A Patient and Public Involvement (PPI) Review Exploring Patient Reported Outcome Measures in Adult CAR T-cell therapy Patients

Background & Aims: Chimeric Antigen Receptor (CAR) T-cell therapy is a novel anti-cancer treatment option for patients with refractory or relapsed haematological malignancies. Preliminary research shows a significant proportion of patients receiving CAR T-cell therapy develop malnutrition and cachexia during treatment, with these nutritional issues associated with adverse patient outcomes. There is a lack of literature and no specific validated measures on patient experience and burden of symptoms for CAR T-cell therapy patients as well as the importance of clinical outcomes for these patients. Patient and public involvement (PPI) is a fundamental feature of proper research execution as it informs issues in the research that are most important in patients. The aim of this review was to identify priority patient-reported outcome measures in CAR T-cell therapy patients using PPI, in addition to exploring patient experiences, burden of symptoms, priorities, and knowledge of nutritional priorities in cancer. The PPI outcomes will also aid to inform the design and development of a future novel cohort study. Methods: Using participatory research (PPI), six adults aged 26e70 years who have received CAR T-cell therapy in the past two years, participated in one-to-one interviews. The interview questions were focused on the aims of identifying patient recommendations regarding clinical outcome measures of interest, their relevance to patient's experience of CAR T-cell therapy, and optimal design of the future cohort research protocol

Non‐steroidal anti‐inflammatory drugs for treatment of cancer cachexia: A systematic review

Cancer cachexia (CC) is a multifactorial syndrome driven by inflammation, defined by ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support. CC leads to progressive functional impairment, with its clinical management complicated and limited therapeutic options available. The objective of this review was to assess the efficacy and safety of non‐steroidal anti‐inflammatory drugs (NSAIDs) on patient‐centred outcomes in patients with CC. In 2013, two systematic reviews concluded that there was insufficient evidence to recommend NSAIDs for clinical management of CC outside of clinical trials. However, clinical trials of multi‐component CC interventions have included NSAIDs as an intervention component, so an up‐to‐date assessment of the evidence for NSAIDs in the treatment of CC is warranted. Four databases (MEDLINE, EMBASE, CENTRAL and CINAHL) and three trial registers (clinicaltrials.gov, WHO ICTRP and ISRCTN) were searched on 16 December 2022. Randomized controlled trials (RCTs) comparing any NSAID (any dose or duration) with a control arm, in adult patients with CC, reporting measures of body weight, body composition, nutrition impact symptoms, inflammation, physical function or fatigue, were eligible for inclusion. Primary outcomes (determined with patient involvement) were survival, changes in muscle strength, body composition, body weight and quality of life. Included studies were assessed for risk of bias using the Revised Cochrane risk‐of‐bias tool for randomized trials. Five studies were included, which investigated Indomethacin (n = 1), Ibuprofen (n = 1) and Celecoxib (n = 3). Four studies were judged to be at high risk of bias for all outcomes, with one study raising concerns for most outcomes. Considerable clinical and methodological heterogeneity amongst the studies meant that meta‐analysis was not appropriate. There was insufficient evidence to determine whether Indomethacin or Ibuprofen is effective or safe for use in patients with CC; RCTs with lower risk of bias are needed. Celecoxib studies indicated it was safe for use in this population at the doses tested (200–400 mg/day) but found contrasting results regarding efficacy, potentially reflecting heterogeneity amongst the studies. There is inadequate evidence to recommend any NSAID for CC. While current clinical trials for CC treatments are shifting towards multi‐component interventions, further research to determine the efficacy and safety of NSAIDs alone is necessary if they are to be included in such multi‐component interventions. Furthermore, the lack of data on patient‐determined primary outcomes in this review highlights the need for patient involvement in clinical trials for C

Non-steroidal anti-inflammatory drugs for treatment of cancer cachexia: a systematic review

Abstract Cancer cachexia (CC) is a multifactorial syndrome driven by inflammation, defined by ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support. CC leads to progressive functional impairment, with its clinical management complicated and limited therapeutic options available. The objective of this review was to assess the efficacy and safety of non‐steroidal anti‐inflammatory drugs (NSAIDs) on patient‐centred outcomes in patients with CC. In 2013, two systematic reviews concluded that there was insufficient evidence to recommend NSAIDs for clinical management of CC outside of clinical trials. However, clinical trials of multi‐component CC interventions have included NSAIDs as an intervention component, so an up‐to‐date assessment of the evidence for NSAIDs in the treatment of CC is warranted. Four databases (MEDLINE, EMBASE, CENTRAL and CINAHL) and three trial registers (clinicaltrials.gov, WHO ICTRP and ISRCTN) were searched on 16 December 2022. Randomized controlled trials (RCTs) comparing any NSAID (any dose or duration) with a control arm, in adult patients with CC, reporting measures of body weight, body composition, nutrition impact symptoms, inflammation, physical function or fatigue, were eligible for inclusion. Primary outcomes (determined with patient involvement) were survival, changes in muscle strength, body composition, body weight and quality of life. Included studies were assessed for risk of bias using the Revised Cochrane risk‐of‐bias tool for randomized trials. Five studies were included, which investigated Indomethacin (n = 1), Ibuprofen (n = 1) and Celecoxib (n = 3). Four studies were judged to be at high risk of bias for all outcomes, with one study raising concerns for most outcomes. Considerable clinical and methodological heterogeneity amongst the studies meant that meta‐analysis was not appropriate. There was insufficient evidence to determine whether Indomethacin or Ibuprofen is effective or safe for use in patients with CC; RCTs with lower risk of bias are needed. Celecoxib studies indicated it was safe for use in this population at the doses tested (200–400 mg/day) but found contrasting results regarding efficacy, potentially reflecting heterogeneity amongst the studies. There is inadequate evidence to recommend any NSAID for CC. While current clinical trials for CC treatments are shifting towards multi‐component interventions, further research to determine the efficacy and safety of NSAIDs alone is necessary if they are to be included in such multi‐component interventions. Furthermore, the lack of data on patient‐determined primary outcomes in this review highlights the need for patient involvement in clinical trials for CC

Epibatidine Blocks Eye-Specific Segregation in Ferret Dorsal Lateral Geniculate Nucleus during Stage III Retinal Waves

The segregation and maintenance of eye-specific inputs in the dorsal lateral geniculate nucleus (dLGN) during early postnatal development requires the patterned spontaneous activity of retinal waves. In contrast to the development of the mouse, ferret eye-specific segregation is not complete at the start of stage III glutamatergic retinal waves, and the remaining overlap is limited to the C/C1 lamina of the dLGN. To investigate the role of patterned spontaneous activity in this late segregation, we disrupted retinal waves pharmacologically for 5 day windows from postnatal day (P) 10 to P25. Multi-electrode array recordings of the retina in vitro reveal that the cholinergic agonist epibatidine disrupts correlated retinal activity during stage III waves. Epibatidine also prevents the segregation of eye-specific inputs in vivo during that period. Our results reveal a novel role for cholinergic influence on stage III retinal waves as an instructive signal for the continued segregation of eye-specific inputs in the ferret dLGN