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Editorial12 September 2023
Editorial: Women in pharmacoepidemiology: 2021

data collection and accessibility for scientific research of outpatient data. Three studies (Barbosa et al. 2022, Frent et al. 2022, Okuyama et al. 2022) used data from pharmacovigilance databases to generate safety data. Okuyama, Galvao et al. 2022 analyzed cross-referenced information from three different health care administrative databases: official death records between 1996 and 2019 from the Mortality Information System in Brazil, hospitalizations between 2008 and 2020 from the Hospital Information System, and cases of poisonings between 2017 and 2020 in health services that have been notified to the National System for Vigilance of Notifiable Diseases. The analysis shows that the reports were more frequent among adults, particularly women, and due to accidents, with exposure to paracetamol identified as a concern for preventable intoxications, hospitalizations and deaths. Barbosa et al. (Barbosa, Silva et al. 2022) identified early safety signals of antibacterial agents to support pharmacovigilance systems using data from a Brazilian database (Vigimed/VigiFlow) from December 2018 to December 2021. Vancomycin was the most reported antibiotic, followed by ceftriaxone and piperacillin and tazobactam. Three serious events were associated with ceftazidime and avibactam, a new drug in the Brazilian market. Frent et al. (Frent, Leucuta, Bucsa, Farcas, Casoinic and Mogosan 2022) performed a descriptive analysis of cases of acute renal failure and nephrolithiasis reported from Sodium-Glucose Co-Transporter 2 (SGLT2) inhibitors in VigiBase to September 2021. The vast majority of acute renal failure and nephrolithiasis reports were considered serious. Canagliflozin was the gliflozin most involved in cases of acute renal failure and nephrolithiasis.Healthcare records are another important source of real-world data. Healthcare records play a crucial role in generating RWD in the field of healthcare and medical research. One way that healthcare records contribute to generating real-world evidence is through observational studies using de-identified patient data from healthcare records. A cross-sectional database study in Switzerland (Rachamin et al. 2022) used medical records to determine patient age-and sex-specific prevalence rates of polypharmacy, and rates of prescribing of the most frequently used medication classes; they also explored practitioner variability in prescribing practices in Swiss general practitioners. The prevalence of polypharmacy in the adult Swiss general practice population was determined to be 24%, increasing with age: from 6% in patients aged 18-40 years to 65% in patients aged 81-92 years. Women had higher rates of polypharmacy than men.The difference was more pronounced at younger ages, and interestingly, hormonal contraceptives did not relevantly contribute to the difference. The most clear drivers of the differing rates of polypharmacy in the younger population were higher prescription rates of vitamins, mineral supplements, and antianemic preparations in female patients. Men were more often prescribed agents targeting the cardiovascular system (such as antihypertensive agents, antithrombotic agents, and lipid modifying agents), whereas most other medications were more often prescribed to women. A cohort study (Gorgui et al. 2022) undertaken in Canada involving the linkage of three Quebec databases was undertaken to quantify the risk of babies being born small for gestational age (SGA) and very small for gestational age (VSGA) with the use of medically assisted reproduction. While no association was observed between medically assisted reproduction and SGA or VSGA in the study population; medically assisted reproduction was associated with an increased risk for SGA among preterm pregnancies; no increased risk of SGA was observed in term pregnancies. Another cohort study (Oh et al. 2022) examined the association between gabapentin use and neurocognitive changes in older adults using the National Alzheimer's Coordinating Center Uniform Data Set (NACC UDS). The NACC UDS has rich data and is an example of how building a database with real-world data focused on answering research questions can contribute to decision making in health. This data set provided a greater sample size compared with previous studies in this population and was able to measure the association between gabapentin initiation and neurocognition with various clinically relevant outcomes. The results provided evidence that gabapentin was associated with increased odds of global cognitive decline, functional status decline, and motor function change in the two years following gabapentin initiation. Considering that gabapentin may block calcium channels in the brain, it was hypothesized that it would have a neuroprotective effect, but these findings did not support this assumption. The authors concluded that further experimental studies are needed to examine the mediators of gabapentin use and neurocognitive changes.On the other hand, systematic reviews with meta-analyses (SR-MA) also play a crucial role in informing healthcare decisions, policy-making, and advancing scientific knowledge. Two systematic reviews and meta-analyses published in this Research Topic were designed to complement the knowledge obtained from randomized control trials and observational studies of primary data to evaluate the real-world effectiveness of medications. These reviews (Castro et al. 2022, Queiroz et al. 2022) summarized the evidence produced from observational studies involving administrative databases of different drug classes of disease-modifying drugs (DMARDs) in patients with rheumatoid arthritis (RA). The meta-analysis by Queiroz et al.(Queiroz, Castro, Albuquerque, Brandão, Gerlack, Pereira, Barros, Andrade, Bastos, Azevedo, Carreiro, Barreto and Santos 2022) did not suggest there is an increased risk of adverse events associated with the use of biologics for the treatment of RA, indicating a lower risk of cardiovascular events with abatacept than tumor necrosis factor inhibitors (TNFi) (low to very low certainty of the evidence). The meta-analysis by Castro et al. (Castro, Queiroz, Albuquerque, Brandão, Gerlack, Pereira, Barros, Andrade, Bastos, Azevedo, Carreiro, Barreto and Santos 2022) synthesized data on 182,098 RA patients across 21 studies included. They concluded that biologics effectively treat patients with RA, with higher effectiveness for non-TNFi and Janus kinase inhibitors (JAKi) than with TNFi. A policy brief is another type of evidence synthesis combining research evidence specific to stakeholders' contextual knowledge. The policy brief from Fulone et al. (Fulone et al. 2022) identified evidence-based strategies to improve adherence to preventive measures against COVID-19 at the community level. Three evidencebased strategies were identified: i. Risk communication; ii. Health education to the general public, and iii. Financial support and access to essential supplies and services. The evidence showed that an increase in knowledge, transparent communication, and public awareness about the risks of COVID-19 and the benefits of adopting preventive measures result in changes in people's attitudes and behavior, which can increase adherence. These strategies can guide future actions and the formulation of public policies to improve adherence to preventive measures in the community in future epidemics. Finally, this Research Topic also includes a protocol on a scoping review (Leal et al. 2022) describing the methodology for assessing the available literature on emulation target trials to study outcomes in women exposed to medications in the preconception, perinatal, or postpartum periods.To conclude, this first Research Topic on Women in Pharmacoepidemiology highlights the range of robust research that is being performed by women in science, and pharmacoepidemiology in particular, across the globe today. Research is varied, and complementary, and is being undertaken across the life course, from conception to adulthood. However, the lack of true global representation of women in science is a significant issue that has persisted for many years and requires a multi-faceted approach to address the issue. Efforts to increase the representation of women in science should be a priority for governments, educational institutions, scientific organizations, and society as a whole. By breaking down barriers and creating more inclusive environments, we can unlock the full potential of women in advancing scientific discovery and innovation. We need to do better in the future to promote the work of women scientists all over the world. It is with great pleasure that we are presenting Women in Pharmacoepidemiology 2021.

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Background Gabapentin is increasingly prescribed to older adults, which raises concerns about its potential to cause neurocognitive changes. Therefore, we aimed to examine the association of gabapentin use with neurocognitive changes (i.e., cognitive decline, functional status decline, and motor function change) in older adults. Methods We conducted a retrospective cohort study using the National Alzheimer’s Coordinating Center Uniform Data Set (UDS; September 2005-March 2021 data freeze). From the eligible sample (≥age 65 years), we identified cognitively normal new-users of gabapentin and the visit they initiated gabapentin (i.e., index visit). Initiators were matched to randomly selected nonusers on year of UDS enrollment and visit number from enrollment to index. Cognitive decline was defined as any increase in the Clinical Dementia Rating global score (CDRGLOB) and as a 1-point increase in CDR sum of boxes (CDR-SB). Functional status decline was defined as a 3-point increase in the sum of the Functional Activities Questionnaire (FAQ) and as 0.3-point increase in mean FAQ. Decline in motor function was defined as new clinician reports of gait disorder, falls, and slowness. To mitigate confounding and selection bias, we used joint stabilized inverse probability of treatment weights and stabilized inverse probability of censoring weights. All analyses were conducted comparing index to index+1 and index+2 visits. Results From the eligible UDS participants (N=23,059), we included 480 initiators (mean age [SD]: 78.7 [6.9]; male 34.4%); 4,320 nonusers (78.3 [7.0]; 34.4%). Gabapentin initiation was significantly associated with cognitive/functional status decline: worsening CDRGLOB at index+1 visit (odds ratio [95% confidence interval]: 1.55 [1.07, 2.25]); CDR-SB at index+1 visit (1.94 [1.22, 3.09]); and mean of FAQ at index+2 visit (1.78 [1.12, 2.83]). After excluding initiators with extant motor dysfunction (n=21), we identified 459 initiators (78.7 [6.9]; 34.0%) and 4,131 nonusers (78.2 [6.9]; 34.7%); in this sample, gabapentin initiation was associated with increased falls at the index+2 visit (2.51 [1.19, 5.31]). Conclusions Gabapentin initiation was significantly associated with deleterious neurocognitive changes among older adults with initially normal cognition. Further studies are needed to examine the risk/benefit of prescribing gabapentin in older adults.

65,051 views

38 citations

SYSTEMATIC REVIEW
11 August 2022
Safety of biological therapy in patients with rheumatoid arthritis in administrative health databases: A systematic review and meta-analysis
Mariana Jorge de Queiroz, 11 more and Djanilson Barbosa Santos

7,766 views

17 citations

SYSTEMATIC REVIEW
11 August 2022
Real-world effectiveness of biological therapy in patients with rheumatoid arthritis: Systematic review and meta-analysis
Caroline Tianeze de Castro, 11 more and Djanilson Barbosa dos Santos

13,461 views

28 citations

PROTOCOLS
22 July 2022
The Use of the Target Trial Approach in Perinatal Pharmacoepidemiology: A Scoping Review Protocol
Lisiane Freitas Leal, 4 more and Robert William Platt

4,583 views

2 citations

MINI REVIEW
18 July 2022
Major areas of interest of artificial intelligence research applied to health care administrative data: a scoping review
Olga Bukhtiyarova, 4 more and Caroline Sirois

3,227 views

5 citations

ORIGINAL RESEARCH
14 February 2022
Prescription Rates, Polypharmacy and Prescriber Variability in Swiss General Practice—A Cross-Sectional Database Study
Yael Rachamin, 5 more and Stefan Markun

4,254 views

14 citations