Real-world Observational Study Research Articles

Comparison of Budesonide/formoterol versus Fluticasone furoate/vilanterol as maintenance and reliever therapy for asthma control: a real-world observational study

BackgroundPrevious studies have reported reduced acute exacerbation rates and improved symptom control in asthma patients treated using inhaled corticosteroids plus formoterol maintenance and reliever therapy (MART). Fluticasone furoate (FF) and vilanterol (VIL) also provide rapid bronchodilation and sustained anti-inflammatory effects, however no studies have investigated FF/VIL as MART for asthma control.MethodsFrom October 1, 2021 to September 30, 2023, this retrospective study included asthma patients classified as step 3 or 4 according to the Global Initiative for Asthma guidelines, who were then divided into two groups. One group received BUD/FOR as MART, while the other received FF/VIL as MART. Pulmonary function tests, exacerbation rates, Asthma Control Test (ACT), fractional exhaled nitric oxide (FeNO) levels, and blood eosinophil counts were measured before and after 12 months of treatment.ResultsA total of 161 patients were included, of whom 36 received BUD/FOR twice daily as MART, and 125 received FF/VIL once daily as MART. After 12 months of treatment, the FF/VIL group showed a significant increase in ACT scores by 1.57 (p < 0.001), while the BUD/FOR group had an increase of 0.88 (p = 0.11). In terms of FeNO levels, the BUD/FOR group experienced a decline of -0.2 ppb (p = 0.98), whereas the FF/VIL group had a mild increase of + 0.8 ppb (p = 0.7). Notably, there was a significant difference in the change of FeNO between the two groups (∆ FeNO: -0.2 ppb in BUD/FOR; + 0.8 ppb in FF/VIL, p < 0.001). There were no significant alterations observed in FEV1, blood eosinophil count, or acute exacerbation decline in either group.ConclusionsIn the current study, patients treated with FF/VIL as MART showed improvements in ACT scores, while those treated with BUD/FOR as MART exhibited a reduction in FeNO levels. However, the difference between the two treatment groups did not reach clinical significance. Thus, FF/VIL as MART showed similar effectiveness to BUD/FOR as MART.

Exploring school acceptance and children’s consumption of bean-based lunchtime meals; an observational real-world study

Exploring school acceptance and children’s consumption of bean-based lunchtime meals; an observational real-world study

A multi-center real-life prospective study of axicabtagene ciloleucel versus tisagenlecleucel toxicity and outcomes in Large B-Cell Lymphomas.

This real-world prospective observational study across 21 Italian centers (CART-SIE) compares axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) outcomes in 485 relapsed-refractory large B-cell lymphoma patients with baseline characteristics matched by Stabilized Inverse Propensity-Score Weighting. Axi-cel versus tisa-cel had higher all-grade cytokine release syndrome (78.6% vs 89.3%, p=0.0017) and neurotoxicity (9.9% vs 32.2%, p<0.0001), but also superior progression-free survival (PFS) at one year (46.5% vs 34.1%, p=0.0009). Even among patients who failed bridging therapy, axi-cel PFS was superior to tisa-cel (37.5% vs 22.7%, p=0.0059). Differences in overall survival (OS) and high-grade immune toxicities were not significant. The CAR-HEMATOTOX score not only predicted hematologic toxicity but also 1-year survival outcomes (51.5% in CAR-HEMATOTOX high vs. 77.2% in CAR-HEMATOTOX low, p<0.0001). Twenty patients developed second primary malignancies, including two cases of T-cell neoplasms. These findings enable more informed selection of anti-CD19 CAR T-cell therapy balancing bridging, safety and efficacy considerations for individual patients.

PIONEER REAL Sweden: A Multicentre, Prospective, Real-World Observational Study of Oral Semaglutide Use in Adults with Type2 Diabetes in Swedish Clinical Practice.

The study was designed to assess outcomes with once-daily oral semaglutide in adults with type2 diabetes (T2D) naïve to injectable glucose-lowering agents, in Swedish clinical practice. In this non-interventional, multicentre study, participants initiated oral semaglutide and were followed for 34-44weeks. The primary endpoint was glycated haemoglobin (HbA1c) change from baseline to end of study (EOS). Secondary endpoints included body weight (BW) change from baseline to EOS, proportion of participants achieving HbA1c < 7%, and proportion achieving both a HbA1c reduction ≥ 1% and BW reduction of ≥ 3% or ≥ 5%, at EOS. Participants completed Diabetes Treatment Satisfaction Questionnaires (DTSQ status/change) and a dosing conditions questionnaire. A total of 187 participants (mean age 62.5years) initiated oral semaglutide. Baseline mean HbA1c and BW were 7.8% (n = 177) and 96.9kg (n = 165), respectively. Estimated mean changes in HbA1c and BW were - 0.88%-points (95% confidence interval [CI] - 1.01 to - 0.75; P < 0.0001) and - 4.72% (95%CI - 5.58 to - 3.86; P < 0.0001), respectively. At EOS, 64.6% of participants had HbA1c < 7%, and 22.9% achieved HbA1c reduction of ≥ 1% and BW reduction of ≥ 5%. DTSQ status and change scores improved by 1.44 (P = 0.0260) and 12.3 points (P < 0.0001), respectively. Oral semaglutide was easy or very easy to consume for 86.4% of participants. Most common adverse events (AEs) were gastrointestinal disorders; nine participants (4.8%) had serious AEs; one (0.5%) experienced severe hypoglycaemia. In this real-world study population, we observed significant reductions in HbA1c and BW in people living with T2D when prescribed semaglutide tablets as part of routine clinical practice in Sweden, with improved treatment satisfaction among participants and no new safety concerns. NCT04601753.

Treatment patterns and outcomes in KRASG12C‐positive advanced NSCLC patients previously treated with immune checkpoint inhibitors: A Canada-wide real-world, multi-center, retrospective cohort study

ObjectivesKRAS mutations, particularly KRASG12C, are prevalent in non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICIs) have been a frontline treatment, but recently developed KRASG12C-selective inhibitors, such as sotorasib, present new therapeutic options. We conducted a multi-center retrospective cohort study to gain insights into real-world treatment patterns and outcomes in patients with KRASG12C-positive advanced NSCLC receiving systemic therapy post-ICI treatment. MethodsFrom the CAnadian CAncers With Rare Molecular Alterations-Basket Real-world Observational Study (CARMA-BROS), a cohort of 102 patients with KRASG12C-positive advanced NSCLC across 9 Canadian centers diagnosed between 2015 and 2021 was analyzed. Clinico-demographic and treatment data were obtained from electronic health records. Survival outcomes were assessed using Kaplan-Meier curves and Cox proportional hazards models. ResultsThe patients (median age 66 years; 58 % female; 99 % current/former tobacco exposure; 59 % PD-L1 ≥ 50 %), exhibited heterogeneous treatment patterns post-ICI. Most patients received ICIs as a first-line therapy, with varying subsequent lines including chemotherapy and targeted therapy. In patients receiving systemic therapy post-ICI, median overall survival was 12.6 months, and real-world progression-free survival was 4.7 months. KRASG12C-selective targeted therapy post-ICI (n = 20) showed longer real-world progression-free survival compared to single-agent chemotherapy (aHR = 0.39, p = 0.012). ConclusionThis study contributes valuable real-world data on KRASG12C-positive advanced NSCLC post-ICI treatment. The absence of a standard treatment sequencing post-ICI underscores the need for further investigation and consensus-building in the evolving landscape of KRASG12C-targeted therapies.

A real-world observational study on the effect of Qingre Lishi decoction on glycemic profile using continuous glucose monitoring in obese type 2 diabetes adults.

To observe the clinical efficacy and safety of the Qingre Lishi decoction in treating of newly diagnosed overweight and obese patients with type 2 diabetes mellitus (T2DM) from an evidence-based medical perspective. 70 cases of overweight and obese patients with newly diagnosed T2DM treated in the outpatient clinic of the Department of Endocrinology of the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from December 2021 to November 2022 were selected, of which 35 cases were in the observation group and 35 cases were in the control group. The observation group was treated with the Qingre Lishi decoction add lifestyle intervention, and the control group was treated with lifestyle intervention only. We compared and analyzed the fasting blood glucose (FPG), 2-hour postprandial glucose (2hPG), the occurrence of adverse reactions, and the related indexes provided by wearing the CGM device during the observation period of the patients in the two groups. 53 participants completed the clinical trial. In relation of glycemic control, a decreasing trend has shown in both groups, with the decreases in FPG, 2hPG, eHbA1c, and MG in the observation group being higher than those in the control group (P<0.05). In regard to blood glucose attainment, at the 28d, the attainment rate of patients in the observation group with TIR>80% was 87.10%, and the magnitude of changes in the rise of TIR and the fall of TAR was significantly better than that in the control group (P<0.01). In terms of blood glucose fluctuation, CV and SD of the patients in the observation group decreased compared with the 0d; the magnitude of daytime blood glucose fluctuation was significantly alleviated compared with that of the control group. The degree of decrease in LAGE, MAGE, and MODD was significantly lower than that of the control group (P<0.01). The Qingre Lishi decoction can effectively improve the hyperglycemic condition of overweight and obese patients with newly diagnosed T2DM. It can reduce blood glucose, alleviate blood glucose fluctuations, reduce the incidence of hypoglycemia, and improve patients' adherence and self-confidence in controlling blood glucose. https://itmctr.ccebtcm.org.cn/, identifier ITMCTR2024000006.

Quality of life and tolerability of B-cell directed therapy of multiple sclerosis with ofatumumab in a patient-centered real-world observational study.

Ofatumumab (Kesimpta®) is a subcutaneous CD20-targeting antibody approved in Germany in 2021 for the treatment of relapsing multiple sclerosis (RMS). After careful instruction, patients can administer the treatment themselves. We previously reported data of 101 patients (Klimas et al. in Nervenarzt 94:923-933, 2023). The objective of this longitudinal study is to explore the tolerability and acceptability of ofatumumab from a patient perspective over a follow up period of 6months. In this prospective observational real-world study, we report follow up data of 81 patients. We evaluated sociodemographic data, disease duration, duration and side effects of ofatumumab use, expanded disability status scale (EDSS), Beck Depression Inventory II (BDI-II), Short-Form 36 (SF-36), Fatigue Scale of Motor and Cognitive Functions (FSMC), and modified Multiple Sclerosis Functional Composite Test (MSFC). In addition, we asked for subjective treatment outcomes, such as impact on quality of life, walking distance, concentration, mood, medication adherence, fatigue and the subjective course of MS on a numerical rating scale (1 = very negative; 5 = very positive). Furthermore, treatment discontinuations were recorded. The average duration of ofatumumab treatment was 10months. In comparison to previous published data of our cohort, patients reported a significant increase in headache (10% up to 26%, p = 0.004) and limb pain (5% up to 26%, p < 0.001) as persistent side effects after the injections. More patients reported a very positive effect (p < 0.0001) on quality of life. 4 confirmed relapses occurred but no EDSS worsening, and no treatment discontinuations were documented during the observation period. As previously described, our prospective study indicates that patients have a good tolerability of ofatumumab, precisely because of the mild and few side effects at the first administration. However, the longer the observation period, the more headaches and limb pain occurred after the injections. Despite this, patients' subjective quality of life improved. There were no discontinuations during the follow-up period, with the limitation of a high loss to follow-up.

Lipid goal achievement one month after myocardial infarction: Observational real-world study from Polish population.

Lipid goal achievement one month after myocardial infarction: Observational real-world study from Polish population.

Clinical and structural insights into the rare but oncogenic HER2-activating missense mutations in non-small cell lung cancer: a retrospective ATLAS cohort study

BackgroundUnlike human epidermal growth factor receptor 2 (HER2) amplification or exon 20 insertions, missense mutations in the extracellular domain (ECD), transmembrane domain (TMD), and intracellular domain (ICD) of the HER2 protein have been implicated as oncogenic in non-small cell lung cancer (NSCLC). However, their molecular subtypes, structural disparities, and clinical responses to current medical treatments, particularly HER2-targeted tyrosine kinase inhibitors (TKIs), remain unclear in NSCLC and warrant investigation.MethodsA real-world observational ATLAS study was conducted to gather and analyze therapeutic outcomes of chemotherapy or TKIs for heterogeneous HER2 missense mutations in NSCLC. Computational models of typical ECD, TMD, and ICD mutations were utilized to explore their structural variances.ResultsWe screened 37 eligible patients with HER2-activating missense mutations, of which 35 patients who had received chemotherapy or HER2-targeted TKIs as first-line therapy were available for response assessment. The median progression-free survival (PFS) for chemotherapy was 4.43 months (95% confidence interval [CI], 3.77–5.10), with an objective response rate (ORR) of 26.1% (6/23) and a disease control rate (DCR) of 17/23 (73.9%). The administration of afatinib, dacomitinib, and pyrotinib, HER2-targeted TKIs, achieved a median PFS of 4.65 months, with an ORR of 33.3% (4/12) and a DCR of 83.3% (10/12). Molecular modeling and computational simulations of ECD, TMD, and ICD mutations revealed their distinct structural characteristics.ConclusionIn comparison to chemotherapy, HER2-targeted TKIs demonstrated similar activity and PFS benefits for HER2-activating missense mutations in NSCLC.

Impact of SGLT2 Inhibitors on Very Elderly Population with Heart Failure with Reduce Ejection Fraction: Real Life Data.

(1) Background: The validation of new lines of therapy for the elderly is required due to the progressive ageing of the world population and scarce evidence in elderly patients with HF with reduced ejection fraction (HFrEF). The purpose of our study is to analyze the effect of SGLT2 inhibitors (SGLT2i) in this subgroup of patients. (2) Methods: A single-center, real-world observational study was performed. We consecutively enrolled all patients aged ≥ 75 years diagnosed with HFrEF and for treatment with SGLT2i, and considered the theoretical indications. (3) Results: A total of 364 patients were recruited, with a mean age of 84.1 years. At inclusion, the mean LVEF was 29.8%. Median follow-up was 33 months, and there were 122 deaths. A total of 55 patients were under SGLT2i treatment. A multivariate Cox logistic regression test for all-cause mortality was performed, and only SGLT2i (HR 0.39 [0.19-0.82]) and glomerular filtration rate (HR 0.98 [0.98-0.99]) proved to be protective factors. In parallel, we conducted a propensity-score-matched analysis, where a significant reduction in all-cause mortality was associated with the use of SGLT2i treatment (HR 0.39, [0.16-0.97]). (4) Conclusions: Treatment with SGLT2i in elderly patients with HFrEF was associated with a lower rate of all-cause mortality. Our data show that SGLT2i therapy could improve prognosis in the elderly with HFrEF in a real-world study.

The role of day-case thoracoscopy at a district general hospital: A real world observational study

ObjectiveTo assess the feasibility and safety of talc pleurodesis performed as part of day-case medical thoracoscopy. MethodsA Richard Wolf® 5 mm mini thoracoscope through a 5.5 mm port was used with eligible cases having talc poudrage followed by insertion of indwelling pleural catheter (IPC). District nurses drain the IPC daily for the first 5 days. Once the drain output is <150 mL, the frequency is progressively reduced to once weekly. The drain is removed after two consecutive dry taps 1 week apart. ResultsOverall, 51 patients underwent day-case thoracoscopy. Median time to removal of IPC for our day-case protocol was 14 days. There were seven deaths within 70 days among 41 patients with malignant pleural effusion in the day-case cohort, compared to eight deaths in the 33 conventional thoracoscopy controls. Overall, the day-case cohort observed a statistically significant reduction in all-cause mortality at 180 days compared to the conventional cohort (log rank p = 0.024). The average cost per patient of the day-case and inpatient cohort was £1,328.0 ± 106.0 and £1,835.0 ± 295.0 (p = 0.961). ConclusionThis study suggests that thoracoscopy and talc poudrage can be performed safely as a day-case procedure. Further data are needed to ascertain long-term outcomes.

No Differences in Kidney Function Decline Between People With Type 2 Diabetes Starting a Sodium-Glucose Cotransporter 2 Inhibitor or a Glucagon-like Peptide-1 Receptor Agonist: A Real-world Retrospective Comparative Observational Study

Diabetic nephropathy represents the leading cause of end-stage kidney disease in developed countries. Cardiovascular outcome trials have found that in participants who received a glucagon-like peptide-1 receptor agonist (GLP1RA) and a sodium-glucose cotransporter 2 inhibitor (SGLT2i), the risk of incidence and progression of diabetic nephropathy in type 2 diabetes mellitus was reduced. The aim of this study was to compare the decline in estimated glomerular filtration rate (eGFR) among people taking a GLP1RA with that among people taking an SGLT2i in a real-world setting. Data for 478 patients with type 2 diabetes mellitus who initiated therapy with a GLP1RA (n = 254) or an SGLT2i (n = 224) between January 1, 2018 and December 31, 2021 were extracted. The primary outcome was any reduction ≥30% in eGFR after the start of therapy. Weight loss and drug discontinuation were also assessed. Over a median follow-up of 24 months, an eGFR reduction ≥30% occurred in 34 of 254 patients (13.4%) starting a GLP1RA and in 26 of 223 patients (11.6%) starting an SGLT2i (hazard ratio = 0.89; 95% CI, 0.54-1.49; P = 0.67). Median eGFR change over the whole follow-up was similar between groups (SGLT2i: median, -2 mL/min/1.73 m2; 25th, 75th percentile, -13, 8 mL/min/1.73 m2; GLP1RA: median, 0 mL/min/1.73 m2; 25th, 75th percentile, -10, 7 mL/min/1.73 m2; P = 0.54). No worsening of kidney function was observed, even when considering the ratio eGFR mean. The value of eGFR at baseline indicated a statistically significant indirect correlation with the observed absolute value of eGFR change over the follow-up (ρ = -0.36; P < 0.001). The difference in eGFR changes over time observed by eGFR categories was statistically significant (P = 0.0001) in both treatment groups. No significant differences in weight loss and drug discontinuations were observed between groups. Although acting on different molecular mechanisms, both GLP1RA and SGLT2i might have similar effects on eGFR decline in diabetes, as suggested by the results of the present study conducted in a real-world setting. (Clin Ther. 2024;46:XXX-XXX) © 2024 Elsevier HS Journals, Inc.

Association of smoking cessation patterns and untreated smoking with glaucoma, cataract, and macular degeneration: a population-based retrospective study

This study aims to assess the association between nicotine replacement therapy (NRT), varenicline, and untreated smoking with the risk of developing eye disorders. We employed a new-user design to investigate the association between NRT use and the incidence of eye disorders by the Taiwan National Health Insurance program. This study included 8416 smokers who received NRT and 8416 smokers who did not receive NRT (control group) matched using propensity scores between 2007 and 2018. After adjustment for relevant factors, a multivariable Cox regression analysis revealed that compared with untreated smokers, NRT use was associated with a significantly reduced risk of macular degeneration (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.13–0.87, P = 0.024). When stratified by dose, short-term NRT use (8–28 defined daily doses) was associated with significantly lower risk of glaucoma (HR: 0.35; 95% CI: 0.16–0.80, P = 0.012) and a trend toward reduced risk of cataract (HR: 0.60; 95% CI: 0.36–1.01, P = 0.053) compared to no treatment. However, these associations were not observed with long-term NRT use. The results of this real-world observational study indicate that NRT use, particularly short-term use, was associated with a lower risk of certain eye disorders compared to no treatment for smoking cessation. Long-term NRT use did not demonstrate the same benefits. Thus, short-term NRT may be a beneficial treatment strategy for reducing the risk of eye disorders in smokers attempting to quit. However, further evidence is required to verify these findings and determine the optimal duration of NRT use.

Intensity level in crosstraining sessions in obese women: a real-world study

Objective: The objectives were to measure psychophysiological responses during crosstraining sessions in obese women, focusing on heart rate (HR), blood pressure (BP), caloric expenditure, and perceived effort (RPE). Additionally, it examined the relationship between caloric expenditure and effort intensity. Methods: This real-world observational study involved ten obese women (average age: 31.5 ± 6.2 years, BMI: 34.2 ± 3.7 kg/m², crosstraining experience: 5.3 ± 3.4 months). Participants underwent three individual crosstraining sessions. Each session's training type and duration were recorded. BP was measured before and after, along with HR at rest, average HR, peak HR, and RPE post-workout. Internal load and caloric expenditure were calculated. Results: Among 30 observed sessions, there were no significant differences in training duration by type. Caloric expenditure averaged 272.3 ± 76 kcal. Systolic BP increased significantly (from 129 ± 8 mmHg to 160 ± 16.5 mmHg), as did diastolic BP (from 90.3 ± 6.7 mmHg to 113.6 ± 14.9 mmHg, p &lt; 0.001). Mean HR was 136.9 ± 14.8 bpm (73.6 ± 7.3% of HRmax), and peak HR reached 181.9 ± 12.1 bpm (97.8 ± 6.1% of HRmax). Participants spent more time at or above 80% of predicted HRmax. Mean RPE was 5.7 ± 2.2 a.u., significantly correlating with exercise time above ≥90% of HRmax (r = 0.37; p = 0.046, effect size = 0.39). Conclusions: Crosstraining sessions in obese women raised BP, induced high caloric expenditure, and imposed significant cardiorespiratory demands, classifying these sessions as high-intensity. This intensity closely correlates with energy expenditure. Keywords: Heart Rate; Aortic Pressures; High-Intensity Interval Training; Sport; Obesity; Crosstraining.

Improvement and Maintenance of Clinical Outcomes in a Digital Mental Health Platform: Findings From a Longitudinal Observational Real-World Study.

Digital mental health services are increasingly being provided by employers as health benefit programs that can improve access to and remove barriers to mental health care. Stratified care models, in particular, offer personalized care recommendations that can offer clinically effective interventions while conserving resources. Nonetheless, clinical evaluation is needed to understand their benefits for mental health and their use in a real-world setting. This study aimed to examine the changes in clinical outcomes (ie, depressive and anxiety symptoms and well-being) and to evaluate the use of stratified blended care among members of an employer-sponsored digital mental health benefit. In a large prospective observational study, we examined the changes in depressive symptoms (9-item Patient Health Questionnaire), anxiety symptoms (7-item Generalized Anxiety Disorder scale), and well-being (5-item World Health Organization Well-Being Index) for 3 months in 509 participants (mean age 33.9, SD 8.7 years; women: n=312, 61.3%; men: n=175, 34.4%; nonbinary: n=22, 4.3%) who were newly enrolled and engaged in care with an employer-sponsored digital mental health platform (Modern Health Inc). We also investigated the extent to which participants followed the recommendations provided to them through a stratified blended care model. Participants with elevated baseline symptoms of depression and anxiety exhibited significant symptom improvements, with a 37% score improvement in depression and a 29% score improvement in anxiety (P values <.001). Participants with baseline scores indicative of poorer well-being also improved over the study period (90% score improvement; P=.002). Furthermore, over half exhibited clinical improvement or recovery for depressive symptoms (n=122, 65.2%), anxiety symptoms (n=127, 59.1%), and low well-being (n=82, 64.6%). Among participants with mild or no baseline symptoms, we found high rates of maintenance for low depressive (n=297, 92.2%) and anxiety (n=255, 86.7%) symptoms and high well-being (n=344, 90.1%). In total, two-thirds of the participants (n=343, 67.4%) used their recommended care, 16.9% (n=86) intensified their care beyond their initial recommendation, and 15.7% (n=80) of participants underused care by not engaging with the highest level of care recommended to them. Participants with elevated baseline depressive or anxiety symptoms improved their mental health significantly from baseline to follow-up, and most participants without symptoms or with mild symptoms at baseline maintained their mental health over time. In addition, engagement patterns indicate that the stratified blended care model was efficient in matching individuals with the most effective and least costly care while also allowing them to self-determine their care and use combinations of services that best fit their needs. Overall, the results of this study support the clinical effectiveness of the platform for improving and preserving mental health and support the utility and effectiveness of stratified blended care models to improve access to and use of digitally delivered mental health services.

The impact of intensive blood pressure management in the post-thrombolysis setting: a real-world observational study.

Systolic blood pressure (SBP) >180mmHg following stroke thrombolysis has been associated with increased bleeding and poorer outcome. Aiming for the guideline SBP of <180mmHg often leads to SBP overshoot, as treatment is only triggered if this threshold is passed. We tested whether a lower target would result in fewer high SBP protocol violations. This is a single-centre, sequential comparison of two blood pressure protocols. Between 2013 and 2017, the guideline-based post-thrombolysis SBP target of <180mmHg was compared with a new protocol aiming for 140-160mmHg. The primary outcome was rate of patients with SBPs >180mmHg. Secondary outcomes included rates of SBP <120 mmHg, antihypertensive infusion use, symptomatic intracerebral haemorrhage (sICH) and 3-month functional independence (modified Rankin Score [mRS] 0-2). Results were adjusted for age, baseline function and stroke severity using regression analysis. During the 23 months preceding and 18 months following the transition to the new protocol, 68 and 100 patients were thrombolysed respectively. Baseline characteristics were similar between groups. The odds of one or more SBPs >180mmHg trended lower in the intensive group (adjusted odds ratio [aOR] 0.61; 95% confidence interval [CI] 0.32-1.17; p=0.14). There was a higher rate of SBPs <120mmHg (aOR 3.09; 95% CI 1.49-6.40; p=0.002) in the intensive BP protocol group. sICH rate and 3-month mRS 0-2 were similar between groups. The more intensive post-thrombolysis BP protocol was associated with a significant increase in sub-optimally low BP events, with a non-significant trend toward fewer high BP protocol violations and unaffected patient outcomes.

Factors associated with immune responses to SARS-CoV-2 vaccination in individuals with autoimmune diseases.

Patients with autoimmune diseases are at higher risk for severe infection due to their underlying disease and immunosuppressive treatments. In this real-world observational study of 463 patients with autoimmune diseases, we examined risk factors for poor B and T cell responses to SARS-CoV-2 vaccination. We show a high frequency of inadequate anti-spike IgG responses to vaccination and boosting in the autoimmune population but minimal suppression of T cell responses. Low IgG responses in B cell-depleted patients with multiple sclerosis (MS) were associated with higher CD8 T cell responses. By contrast, patients taking mycophenolate mofetil (MMF) exhibited concordant suppression of B and T cell responses. Treatments with highest risk for low anti-spike IgG response included B cell depletion within the last year, fingolimod, and combination treatment with MMF and belimumab. Our data show that the mRNA-1273 (Moderna) vaccine is the most effective vaccine in the autoimmune population. There was minimal induction of either disease flares or autoantibodies by vaccination and no significant effect of preexisting anti-type I IFN antibodies on either vaccine response or breakthrough infections. The low frequency of breakthrough infections and lack of SARS-CoV-2-related deaths suggest that T cell immunity contributes to protection in autoimmune disease.

Survival outcomes with adjuvant immunotherapy after hepatic resection in patients with intermediate/advanced (BCLC stage B/C) hepatocellular carcinoma: Insights from a propensity-matched multicenter study.

4096 Background: With the growing interest in adjuvant immunotherapy for reducing recurrence and improving prognosis after hepatic resection in hepatocellular carcinoma (HCC), particularly in high-risk patients, this study aims to evaluate the impact of adjuvant immunotherapy on long-term recurrence and survival in patients with intermediate/advanced HCC. Methods: A prospective multicenter database was utilized to identify patients who underwent curative-intent resection for Barcelona Clinic Liver Cancer (BCLC) stage B/C HCC. Propensity score matching (PSM) was employed to equate recurrence-free survival (RFS) and overall survival (OS) between patients receiving adjuvant immune checkpoint inhibitors (ICIs) and those who did not. Multivariate Cox-regression analysis was used to identify independent predictors of RFS and OS. Results: Out of 627 patients, 109 (23.3%) received adjuvant immunotherapy, with most ICI-related adverse reactions being grade I-II. The ICI agents used among these 109 patients were tislelizumab (51.4%, n=56), sintilimab (29.3%, n=32), camrelizumab (9.2%, n=10), pembrolizumab (6.4%, n=7), and toripalimab (3.7%, n=4). All patients receiving adjuvant immunotherapy completed at least 3 months of ICI treatment, with no patients discontinuing the treatment due to irAEs. PSM resulted in 99 matched pairs with comparable baseline characteristics. In this cohort, patients receiving adjuvant immunotherapy showed significantly improved median RFS (29.6 vs. 19.3 months, P=0.031) and OS (35.1 vs. 27.8 months, P=0.036) compared to those who did not. Multivariable analyses confirmed adjuvant immunotherapy as an independent factor for better RFS (HR: 0.630; 95% CI: 0.435-0.914; P=0.015) and OS (HR: 0.601; 95% CI: 0.401-0.898; P=0.013). Subgroup analyses suggested prognostic benefits of adjuvant immunotherapy in both intermediate and advanced-stage HCC. Conclusions: This real-world observational study indicates that adjuvant immunotherapy is associated with improved RFS and OS in patients undergoing curative-intent resection for intermediate/advanced HCC. These findings support the need for future randomized controlled trials to establish definitive evidence for this high-risk population.

Different dosing strategies of pembrolizumab in the treatment of NSCLC: A real-world retrospective observational study.

e23264 Background: Immune checkpoint inhibitors lack a dose-response relationship, allowing optimisation of dosing strategies that may reduce drug use. Pembrolizumab received its initial regulatory approval for the treatment of non-small cell lung cancer (NSCLC) at weight-based dosing (2 mg/kg every 3 weeks (Q3W)), as employed in pivotal clinical trials demonstrating its efficacy and safety. This dosing regimen was later replaced by the currently approved flat-dosing (200 mg Q3W or 400 mg Q6W) in all indications, potentially increasing drug use. This retrospective observational study evaluates differences in pembrolizumab use for different dosing strategies in a real-world patient cohort. Methods: Overall, 124 advanced NSCLC patients, treated with first-line pembrolizumab monotherapy at a single institution, were included. During the observation period, pembrolizumab flat-dosing was employed, with possible extensions of treatment administrations. Patient and treatment data were obtained from medical records. Duration of treatment was calculated from day 1 of first cycle to last day of last cycle, excluding treatment delays due to adverse events. Pembrolizumab use was calculated for 3 dosing strategies: i) as actually received, ii) as flat-dosing, iii) as body-weight dosing, capped at 200 mg Q3W. It is presented as median dose Q3W and cummulative dose in the whole cohort. Results: Included patients had a median weight of 73 kg (IQR: 65-84) and received a total of 1600 mg of pembrolizumab (IQR: 800-3600) over 24 weeks (IQR: 12-60). The median pembrolizumab dose was i) 190 mg Q3W (IQR: 172-200) as actually received by patients, and would be ii) 200 mg Q3W (IQR: 200-200) in case of flat dosing, and iii) 146 mg Q3W (IQR: 130-168) in case of body-weight dosing. Overall, total pembrolizumab dose in the whole cohort was i) 283,600 mg actually used, and would be ii) 327,800 mg in flat-dosing, and iii) 251,200 mg body-weight dosing, resulting in a 23.4% reduction of drug use in weight-adjusted vs flat-based dosing. Conclusions: Pembrolizumab dosing adjusted to body weight, as initially approved, would reduce drug use vs the currently approved flat-dosing, reaching nearly a 25% reduction in our cohort of patients.

Comprehensive Observational and Longitudinal study on the Outbreak of Stroke-related Spasticity focusing on the Early Onset management with Botulinum NeuroToxin (COLOSSEO-BoNT): protocol for a real-world prospective observational study on upper limb spasticity

IntroductionPoststroke spasticity (PSS) affects up to 40% of patients who had a stroke. Botulinum neurotoxin type A (BoNT-A) has been shown to improve spasticity, but the optimal timing of its...