Analysis Of Individual Patient Data Research Articles

LB-11 | Revascularization Strategies in Patients with Peripheral Arterial Disease Involving the Femoropopliteal Arteries: A Pooled Analysis of Individual Patient Data

LB-11 | Revascularization Strategies in Patients with Peripheral Arterial Disease Involving the Femoropopliteal Arteries: A Pooled Analysis of Individual Patient Data

Prognostic Value of Microvascular Resistance Reserve After Percutaneous Coronary Intervention in Patients With Myocardial Infarction.

The microvascular resistance reserve (MRR) has recently been introduced as a novel index to assess the vasodilatory capacity of the microcirculation, independent of epicardial disease. The prognostic value of MRR in ST-segment elevation myocardial infarction (STEMI) is unknown. The aim of this analysis was to investigate the prognostic value of MRR in patients with STEMI and to compare MRR with cardiovascular magnetic resonance imaging parameters. From a pooled analysis of individual patient data from 6 cohorts that measured the index of microcirculatory resistance (IMR) directly after primary percutaneous coronary intervention in patients with STEMI (n=1,265), a subgroup analysis was performed in patients in whom both MRR and IMR were available. The primary endpoint was the composite of all-cause mortality or hospitalization for heart failure. Both MRR and IMR could be calculated in 446 patients. The optimal cutoff of MRR to predict the primary endpoint in this STEMI population was 1.25. During a median follow-up of 3.1 years (Q1-Q3: 1.5-6.1 years), the composite of all-cause mortality or hospitalization for heart failure occurred in 27.3% and 5.9% of patients (HR: 4.16; 95%CI: 2.31-7.50; P< 0.001) in the low MRR (≤1.25) and high MRR (>1.25) groups, respectively. Both IMR and MRR were independent predictors of the composite of all-cause mortality or hospitalization for heart failure. MRR measured directly after primary percutaneous coronary intervention was an independent predictor of the composite of all-cause mortality or hospitalization for heart failure during long-term follow-up.

Statin Therapy for Secondary Prevention in Ischemic Stroke Patients With Cerebral Microbleeds.

The association between statin use and the risk of intracranial hemorrhage (ICrH) following ischemic stroke (IS) or transient ischemic attack (TIA) in patients with cerebral microbleeds (CMBs) remains uncertain. This study investigated the risk of recurrent IS and ICrH in patients receiving statins based on the presence of CMBs. We conducted a pooled analysis of individual patient data from the Microbleeds International Collaborative Network, comprising 32 hospital-based prospective studies fulfilling the following criteria: adult patients with IS or TIA, availability of appropriate baseline MRI for CMB quantification and distribution, registration of statin use after the index stroke, and collection of stroke event data during a follow-up period of ≥3 months. The primary endpoint was the occurrence of recurrent symptomatic stroke (IS or ICrH), while secondary endpoints included IS alone or ICrH alone. We calculated incidence rates and performed Cox regression analyses adjusting for age, sex, hypertension, atrial fibrillation, previous stroke, and use of antiplatelet or anticoagulant drugs to explore the association between statin use and stroke events during follow-up in patients with CMBs. In total, 16,373 patients were included (mean age 70.5 ± 12.8 years; 42.5% female). Among them, 10,812 received statins at discharge, and 4,668 had 1 or more CMBs. The median follow-up duration was 1.34 years (interquartile range: 0.32-2.44). In patients with CMBs, statin users were compared with nonusers. Compared with nonusers, statin therapy was associated with a reduced risk of any stroke (incidence rate [IR] 53 vs 79 per 1,000 patient-years, adjusted hazard ratio [aHR] 0.68 [95% CI 0.56-0.84]), a reduced risk of IS (IR 39 vs 65 per 1,000 patient-years, aHR 0.65 [95% CI 0.51-0.82]), and no association with the risk of ICrH (IR 11 vs 16 per 1,000 patient-years, aHR 0.73 [95% CI 0.46-1.15]). The results in aHR remained consistent when considering anatomical distribution and high burden (≥5) of CMBs. These observational data suggest that secondary stroke prevention with statins in patients with IS or TIA and CMBs is associated with a lower risk of any stroke or IS without an increased risk of ICrH. This study provides Class III evidence that for patients with IS or TIA and CMBs, statins lower the risk of any stroke or IS without increasing the risk of ICrH.

Anti-EGFR Rechallenge in Patients With Refractory ctDNA RAS/BRAF wt Metastatic Colorectal Cancer

The available evidence regarding anti-epidermal growth factor receptor (EGFR) inhibitor rechallenge in patients with refractory circulating tumor DNA (ctDNA) RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) is derived from small retrospective and prospective studies. To evaluate the efficacy of anti-EGFR rechallenge in patients with refractory ctDNA RAS/BRAF wt mCRC. This nonrandomized controlled trial used a pooled analysis of individual patient data from patients with RAS/BRAF wt ctDNA mCRC enrolled in 4 Italian trials (CAVE, VELO, CRICKET, and CHRONOS) and treated with anti-EGFR rechallenge between 2015 and 2022 (median [IQR] follow-up, 28.1 [25.8-35.0] months). Patients received anti-EGFR rechallenge therapy, including cetuximab plus avelumab, trifluridine-tipiracil plus panitumumab, irinotecan plus cetuximab, or panitumumab monotherapy. Overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and disease control rate (DCR) were calculated. Exploratory subgroup analysis evaluating several clinical variables was performed. Safety was reported. Overall, 114 patients with RAS/BRAF wt ctDNA mCRC (median [IQR] age, 61 [29-88] years; 66 men [57.9%]) who received anti-EGFR rechallenge as experimental therapy (48 received cetuximab plus avelumab, 26 received trifluridine-tipiracil plus panitumumab, 13 received irinotecan plus cetuximab, and 27 received panitumumab monotherapy) were included in the current analysis. Eighty-three patients (72.8%) had received 2 previous lines of therapy, and 31 patients (27.2%) had received 3 or more previous lines of therapy. The ORR was 17.5% (20 patients), and the DCR was 72.3% (82 patients). The median PFS was 4.0 months (95% CI, 3.2-4.7 months), and the median OS was 13.1 months (95% CI, 9.5-16.7 months). The subgroup of patients without liver involvement had better clinical outcomes. The median PFS was 5.7 months (95% CI, 4.8-6.7 months) in patients without liver metastasis compared with 3.6 months (95% CI, 3.3-3.9 months) in patients with liver metastasis (hazard ratio, 0.56; 95% CI, 0.37-0.83; P = .004). The median OS was 17.7 months (95% CI, 13-22.4 months) in patients without liver metastasis compared with 11.5 months (95% CI, 9.3-13.9 months) in patients with liver metastasis (hazard ratio, 0.63; 95% CI, 0.41-0.97; P = .04). Treatments showed manageable toxic effects. These findings suggest that anti-EGFR rechallenge therapy has promising antitumor activity in patients with refractory ctDNA RAS/BRAF wt mCRC. Within the limitation of a subgroup analysis, the absence of liver metastases was associated with significant improved survival. ClinicalTrials.gov Identifiers: NCT02296203; NCT04561336; NCT03227926; NCT05468892.

Неоадъювантная терапия резектабельной меланомы кожи в России: опыт трех онкологических центров

Introduction. Neoadjuvant therapy of skin melanoma is a relatively new and dynamically developing area in the treatment of this malignant tumor. This article represents the results of an analysis of the clinical outcomes of patients receiving neoadjuvant systemic immunotherapy (NST) in 3 research centers in Russia. Material and methods. A combined analysis of the blinded individual patient data was performed in January 2024. The criteria for including data in the analysis were the availability of information about the disease and its prevalence, the course of NST, the pathomorphological response and treatment outcomes. Results. Data were obtained from three research centers on 77 patients who started receiving therapy in the period from Oct. 2020 to Jul. 2023. NST with prolgolimab was performed in 59 (76.6%) pts, pembrolizumab in 13 (16.9%) pts and ipilimumab 3 mg/kg + nivolumab 1 mg/kg in 5 (6.5%) pts. The average number of cycles was 3.6 (95%CI 3.2–4.0), the average duration of HCT was 45.5 days (95% CI 39.3–51.6). The pathomorphological response to treatment in accordance with INMC criteria was assessed in 61 patients: 25 (41.0%) had a complete response, 6 (9.8%) had an almost complete response, 7 (11.5%) had a partial response and 23 (37.7%) had no response or disease progression. With a median follow-up period of 10.2 months (95% CI from 7.1 to 13.2 months) median relapse-free survival in patients with complete, near-to- complete and partial pathomorphological response to treatment was not achieved, while in the group of non-responders was 14.4 months (95% CI 4.3 to 24.6 months), p = 0.014. Subsequent adjuvant therapy was performed in 46 (59.7%) patients, while adjuvant therapy had a statistically significant effect on survival only in patients with non-response. Conclusions. The results of our study confirm the significant potential of NST in the treatment of resectable stage IIIB-D skin melanoma. Prospective well-organized studies are required to address the issue of de-escalation of surgery and adjuvant therapy.

Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials

In the STEP-HFpEF (NCT04788511) and STEP-HFpEF DM (NCT04916470) trials, the GLP-1 receptor agonist semaglutide improved symptoms, physical limitations, bodyweight, and exercise function in people with obesity-related heart failure with preserved ejection fraction. In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, we aimed to provide a more definitive assessment of the effects of semaglutide across a range of outcomes and to test whether these effects were consistent across key patient subgroups. We conducted a prespecified pooled analysis of individual patient data from STEP-HFpEF and STEP-HFpEF DM, randomised, double-blind, placebo-controlled trials at 129 clinical research sites in 18 countries. In both trials, eligible participants were aged 18 years or older, had heart failure with a left ventricular ejection fraction of at least 45%, a BMI of at least 30 kg/m2, New York Heart Association class II-IV symptoms, and a Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS; a measure of heart failure-related symptoms and physical limitations) of less than 90 points. In STEP-HFpEF, people with diabetes or glycated haemoglobin A1c concentrations of at least 6·5% were excluded, whereas for inclusion in STEP-HFpEF DM participants had to have been diagnosed with type 2 diabetes at least 90 days before screening and to have an HbA1c of 10% or lower. In both trials, participants were randomly assigned to either 2·4 mg semaglutide once weekly or matched placebo for 52 weeks. The dual primary endpoints were change from baseline to week 52 in KCCQ-CSS and bodyweight in all randomly assigned participants. Confirmatory secondary endpoints included change from baseline to week 52 in 6-min walk distance, a hierarchical composite endpoint (all-cause death, heart failure events, and differences in changes in KCCQ-CSS and 6-min walk distance); and C-reactive protein (CRP) concentrations. Heterogeneity in treatment effects was assessed across subgroups of interest. We assessed safety in all participants who received at least one dose of study drug. Between March 19, 2021 and March 9, 2022, 529 people were randomly assigned in STEP-HFpEF, and between June 27, 2021 and Sept 2, 2022, 616 were randomly assigned in STEP-HFpEF DM. Overall, 1145 were included in our pooled analysis, 573 in the semaglutide group and 572 in the placebo group. Improvements in KCCQ-CSS and reductions in bodyweight between baseline and week 52 were significantly greater in the semaglutide group than in the placebo group (mean between-group difference for the change from baseline to week 52 in KCCQ-CSS 7·5 points [95% CI 5·3 to 9·8]; p<0·0001; mean between-group difference in bodyweight at week 52 -8·4% [-9·2 to -7·5]; p<0·0001). For the confirmatory secondary endpoints, 6-min walk distance (mean between-group difference at week 52 17·1 metres [9·2 to 25·0]) and the hierarchical composite endpoint (win ratio 1·65 [1·42 to 1·91]) were significantly improved, and CRP concentrations (treatment ratio 0·64 [0·56 to 0·72]) were significantly reduced, in the semaglutide group compared with the placebo group (p<0·0001 for all comparisons). For the dual primary endpoints, the efficacy of semaglutide was largely consistent across multiple subgroups, including those defined by age, race, sex, BMI, systolic blood pressure, baseline CRP, and left ventricular ejection fraction. 161 serious adverse events were reported in the semaglutide group compared with 301 in the placebo group. In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, semaglutide was superior to placebo in improving heart failure-related symptoms and physical limitations, and reducing bodyweight in participants with obesity-related heart failure with preserved ejection fraction. These effects were largely consistent across patient demographic and clinical characteristics. Semaglutide was well tolerated. Novo Nordisk.

Intermediate clinical endpoints in early-stage breast cancer: an analysis of individual patient data from the Gruppo Italiano Mammella and Mammella Intergruppo trials

Intermediate clinical endpoints (ICEs) are frequently used as primary endpoint in randomised trials (RCTs). We aim to assess whether changes in different ICEs can be used to predict changes in overall survival (OS) in adjuvant breast cancer trials. Individual patient level data from adjuvant phase III RCTs conducted by the Gruppo Italiano Mammella (GIM) and Mammella Intergruppo (MIG) study groups were used. ICEs were computed according to STEEP criteria. Using a two-stage meta-analytic model, we assessed the surrogacy of each ICE at both the outcome (i.e., OS and ICE are correlated irrespective of treatment) and trial (i.e., treatment effects on ICE and treatment effect on OS are correlated) levels. The following ICEs were considered as potential surrogate endpoints of OS: disease-free survival (DFS), distant disease-free survival (DDFS), distant relapse-free survival (DRFS), recurrence-free survival (RFS), recurrence-free interval (RFI), distant recurrence-free interval (DRFI), breast cancer-free interval (BCFI), and invasive breast cancer-free survival (IBCFS). The estimates of the degree of correlation were obtained by copula models and weighted linear regression. Kendall's τ and R2≥0.70 were considered as indicators of a clinically relevant surrogacy. Among the 12,397 patients enrolled from November 1992 to July 2012 in six RCTs, median age at enrolment was 57 years (interquartile range (IQR) 49-65). After a median follow-up of 10.3 years (IQR 6.4-14.5), 2131 (17.2%) OS events were observed, with 1390 (65.2%) attributed to breast cancer. At the outcome-level, Kendall's τ ranged from 0.69 for BCFI to 0.84 for DRFS. For DFS, DDFS, DRFS, RFS, RFI, DRFI, BCFI, and IBCFS endpoints, over 95% of the 8-year OS variability was attributable to the variation of the 5-year ICE. At the trial-level, treatment effects for the different ICEs and OS were strongly correlated, with the highest correlation for RFS and DRFS and the lowest for BCFI. Our results provide evidence supporting the use of DFS, DDFS, DRFS, RFS, RFI, DRFI, and IBCFS as primary endpoint in breast cancer adjuvant trials. This analysis was supported by the Italian Association for Cancer Research ("Associazione Italiana per la Ricerca sul Cancro", AIRC; IG 2017/20760) and by Italian Ministry of Health-5×1000 funds (years 2021-2022).

Prognostic Impact of Prostate-Specific Antigen at 6 Months After Radiotherapy in Localized Prostate Cancer: An Individual Patient Data Analysis of Randomized Trials.

We sought to evaluate the prognostic impact of prostate-specific antigen (PSA) at 6 months after completion of radiotherapy (RT) in patients treated with RT alone, RT plus short-term (st; 3-6 months), and RT plus long-term (lt; 24-36 months) androgen-deprivation therapy (ADT). Individual patient data were obtained from 16 randomized trials evaluating RT ± ADT for localized prostate cancer (PCa) between 1987 and 2011. The lowest PSA recorded within 6 months after RT completion was identified and categorized as < or ≥0.1 ng/mL. The primary outcomes were metastasis-free survival (MFS), PCa-specific mortality (PCSM), and overall survival (OS), from 12 months after random assignment. Ninety-eight percent (n = 2,339/2,376) of patients allocated to RT alone, 84% (n = 4,756/5,658) allocated to RT + stADT, and 77% (n = 1,258/1,626) allocated to RT + ltADT had PSA ≥0.1 ng/mL within 6 months after completing RT. PSA ≥0.1 ng/mL was associated with lower MFS and OS and higher PCSM among patients allocated to RT ± ADT (RT - MFS: hazard ratio [HR], 2.24 [95% CI, 1.21 to 4.16]; PCSM: subdistribution hazard ratio [sHR], 1.82 [0.51 to 6.49]; OS: HR, 1.72 [0.97 to 3.05]; RT + stADT - MFS: HR, 1.27 [1.12 to 1.44]; PCSM: sHR, 2.10 [1.52 to 2.92]; OS: HR, 1.26 [1.11 to 1.44]; RT + ltADT - MFS: HR, 1.58 [1.27 to 1.96]; PCSM: sHR, 1.97 [1.11 to 3.49]; OS: HR, 1.59 [1.27 to 1.99]). Five-year MFS rates among patients allocated to RT, RT + stADT, and RT + ltADT were 91% versus 79%, 83% versus 76%, and 87% versus 74%, respectively, based on PSA < or ≥0.1 ng/mL. PSA ≥0.1 ng/mL within 6 months after RT completion was prognostic for lt outcomes in patients treated with RT ± ADT for localized PCa. This can be used to counsel patients treated with RT ± ADT and in guiding clinical trial design evaluating novel systemic therapies with RT + ADT as well as (de)intensification strategies.

Andexanet alfa versus non-specific treatments for intracerebral hemorrhage in patients taking factor Xa inhibitors - Individual patient data analysis of ANNEXA-4 and TICH-NOAC.

Data comparing the specific reversal agent andexanet alfa with non-specific treatments in patients with non-traumatic intracerebral hemorrhage (ICH) associated with factor-Xa inhibitor (FXaI) use are scarce. The study aimed to determine the association between the use of andexanet alfa compared with non-specific treatments with the rate of hematoma expansion and thromboembolic complications in patients with FXaI-associated ICH. We performed an individual patient data analysis combining two independent, prospective studies: ANNEXA-4 (180 patients receiving andexanet alfa, NCT02329327) and TICH-NOAC (63 patients receiving tranexamic acid or placebo ± prothrombin complex concentrate, NCT02866838). The primary efficacy outcome was hematoma expansion on follow-up imaging. The primary safety outcome was any thromboembolic complication (ischemic stroke, myocardial infarction, pulmonary embolism, or deep vein thrombosis) at 30 days. We used binary logistic regression models adjusted for baseline hematoma volume, age, calibrated anti-Xa activity, times from last intake of FXaI, and symptom onset to treatment, respectively. Among 243 participants included, the median age was 80 (IQR 75-84) years, baseline hematoma volume was 9.1 (IQR 3.4-21) mL and anti-Xa activity 118 (IQR 78-222) ng/mL. Times from last FXaI intake and symptom onset to treatment were 11 (IQR 7-16) and 4.7 (IQR 3.0-7.6) h, respectively. Overall, 50 patients (22%) experienced hematoma expansion (ANNEXA-4: n=24 (14%); TICH-NOAC: n=26 (41%)). After adjusting for pre-specified confounders (baseline hematoma volume, age, calibrated anti-Xa activity, times from last intake of FXaI, and symptom onset to treatment, respectively), treatment with andexanet alfa was independently associated with decreased odds for hematoma expansion (aOR 0.33, 95% CI 0.13-0.80, p = 0.015). Overall, 26 patients (11%) had any thromboembolic complication within 30 days (ANNEXA-4: n=20 (11%); TICH-NOAC: n=6 (10%)). There was no association between any thromboembolic complication and treatment with andexanet alfa (aOR 0.70, 95% CI 0.16-3.12, p = 0.641). The use of andexanet alfa compared to any other non-specific treatment strategy was associated with decreased odds for hematoma expansion, without increased odds for thromboembolic complications.

3 Young Investigator Awardee - Intermediate clinical endpoints in early-stage breast cancer: an analysis of individual patient data from the Gruppo Italiano Mammella (GIM) and Mammella Intergruppo trials (MIG)

3 Young Investigator Awardee - Intermediate clinical endpoints in early-stage breast cancer: an analysis of individual patient data from the Gruppo Italiano Mammella (GIM) and Mammella Intergruppo trials (MIG)

Safety and efficacy of pyronaridine–artesunate paediatric granules in the treatment of uncomplicated malaria in children: insights from randomized clinical trials and a real-world study

BackgroundChildren are particularly at risk of malaria. This analysis consolidates the clinical data for pyronaridine–artesunate (PA) paediatric granules in children from three randomized clinical trials and a real-world study (CANTAM).MethodsAn integrated safety analysis of individual patient data from three randomized clinical trials included patients with microscopically-confirmed Plasmodium falciparum, body weight ≥ 5 kg to < 20 kg, who received at least one dose of study drug (paediatric safety population). PA was administered once daily for 3 days; two trials included the comparator artemether–lumefantrine (AL). PCR-adjusted day 28 adequate clinical and parasitological response (ACPR) was evaluated. Real-world PA granules safety and effectiveness was also considered.ResultsIn the integrated safety analysis, 63.9% (95% CI 60.2, 67.4; 426/667) of patients had adverse events following PA and 62.0% (95% CI 56.9, 66.9; 222/358) with AL. Vomiting was more common with PA (7.8% [95% CI 6.0, 10.1; 52/667]) than AL (3.4% [95% CI 1.9, 5.8; 12/358]), relative risk 2.3 (95% CI 1.3, 4.3; P = 0.004), occurring mainly following the first PA dose (6.7%, 45/667), without affecting re-dosing or adherence. Prolonged QT interval occurred less frequently with PA (3.1% [95% CI 2.1, 4.8; 21/667]) than AL (8.1% [95% CI 5.7, 11.4; 29/358]), relative risk 0.39 (95% CI 0.22, 0.67; P = 0.0007). In CANTAM, adverse events were reported for 17.7% (95% CI 16.3, 19.2; 460/2599) of patients, most commonly vomiting (5.4% [95% CI 4.6, 6.4; 141/2599]), mainly following the first dose, (4.5% [117/2599]), with all patients successfully re-dosed, and pyrexia (5.4% [95% CI 4.6, 6.3; 140/2599]). In the two comparative clinical trials, Day 28 ACPR in the per-protocol population for PA was 97.1% (95% CI 94.6, 98.6; 329/339) and 100% (95% CI 99.3, 100; 514/514) versus 98.8% (95% CI 95.7, 99.9; 165/167) and 98.4% (95% CI 95.5, 99.7; 188/191) for AL, respectively. In CANTAM, PA clinical effectiveness was 98.0% (95% CI 97.3, 98.5; 2273/2320).ConclusionsAnti-malarial treatment with PA paediatric granules administered once daily for 3 days was well tolerated in children and displayed good clinical efficacy in clinical trials, with effectiveness confirmed in a real-world study.Trial registration Clinicaltrials.gov: SP-C-003-05: identifier NCT00331136; SP-C-007-07: identifier NCT0541385; SP-C-021-15: identifier NCT03201770. Pan African Clinical Trials Registry: SP-C-013-11: identifier PACTR201105000286876

Intracerebral haemorrhage in patients taking different types of oral anticoagulants: a pooled individual patient data analysis from two national stroke registries

BackgroundWe investigated outcomes in patients with intracerebral haemorrhage (ICH) according to prior anticoagulation treatment with Vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) or no anticoagulation.MethodsThis is an individual patient...

Differences in psychological treatment outcomes by ethnicity and gender: an analysis of individual patient data.

There are discrepancies in mental health treatment outcomes between ethnic groups, which may differ between genders. NHS Talking Therapies for anxiety and depression provide evidence-based psychological therapies for common mental disorders. This study examines the intersection between ethnicity and gender as factors associated with psychological treatment outcomes. Aims were to explore by gender: (1) differences in psychological treatment outcomes for minoritized ethnic people compared to White-British people, (2) whether differences are observed when controlling for clinical and socio-demographic factors associated with outcomes, and (3) whether organization-level factors moderate differences in outcomes between ethnic groups. Patient data from eight NHS Talking Therapies for anxiety and depression services (n = 98,063) was used to explore associations between ethnicity and outcomes, using logistic regression. Stratified subsamples were used to separately explore factors associated with outcomes for males and females. In adjusted analyses, Asian (OR = 0.82 [95% CI 0.78; 0.87], p < .001, 'Other' (OR = 0.79 [95%CI 0.72-0.87], p < .001) and White-other (0.93 [95%CI 0.89-0.97], p < .001) ethnic groups were less likely to reliably recover than White-British people. Asian (OR = 1.48 [95% CI 1.35-1.62], p < .001), Mixed (OR = 1.18 [95% CI 1.05-1.34], p = .008), 'Other' (OR = 1.60 [95% CI 1.38-1.84], p < .001) and White-other (OR = 1.18 [95% CI 1.09-1.28], p < .001) groups were more likely to experience a reliable deterioration in symptoms. Poorer outcomes for these groups were consistent across genders. There was some evidence of interactions between ethnic groups and organization-level factors impacting outcomes, but findings were limited. Across genders, Asian, 'Other' and White-other groups experienced worse treatment outcomes across several measures in adjusted models. Reducing waiting times or offering more treatment sessions might lead to increased engagement and reduced drop-out for some patient groups.

Outcomes following surgical interventions for hypothalamic hamartomas: protocol for a systematic review and individual patient data meta-analysis

IntroductionHypothalamic hamartomas (HHs) are deep-seated congenital lesions that typically lead to pharmacoresistant epilepsy and a catastrophic encephalopathic syndrome characterised by severe neuropsychological impairment and decline in quality of life. A...

Potential synergistic effects of cranial radiotherapy and atezolizumab in non-small cell lung cancer: an analysis of individual patient data from seven prospective trials.

The impact of cranial radiotherapy (RT) on overall survival (OS) of patients with brain metastasis (BM) from non-small cell lung cancer (NSCLC) receiving programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors remains unclear. We aimed to examine the effect of previous cranial RT on the efficacy and neurological toxicity of PD-1/PD-L1 inhibitors in the treatment of patients with NSCLC. Patient-level data from seven prospective trials involving atezolizumab for the treatment of NSCLC [BIRCH (NCT02031458), FIR (NCT01846416), IMpower130 (NCT02367781), IMpower131 (NCT02367794), IMpower150 (NCT02366143), OAK (NCT02008227), and POPLAR (NCT01903993)] were pooled. Patients with baseline BM were divided into two subgroups based on previous cranial RT before initiation of treatment: patients with previously irradiated BM (iBM) and patients with non-irradiated BMs (niBM). The per-protocol population consisted of 4,714 patients, including 3,176 in the atezolizumab group and 1,538 in the comparator chemotherapy group. In the atezolizumab group, OS was better in patients with BM (n=308) compared to patients without BM (n=2,868) [hazard ratio (HR): 0.83; 95% confidence interval (CI): 0.70-0.98; P=0.028]. Among patients with BM, patients with iBM (n=280) had a numerically longer OS (HR: 0.66; 95% CI: 0.41-1.07; P=0.090) than those with niBM (n=28). Intriguingly, OS was longer in patients with iBM than those without BM before (HR: 0.83; 95% CI: 0.70-0.99; P=0.043) and after (HR: 0.40; 95% CI: 0.32-0.49; P<0.0001) propensity score matching, while OS was similar between patients with niBM and those without BM. The survival advantage of patients with iBM over those without BM was not observed in the chemotherapy group. Atezolizumab-related serious neurological adverse events occurred in 16 (0.6%) patients without BM, none in those with niBM, and 2 (0.7%) patients with iBM. These data suggest potential synergistic effects of cranial RT and anti-PD-(L)1 therapy in NSCLC patients, which warrants further validation.

Mechanical Circulatory Support Strategies in Takotsubo Syndrome with Cardiogenic Shock: A Systematic Review.

Takotsubo syndrome is, by definition, a reversible form of acute heart failure. If cardiac output is severely reduced, Takotsubo syndrome can cause cardiogenic shock, and mechanical circulatory support can serve as a bridge to recovery. To date, there are no recommendations on when to use mechanical circulatory support and on which device is particularly effective in this context. Our aim was to determine the best treatment strategy. A systematic literature research and analysis of individual patient data was performed in MEDLINE/PubMed according to PRISMA guidelines. Our research considered original works published until 31 July 2023. A total of 93 publications that met the inclusion criteria were identified, providing individual data from 124 patients. Of these, 62 (50%) were treated with veno-arterial extracorporeal life support (va-ECLS), and 44 (35.5%) received a microaxial left ventricular assist device (Impella). Eighteen patients received an Impella CP and twenty-one an Impella 2.5. An intra-aortic balloon pump (IABP) without other devices was used in only 13 patients (10.5%), while other devices (BiVAD or Tandem Heart) were used in 5 patients (4%). The median initial left ventricular ejection fraction was 20%, with no difference between the four device groups except for the IABP group, which was less affected by cardiac output failure (p = 0.015). The overall survival was 86.3%. Compared to the other groups, the time to cardiac recovery was shorter with Impella (p < 0.001). Though the Impella treatment is new, our analysis may show a significant benefit of Impella compared to other MCS strategies for cardiogenic shock in Takotsubo syndrome.

Psychological precursors of epileptic seizures.

Psychological stress is the most commonly self-reported precursor of epileptic seizures. However, retrospective and prospective studies remain inconclusive in this regard. Here, we explored whether seizures would be preceded by significant changes in reported stressors or resource utilization. This study is based on high-frequency time series through daily online completion of personalized questionnaires of 9-24 items in epilepsy outpatients and compared responses 1-14 days before seizures with interictal time series. Fourteen patients (79% women, age = 23-64 years) completed daily questionnaires over a period of 87-898 days (median = 277 days = 9.2 months). A total of 4560 fully completed daily questionnaires were analyzed, 685 of which included reported seizure events. Statistically significant changes in preictal compared to interictal dynamics were found in 11 of 14 patients (79%) across 41 items (22% of all 187 items). In seven of 14 patients (50%), seizures were preceded by a significant mean increase of stressors and/or a significant mean decrease of resource utilization. This exploratory analysis of long-term prospective individual patient data on specific stressors and personal coping strategies generates the hypothesis that medium-term changes in psychological well-being may precede the occurrence of epileptic seizures in some patients.

Is resection an alternative to transplantation in locally advanced hepatoblastoma? A Systematic review and analysis of pooled individual patient data

Is resection an alternative to transplantation in locally advanced hepatoblastoma? A Systematic review and analysis of pooled individual patient data

Baseline symptom severity and efficacy of Silexan in patients with anxiety disorders: A symptom-based, patient-level analysis of randomized, placebo-controlled trials.

The influence of baseline severity on the efficacy of Silexan, a proprietary essential oil from Lavandula angustifolia, in anxiety disorders has not been investigated in a pooled dataset. We report on an individual patient data analysis of all five double-blind, randomized, placebo-controlled trials with Silexan in anxiety disorders. Eligible participants received Silexan 80mg/d or placebo for 10 weeks. Analyses were based on the Hamilton Anxiety Rating Scale (HAMA), its psychic and somatic anxiety subscores, and the Clinical Global Impressions (CGI) scale. To correlate baseline severity with outcome, patients were segregated into mild, moderate, and severe cases. Altogether 1,172 patients (Silexan, n=587; placebo, n=585) were analyzed. For the HAMA total score, we found a significant association between the score at baseline and the treatment effect of Silexan versus placebo at week 10 (p<0.001). HAMA items from the somatic domain scored lower at baseline and showed less improvement than items from the psychic domain, particularly in patients with mild or moderate baseline symptoms. For CGI item 2 (global improvement), significant efficacy favoring Silexan were observed in mild, moderate, and severe baseline symptom severity. Although significant improvements were found for all subsets, the more severe the initial symptoms, the greater the treatment effects documented by the HAMA. Overall this analysis confirms that Silexan is an effective treatment option in early or mild stages of anxiety disorder. Given its favorable safety profile, Silexan can thus fill a therapeutic gap in the treatment of (subsyndromal) anxiety disorders.

Association of previously irradiated stable brain metastases with outcomes of atezolizumab-treated non-small cell lung cancer: A pooled analysis of individual patient data from three randomized trials.

Association of previously irradiated stable brain metastases with outcomes of atezolizumab-treated non-small cell lung cancer: A pooled analysis of individual patient data from three randomized trials.