Introduction: Therapeutic targeting of inhibitors of the immune response has reached the clinical setting. Inhibitors of the novel receptor LAG3, which negatively regulates T-cell activation, are under investigation. Here we explore the presence and prognostic role of LAG3 in cancer.Methods: A systematic search of electronic databases identified publications exploring the effect of LAG3 on overall survival (OS) and (for early-stage cancers) disease-free survival (DFS). Hazard ratios (HR) were pooled in a meta-analysis using generic inverse-variance and random effect modeling. Subgroup analyses were conducted based on disease site and tumor type.Results: Fifteen studies met the inclusion criteria. LAG3 was associated with better overall survival [HR 0.81, 95% confidence interval (CI) 0.66–0.99; P = 0.04], with subgroup analysis showing no significant differences between disease-site subgroups. The beneficial effect of LAG3 on OS was of greater magnitude in early-stage malignancies (HR 0.73, 95% CI 0.60–0.88) than in the metastatic setting (HR 1.20, 95% CI 0.70–2.05), but this difference was not statistically significant (subgroup difference p = 0.18). LAG3 did not have a significant association with DFS [HR 1.02, 95% confidence interval (CI) 0.77–1.37; P = 0.87], with subgroup analysis showing worse DFS in patients with lymphoma and improved DFS in those with breast cancer.Conclusions: High expression of LAG3 is associated with favorable overall survival in several solid tumors. A trend toward an association in early-stage disease suggests the importance of immune surveillance in this setting.
Background Clinical practice guidelines (CPGs) are crucial to the practice of evidence‐based medicine. Declared author financial conflicts of interest (FCOIs) are common in CPGs and have been associated with endorsement of treatment. Less is known about undeclared FCOIs. Methods The American Society of Clinical Oncology (ASCO) website was searched to identify all CPGs for systemic therapy published between August 2013 and June 2018. Data on self‐reported author FCOIs and funding sources were extracted. The Open Payments database was then searched to identify compensation to CPG authors. Concordance between declared and undeclared but verified FCOIs was assessed with Cohen's κ. Results For 26 CPGs, 314 nonduplicate authors were identified; 184 of these authors (59%) disclosed FCOIs. Among the remaining 130 authors, data in Open Payments were unavailable for 71 authors (non‐US residents or authors affiliated with a nonprofit organization). Among the 59 authors who declared no FCOIs and for whom Open Payments data were available, 55 (93%) had received payment from industry. The κ value for agreement between disclosed and verified FCOIs was 0.092. Among the 243 authors with FCOIs verifiable via Open Payments, 239 (98%) received payment from industry. Thirty‐four authors (62%) received more than $1000 in nonresearch funding, and 19 (35%) received more than $5000. Among the 52 first and last authors, 44 (85%) received payment from industry; 14 of these payments (32%) were not declared. Conclusions FCOIs among authors of ASCO CPGs are common and are not disclosed by a substantial proportion of authors with Open Payments data. Improved transparency of FCOIs should become standard practice among CPG authors. Professional societies and journal editors need to create a mechanism to verify self‐reported FCOIs.
Off-label use of antipsychotic medication is increasing, particularly the use of quetiapine for sleep, owing to its sedating properties. 1 This is a cause for concern given important adverse effects, including drug-induced diabetes and parkinsonism, weight gain, neuroleptic malignant syndrome, oversedation, and risk of arrhythmia. 2 We describe quetiapine use in a prospective cohort of medical inpatients and the proportion of inhospital use that is perpetuated on discharge. Methods | In our 52-bed medical clinical teaching unit (CTU) (Royal Victoria Hospital; 417 beds, Montreal, Quebec, Canada), we prospectively enrolled all consecutive inpatients 60 years or older between December 2013 and April 2015. There were no exclusion criteria. Patient data were abstracted from medical records at discharge or death, and were analyzed in March 2016. One of us (P.D.) retrospectively reviewed all medical records for quetiapine dose and indication. In the absence of a documented comorbid psychiatric condition (eg, schizophrenia, major depressive, or bipolar affective disorder) or evidence of delirium it was inferred that once-nightly quetiapine was being given for sleep. Categorical variables were compared using χ 2 and continuous variables using Wilcoxon rank-sum or the Kruskal-Wallis test as appropriate. The study was approved by the McGill University Health Centre research ethics board.
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