Real­world evidence of advanced non­small cell lung carcinoma treated with an immune checkpoint inhibitor plus chemotherapy.

Immunotherapy is an effective treatment strategy for patients with advanced non-small cell lung cancer (NSCLC). Although clinical trials on immunotherapy have provided promising results, real-world research in clinical practice is needed to assess the effectiveness and safety of immunotherapy. The present study aimed to characterize real-world outcomes in patients with advanced NSCLC treated with immune checkpoint inhibitor (ICI)-based regimens. The medical records of patients with advanced NSCLC, who were treated with programmed cell death protein-1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) inhibitors, were reviewed for data collection. The primary objectives were to evaluate progression-free survival (PFS) and overall survival (OS). Therefore, multiple Cox regression models were used to investigate the predictive factors for survival outcomes. Furthermore, survival curves for PFS and OS were created using Kaplan-Meier estimates and compared using the log-rank test. The present study included a total of 133 patients with advanced NSCLC who received therapy with ICIs between January 1, 2019 and December 31, 2022. The final follow-up date was August 24, 2023. The median PFS and OS times were 9.8 and 27.2 months, respectively. Univariate Cox regression analysis demonstrated that sex, clinical stage, PD-L1 status, previous systemic therapy, and brain and liver metastases were associated with PFS, while Eastern Cooperative Oncology Group (ECOG) status, clinical stage, PD-L1 status and brain metastasis were associated with OS. Furthermore, multivariate Cox regression analysis demonstrated that a PD-L1 tumor proportion score (TPS) of ≥50% was an indicator of favorable PFS and OS. An ECOG performance status score of ≥1 was also associated with poor OS but not with PFS. Furthermore, brain metastasis was an indicator for poor PFS and OS, while liver metastasis was only associated with a poor PFS. Finally, the results of the present study demonstrated that PD-L1 status was an independent predictor for PFS and OS in patients with advanced NSCLC, especially adenocarcinoma, who were treated with ICIs plus chemotherapy. The results also suggested that patients with a PD-L1 TPS of ≥50% could benefit when the aforementioned regimens were administrated as a first-line or later-line therapy.

Bridging the Gap: Comparing Patient-Clinician Views on Treatment Goals and Communication in the Management of Atopic Dermatitis Within the Asia-Pacific Region.

INTRODUCTION: It remains unclear how patients with atopic dermatitis (AD) and clinicians perceive the level of patient-clinician communication and if there could be potential lapses. This cross-sectional study aims to compare perspectives between patients with AD and dermatologists regarding communication and treatment expectations in Asia. METHODS: Moderate-to-severe patients with AD and practicing dermatologists were recruited from eight Asia-Pacific territories, including Mainland China, Hong Kong, India, Japan, Singapore, South Korea, Taiwan, and Thailand. Patients and dermatologists completed separate surveys designed to elicit their expectations regarding AD management, and their perceived level of patient-clinician communication. Patients were also asked about their treatment satisfaction and whether they prefer additional treatment beyond what was prescribed. Demographic information and responses were analyzed using descriptive statistics. The study was reviewed by the institutional review board in each territory, and all participants provided informed consent. RESULTS: A total of 1103 patients and 271 dermatologists completed the surveys. Both patients and dermatologists were largely aligned in their top treatment goals in AD management. However, greater proportions of patients prioritized the prevention of exacerbation (78.0% versus 47.2%), minimization of treatment adverse effects (46.4% versus 9.1%), and improvement in mental health (16.0% versus 4.9%), compared with dermatologists. Although patient-clinician communication was observed to be generally good, 10.9% of patients reported dissatisfaction with communication in AD management. The majority of patients were either "very satisfied" or "satisfied" with their latest acute AD treatment, but 65.5% of patients still desired additional treatment. CONCLUSIONS: This multinational study has provided insights on the perspectives of Asian patients and dermatologists in treatment goals, AD management, and communication. In general, both patients and dermatologists were aligned in treatment goals and there was satisfactory patient-clinician communication in most aspects. However, potential areas of improvement have been identified to further enhance patient-centered care.

Association of Changes in A1C Following Continuous Glucose Monitoring Acquisition in People with Sub-Optimally Treated Type 2 Diabetes Taking GLP-1 RA Therapy.

INTRODUCTION: Both glucagon-like peptide-1 receptor agonists (GLP-1 RA) and continuous glucose monitoring (CGM) improve glycemia in patients with type 2 diabetes (T2D). However, it is unknown whether adding CGM to GLP-1 RA therapy further improves A1c. We evaluated changes in A1c levels 6 months after initiation of FreeStyle Libre (FSL) in adults with sub-optimally controlled T2D already on GLP-1 RA therapy. METHODS: This retrospective, observational study used Optum's de-identified Market Clarity Data, a linked electronic health record-claims database to assess changes in A1c after FSL acquisition. Inclusion criteria were T2D diagnosis, ≥ 18 years, baseline A1c ≥ 8%, with the first FSL acquisition between 2018 and 2022. Patients were required to be on GLP-1 RA prior to FSL with at least one GLP-1 RA prescription within 90 days of FSL acquisition. GLP-1 RA initiation was defined as the earliest GLP-1 RA prescription from 2017 onwards. Paired changes in A1c were assessed at 6 months after initial FSL acquisition. RESULTS: The study cohort included 1454 adults with T2D (age 55 ± 10 years, 52% male, 38% with intensive insulin therapy, median 471 days from GLP-1 RA initiation to FSL, and baseline A1c 9.8 ± 1.5%). After FSL acquisition, patients experienced an A1c decrease of 1.5 ± 1.9% (p < 0.001). Patients with a baseline A1c > 10% had the largest reduction (n = 497, - 2.7 ± 2.2%, p < 0.001). Significant improvements were observed in subgroups based on insulin therapy and GLP-1 RA formulation. Those initiating GLP-1 RA therapy > 24 months before FSL acquisition also showed improvements in A1c (n = 478; - 1.3 ± 1.7%, p < 0.001). CONCLUSIONS: In a large, real-world study of adults with T2D, those on prior GLP-1 RA therapy experienced significant A1c improvements after acquiring FSL, irrespective of GLP-1 RA duration, GLP-1 RA formulation, or insulin therapy type. These findings support the use of FSL in adults with T2D treated with GLP-1 RA.

Development of Interoperable Computable Phenotype Algorithms for Adverse Events of Special Interest to Be Used for Biologics Safety Surveillance: Validation Study.

BACKGROUND: Adverse events associated with vaccination have been evaluated by epidemiological studies and more recently have gained additional attention with the emergency use authorization of several COVID-19 vaccines. As part of its responsibility to conduct postmarket surveillance, the US Food and Drug Administration continues to monitor several adverse events of special interest (AESIs) to ensure vaccine safety, including for COVID-19. OBJECTIVE: This study is part of the Biologics Effectiveness and Safety Initiative, which aims to improve the Food and Drug Administration's postmarket surveillance capabilities while minimizing public burden. This study aimed to enhance active surveillance efforts through a rules-based, computable phenotype algorithm to identify 5 AESIs being monitored by the Center for Disease Control and Prevention for COVID-19 or other vaccines: anaphylaxis, Guillain-Barré syndrome, myocarditis/pericarditis, thrombosis with thrombocytopenia syndrome, and febrile seizure. This study examined whether these phenotypes have sufficiently high positive predictive value (PPV) to ensure that the cases selected for surveillance are reasonably likely to be a postbiologic adverse event. This allows patient privacy, and security concerns for the data sharing of patients who had nonadverse events can be properly accounted for when evaluating the cost-benefit aspect of our approach. METHODS: AESI phenotype algorithms were developed to apply to electronic health record data at health provider organizations across the country by querying for standard and interoperable codes. The codes queried in the rules represent symptoms, diagnoses, or treatments of the AESI sourced from published case definitions and input from clinicians. To validate the performance of the algorithms, we applied them to electronic health record data from a US academic health system and provided a sample of cases for clinicians to evaluate. Performance was assessed using PPV. RESULTS: With a PPV of 93.3%, our anaphylaxis algorithm performed the best. The PPVs for our febrile seizure, myocarditis/pericarditis, thrombocytopenia syndrome, and Guillain-Barré syndrome algorithms were 89%, 83.5%, 70.2%, and 47.2%, respectively. CONCLUSIONS: Given our algorithm design and performance, our results support continued research into using interoperable algorithms for widespread AESI postmarket detection.

A retrospective analysis of treatment patterns, overall survival, and real-world disease-free survival in early-stage non-small cell lung cancer following complete resection.

BACKGROUND: Real-world data regarding patient characteristics, adjuvant treatment patterns, and long-term survival outcomes are needed to better understand unmet needs among patients with completely resected early-stage non-small cell lung cancer (NSCLC). METHODS: Electronic medical records from the U.S.-based ConcertAI Patient360™ database were analyzed in patients with stage IB-IIIA NSCLC who underwent complete resection prior to March 1, 2016. Patients were followed until death or July 1, 2021. This study evaluated adjuvant chemotherapy use, and overall survival (OS) and real-world disease-free survival (rwDFS) outcomes using the Kaplan-Meier method. The correlation between OS and rwDFS was assessed using the Kendall rank test. Among patients who did not recur 5 years following surgery, landmark analyses of OS and rwDFS were conducted to understand the subsequent survival impact of remaining disease-free for at least 5 years. RESULTS: Data from 441 patients with completely resected stage IB-IIIA NSCLC were included. About 35% of patients received adjuvant chemotherapy post-resection. Median OS and rwDFS from resection were 83.1 months and 42.4 months, respectively. The 5-year OS and rwDFS rates were 65.7% and 42.1%, respectively. OS and rwDFS were positively correlated (Kendall rank correlation coefficient = 0.67; p < 0.0001). Among patients without recurrence within 5 years after resection, the subsequent 5-year OS and rwDFS survival rates were 52.9% and 36.6%, respectively. CONCLUSIONS: Use of adjuvant chemotherapy was low, and the overall 5-year OS rate remained low despite all patients having undergone complete resection. Patients who remained non-recurrent over time had favorable subsequent long-term survival.

A rare partnership: patient community and industry collaboration to shape the impact of real-world evidence on the rare disease ecosystem.

People with rare lysosomal storage diseases face challenges in their care that arise from disease complexity and heterogeneity, compounded by many healthcare professionals being unfamiliar with these diseases. These challenges can result in long diagnostic journeys and inadequate care. Over 30 years ago, the Rare Disease Registries for Gaucher, Fabry, Mucopolysaccharidosis type I and Pompe diseases were established to address knowledge gaps in disease natural history, clinical manifestations of disease and treatment outcomes. Evidence generated from the real-world data collected in these registries supports multiple stakeholders, including patients, healthcare providers, drug developers, researchers and regulators. To maximise the impact of real-world evidence from these registries, engagement and collaboration with the patient communities is essential. To this end, the Rare Disease Registries Patient Council was established in 2019 as a partnership between the Rare Disease Registries and global and local patient advocacy groups to share perspectives on how registry data are used and disseminated. The Patient Council has resulted in a number of patient initiatives including patient representation at Rare Disease Registries advisory boards; development of plain language summaries of registry publications to increase availability of real-world evidence to patient communities; and implementation of digital innovations such as electronic patient-reported outcomes, and patient-facing registry reports and electronic consent (in development), all to enhance patient engagement. The Patient Council is building on the foundations of industry-patient advocacy group collaboration to fully integrate patient communities in decision-making and co-create solutions for the rare disease community.

Metabolic syndrome and depression: evidence from a cross-sectional study of real-world data in Japan.

BACKGROUND: Both metabolic syndrome (MetS) and depression are high priority health problems, especially for working age. Numerous studies have explored the link between metabolic syndrome and depression; however, not all of them have consistently demonstrated an association. The objective of this study was to determine whether there is an association between MetS and depression by analyzing extensive real-world data (RWD). METHODS: Our data was drawn from insurance claims and health checkups of local government officials across all prefectures in Japan except for Tokyo in the 2019 fiscal year. According to the number of months with diagnosis of depression and prescription of antidepressants, the study participants were classified into the following categories: Certainly not Depression (CN), Possibly not Depression (PN), Possible Depression (PD), and Certain Depression (CD). Associations between MetS and its components-visceral obesity, hypertension, hyperlipidemia, and diabetes- and these categories of depression were analyzed by logistic regression. RESULTS: The depression categories of the 130,059 participants were as follows: CN 85.2%; PN 6.9%; PD 3.9%; and CD 4.1%. For men, the adjusted odds ratio (AOR) for MetS were PN 0.94 (95% CI: 0.86-1.02), PD 1.31 (1.19-1.43), and CD 1.63 (1.50-1.76), with reference to CN. For women, AOR of MetS were PN 1.10 (0.91-1.32), PD 1.54 (1.24-1.91), and CD 2.24 (1.81-2.78). Among the MetS components, visceral obesity, hyperlipidemia, and diabetes were significantly associated with depression categories. CONCLUSIONS: In this study, we found a significant association between MetS and depression, this association being similar to that previously reported. Our findings provide robust evidence for linkage between MetS and depression, suggesting that analysis of RWD is useful for providing concrete evidence.

[CAR T-cell therapy for malignant lymphoma].

Advances in understanding of the pathogenesis of B-cell lymphoma have led to development of various novel targeted therapies. Among them, CD19-targeted chimeric antigen receptor (CAR) T-cell therapies for relapsed and refractory B-cell lymphomas have shown remarkable efficacy in clinical trials, and three CAR T-cell products are now available in Japan. Real-world evidence (RWE) has shown that these products can provide comparable efficacy to clinical trials in clinical practice, where CAR T-cells were administered in patients with wider range of backgrounds. This finding will certainly broaden the role of CAR T-cell therapies in the treatment of B-cell lymphoma. However, since about half of the patients treated with CAR T-cell therapy progress thereafter, there is an urgent need for risk stratification and optimized management of refractory cases. Here, we review the results of clinical trials and RWE of CAR T-cell therapy in B-cell lymphoma.

CURE: A deep learning framework pre-trained on large-scale patient data for treatment effect estimation.

Treatment effect estimation (TEE) aims to identify the causal effects of treatments on important outcomes. Current machine-learning-based methods, mainly trained on labeled data for specific treatments or outcomes, can be sub-optimal with limited labeled data. In this article, we propose a new pre-training and fine-tuning framework, CURE (causal treatment effect estimation), for TEE from observational data. CURE is pre-trained on large-scale unlabeled patient data to learn representative contextual patient representations and fine-tuned on labeled patient data for TEE. We present a new sequence encoding approach for longitudinal patient data embedding both structure and time. Evaluated on four downstream TEE tasks, CURE outperforms the state-of-the-art methods, marking a 7% increase in area under the precision-recall curve and an 8% rise in the influence-function-based precision of estimating heterogeneous effects. Validation with four randomized clinical trials confirms its efficacy in producing trial conclusions, highlighting CURE's capacity to supplement traditional clinical trials.

Improvement in quality of life after asfotase alfa treatment in adults with pediatric-onset hypophosphatasia: data from 5 patient-reported outcome measures.

Hypophosphatasia (HPP) is a rare, inherited metabolic disorder caused by deficient tissue-nonspecific alkaline phosphatase activity. This study assessed the impact of treatment with asfotase alfa on patient-reported outcomes (PROs) in adults with pediatric-onset HPP. A longitudinal, telephone-based survey was administered to eligible individuals enrolled in a patient support program. Interviews were conducted at study entry (prior to asfotase alfa initiation) and after 3, 6, and 12 mo. PROs-Patient Health Questionnaire-9 [PHQ-9], Work Productivity and Activity Impairment Questionnaire: Specific Health Problem [WPAI:SHP], Patient-Reported Outcomes Measurement Information System 29 [PROMIS-29], and Routine Assessment of Patient Index Data 3 [RAPID3]-were assessed at each time point. Appropriate statistical tests were performed to assess score changes. Among 50 enrolled patients (mean age: 46 yr [SD: 15.4]; 80% female; 94% White), 49 were evaluable at 3 mo, 44 at 6 mo, and 29 at 12 mo. By month 3, statistically significant improvements from baseline were detected in PHQ-9 scores (10.6 vs 5.8 [P < .0001]), PROMIS-29 domain scores (overall physical function: 38.0 vs 43.0 [P = .001]; anxiety: 57.5 vs 51.5 [P = .0011]; fatigue: 63.3 vs 55.3 [P < .0001]; sleep disturbances: 58.8 vs 54.3 [P = .0099]; ability to participate in social roles and activities: 42.6 vs 47.7 [P = .0012]; and pain interference: 63.8 vs 58.4 [P = .001]), and RAPID3 domain scores (functional status: 2.7 vs 1.1 [P < .0001]; pain tolerance: 6.0 vs 3.2 [P < .0001]; and global health estimate: 5.1 vs 2.7 [P < .0001]). Improvements persisted at month 12. Patients also showed improvements in WPAI:SHP domain scores at month 6 (presenteeism: 39.6% vs 14.1% [P < .0001] and work productivity loss: 41.9% vs 14.1% [P < .0001]). Treatment with asfotase alfa was associated with improved quality of life across several domains.

Characterization of psoriasis patients in special body areas: real-world evidence from the Chinese Psoriasis Standardized Diagnosis and Treatment Center.

BACKGROUND: While extensive research has provided a wealth of information on psoriasis in general, there remains a critical gap in understanding the unique characteristics of psoriasis in special body areas, such as the scalp, nails, palms, and genitals. OBJECTIVE: To investigate the characterization and treatment of psoriasis patients in special body areas. METHODS: The study was a retrospective analysis of patients with psoriasis enrolled in the Psoriasis Standardized Diagnosis and Treatment Center Project between January 2020 and September 2021. RESULTS: The study encompassed 346 patients, 81% of them had psoriasis in at least two special body areas, with the nails as the most common area. Patients with genital psoriasis reported higher Dermatology Life Quality Index (DLQI) scores. A higher propensity for scalp and palmoplantar psoriasis was noted in patients with genital psoriasis. The proportion of patients treated with biologics rose, as the number of specific areas involved increased. CONCLUSIONS: Patients with genital psoriasis are more likely to have scalp and palmoplantar psoriasis. This study highlights the significant escalation in the proportion of biologics when the involvement of special body areas was ≥2.

Estimating vaccine effectiveness against COVID-19 using cause-specific sick leave as an indicator: a nationwide population-based cohort study, Norway, July 2021 - December 2022.

BACKGROUND: Due to changes in testing policy and increased use of rapid tests, other indicators for SARS-CoV-2 infections are needed to monitor vaccine effectiveness (VE). We aimed to estimate VE against COVID-19 sick leave (> 3 days, certified by a medical professional) among employed individuals (25-64-years-old) in Norway. METHODS: We performed a nationwide cohort study by collating data from the Emergency preparedness register for COVID-19. We used adjusted Cox proportional hazard models with vaccine status as a time-varying covariate and presented results as adjusted hazard ratios (aHRs) with corresponding 95% confidence intervals. Separate models were run against sick leave and against SARS-CoV-2 infections during the Delta period (June-December 2021), and against sick leave during the Omicron period (January-December 2022) when SARS-CoV-2 PCR-testing was replaced by rapid self-tests and infections were underreported. RESULTS: We included 2,236,419 individuals during the Delta period, of whom 73,776 (3.3%) had a reported infection and 54,334 (2.4%) were registered with sick leave. Of the 2,206,952 included individuals in the Omicron period, 300,140 (13.6%) were registered with sick leave. During the Delta period, 55% (26,611) of individuals who had registered sick leave also had a positive test, compared to 32% (96,445) during the Omicron period. The VE against sick leave during the Delta period followed a similar waning pattern to that against SARS-CoV-2 infections. After the second and third dose, the lowest aHRs were estimated for 2-7 days after vaccination for both sick leave (0.25; 95%CI 0.24-0.26 and 0.26; 95% CI 0.24-0.29) and infection ( 0.16; 95% CI 0.15-0.17 and 0.18; 95% CI 0.16-0.19) respectively. During the Omicron period, aHRs for sick leave were higher than during the Delta period, but the lowest aHRs were still found in 2-7 weeks after receiving the second (0.61; 95% CI 0.59-0.64) or third dose (0.63; 95% CI 0.62-0.64). CONCLUSION: Our results showed that sick leave could be a relevant indicator for VE in the surveillance of COVID-19 and a finding that may be important in the surveillance of other respiratory infection.

Current type 2 diabetes guidelines: Individualized treatment and how to make the most of metformin.

Evidence-based guidelines provide the premise for the delivery of quality care to preserve health and prevent disabilities and premature death. The systematic gathering of observational, mechanistic and experimental data contributes to the hierarchy of evidence used to guide clinical practice. In the field of diabetes, metformin was discovered more than 100 years ago, and with 60 years of clinical use, it has stood the test of time regarding its value in the prevention and management of type 2 diabetes. Although some guidelines have challenged the role of metformin as the first-line glucose-lowering drug, it is important to point out that the cardiovascular-renal protective effects of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists were gathered from patients with type 2 diabetes, the majority of whom were treated with metformin. Most national, regional and international guidelines recommend metformin as a foundation therapy with emphasis on avoidance of therapeutic inertia and early attainment of multiple treatment goals. Moreover, real-world evidence has confirmed the glucose-lowering and cardiovascular-renal benefits of metformin accompanied by an extremely low risk of lactic acidosis. In patients with type 2 diabetes and advanced chronic kidney disease (estimated glomerular filtration rate 15-30 mL/min/1.73m2), metformin discontinuation was associated with an increased risk of cardiovascular-renal events compared with metformin persistence. Meanwhile, it is understood that microbiota, nutrients and metformin can interact through the gut-brain-kidney axis to modulate homeostasis of bioactive molecules, systemic inflammation and energy metabolism. While these biological changes contribute to the multisystem effects of metformin, they may also explain the gastrointestinal side effects and vitamin B12 deficiency associated with metformin intolerance. By understanding the interactions between metformin, foods and microbiota, healthcare professionals are in a better position to optimize the use of metformin and mitigate potential side effects. The United Kingdom Prospective Diabetes Study and the Da Qing Diabetes Prevention Program commenced 40 years ago provided the first evidence that type 2 diabetes is preventable and treatable. To drive real-world impact from this evidence, payors, practitioners and planners need to co-design and implement an integrated, data-driven, metformin-based programme to detect people with undiagnosed diabetes and prediabetes (intermediate hyperglycaemia), notably impaired glucose tolerance, for early intervention. The systematic data collection will create real-world evidence to bring out the best of metformin and make healthcare sustainable, affordable and accessible.

The effects of reward and punishment on the performance of ping-pong ball bouncing.

Introduction: Reward and punishment modulate behavior. In real-world motor skill learning, reward and punishment have been found to have dissociable effects on optimizing motor skill learning, but the scientific basis for these effects is largely unknown. Methods: In the present study, we investigated the effects of reward and punishment on the performance of real-world motor skill learning. Specifically, three groups of participants were trained and tested on a ping-pong ball bouncing task for three consecutive days. The training and testing sessions were identical across the three days: participants were trained with their right (dominant) hand each day under conditions of either reward, punishment, or a neutral control condition (neither). Before and after the training session, all participants were tested with their right and left hands without any feedback. Results: We found that punishment promoted early learning, while reward promoted late learning. Reward facilitated short-term memory, while punishment impaired long-term memory. Both reward and punishment interfered with long-term memory gains. Interestingly, the effects of reward and punishment transferred to the left hand. Discussion: The results show that reward and punishment have different effects on real-world motor skill learning. The effects change with training and transfer readily to novel contexts. The results suggest that reward and punishment may act on different learning processes and engage different neural mechanisms during real-world motor skill learning. In addition, high-level metacognitive processes may be enabled by the additional reinforcement feedback during real-world motor skill learning. Our findings provide new insights into the mechanisms underlying motor learning, and may have important implications for practical applications such as sports training and motor rehabilitation.

Efficacy comparison of fruquintinib, regorafenib monotherapy or plus programmed death-1 inhibitors for microsatellite stable metastatic colorectal cancer.

BACKGROUND: Regorafenib (R) and fruquintinib (F) are the standard third-line regimens for colorectal cancer (CRC) according to the National Comprehensive Cancer Network guidelines, but both have limited efficacy. Several phase 2 trials have indicated that R or F combined with immune checkpoint inhibitors can reverse immunosuppression and achieve promising efficacy for microsatellite stable or proficient mismatch repair (MSS/pMMR) CRC. Due to the lack of studies comparing the efficacy between F, R, F plus programmed death-1 (PD-1) inhibitor, and R plus PD-1 inhibitors (RP), it is still unclear whether the combination therapy is more effective than monotherapy. AIM: To provide critical evidence for selecting the appropriate drugs for MSS/pMMR metastatic CRC (mCRC) patients in clinical practice. METHODS: A total of 2639 CRC patients were enrolled from January 2018 to September 2022 in our hospital, and 313 MSS/pMMR mCRC patients were finally included. RESULTS: A total of 313 eligible patients were divided into F (n = 70), R (n = 67), F plus PD-1 inhibitor (FP) (n = 95) and RP (n = 81) groups. The key clinical characteristics were well balanced among the groups. The median progression-free survival (PFS) of the F, R, FP, and RP groups was 3.5 months, 3.6 months, 4.9 months, and 3.0 months, respectively. The median overall survival (OS) was 14.6 months, 15.7 months, 16.7 months, and 14.1 months. The FP regimen had an improved disease control rate (DCR) (P = 0.044) and 6-month PFS (P = 0.014) and exhibited a better trend in PFS (P = 0.057) compared with F, and it was also significantly better in PFS than RP (P = 0.030). RP did not confer a significant survival benefit; instead, the R group had a trend toward greater benefit with OS (P = 0.080) compared with RP. No significant differences were observed between the R and F groups in PFS or OS (P > 0.05). CONCLUSION: FP is superior to F in achieving 6-month PFS and DCR, while RP is not better than R. FP has an improved PFS and 6-month PFS compared with RP, but F and R had similar clinical efficacy. Therefore, FP may be a highly promising strategy in the treatment of MSS/pMMR mCRC.

Investigating the Variability among Indicators for Quantifying Antimicrobial Use in the Intensive Care Units: Analysis of Real-world Evidence.

This study investigated variability among four indicators for quantifying antimicrobial use in intensive care units (ICUs): defined daily doses (DDD), prescribed daily doses (PDD), duration of therapy (DOT), and length of therapy (LOT) and recommended the most clinically relevant approach. Retrospective data from patients who had received at least one antimicrobial was analyzed. Patients whose records were incomplete or expired were excluded. Duration of therapy (24433/1000 PDs) and LOTs (12832/1000 PDs) underestimated the overall consumption of antimicrobials compared with DDD of 28391/1000 PDs. Whereas PDD (46699/1000 PDs) overestimated it. Comparison analysis detected % differences of 13.94, 23.92, and 54.80% between DDD and DOT, DDD and PDD, and DDD and LOT, indicators respectively. Linear regression revealed stronger (r 2 = 0.86), moderate (r 2 = 0.50), and moderate (r 2 =0.60) correlation between DDD and DOT, DDD and PDD and DDD and LOT indicators respectively. According to findings, combining DOT and DDD is a more practical method to quantify antimicrobial consumption in hospital ICUs. How to cite this article: Deshwal PR, Tiwari P. Investigating the Variability among Indicators for Quantifying Antimicrobial Use in the Intensive Care Units: Analysis of Real-world Evidence. Indian J Crit Care Med 2024;28(7):662-676.

Addressing data imbalance in Sim2Real: ImbalSim2Real scheme and its application in finger joint stiffness self-sensing for soft robot-assisted rehabilitation.

The simulation-to-reality (sim2real) problem is a common issue when deploying simulation-trained models to real-world scenarios, especially given the extremely high imbalance between simulation and real-world data (scarce real-world data). Although the cycle-consistent generative adversarial network (CycleGAN) has demonstrated promise in addressing some sim2real issues, it encounters limitations in situations of data imbalance due to the lower capacity of the discriminator and the indeterminacy of learned sim2real mapping. To overcome such problems, we proposed the imbalanced Sim2Real scheme (ImbalSim2Real). Differing from CycleGAN, the ImbalSim2Real scheme segments the dataset into paired and unpaired data for two-fold training. The unpaired data incorporated discriminator-enhanced samples to further squash the solution space of the discriminator, for enhancing the discriminator's ability. For paired data, a term targeted regression loss was integrated to ensure specific and quantitative mapping and further minimize the solution space of the generator. The ImbalSim2Real scheme was validated through numerical experiments, demonstrating its superiority over conventional sim2real methods. In addition, as an application of the proposed ImbalSim2Real scheme, we designed a finger joint stiffness self-sensing framework, where the validation loss for estimating real-world finger joint stiffness was reduced by roughly 41% compared to the supervised learning method that was trained with scarce real-world data and by 56% relative to the CycleGAN trained with the imbalanced dataset. Our proposed scheme and framework have potential applicability to bio-signal estimation when facing an imbalanced sim2real problem.

COPD Exacerbations Before and During COVID-19 in France, Germany, Italy, the UK and the US.

Background: Exacerbations of chronic obstructive pulmonary disease (COPD) were reported less frequently during the COVID-19 pandemic. We report real-world data on COPD exacerbation rates before and during this pandemic. Methods: Exacerbation patterns were analysed using electronic medical records or claims data of patients with COPD before (2017-2019) and during the COVID-19 pandemic (2020 through early 2022) in France, Germany, Italy, the United Kingdom and the United States. Data from each country were analysed separately. The proportions of patients with COPD receiving maintenance treatment were also estimated. Results: The proportion of patients with exacerbations fell 45-78% across five countries in 2020 versus 2019. Exacerbation rates in most countries were reduced by >50% in 2020 compared with 2019. The proportions of patients with an exacerbation increased in most countries in 2021. Across each country, seasonal exacerbation increases seen during autumn and winter in pre-pandemic years were absent during the first year of the pandemic. The percentage of patients filling COPD prescriptions across each country increased by 4.53-22.13% in 2019 to 9.94-34.17% in 2021. Conclusion: Early, steep declines in exacerbation rates occurred in 2020 versus 2019 across all five countries and were accompanied by a loss of the seasonal pattern of exacerbation.

The prediagnostic general practitioner care of sarcoma patients: A real-world data study.

BACKGROUND: Limited understanding exists regarding early sarcoma symptoms presented during general practitioner (GP) consultations. The study explores GP visit patterns and recorded diagnoses in the 12 months preceding sarcoma diagnosis. METHODS: Sarcoma cases diagnosed from 2010 to 2020 were identified through the Netherlands Cancer Registry alongside general practice data. Sarcoma cases were age and gender matched to cancer-free controls (2:1 or 1:1 ratio). RESULTS: A total of 787 individuals with soft-tissue sarcoma (STS) and 188 individuals with bone sarcoma (BS) were identified. There was a significant difference in monthly GP contacts from 4 months to the last month before STS diagnosis, and 2 months before BS diagnosis between cases and controls. Most prevalent diagnoses recorded by the GP for STS cases included musculoskeletal neoplasm (26.6%), uncomplicated hypertension (15.6%), and cystitis/other urinary infections (12.2%). For BS cases, musculoskeletal neoplasm (42.8%), knee symptoms/complaints (9.7%), and shoulder symptoms/complaints (9.7%) were most frequent. CONCLUSIONS AND DISCUSSION: A significant difference in GP contacts between cases and controls preceding sarcoma diagnosis. STS cases were predominantly diagnosed with nonspecific symptoms, whereas BS cases with diagnoses more suggestive of BS. Better understanding of the prediagnostic trajectory could aid GPs in early identification of sarcoma.

Evaluation of serial QuantiFERON-TB Gold in tube test results and tuberculosis infection status in patients with psoriasis receiving anti-IL-17 treatment (secukinumab and ixekizumab): Real-world data from a tuberculosis-endemic country.

BACKGROUND: In comparison with TNF-α inhibitors, anti-IL-17A agents are considered to have a lower risk of active tuberculosis (TB) or latent TB infection (LTBI) reactivation. METHODS: In this study, we aimed to evaluate the TB infection status and serial QuantiFERON-TB-Gold in tube test (QFT) results of psoriasis patients using IL-17 inhibitors (secukinumab [SEC] and ixekizumab [IXE]) in a real-world setting from a tuberculosis-endemic country. Patients who used an anti-IL-17 agent for at least 3 months in our follow-up were included in the study. Patients' clinical and demographic features, baseline QFT results and latest QFT results (if any), and TB infection status were noted from the past medical records. RESULTS: A total of 717 patients, of whom 333 (46.4%) were female, were included in the study. The cumulative exposure time to an anti-IL-17 agent was 14,147 patient-months, 9743 patient-months for SEC and 4404 patient-months for IXE. Also, 459 (SEC = 305/IXE = 154) patients used an anti-IL-17 agent for ≥ 12 months. Of these, 125 had positive baseline QFT results. In all, 334 had negative baseline QFT results. The latest QFT result of 309 was also negative (persistent seronegative group). During follow-up, the QFT results of 10 patients changed from negative to positive (positive seroconversion group). Seven of them were using SEC and three were using IXE, respectively. No case of active TB infection was detected. CONCLUSION: In our study, the positive seroconversion rate of 10/334 seems high, but this did not translate to active disease. However, closer monitoring may be required, especially in patients with advanced age, the presence of PsA, long disease duration and long anti-IL-17 treatment duration.