Real-world Study Research Articles

Predictive Factors for Primary and Secondary Nonresponders to Upadacitinib in Patients with Moderate-to-Severe Atopic Dermatitis: A Real-World Study.

Background: Some patients with atopic dermatitis (AD) do not sufficiently respond to upadacitinib, a Janus kinase 1 inhibitor. However, predictive factors for nonresponders remain unclear in real-world practice. Objective: To identify predictive factors for primary and secondary nonresponders to upadacitinib 15 mg; primary nonresponders are defined as patients with investigator's global assessment (IGA) >2 at week 12, while secondary nonresponders are defined as patients with IGA ≤2 at week 12 and IGA >2 at week 24. Methods: A prospective study was conducted from August 2021 to March 2024, involving 204 Japanese AD patients treated with upadacitinib 15 mg. Baseline clinical and laboratory indexes were compared between nonresponders and responders. Results: Primary nonresponders showed higher baseline eczema area and severity index (EASI), immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) compared with responders. Secondary nonresponders had a higher proportion of previous systemic therapies, dupilumab, and corticosteroids. Conclusions: Higher baseline EASI, IgE, TARC, LDH, NLR, CRP, SII, and SIRI may predict primary nonresponders to upadacitinib 15 mg, while previous systemic dupilumab or corticosteroids may predict secondary nonresponders.

Investigating Sodium-Glucose Cotransporter 2 Inhibitors Versus Other Glucose-Lowering Drugs on Ventricular Arrhythmias or Sudden Cardiac Death Using the US FDA Adverse Event Reporting System.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reported to exhibit antiarrhythmic effects. However, there is conflicting evidence regarding the association between SGLT2 inhibitors and ventricular arrhythmias or sudden cardiac death (SCD). We utilized the US FDA Adverse Event Reporting System (FAERS) database to investigate the reporting frequencies of SGLT2 inhibitors with ventricular arrhythmias and SCD compared to other glucose-lowering drugs (ATC-A10B). We used the web data mining tool AERSMine to mine reports of ventricular arrhythmias and SCD from FAERS to compare SGLT2 inhibitors versus other glucose-lowering drugs. The mining range was from 2004q1 to 2023q3. Disproportionality analysis used the proportional reporting ratio (PRR) with 95% confidence interval (CI) and information component (IC) with 95% credible interval. From 2004q1 to 2023q3, a total of 121,129 adverse events were reported for SGLT2 inhibitors, with a total of 1,127,485 in the ATC-A10B group. Ventricular arrhythmias reporting frequency in the SGLT2 inhibitors group was similar to that of the control group (1.36/1000 reports vs 1.55/1000 reports; p = 0.10), with a PRR of 0.88 (95%CI 0.75-1.03). However, the reporting frequency of SCD in the SGLT2 inhibitors group was significantly lower than that of the control group (1.43 vs 4.70/1000; p < 0.001), with a PRR of 0.30 (95%CI 0.26-0.35), and this trend was observed within individual molecules of SGLT2 inhibitors. During the sensitivity analysis process, the results obtained when restricting the scope of data mining to between 2013q1 and 2023q3 were similar to those obtained when using data from 2004q1 to 2023q3. In this drug pharmacovigilance assessment, the reporting frequency of ventricular arrhythmias associated with SGLT2 inhibitors was similar to that of other antidiabetic medications, while the reporting frequency of SCD related to SGLT2 inhibitors was lower. This real-world study evidence complements existing clinical evidence.

Cervical lymph node dissection fails to improve survival in T2N0M0 glottic squamous cell carcinoma: a large-scale real-world study.

This study aimed to evaluate the therapeutic efficacy of cervical lymph node dissection in patients with T2N0M0 glottic squamous cell carcinoma. Among 260,068 head and neck cancer patients, 861 cases of T2N0M0 glottic squamous cell carcinoma were selected, of which 113 underwent selective lymph node dissection, and 748 did not receive dissection. The overall survival rates and disease-specific survival rates were compared between the two groups to assess efficacy. There was no significant difference in overall survival rates (median survival time of 57 months vs. 62 months, p = 0.34) and disease-specific survival rates (p = 0.79) between the two groups. Patients aged ≥ 60 years were at a higher risk, whereas neck dissection, gender, and degree of differentiation did not show significant risk differences in this study. Cervical lymph node dissection in patients with T2N0 glottic squamous cell carcinoma did not demonstrate a significant advantage in survival rates.

Kidney outcomes associated with SGLT2 inhibitors compared to other glucose-lowering drugs: a real-world study from China

ObjectiveThis study aimed to investigate the association between the utilization of Sodium-dependent glucose cotransporters inhibitors (SGLT2i) in real-world settings and kidney outcomes in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) in mainland China.MethodsIn a retrospective analysis of electronic medical records from West China Hospital of Sichuan University, patients with T2D and CKD were included. Patients were divided into two groups, those initiating treatment with SGLT2i and those receiving other glucose-lowering drugs (oGLDs). The primary focus lies in examining the impact of SGLT2i on the decline slope of eGFR and major kidney events in these patients.ResultsWe enrolled 944 patients diagnosed with both T2D and CKD. Out of these, 605 patients were prescribed SGLT2i, while the remaining 339 patients received oGLDs. The median follow-up duration were 16.8 months and 20.6 months, respectively. Throughout the follow-up period, we observed a significant decrease in the rate of eGFR decline in patients using SGLT2i (4.94 mL/min/1.73 m2 per year reduction compared to oGLDs, 95% CI: 4.73–5.15). A total of 101 kidney composite endpoint events occurred, with 31 events in the SGLT2i group and 70 events in the oGLDs group. The use of SGLT2i was associated with a 65% decrease in the risk of kidney composite endpoint events (hazard ratio 0.35, 95% CI 0.19–0.63).ConclusionsIn clinical practice, SGLT2i have shown favorable effects on kidney prognosis in patients with T2D and CKD in mainland China. These effects remain consistent across patients with varying risks of CKD progression.Clinical Trial Registration NumberChiCTR2300068497.

Cluster headache and galcanezumab: the first real-world Brazilian study and an expert consensus on its use among other treatments

ObjectiveTo present the first Brazilian real-world results with galcanezumab and provide a consensus expert opinion on the prophylactic treatment of cluster headache (CH) in Brazil.MethodsThe first part of the study (real-world results) was observational, prospective, uncontrolled, and descriptive. A sample of 44 consecutive patients with episodic or chronic CH were evaluated and treated in a traditional tertiary clinic from March 2020 to June 2024. The second part (consensus expert opinion) consisted of a survey completed by ten Brazilian headache clinicians with at least 25 years of clinical experience, who published at least 15 headache papers and attended at least 15 national or international headache conferences.ResultsForty-four patients (86.4% men, 13.6% women) were included. The average age was 45.9 ± 14.2 years. The diagnosis was made 27.3 ± 13.6 years after the onset of headache bouts. In 84.1% of the patients, CH was classified as episodic. Verapamil, lithium, or verapamil plus lithium were prescribed to respectively, 25%, 9.1%, and 6.8% of patients. Galcanezumab was prescribed to all and the majority (65.9%) used a dose of 300 mg once. There was a reduction in headache frequency of ≥ 50% at 3 weeks in 65.9% of patients for all doses of galcanezumab, and in 72.4% of those using galcanezumab 300 mg. Verapamil was recommended as a first-line treatment by 6 of 10 experts and a second-line treatment by the other 4 experts; galcanezumab was recommended as a first-line treatment by 4 of 10 experts and as a second-line treatment by 3 of 10 experts.ConclusionsThis study presented the first real-world data with galcanezumab in Brazilian patients with CH and showed a reduction in headache frequency in most patients. A survey of Brazilian experts not meant to represent the country’s guidelines, favored galcanezumab as either the first or the second option in prophylaxis. Collectively, these results highlighted galcanezumab’s promising efficacy as a new tool in CH patients.

Respiratory outcomes of onasemnogene abeparvovec treatment for spinal muscular atrophy: national real-world cohort study

Onasemnogene abeparvovec (OA) is a novel gene replacement therapy for patients with spinal muscular atrophy (SMA). This study provides real-world respiratory data for pediatric SMA patients receiving OA who were assessed before and one year after treatment in a multicenter cohort study conducted from 2019 to 2021. Twenty-five OA-treated SMA patients (23 with type 1 and 2 with type 2; median age at treatment 6.1 months, with a range of 0.36–23 months) were included. Sixteen were treatment-naïve, and nine had received various prior treatments. Two patients died due to respiratory failure during the study period. Of the remaining 23 patients, four were put on non-invasive ventilation (NIV), bringing ventilated patients to a total of ten during the post-treatment year. Three patients required permanent NIV support, while 13 did not require any respiratory support. Ventilation time decreased from 14.3 to 11.1 hours per day, and respiratory hospitalizations decreased by 26% (from 0.76 to 0.57 per life year). Fifteen of the 23 patients maintained full oral nutrition at study closure compared to 20 of the 25 at study initiation. This real-world data analysis demonstrates that OA may improve respiratory outcomes in SMA patients. Importantly, compounding factors, such as age at treatment initiation, treatment combinations, and natural history, may influence the respiratory course, thus highlighting the need for standardized long-term management.What is Known:• Respiratory failure is a leading cause of mortality in untreated spinal muscular atrophy type 1 patients.• Onasemnogene abeparvovec (OA) improves neurological outcomes, but real-world respiratory data are limited.What is New:• Our real-world analysis suggests OA may improve respiratory outcomes.• Age at treatment and treatment combinations may also influence respiratory trajectory.

Evidence for therapeutic use of cannabidiol for nail-patella syndrome-induced pain in a real-world pilot study

Nail-patella syndrome (NPS) is a rare genetic disease characterized by dysplastic nails, patella abnormalities, skeletal malformation, and chronic pain. Although chronic pain in NPS is mainly due to bone and musculoskeletal symptoms, it can also result from neurological dysfunction. Conventional analgesics are often insufficient to relieve NPS-associated chronic pain. Cannabinoids, which act on the serotonergic and/or noradrenergic pain systems, may therefore represent valuable non-psychoactive alternatives for managing pain in these patients. The effectiveness and safety of synthetic cannabidiol (CBD) for the management of NPS-associated pain was assessed using real-world data from a pilot cohort of patients with NPS who received a 3-month treatment with oral CBD. The treatment (median dose of 900 mg/day) was associated with a significant reduction in pain intensity (mean score of 7.04 ± 0.24 at initiation versus 4.04 ± 0.38 at 3 months, N = 28, p < 0.0001), which correlated with changes in the peripheral concentration of noradrenaline (r = 0.705, 95% CI [0.44–0.86], p < 0.0001). Health-related quality of life and other NPS-associated symptoms also improved in most patients. CBD treatment was well tolerated and no elevations in liver enzyme levels were reported. Synthetic CBD therefore appears to be a safe and effective treatment option for managing NPS-associated chronic pain.

Research on cross-provincial power trading strategy considering the medium and long-term trading plan

To accommodate China’s electricity market reforms integrating medium and long-term (MLT) transactions and spot transactions, and to boost renewable energy consumption through the spot market, this paper proposes an optimized cross-provincial electricity trading strategy model based on a two-layer game framework. The proposed model incorporates an MLT green certificate contract decomposition method, enabling nested optimization of green certificate contracts and scheduling plans for cross-provincial power transactions. To encourage broader participation, a bilateral green certificate trading framework is established, which globally optimizes green certificate allocation to increase benefits for market participants. A Nash-Stackelberg game model is introduced to address complex game interactions among multiple participants under the green certificate mechanism and the limitation of assuming complete rationality. The game model combines supply and demand sides with an embedded demand-side evolutionary game. Additionally, an improved Aquila optimization algorithm (IAOA) is developed to accurately calculate electricity supply and demand. The algorithm integrates a Circle chaotic map, Sobol sequence, random walk strategy, and filtering technology to enhance optimization capabilities and manage complex constraints. The algorithm is then embedded with a distributed iterative approach to achieve equilibrium strategies. A real-world case study was conducted to validate the feasibility and effectiveness of the proposed model. The results demonstrate that the proposed approach effectively achieves equilibrium, optimizes trading strategies, and fosters win-win, coordinated development among participants in the cross-provincial electricity market.

A real-world study: third-line treatment options for metastatic colorectal cancer

BackgroundNumerous third-line treatment options exist for colorectal cancer. This study aims to assess the efficacy and safety of third-line therapies, including TKIs (fruquintinib, regorafenib) combined with PD-1 inhibitors, and trifluridine/tipiracil combined with bevacizumab, in patients with refractory microsatellite stable metastatic colorectal cancer who have progressed or are intolerant following standard first- and second-line treatments.Materials and methodsThis retrospective analysis collected data from patients with microsatellite stable advanced colorectal adenocarcinoma, diagnosed through histopathology and treated at Henan Provincial Cancer Hospital from May 2019 to April 2023. We compared the efficacy and safety of fruquintinib combined with PD-1 inhibitors, regorafenib combined with PD-1 inhibitors, and trifluridine/tipiracil combined with bevacizumab.ResultsAmong 60 eligible patients with refractory microsatellite stable metastatic colorectal adenocarcinoma, 29 (48.3%) received fruquintinib combined with PD-1 inhibitors, 15 (25%) received regorafenib combined with PD-1 inhibitors, and 16 (26.7%) received trifluridine/tipiracil combined with bevacizumab. The average follow-up period was 12.6 months (ranging from 2.3 to 37.6 months). After third-line treatment, the overall objective response rate (ORR) was 8.6%, and the disease control rate (DCR) was 78.6%. The median overall survival (OS) for the regorafenib, fruquintinib, and trifluridine/tipiracil groups was 19.2 months, 14.0 months, and 16.2 months, respectively, with no statistically significant differences observed. However, there were statistically significant differences in progression-free survival (PFS); the median PFS for the regorafenib group was 6.3 months, for the fruquintinib group was 4.2 months, and for the trifluridine/tipiracil group was 5.4 months. Pairwise comparisons indicated that the PFS for the regorafenib group was similar to that for the trifluridine/tipiracil group, both of which were superior to the fruquintinib group. Cox univariate regression analysis revealed that the presence of liver and peritoneal metastases was associated with PFS in third-line treatment.ConclusionIn the third-line treatment of colorectal cancer, regorafenib combined with PD-1 inhibitors and trifluridine/tipiracil combined with bevacizumab showed superiority over fruquintinib combined with PD-1 inhibitors in terms of PFS, but no statistically significant difference in OS was noted among the three groups.

Clinical characteristics of adult asthma patients hospitalized by COVID-19 in Mexico City: a real-world study

Background The COVID-19 pandemic raised concerns about whether individuals with chronic respiratory diseases, such as asthma, were at higher risk of severe outcomes. Although several studies were published on this topic, not all included asthma as a risk factor. Therefore, describing the clinical characteristics of COVID-19-infected asthma patients in a specialized respiratory center is valuable as a real-life study. Objective To investigate the clinical characteristics and disease severity in SARS-CoV-2-infected adults with pre-existing asthma hospitalized at the National Institute of Respiratory Diseases (INER) in Mexico City. Methods We conducted a retrospective, observational study on adults with confirmed COVID-19 hospitalized from March 2020 to June 2021. Out of 2,249 reviewed medical records, we identified asthmatic patients and compared them with a matched non-asthmatic control group to assess asthma’s impact on COVID-19 severity and outcomes. Results Based on the clinical records, asthma prevalence among hospitalized patients was low (1.51%); of these, 73% had allergic and 27% had non-allergic asthma. COVID-19 severity did not vary significantly between asthma phenotypes, although there was higher mortality among patients with non-allergic asthma. Most patients in both groups developed a severe form of the disease and higher mortality rates than non-asthmatics, though the differences were not statistically significant. Conclusion Asthma prevalence among patients with COVID-19 was low, but mortality was higher in asthma patients. Although the small sample size limits the generalizability of these findings, this study in a Mexican population hospitalized in a reference hospital provides insights for improving asthma management in future pandemics.

The effect of transition timing of regorafenib on treatment outcomes in unresectable hepatocellular carcinoma: a real-world study.

Regorafenib is the recommended second-line therapy for unresectable hepatocellular carcinoma (uHCC). Our study aimed to assess the effect of transition timing to second-line therapy with regorafenib on treatment outcomes in uHCC patients. In this retrospective study, patients were categorized into prompt transition group (PT group) or delayed transition group (DT group) based on the transition timing to second-line therapy with regorafenib following the first or subsequent occurrence of progressive disease during first-line treatment. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. There were 85 and 122 patients in the PT and DT groups, respectively. The PT group demonstrated significantly better median PFS [4.5months (95% CI 3.8-6.0) vs. 3.4months (95% CI 2.8-4.1); HR 0.641; 95% CI 0.478-0.859; p = 0.003], ORR (24.7% vs. 9.8%, p = 0.007), DCR (69.4% vs. 54.9%, p = 0.049), and median OS [17.5months (95% CI 13.4-not reached) vs. 10.4months (95% CI 7.9-15.6); HR 0.613; 92% CI 0.432-0.871, p = 0.006] compared to the DT group. Moreover, the overall safety profiles were comparable between groups. The prompt transition to second-line therapy with regorafenib following first-line treatment progression suggests better treatment outcomes and potentially longer survival than in patients who delay the transition to second-line therapy.

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.

Blood-based tumor mutational burden impacts clinical outcomes of immune checkpoint inhibitor treated breast and prostate cancers

BackgroundBreast and prostate tumors are known to be less responsive to immune checkpoint inhibitors (ICIs). Tissue-based tumor mutation burden (tTMB) has emerged as a predictive biomarker of response to ICIs, including in these “cold tumors”. In clinical practice, when tTMB is not available, blood-based TMB score (bTMB) can be used to consider treatment with ICIs.MethodsThis retrospective, real-world study included a final cohort of metastatic breast and prostate cancer patients treated with an ICI following a liquid biopsy test. Multiple bTMB-High cut-offs were assessed. Clinical, genomic, and outcomes data were collected. We hypothesized that a cut-off of bTMB ≥10 mut/Mb is not a strong predictor of response to ICIs in this setting. The Guardant Health genomic database (GHGD) was then queried (N = 13,992) for associations of bTMB with genomic alterations.ResultsIn the clinical cohort (N = 48), ICI treatment is offered after a median of 3 (1–9) lines of treatment. The median bTMB is 16.4 (10–186) mut/Mb. The median time on ICI and PFS is 2.1 (0–1.7) and 3.1 months (95%CI, 1.6–4.6) respectively; no difference by MSI/MMR status (p = 0.152). Response rate among eligible patients (n = 36) is 16.7%; only N = 1/6 in bTMB <16 mut/Mb. High bMSI is associated with higher bTMB (correlation test, r = 0.66, p = 0.000). In the GHGD, patients with bTMB high have significantly more alterations than bTMB low and TP53, PIK3CA, ATM, ESR1, NF1, BRCA2, ARID1A, and APC were the most frequently altered genes.ConclusionsIn this study, the practice of offering an ICIs based on bTMB was uncommon and did not independently predict ICI benefits in patients with refractory, advanced breast and prostate cancers.

Initial experience with brolucizumab for neovascular age-related macular degeneration (nAMD) in India - Multicentric, real-world study.

To evaluate the anatomic and visual outcomes and safety profile of initial Indian eyes with neovascular age-related macular degeneration (nAMD) treated with intravitreal injection (IVI) of brolucizumab. This retrospective multicentric, real-world study enrolled consecutive eyes with nAMD that were treated with IVI brolucizumab after it was launched in India in October 2020. Data collected for each eye included best-corrected visual acuity (BCVA), central subfield thickness (CSFT), subretinal fluid (SRF), and intraretinal fluid (IRF) status at 6, 12, and 24 months follow-up. Also recorded were the lens status, treatment protocol, number of injections received before enrollment (in switch-over cases), total number of injections, and adverse effects noticed during the study period. Primary outcomes were change in BCVA, CSFT at follow-up visits, and incidence of intraocular inflammation (IOI). Secondary outcomes were profile of macular neovascularization, treatment protocols, mean number of injections, and maximum injection-free interval observed in eyes treated by pro-re-nata (PRN) protocol. In total, 331 eyes received a mean of 3.55 ± 1.83 injections. Most frequent treatment protocol was PRN (53%). BCVA data was available for 100%, 96%, and 74% eyes at 6, 12, and 24 months follow-up. BCVA and CSFT improved significantly (P < 0.001) at all follow-ups. Two hundred and seventy-six (83.38%) out of 331 eyes received more than one injection; out of these, 241 (87.3%) eyes that were treated by PRN protocol could achieve mean "maximum injection-free interval" of 19.43 ± 8.82 weeks. IOI and retinal vasculitis were reported in 2.11% (7/331) and 0.60% (2/331) eyes, respectively. None of the eyes with IOI or vasculitis lost any vision at the final follow-up. This study demonstrated favorable visual and anatomic outcomes and safety profile for eyes with nAMD treated by IVI brolucizumab. Mean maximum injection-free interval in eyes treated with PRN was 19 weeks.

Effect of alemtuzumab on fatigue, quality of life, and patient/caregiver-reported outcomes in relapsing-remitting multiple sclerosis – a real-world evidence study

BackgroundAlemtuzumab is approved in the European Union for treating highly active relapsing-remitting multiple sclerosis (RRMS). Patient-reported outcomes measure the treatment impact on quality of life (QoL), including fatigue, a common symptom in multiple sclerosis (MS). Chronic diseases like MS also affect the patient's caregiver. Thus, understanding the impact on both patients and caregivers is essential for a comprehensive view of MS treatment outcomes. MethodsThis multi-center prospective, observational study assessed RRMS patients undergoing alemtuzumab treatment, and their caregivers across three European countries (Denmark, Norway, and Italy). The study visits were conducted at baseline, and at Months 3, 6, 12, 18, 24, and 36 (± 1 month). The primary endpoint assessed the effect of alemtuzumab on MS-related fatigue (Fatigue Scale for Motor and Cognitive Functions [FSMC] score). Secondary endpoints included changes in cognition (Symbol Digit Modalities Test [SDMT]), depression (Beck Depression Inventory-Version II [BDI-II]), QoL (29-item Multiple Sclerosis Impact Scale [MSIS-29]), treatment satisfaction (Treatment Satisfaction Questionnaire for Medication [TSQM]), working capacity/daily life activity (Health-Related Productivity Questionnaire [HRPQ]), and clinical evaluation (number of relapses, improvement in Expanded Disability Status Scale [EDSS] score, and need for re-treatment with alemtuzumab/any other treatment). Exploratory endpoints included caregiver perception of patient's QoL, caregiver QoL, and caregiver burden. The sample size (N=80) was determined based on the 2-sided t-test at 5% significance level. Data were analyzed descriptively. Safety was also evaluated. ResultsOf 87 enrolled patients, 72.4% (n=63) completed all follow-ups. Significant improvement was observed in fatigue (p<0.01), with a median (min, max) FSMC score change of -7.3 (-56.0, 34.0) units at the end-of-study (EOS), and clinically relevant improvement (≥ 9 units) noted in approximately 12.5 months. SDMT (3-5 units, p<0.05), BDI-II (median score of 9.5, i.e., no depression, p<0.01), and MSIS-29 (median change in physical and psychological impact scores -9.2, p<0.01 and -14.8, p<0.001, respectively) improved significantly from baseline to EOS. Global treatment satisfaction (p<0.001), effectiveness (p<0.05), and side effects (p<0.05) significant improved exept at EOS, whereas treatment convenience remained same throughout the study. The percentage of patients with at least one relapse was similar each year of the study (10.8%-13.2%). A statistically significant improvement (p<0.05) in EDSS was reported over time. At EOS, 4.5% patients needed retreatment with alemtuzumab. Caregivers also reported improvement in patients’ QoL over time, but the median change from baseline (physical and psychological impact scores: -10.0 and -14.8, respectively) was not statistically significant (p>0.05). Caregivers reported similar QoL and caregiver burden at baseline and EOS, apart from an increase in emotional QoL. Headache (51.2%), pyrexia (44.2%), and rash (34.9%) were the most common adverse events (AEs). Majority of the AEs were either mild or moderate, apart from 25 severe AEs. Three patients discontinued prematurely, of which one patient died of sepsis related to treatment. ConclusionThis real-world study showed beneficial impact of alemtuzumab on fatigue, cognition, depression, QoL, and treatment satisfaction. Improvement in patient disability, and caregiver-reported outcomes indicated enhanced patients’ QoL.

Real-life study on the effectiveness and safety of sofosbuvir/velpatasvir-based antiviral agents for HCV eradication in Chinese patients

BackgroundHepatitis C virus (HCV) eradication with Sofosbuvir/velpatasvir (SOF/VEL) represents a significant advancement, offering hope for eliminating the virus in diverse patient populations. But real-world data on its effectiveness and safety remains scarce for patients with chronic hepatitis C (CHC) in China, especially those with HCV GT3b, cirrhosis, HCC, or HCV/HBV, HCV/HIV, or HCV/HBV/HIV coinfection. MethodsIn this real-world prospective observational study, we recruited patients from West China Hospital and Public Health Clinical Center of Chengdu in China. Patients included adults chronically infected with any HCV genotype, either with or without cirrhosis, HCC, HCV/HBV, HCV/HIV, or HCV/HBV/HIV coinfection. Patients were administered with SOF/VEL (400/100 mg) ± ribavirin (RBV) once daily for 12 weeks. The primary effectiveness endpoint was sustained virological response at post-treatment Week 12 (SVR12). Adverse events (AEs) were evaluated during treatment. ResultsThe study included 483 patients, with HCV genotypes 1, 2, 3, 6 and uncertain. Among them, 35.4% (171/483, ITT) and 36.7% (166/452, mITT) received SOF/VEL + RBV. At EOT, 99.2% (ITT, 479/483) and 99.1% (mITT, 448/452) of patients had undetectable HCV RNA. The SVR12 rates were 92.8% (ITT, 448/483) and 99.1% (mITT, 448/452). In mITT analysis, the SVR12 for patients infected with HCV GT3b, patients with cirrhosis or HCC, and patients coinfected with HBV/HIV was 99.2% (130/131), 99.4% (168/169), and 97.6% (40/41), respectively. ALBI (-3.01 vs. -3.18 P<0.001), FIB4 (2.53 vs. 1.88, P=0.004) and APRI (0.99 vs. 0.44, P<0.001) showed a significant decrease from baseline to SVR12. None of the involved patients experienced grade 3-5 AEs. ConclusionsAlthough included a high proportion of patients with HCV GT3b, cirrhosis, HCC, or HCV/HBV, HCV/HIV, or HCV/HBV/HIV coinfection, SOF/VEL ± RBV was highly effective and well tolerated in patients with CHC in China.

The status of blood glucose monitoring and its influencing factors in Chinese patients with type 2 diabetes initiating premixed insulin: A prospective real-world study

ObjectiveThis study aimed to assess the current state of self-monitoring of blood glucose (SMBG) in Chinese patients initiating premixed insulin and its influential factors. Research Design and MethodsThis is a single-arm, multi-center, prospective real-world study enrolling a total of 8214 adult patients with type 2 diabetes mellitus (T2DM) newly initiated premixed insulin analogues. Each patient was followed up for 12 weeks, and the data related to SMBG was collected at week 1, week 4, week 8 and week 12, while data related to glycated hemoglobin were collected at week 1 and week 12. The primary outcome was the frequency of SMBG over 12 weeks. ResultsAt week 12, 83.3 % monitored blood glucose at least once, while 20.3 % of participants continued SMBG every week. The average monitoring frequency was 4.78 times/week over the first 4 weeks and 3.33 times/week over 12 weeks. The patients with a higher frequency of SMBG had better control of blood glucose. ConclusionsThis study found that most T2DM patients would take SMBG but the adherence decreased over time. The adherence to SMBG in Chinese T2DM patients was influenced by age, insulin dosage, education level, and diabetes duration. SMBG benefited the improvement of glycemic control.

A multisite observational real-world study on the effectiveness of repetitive transcranial magnetic stimulation therapy for patients with treatment-resistant depression in Japan

The objective of this study was to reveal the effectiveness of repetitive transcranial magnetic stimulation (rTMS) for Japanese patients with treatment-resistant depression (TRD) in clinical practice, based on real-world data from a nationwide multicenter observational study in Japan.Clinical data of patients with TRD treated with rTMS (NeuroStar TMS treatment system) under public insurance coverage were retrospectively collected from 21 institutes nationwide between June, 2019 and December, 2023. Depression severity was assessed by the 17-item Hamilton Depression Rating Scale (HAMD-17). Response and remission were defined as ≥50% reduction from baseline and ≤7 points on the HAMD-17, respectively. The primary outcome was the changes in the HAMD-17 score from baseline to the endpoint following rTMS. Data from 497 patients with TRD were candidates for this study. The HAMD-17 scores (mean (SD)) improved significantly from 18.9 (5.3) to 9.7 (6.6), respectively. The response and remission rates at the end of rTMS therapy as assessed by the HAMD-17 were 53.5% and 42.8%, respectively. The dropout rate due to adverse effects was 4.2%, and the treatment was generally well tolerated. No convulsive seizures or manic changes were observed. These results indicate that conventional rTMS is effective and safe in Japanese patients with TRD.

An Indian multicentre real-world study on long-term quality of life outcomes following bariatric surgery.

The purpose of this study was to assess the impact of metabolic and bariatric surgery (MBS) on Quality of Life (QoL) in Indian patients with obesity over 10 years. A retrospective chart review was conducted at 11 centres for individuals with MBS between February 2013 and May 2022. Patient medical records provided the source of de-identified data. Data from 2132 individuals with a mean age of 43.28 ± 11.96 years was analysed. There were 37.43% men and 62.57% females in the study population. The study population had a mean preoperative body mass index (BMI) of 45.71 ± 10.38 kg/m2. The Bariatric Analysis and Reporting Outcome System (BAROS) scoring method showed a higher overall QoL score throughout all follow-up periods, with 'very good' outcomes at one, three and 7 years and 'good' outcomes at 5 and 10 years. Improvements in QoL were associated with a substantial improvement (p < .01) in BMI at every follow-up time point. Following MBS, individuals with obesity exhibited a substantial and long-term improvement in their overall QoL for up to 10 years. This study presents Indian data on QoL, which is considered one of the most important decision-making factors for or against an intervention.

Salvage Therapy with Second-Generation Inhibitors for FLT3 Mutated Acute Myeloid Leukemia: A Real-World Study by the CETLAM and PETHEMA Groups

Background/Objectives: Patients with relapsed/refractory (R/R) AML with FLT3 mutation (FLT3mut) have a dismal prognosis. FLT3mut offers a target for therapy in these patients. Gilteritinib (gilter) and quizartinib (quizar) have demonstrated efficacy as single agents in two phase 3 clinical trials. Methods: We retrospectively analyzed the characteristics, treatments, and outcomes of 50 patients with R/R FLT3mut AML who received gilter or quizar as monotherapy in 27 Spanish centers before their commercial availability. Forty-four patients were treated with gilter and six with quizar. Results: The median age was 62.5 years, and 52% were women. Most patients presented with FLT3-ITD mutations (80%); 46% had refractory disease and 54% had relapsed disease at treatment initiation. First-line treatment was chemotherapy in 80% of patients, with 40% of these also receiving midostaurin. Twenty-five patients (50%) had previously received FLT3 inhibitor, and twenty-eight (56%) had received more than one line treatment before starting gilter/quizar. The rates of complete remission (CR), CR without hematological recovery (CRi), and partial remission were 22%, 18%, and 16%, respectively. The median overall survival (OS) and disease-free survival were 4.74 months and 2.99 months, respectively. We observed a significant improvement in OS in patients who had received only one prior line of therapy compared to those who had received two or more therapies (10.77 months vs. 4.24 months, p = 0.016). Multivariate analysis identified failure to achieve CR/CRi, receiving more than one prior line of therapy, age, and white blood cells count as independent prognostic factors for OS. The most common toxicities were febrile neutropenia, liver function abnormalities, and QT interval prolongation. Conclusions: Gilter/quizar monotherapy are effective and tolerable options for patients with R/R FLT3mut AML in a real-world setting. Response and toxicity rates are similar to those reported in the phase 3 trials, despite the more heterogeneous nature of the study population.