Background: Amivantamab, an EGFR-MET bispecific antibody, is the first approved targeted therapy for patients with EGFR Ex20ins NSCLC after prior platinum-based chemotherapy-a population with historically poor outcomes before amivantamab approval. As antitumor activity in single-arm studies typically focuses on responders, the evaluation of outcomes in patients with stable disease (SD) as best response is of clinical interest.
Patients And Methods: Among 114 patients with post-platinum EGFR Ex20ins NSCLC in CHRYSALIS (NCT02609776; data cutoff: March 30, 2021), response was assessed by blinded independent central review via RECIST v1.
Induced pluripotent stem cells (iPSCs) are a powerful tool for biomedical research, but their production presents challenges and safety concerns. Yamanaka and Takahashi revolutionised the field by demonstrating that somatic cells could be reprogrammed into pluripotent cells by overexpressing four key factors for a sufficient time. iPSCs are typically generated using viruses or virus-based methods, which have drawbacks such as vector persistence, risk of insertional mutagenesis, and oncogenesis.
View Article and Find Full Text PDFThe etiopathology of Parkinson's disease has been associated with mitochondrial defects at genetic, laboratory, epidemiological, and clinical levels. These converging lines of evidence suggest that mitochondrial defects are systemic and causative factors in the pathophysiology of PD, rather than being mere correlates. Understanding mitochondrial biology in PD at a granular level is therefore crucial from both basic science and translational perspectives.
View Article and Find Full Text PDFWe assessed relative efficacy and safety of amivantamab versus mobocertinib in patients with non-small-cell lung cancer with exon 20 insertion (exon20ins) mutations who progressed on prior platinum-based chemotherapy. This matching-adjusted indirect comparison used patient-level data from CHRYSALIS (NCT02609776) and aggregate data from a mobocertinib trial (NCT02716116) to match populations on all clinically relevant confounders. While both agents had similar efficacy for time-to-event outcomes, objective response rate was significantly higher for amivantamab.
View Article and Find Full Text PDFPurpose: Older patients are at high risk for poor outcomes after an acute hospital admission. The Transitional Aged Care Programme (TACP) was established by the Australian government to provide a short-term care service aiming to optimise functional independence following hospital discharge. We aim to investigate the association between multimorbidity and readmission amongst patients on TACP.
View Article and Find Full Text PDFAdv Ther
March 2023
Introduction: Patients with advanced, epidermal growth factor receptor (EGFR)-mutated, non-small cell lung cancer (NSCLC) with Exon 20 insertion mutations (Exon20ins) have poor prognoses, exacerbated by a previous lack of specific treatment guidelines and unmet need for targeted therapies. Amivantamab, an EGFR and MET bispecific antibody, demonstrated efficacy and tolerability in patients with advanced EGFR-mutated NSCLC with Exon20ins following platinum-based therapy in CHRYSALIS (NCT02609776; Cohort D+). Since CHRYSALIS was single-arm, individual patient data (IPD)-based adjusted analyses versus similar patients in real-world clinical practice (RWCP) were conducted to generate comparative evidence.
View Article and Find Full Text PDFBackground: In the single-arm CHRYSALIS study, amivantamab showed durable responses and manageable safety in patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations (ex20ins) who progressed on prior platinum-based chemotherapy. External controls can provide context for interpreting amivantamab efficacy.
Methods: External controls were selected from three US-based databases (ConcertAI, COTA, and Flatiron).
Introduction: Real-world clinical outcomes in patients with advanced NSCLC harboring EGFR exon 20 insertion (exon20ins) mutations have not been extensively studied. We conducted a retrospective cohort study to assess the clinical outcomes of EGFR exon20ins compared with common EGFR (cEGFR) mutations.
Methods: Adults with advanced NSCLC harboring any EGFR mutations in the NSCLC Flatiron registry (2011 through May 2020) were included.
Background And Aim: There is an increasing prevalence of chronic disease worldwide, resulting in multiple management challenges. Inflammatory bowel disease (IBD) is an exemplar chronic disease requiring coordinated longitudinal care. We propose that Crohn's Colitis Care (CCCare), a novel IBD-specific, structured electronic medical record is effective at improving data capture and is acceptable to patients.
View Article and Find Full Text PDFObjectives: The burden of epidermal growth factor receptor (EGFR) exon 20 insertion mutation (Exon 20ins) in non-small cell lung cancer is not well understood. A systematic review was conducted to identify evidence on mutation frequency, prognostic impact, clinical, patient-reported, and economic outcomes associated with Exon 20ins.
Materials And Methods: Searches were conducted in Embase and Medline and supplemented with recent conference proceedings.
Background: The objective of this study was to describe the real-world treatment and overall survival (OS) of German patients with a diagnosis of advanced non-small cell lung cancer (aNSCLC), and to explore factors associated with the real-world mortality risk.
Methods: This was a retrospective German claims data analysis of incident aNSCLC patients. Data were available from 01/01/2011 until 31/12/2016.
Chemoimmunotherapy is an emerging combinatorial modality for the treatment of cancers resistant to common first-line therapies, such as chemotherapy and checkpoint blockade immunotherapy. We used biodegradable nanoparticles as delivery vehicles for local, slow and sustained release of doxorubicin, two immune adjuvants and one chemokine for the treatment of resistant solid tumors. Bio-compatible poly(lactic-co-glycolic acid)-PEG nanoparticles were synthesized in an oil/water emulsion, using a solvent evaporation-extraction method.
View Article and Find Full Text PDFWe report direct observations of photon-mediated spin-exchange interactions in an atomic ensemble. Interactions extending over a distance of 500 μm are generated within a cloud of cold rubidium atoms coupled to a single mode of light in an optical resonator. We characterize the system via quench dynamics and imaging of the local magnetization, verifying the coherence of the interactions and demonstrating optical control of their strength and sign.
View Article and Find Full Text PDFBackground: Abiraterone acetate plus prednisone (AA+P), when added to androgen deprivation therapy (ADT), demonstrated significant improvements in overall survival and disease progression over dual placebos added to ADT in the LATITUDE clinical trial (NCT01715285). The objective of this study was to assess event-driven medical resource utilization (MRU) of ADT plus AA+P (ADT+AA+P) versus ADT plus dual placebos (ADT+placebos) in LATITUDE.
Methods: Event-driven MRU data from LATITUDE while patients were on treatment were used for analyses.
Aim: Androgen deprivation therapy (ADT) has long been the gold standard for patients with metastatic hormone-sensitive prostate cancer (mHSPC). Clinical trials have demonstrated significant survival benefits when docetaxel (DOC) or abiraterone acetate (AA) and prednisone (P) are added to ADT, necessitating comparison of these combination treatments.
Methods: A systematic review of randomised controlled trials (RCTs) of AA-/ADT-/DOC-containing treatment regimens in newly diagnosed patients with high-risk and/or high-volume mHSPC identified three RCTs (LATITUDE, CHAARTED and GETUG-AFU 15).
Objectives: Treatment landscape in prostate cancer has changed dramatically with the emergence of new medicines in the past few years. The traditional survival partition model (SPM) cannot accurately predict long-term clinical outcomes because it is limited by its ability to capture the key consequences associated with this changing treatment paradigm. The objective of this study was to introduce and validate a discrete-event simulation (DES) model for prostate cancer.
View Article and Find Full Text PDFBackground: In the LATITUDE trial, addition of abiraterone acetate plus prednisone to androgen deprivation therapy (ADT) improved overall survival compared with placebos plus ADT in patients with newly diagnosed, high-risk, metastatic castration-naive prostate cancer. Understanding the effects of treatments on patient-reported outcomes (PROs) and health-related quality of life (HRQOL) is important for treatment decisions; therefore we aimed to analyse the effects of ADT plus abiraterone acetate and prednisone versus ADT plus placebos on PROs and HRQOL in patients in the LATITUDE study.
Methods: In the multicentre, international, randomised, phase 3 LATITUDE trial, eligible patients were aged 18 years or older, had newly diagnosed, high-risk, metastatic castration-naive prostate cancer confirmed by bone scan (bone metastases) or by CT or MRI (visceral, soft tissue, or nodal metastases), and an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less.
Mol Psychiatry
May 2019
Schizophrenia is highly heritable, yet its underlying pathophysiology remains largely unknown. Among the most well-replicated findings in neurobiological studies of schizophrenia are deficits in myelination and white matter integrity; however, direct etiological genetic and cellular evidence has thus far been lacking. Here, we implement a family-based approach for genetic discovery in schizophrenia combined with functional analysis using induced pluripotent stem cells (iPSCs).
View Article and Find Full Text PDFBackground: The impact of subsequent metastases on costs and medical resource use (MRU) for prostate cancer (PC) patients initially diagnosed with localized disease was estimated.
Methods: Surveillance, Epidemiology, and End Results data, linked to Medicare (1999-2012), were used to identify 7482 patients diagnosed with subsequent metastases 12 months or more after the initial diagnosis of localized PC (cases), and they were matched to 25,709 localized PC patients without subsequent metastases (controls). Patients were followed for costs and MRU from 12 months before their index date (subsequent metastases or a matched date for controls) up to 12 months after it.
is implicated in the pathogenesis of acne vulgaris, which impacts >85% of teenagers. Novel therapies are in high demand and an ethnopharmacological approach to discovering new plant sources of anti-acne therapeutics could contribute to filling this void in effective therapies. The aims of our study were two-fold: (1) To determine if species identified in ethnopharmacological field studies as having traditional uses for skin and soft tissue infection (SSTI) exhibit significantly more activity against than species with no such reported use; and (2) Chemically characterize active extracts and assess their suitability for future investigation.
View Article and Find Full Text PDFTopology and geometry are essential to our understanding of modern physics, underlying many foundational concepts from high-energy theories, quantum information, and condensed-matter physics. In condensed-matter systems, a wide range of phenomena stem from the geometry of the band eigenstates, which is encoded in the matrix-valued Wilson line for general multiband systems. Using an ultracold gas of rubidium atoms loaded in a honeycomb optical lattice, we realize strong-force dynamics in Bloch bands that are described by Wilson lines and observe an evolution in the band populations that directly reveals the band geometry.
View Article and Find Full Text PDFJ Community Support Oncol
April 2016
Background: Metastatic castration-resistant prostate cancer (mCRPC) is typically associated with declining health-related quality of life (HR-QoL).
Objective: To assess patient experience with abiraterone acetate (hereafter abiraterone) plus prednisone longitudinally.
Methods: COU-AA-302 was a phase 3, multinational, randomized, double-blind study that enrolled asymptomatic or mildly symptomatic, chemotherapy-naïve patients with mCRPC.