Real-world Outcomes Research Articles

Enhanced Metabolic Control in a Pediatric Population with Type 1 Diabetes Mellitus Using Hybrid Closed-Loop and Predictive Low-Glucose Suspend Insulin Pump Treatments

Background: Insulin pumps coupled with continuous glucose monitoring sensors use algorithms to analyze real-time blood glucose levels. This allows for the suspension of insulin administration before hypoglycemic thresholds are reached or for adaptive tuning in hybrid closed-loop systems. This longitudinal retrospective study aims to analyze real-world glycemic outcomes in a pediatric population transitioning to such devices. Methods: We evaluated children with type 1 diabetes mellitus (T1D) admitted to the Pediatric Diabetes Department from a major University Hospital in Bucharest, Romania, who transitioned to hybrid closed-loop or predictive low-glucose suspend system from either non-automated insulin pumps or multiple daily injections. The primary outcome was assessing the change in glycated hemoglobin (HbA1c) after initiating these devices. Secondary outcomes analyzed changes in glucose metrics from the 90 days prior to the baseline and follow-up visit. Results: 51 children were included (58.8% girls), the mean age was 10.3 ± 3.7 years, and the mean follow-up duration was 13.2 ± 4.5 months. The analyzed parameters, such as HbA1c (6.9 ± 0.7% vs. 6.7 ± 0.6%, p = 0.023), time in range (69.3 ± 11.2% vs. 76 ± 9.9%, p < 0.001), time in tight range (47.4 ± 10.9% vs. 53.7 ± 10.7%, p < 0.001), time below range (5.6 ± 2.9% vs. 3.5 ± 1.9%, p < 0.001), time above range (25 ± 11.2% vs. 20.4 ± 9.4%, p = 0.001), and coefficient of variation (37.9 ± 4.8% vs. 35.6 ± 4.6%, p = 0.001), showed significant improvements. Conclusions: The application of these sensor-integrated insulin pumps can significantly enhance metabolic control in pediatric populations, minimizing glycemic variations to mitigate complications and enrich the quality of life.

Impact of iron powder and blast furnace slag on the mechanical properties of polymer concrete: An experimental and hyperparameter-tuned ANN-based study

Polymer-based materials have become increasingly used in concrete production and various engineering applications due to their versatile properties. In particular, polymer concrete (PC) has become a preferred reinforcement material in the construction industry. Various studies have been carried out to evaluate the performance of PC and to improve its mechanical properties by adding different admixtures. This study investigates the effects of fine materials such as iron powder (IP) and blast furnace slag (BFS) on the mechanical performance of PC. Within the scope of the study, samples with 5% and 10% IP, 5% and 10% BFS, 2.5% IP + 2.5% BFS and 5% IP + 5% BFS were prepared. These specimens were cured in the same laboratory environment and subjected to mechanical tests at the end of the 7th day. The results of the mechanical tests were compared to reveal the effect of fine materials on the performance of the PC. The potential of an artificial neural network (ANN) model is investigated to replicate real-world outcomes. The findings provide valuable insights into the potential of iron powder and blast furnace slag as admixtures to improve the mechanical properties of PC.

Association of obesity and thyroidectomy-specific perioperative outcomes.

There is limited large-scale data on the effect of obesity on thyroidectomy-specific outcomes. To fill this gap in the literature, this study evaluates the association between obesity and thyroidectomy-specific outcomes using a large real-world surgical outcomes dataset. The 2016-2019 American College of Surgeons National Surgical Quality Improvement Program Targeted Thyroidectomy dataset (ACS NSQIP) was queried. Using an inverse probability weighted (IPW) model, the impact of BMI on the primary (postoperative voice hoarseness, neck hematoma, and hypocalcemia.) and secondary outcomes (operative time and postoperative length of stay) were estimated. BMI was evaluated as per the WHO obesity categories. Sensitivity analysis was performed. 24,370 patients were evaluated with an average BMI of 30.6, a mean age of 51.8years, 77.5% were female, and 7.9 % were Hispanic. In univariate analysis, patients with BMI >30 had a higher risk of postoperative voice hoarseness (6.7 vs. 5.8% and p=0.005) and neck hematoma (2.1 vs. 1.7% and p=0.014) and a lower risk in hypocalcemia rates (3.6% vs. 4.6 % and p<0.001). In the fully adjusted multivariable IPW models, BMI >30 was associated with a higher rate of postoperative voice hoarseness (RR 1.12 and p=0.031) and neck hematoma (RR 1.25 and p=0.024) but a lower rate of hypocalcemia (RR 0.81 and p=0.001). Also, patients with BMI >30 had longer OR time (adjusted difference: 6.33min and p<0.001) and length of stay (adjusted difference: 1.36h and p=0.002). In this national cohort of patients undergoing thyroidectomy, obesity was associated with a decreased rate of hypocalcemia but an increased rate of postoperative voice hoarseness and neck hematoma.

Real-world clinical outcomes and economic burden of metastatic pancreatic ductal adenocarcinoma: a systematic review.

This systematic review summarizes real-world clinical outcomes and economic burden of first-line FOLFIRINOX (FFX)/modified FFX (mFFX) and nab-paclitaxel plus gemcitabine (GnP) in metastatic pancreatic ductal adenocarcinoma in the US. Embase and MEDLINE were searched for materials published since 2014; citations were reviewed in a two-step process. Included studies were qualitatively synthesized. Searches yielded 2,528 citations; 29 were included (17 clinical studies/12 economic studies). In 9/17 clinical studies, median overall survival (mOS) ranged from 4.7 months to 11.4 months for FFX/mFFX, with the unweighted median of the estimates within this range being 9.2 months; for GnP mOS ranged from 3.6 to 9.8 months, and the unweighted median of the estimates was 6.9 months. In 8/17 studies, grade 3/4 anemia, neutropenia, and thrombocytopenia were the most commonly reported adverse events. Across economic burden studies, total costs were similar between the 2 groups. Outpatient, supportive care, and granulocyte colony-stimulating factor costs were higher for the FFX generic regimen, and chemotherapy costs were higher for the GnP branded regimen. Real-world OS in FFX- and GnP-treated populations was shorter than that in clinical trials, and total costs of FFX and GnP were similar, but with differences in cost components.

Real world outcomes in alveolar soft part sarcomas: experience with an ultra-rare sarcoma from a tertiary care centre in North India

Real world outcomes in alveolar soft part sarcomas: experience with an ultra-rare sarcoma from a tertiary care centre in North India

Real-world characteristics and outcomes of patients with high-risk and non-high-risk smoldering multiple myeloma using the Flatiron Health database

This study aimed to provide real-world evidence on progression risk in patients with high-risk smoldering multiple myeloma (SMM). This retrospective, observational study leveraged data from the Flatiron Health database. Eligible patients had SMM and relevant measures to apply Mayo 2018, International Myeloma Working Group (IMWG) 2020, and AQUILA trial risk criteria. Time to progression to active MM (TTP), progression or death (PFS), and death or progression on first-line MM therapy (PFS2) were evaluated using Kaplan–Meier methods and multivariate Cox regression models adjusted for age, Charlson Comorbidity Index, and time from SMM diagnosis to risk classification date. Across the three risk models (Mayo 2018, IMWG 2020, and AQUILA trial), high-risk patients with SMM had 3.0–4.0 times the risk of TTP, 2.1–3.5 times the risk of PFS, and 1.7–3.2 times the risk of PFS2 versus non-high-risk patients (p < 0.001 for all comparisons). Similar results were observed when patients with early treatment, early progression, and/or bone disease were excluded. This study demonstrates that high-risk patients with SMM have worse prognoses than non-high-risk patients, regardless of the criteria used, and highlights a need for early intervention testing.

Long-Term clinical efficacy of liraglutide for type 2 diabetes: real-world evidence and outcomes from Pakistan.

Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated efficacy in improving glycemic control and promoting weight loss in clinical trials. However, real-world data from diverse populations, particularly from South Asia, are limited. The study aims to evaluate the long-term efficacy and safety of liraglutide in a real-world setting among Pakistani patients with type 2 diabetes mellitus (T2DM). A retrospective cohort study of 624 patients initiated on liraglutide was conducted. Data were collected at baseline and 6, 12, 18, and 24 months. Primary outcomes were HbA1c and weight changes. Secondary outcomes included fasting plasma glucose, lipid profile, and blood pressure. Statistical analyses were performed using appropriate methods. In study population the mean HbA1c reduction of -1.45 ± 0.67% was observed at 24 months, with 30.6% achieving HbA1c ≤ 7.5%. A rapid and sustained weight loss of -7.51 kg was achieved, with 27.2% experiencing ≥5% weight loss. Additionally, liraglutide led to a significant reduction in LDL cholesterol, with 46.7% of patients achieving a ≥ 10% reduction at 24 months. Liraglutide was well-tolerated, with a low discontinuation rate of 4.6%. Liraglutide demonstrated sustained efficacy and safety in a diverse Pakistani population with T2DM, regardless of baseline characteristics. These findings support the use of liraglutide as an effective treatment option for T2DM in real-world clinical practice.

Unveiling the nexus of scientific plans and real-world outcomes: A comparative analysis of land use optimization and agent-based simulation results in a natural landscape

Sustainable land management requires balancing the socio-economic needs of local communities with land conservation. Effective land management programs hinge on how well plans align with the demands and actions of land users in natural landscapes. This study aimed to create optimized land use plans for a Jahan-Nama protected area in Iran as the initial step, followed by simulating stakeholder plans and conducting a comparative analysis. A combination of compromise programming and a simulated annealing algorithm, alongside an agent-based model (ABM) to simulate stakeholder preferences, was employed for land use optimization. The study compared the outcomes of eight optimized scenarios that considered both socio-economic needs (social, economic) and environmental sustainability (environmental), along with stakeholder preferences reflected in multi-objective scenarios with varying priorities and a single-use livestock grazing scenario. Findings revealed that the grazing scenario (single-use) offered the highest employment rate (201 individuals) within the study area, but had the lowest economic efficiency (profitability ratio: 13.38). Additionally, the grazing scenario exhibited the highest water consumption (42,200 L/day) and the highest erosion rate compared to the other scenarios. Conversely, the beekeeping and ecotourism scenario emerged as the most economically efficient (profitability ratio: 46.31) with the lowest water consumption (23,000 L/day). Among the scenarios examined, the highest level of agreement was observed for the simulated sites chosen by beekeepers and the beekeeping and ecotourism (BTP) scenario (Kappa = 0.176). Conversely, the economic scenario (EC) had the lowest agreement with the beekeepers' selected sites (Kappa = 0.135). In terms of ecotourism, the results indicated the highest agreement between the tourists' sites and the ecotourism and recreational scenario (Kappa = 0.332 in single-agent mode and 0.405 in multi-agent mode). On the other hand, the livestock grazing scenario had the lowest level of agreement with the tourists' selected sites (Kappa = 0.282 in single-agent mode and 0.362 in multi-agent mode).

Real-World Outcomes of Different Types of Treatment for Diabetic Macular Edema Before and After Approval of Anti-Vascular Endothelium Growth Factor Agents.

Background/Objectives: The object of this study was to determine the outcomes of treatments other than anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) before and after the approval of anti-VEGF therapy in Japan. Methods: This was a retrospective study registered in the database of the Survey of Treatment for DME (STREAT-DME). A total of 1683 patients treated from 2010 to 2017 were included. The patients were divided into two groups: (1) a pre-group, treated before the approval of anti-VEGF agents (2010-2013, n = 771), and (2) a post-group (2014-2017, n = 912). Each group was further categorized based on best-corrected visual acuity (BCVA): (i) improved from poor (>0.3 logMAR units) to good (≤0.3 logMAR units) or (ii) decreased from good to poor. Results: In the pre-group, 18.5% of patients improved from poor to good BCVA out of the total patient population (p < 0.0001), along with 17.3% out of those administered anti-VEGF therapy (p = 0.139), 20.5% of those administered a sub-tenon injection of triamcinolone acetonide (STTA, p = 0.02), 17.7% (p = 0.20) of those administered photocoagulation, and 14.2% of those who underwent pars plana vitrectomy (PPV, p = 0.0001). In the post-group, 21.8% had improved BCVA out of the total patient population (p < 0.0001), along with 27.2% of those undergoing anti-VEGF therapy (p < 0.0001), 16.7% of those administered STTA (p < 0.0001), and 27.2% of those who underwent PPV (p < 0.0001). Conclusions: STTA and PPV are effective to a certain extent, even after the approval of anti-VEGF agents.

Hepatic real-world outcomes with obeticholic acid in primary biliary cholangitis (HEROES): A trial emulation study design.

Primary biliary cholangitis (PBC) is a rare, progressive liver disease. Obeticholic acid (OCA) received accelerated approval for treating patients with PBC in whom ursodeoxycholic acid (UDCA) failed, based on a surrogate endpoint of reduction in alkaline phosphatase. Analysis of the long-term safety extension with 2 external control groups demonstrated a significant increase in event-free survival in OCA-treated patients. This fully real-world evidence study assessed the effect of OCA treatment on the clinical outcomes. This trial emulation used data from the Komodo Healthcare Map™ claims database linked to US national laboratory, transplant, and death databases. Patients with compensated PBC and intolerance/inadequate response to UDCA who initiated OCA therapy were compared with patients who were OCA-eligible but not OCA-treated. The primary endpoint was time to first occurrence of death, liver transplant, or hospitalization for hepatic decompensation, analyzed using a propensity-score weighted Cox proportional hazards model. Baseline prognostic factors were balanced using standardized morbidity ratio weighting. For the primary analysis, 4174 patients contributed 11,246 control index dates; 403 patients contributed OCA indexes. Weighted groups were well balanced. Median (95% CI) follow-up in the OCA and non-OCA arms was 9.3 (8.4-10.6) months and 17.5 (16.2-18.6) months (weighted population; censored at discontinuation). Eight events occurred in the OCA arm, 32 in the weighted control (HR=0.37; 95% CI=0.14-0.75; p<0.001). Effects were consistent for each component of the composite endpoint. We identified a 63% reduced risk of hospitalization for hepatic decompensation, liver transplant, or death in OCA-treated versus non-OCA-treated individuals. HEROES; ClinicalTrials.gov NCT05292872.

Treatment strategies with electrochemotherapy for limb in-transit melanoma: real-world outcomes from a European, retrospective, multicentre analysis: the CLIMATE study

Treatment strategies with electrochemotherapy for limb in-transit melanoma: real-world outcomes from a European, retrospective, multicentre analysis: the CLIMATE study

Real-world occurrence, therapy, and outcome of patients with class 2 or 3 BRAF compared with class 1 BRAF-mutated cancers

Real-world occurrence, therapy, and outcome of patients with class 2 or 3 BRAF compared with class 1 BRAF-mutated cancers

Atrial Fibrillation in Patients Receiving Mavacamten for Obstructive Hypertrophic Cardiomyopathy: Real-World Incidence, Management, and Outcomes.

Atrial Fibrillation in Patients Receiving Mavacamten for Obstructive Hypertrophic Cardiomyopathy: Real-World Incidence, Management, and Outcomes.

Real-world treatment patterns and clinical outcomes in patients with multiple myeloma previously treated with lenalidomide and an anti-CD38 monoclonal antibody

Real-world treatment patterns and clinical outcomes in patients with multiple myeloma previously treated with lenalidomide and an anti-CD38 monoclonal antibody

Real-World Survival Outcomes in Non-Small Cell Lung Cancer: The Impact of Genomic Testing and Targeted Therapies in a Latin American Middle-Income Country.

Targeted therapies are indicated for patients with non-small cell lung cancer (NSCLC) and driver tumor mutations. However, real-world studies on the survival benefits of these agents are limited. This study aimed to evaluate the effect of targeted therapies matched to a genomic alteration on the survival of patients with NSCLC. This retrospective study included 446 patients with advanced NSCLC who underwent next-generation sequencing between 2016 and 2023 at the Instituto Nacional de Cancerología in Mexico. The primary outcomes were progression-free survival (PFS) and overall survival (OS). For the entire cohort, the PFS and OS were 10.71 months (95% CI, 9.35 to 12.06) and 47.77 months (95% CI, 29.67 to 65.86). PFS was significantly longer in patients with actionable mutations treated with targeted therapies (19.41 months [95% CI, 14.27 to 24.55]; P < .001) than in patients without actionable mutations (6.4 months [95% CI, 4.4 to 8.4]) or not treated with targeted therapies (6.6 months [95% CI, 5.3 to 7.89]). Similarly, OS was significantly longer in patients with actionable mutations treated with targeted therapies (89.69 months [95% CI, 45.54 to 133.84]; P < .001) than in patients without actionable mutations (17.11 months [95% CI, 8.65 to 25.57]) or not treated with targeted therapies (22.3 months [95% CI, 12.48 to 32.1]). Survival gains were driven by significant improvements in PFS and OS in patients with EGFR and ALK mutations. This real-world data analysis demonstrated that targeted therapies improve the survival of patients with NSCLC with actionable mutations, which supports a recommendation for widening access to broad-based genomic testing and targeted therapies.

Real-World Prevalence, Treatment Patterns, and Outcomes for Patients With HER2 (ERBB2)-Mutant Metastatic Non-Small Cell Lung Cancer, From a US-Based Clinico-Genomic Database.

Targeted therapies have been shown to improve outcomes in metastatic non-small cell lung cancer (mNSCLC) with driver mutations. We evaluated the real-world prevalence of human epidermal growth factor receptor 2 (HER2; ERBB2) tumor gene mutations among patients with mNSCLC and described historical treatments and outcomes in patients with HER2-mutant mNSCLC, during a period when there was no approved targeted therapy for HER2-mutant mNSCLC. This retrospective observational study used a US nationwide de-identified NSCLC clinico-genomic database. Eligible patients were adults diagnosed with HER2-mutant mNSCLC from January 2014 to July 2021 without co-occuring epidermal growth factor receptor (EGFR) tumor mutations. Descriptive statistics were used to summarize prevalence, baseline characteristics and treatment patterns. Clinical outcomes were estimated with Kaplan-Meier analyses. Among 9206 patients with mNSCLC, 164 (1.78%) met the eligibility criteria (mean age: 67.3 years, 63.4% White, 56.7% female, and 53.0% with a smoking history). 132/164 (80.5%) had at least one line of treatment. Platinum-based chemotherapy (45.5%) and immune checkpoint inhibitor (ICI) with chemotherapy (28.0%) were the most frequently used first-line treatments. The median (95% confidence interval [CI]) real-world (rw) progression-free survival in first-line was 5.5 (4.8, 6.2) months and 3.0 (2.3, 4.2) months in second-line. The median rw overall survival in first-line was 13.2 (10.6, 18.4) months and 8.2 (6.6, 13.2) months in second-line. During this study period, the most common regimens were platinum-based chemotherapy with or without ICI in first and second line, and median rwOS was 13.2 and 8.2 months, respectively. These results indicate the need for more effective targeted therapies in this patient population.

From clinical development to real-world outcomes with inclisiran.

Inclisiran is a small interfering RNA that blocks hepatocyte production of the PCSK9 (proprotein convertase subtilisin/kexin type 9) protein by specifically targeting PCKS9 mRNA in the cytoplasm. This results in reduced degradation of LDL receptors and thus lowers LDL cholesterol by around 50% in addition to other lipid-lowering therapies. beyond 6 years of therapy. This review covers the latest published data and outlines future studies currently in process. To date, half a million doses have been given worldwide with no untoward adverse events thus far. The twice-yearly injections make it potentially very user-friendly. The large phase 3a trials saw no diminution of effect with time up to nearly 7 years. Very large phase 3b randomized controlled trials are underway and may produce significant reductions in major adverse cardiovascular events. Inclisiran has been evaluated in numerous trials, primarily the ORION 9 26 , ORION 10 27 and ORION 11 28 studies, which demonstrated that in patients already on maximally tolerated statin therapy, biannual inclisiran injections reduced LDL cholesterol by up to 52% compared to placebo with a good safety profile. The only observed side effects were mild and transient at the injection site. As mentioned in the accompanying video, this adds to our armamentarium of lipid treatments.

S70 Impact of Precision-Guided Dosing on Clinical Decision Making and Health Care Utilization in Inflammatory Bowel Disease: A 24-Month Real-World Outcome Comparison Before and After Test Implementation

S70 Impact of Precision-Guided Dosing on Clinical Decision Making and Health Care Utilization in Inflammatory Bowel Disease: A 24-Month Real-World Outcome Comparison Before and After Test Implementation

Apalutamide in Metastatic Castration-sensitive Prostate Cancer: Results from the Multicenter Real-world ARON-3 Study

Background and objectiveApalutamide (APA) is a treatment for metastatic castration-sensitive prostate cancer (mCSPC). In the ARON-3 study we investigated real-world experiences with APA treatment for mCSPC. MethodsWe retrospectively assessed real-world clinical outcomes for patients with mCSPC treated with APA in the ARON-3 study. Overall survival (OS) was calculated from APA initiation to death from any cause. PSA90 was defined as a prostate-specific antigen decline of ≥90% from baseline, and PSA0.2 as achievement of a PSA level ≤0.2 ng/ml. Data for adverse events were retrospectively collected from electronic and paper charts and categorized according to Common Terminology Criteria for Adverse Events v5.0. Key findings and limitationsWe included 531 patients with mCSPC treated with APA. High-volume disease was reported for 214 patients (40%), and 56 (11%) had visceral metastases. Median OS was not reached. PSA90 was experienced by 461 patients (87%) and PSA0.2 by 368 (69%). Median OS was significantly longer for patients with PSA90 or PSA0.2 than for subjects without these responses (p < 0.001). The incidence of grade 3–4 fatigue was higher among elderly patients (≥80 yr) than among younger patients (19% vs 5%), but the incidence of other adverse events was comparable between the age groups. Conclusions and clinical implicationsAPA is an effective and tolerable treatment for mCSPC in the real-world setting. Patient summaryThe ARON-3 project collects data for patients with prostate cancer treated in multiple centers worldwide to assess outcomes in the real-world setting. We analyzed data for patients with metastatic hormone-sensitive prostate cancer receiving apalutamide. Our results show that apalutamide is a safe and effective drug in the real-world setting as well as in clinical trials.

Outcomes with loncastuximab tesirine following CAR T-cell therapy in patients with relapsed or refractory diffuse large B-cell lymphoma

The efficacy of loncastuximab tesirine (lonca) following chimeric antigen receptor T-cell therapy (CAR-T) progression/failure is unknown. Hence, we sought to examine real-world use and outcomes of lonca following CAR-T in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in the USA. In this retrospective study, we included adults (age ≥ 18 years) with R/R DLBCL who received lonca monotherapy as third- (3 L) or fourth line (4 L) treatment after progressing on second line (2 L) or 3 L CAR-T, respectively. Post-CAR-T lonca outcomes included response rates (overall response rate [ORR] and complete response [CR] rate), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). A total of 118 patients were included in the analysis with 95 receiving lonca following 2 L CAR-T (median age:66 years; 61% male) and 23 following 3 L CAR-T (median age:57 years; 43% male). Patients with 2 L CAR-T/3 L lonca had an ORR of 73% (CR rate of 34%). With a median follow-up of 8.5 months following lonca initiation, median DOR, PFS, and OS were not reached. The DOR, PFS, and OS at 12 months were 68%, 77%, and 84%, respectively. Patients with 3 L CAR-T/4 L lonca had an ORR of 78% (CR rate of 17%). With a median follow-up of 13 months following lonca initiation, the median DOR and PFS were 7.6 and 12.0 months, while median OS was not reached. OS at 12 months was 95%. In this study, we found that lonca monotherapy was an effective treatment option in R/R DLBCL in 3 L and 4 L settings including those who were resistant to or progressed after CAR-T.