Use of administrative claims data in observational studies of antirheumatic medication effects on pregnancy outcomes: a scoping review protocol.

OBJECTIVE: The primary objective of this review is to examine which disease-modifying antirheumatic drugs (DMARDs) and biologics used to treat pregnant individuals with rheumatic conditions have been reported in observational studies using population-based health administrative data. The secondary objective is to describe which adverse pregnancy outcomes (both maternal and neonatal) have been reported, their definitions, and corresponding diagnostic and/or procedural codes. INTRODUCTION: Pregnant individuals are typically excluded from drug trials due to unknown potential risks to both the pregnant person and fetus, leaving most antirheumatic drugs understudied for use in pregnancy. Despite these substantial knowledge gaps, most pregnant individuals continue to be maintained on antirheumatic medications due to the benefits generally outweighing the risks. In contrast to previous systematic reviews of findings from randomized trials, our scoping review aims to leverage this real-world data to generate real-world evidence of antirheumatic drug safety during pregnancy. INCLUSION CRITERIA: Articles must report on observational studies using population-based health administrative data from pregnant individuals with rheumatic conditions (rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and psoriatic arthritis) receiving antirheumatic drug therapy (DMARDs and biologics). Randomized trials, reviews, case studies, opinion pieces, and abstracts will be excluded. METHODS: Electronic databases (MEDLINE [Ovid], Embase [Ovid], CINAHL [EBSCOhost]) and gray literature (OpenGrey, Health Services Research Projects in Progress, World Health Organization Library, and Google Scholar) will be searched for relevant evidence. Search terms will combine 4 concepts: rheumatic diseases, drug therapy, pregnancy, and health care administrative data. Identified articles will be independently screened, selected, and extracted by 2 researchers. Data will be analyzed descriptively and presented in tables. REVIEW REGISTRATION: Open Science Framework https://osf.io/5e6tp.

Effects of the July 2018 worldwide valsartan recall and shortage on global trends in antihypertensive medication use: a time-series analysis in 83 countries.

OBJECTIVES: This study aims to examine the effects of the July 2018 worldwide valsartan recall and shortage on global trends of antihypertensive medication use in 83 countries. METHODS: A time-series analysis of monthly purchases of valsartan, other angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) across 83 countries from January 2017 to July 2020 was conducted using the IQVIA MIDAS database. Trends in outcomes were investigated globally and by economic level (developed vs developing economies). The valsartan recall's impact on antihypertensive use was assessed with interventional autoregressive integrated moving average modelling. RESULTS: Global valsartan utilisation trends decreased significantly by 15.7% (-61 166 515 SU; p<0.0001), while global purchases of other ARBs increased by 44.8% (+958 069 420 SU; p=0.8523) and ACEIs increased by 1.6% (+44 106 747 SU; p=0.1102). Of the 32 developed countries, 20 (62.5%) showed a decline in 1-month percentage change in valsartan purchases, whereas only 10 out of 33 developing countries (30.3%) experienced a decrease in valsartan purchases. Mean 1-month, 3-month and 6-month percentage changes for developed countries were -1.2%, -9.3% and -12.2%, respectively, while the changes for developing countries were 25.0%, 7.3% and -1.2%. CONCLUSIONS: Global valsartan purchases substantially decreased post-recall, highlighting the far-reaching impacts of drug shortages. Opposing utilisation trends by economic level raise concerns of potential distribution of contaminated medications from developed countries to developing countries. Concerted actions for equitable global access to quality medications and mitigation of drug shortages are needed.

Early observations of Tier-3 drug shortages on purchasing trends across Canada: A cross-sectional analysis of 3 case-example drugs.

BACKGROUND: To curb the growing impact of drug shortages, Health Canada developed the Tiered Notification and Communication Framework which assigns potential shortages a corresponding tiered status. Tier-3 is assigned to shortages with the greatest potential impact on the healthcare system. This study aims to describe drug purchasing trends in response to Tier-3 shortages using three case-examples. METHODS: We conducted a time-series analysis of monthly purchasing data for three out of 17 Tier-3 drug shortages (hydralazine, sarilumab, and medroxyprogesterone acetate) with publicly available reports in July 2021 and available IQVIA MIDAS data from January 2016 to December 2021. We assessed percent changes in purchasing at 1-, 3-, and 6-months after the onset of each Tier-3 drug shortage and interventional ARIMA modelling was used to assess the statistical significance. RESULTS: Medroxyprogesterone acetate experienced a significant shift (p = 0.0370) in purchasing following its shortage, and the 1-, 3-, and 6-month percent changes were +14.9%, +6.8% and -3.1%, respectively. Hydralazine and sarilumab did not show a significant shift. The 1-, 3-, and 6-month percent changes for hydralazine were +15.5%, +10.2%, and +9.6% respectively and +25.2%, +45.1% and +39.2 for sarilumab. CONCLUSIONS: These results indicate that drugs assigned a Tier-3 status may not show declines in purchasing in the months following status assignment, which may be due to policy responses following the assignment. However, more insight is needed into the mechanisms through which these policy measures impact shortages and whether they are functioning as intended.

Improved imaging and preservation of lysosome dynamics using silver nanoparticle-enhanced fluorescence.

The dynamics of living cells can be studied by live-cell fluorescence microscopy. However, this requires the use of excessive light energy to obtain good signal-to-noise ratio, which can then photobleach fluorochromes, and more worrisomely, lead to phototoxicity. Upon light excitation, noble metal nanoparticles such as silver nanoparticles (AgNPs) generate plasmons, which can then amplify excitation in direct proximity of the nanoparticle's surface and couple to the oscillating dipole of nearby radiating fluorophores, modifying their rate of emission and thus, enhancing their fluorescence. Here, we show that AgNPs fed to cells to accumulate within lysosomes enhanced the fluorescence of lysosome-targeted Alexa488-conjugated dextran, BODIPY-cholesterol, and DQ-BSA. Moreover, AgNP increased the fluorescence of GFP fused to the cytosolic tail of LAMP1, showing that metal enhanced fluorescence can occur across the lysosomal membrane. The inclusion of AgNPs in lysosomes did not disturb lysosomal properties such as lysosomal pH, degradative capacity, autophagy and autophagic flux, and membrane integrity, though AgNP seemed to increase basal lysosome tubulation. Importantly, by using AgNP, we could track lysosome motility with reduced laser power without damaging and altering lysosome dynamics. Overall, AgNP-enhanced fluorescence may be a useful tool to study the dynamics of the endo-lysosomal pathway while minimizing phototoxicity.