs to extract preventive care criteria, risk factors, and preventive care services paves the way for the future integration of these guidelines into the EHR.