Frequency of postoperative cognitive dysfunction after non-cardiac surgery and its impact on functional outcomes: protocol for a systematic review.

INTRODUCTION: Older surgical candidates are at increased risk of a phenomenon known as postoperative cognitive dysfunction (POCD). Several studies have looked at the incidence of POCD at different time points following surgery, using different study methods. Fewer have assessed whether changes in cognition after surgery are attributable to surgery and how they impact patient function and quality of life. The aim of this systematic review is to summarise and appraise studies addressing any of the following research questions (RQs): (RQ1) what is the frequency of POCD after non-cardiac surgery?; (RQ2) is non-cardiac surgery associated with an increased risk of cognitive decline?; (RQ3) is POCD after non-cardiac surgery associated with patient-important outcomes? METHODS AND ANALYSIS: This protocol adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. Three electronic databases (MEDLINE, PsycINFO and EMBASE) will be systematically searched from their inception date. Identified studies will be screened by two reviewers for eligibility using Covidence, and data will be extracted into a standardised electronic form. We will evaluate methodological quality of included studies using the Quality In Prognosis Studies and its adaptation to the overall prognosis question, and the CLARITY risk of bias for cohort and case-control studies. For RQ1, we will estimate an average POCD frequency at different time points by performing a meta-analysis of included studies when appropriate. For RQ2 and RQ3, we will extract and meta-analyse the effect measures for the association of surgery with cognitive decline when compared with the non-surgical comparator, and association of cognitive changes with functional changes, quality of life and other patient-important outcomes based on available evidence. We will narratively summarise and discuss the different methods implemented in the existing studies to answer the three RQs, and when meta-analysis is deemed infeasible, we will qualitatively report the results of the included studies. ETHICS AND DISSEMINATION: This project involves the collection and analysis of data from previously published studies and therefore does not require ethics approval. We plan to present the findings of this research project at peer-reviewed conferences and publish the results in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42022370674.

Availability of Safe and Effective Therapeutic Options to Pregnant and Lactating Individuals Following the United States Food and Drug Administration Pregnancy and Lactation Labeling Rule.

OBJECTIVE: To explore the extent and type of pregnancy and lactation data of newly approved prescription drugs and assess whether the presented recommendations are data-driven, as required by the US Food and Drug Administration Pregnancy and Lactation Labeling Rule implemented in 2015. STUDY DESIGN: In this descriptive analysis, we reviewed pregnancy and lactation data of all new molecular entities approved between 2001 and 2020 in their most updated labeling. Information was collected regarding the pregnancy and lactation risk statements, the source of pregnancy and lactation data, and the design and methods of pregnancy and lactation studies in the labeling. RESULTS: Of the 422 new molecular entities, the key advisory statement for use of 133 (32%) drugs in pregnancy and 194 (46%) drugs in lactation were classified as "against use." Less than 2% of all drugs had a key advisory statement that supported their use during pregnancy or lactation. The sources of data regarding use in pregnancy were studies in human and animals in 46 (11%) and 348 (82%) drugs, respectively. For use during lactation, data included studies in human and animals in 23 (5%) and 251 (59%) drugs, respectively. The key advisory recommendation was consistent with the available human information in 4 (8%) drugs in pregnancy and 3 (13%) drugs in lactation. Prescription drug labeling contains limited data to support informed decision-making for the use of prescription drugs during pregnancy/lactation. Close collaboration among stakeholders is required to enhance the availability of data in this population.