Shortages of antiseizure medications in Australia and the association with patient switching, and adherence in a community setting.

PURPOSE: To quantify sponsor-reported shortages of oral antiseizure medications in Australia, estimate the number of patients impacted, and the association between shortages and brand or formulation switching, and changes in adherence. METHODS: A retrospective cohort study of sponsor-reported shortages (defined as where the supply of a medicine will not or will not be likely to meet the demand over a 6-month period) of antiseizure medications reported to the Medicine Shortages Reports Database (Therapeutic Goods Administration, Australia); cross-referencing shortages to the IQVIA-NostraData Dispensing Data (LRx) database, a deidentified, population-level dataset collecting longitudinal dispensation data on individual patients from ∼75% of Australian community pharmacy scripts. RESULTS: Ninety-seven sponsor-reported ASM shortages were identified between 2019 and 2020; of those, 90 (93%) were shortages of generic ASM brands. Of 1,247,787 patients dispensed ≥1 ASMs, 242,947 (19.5%) were impacted by shortages. Sponsor-reported shortages occurred more frequently before the COVID-19 pandemic versus during the pandemic, however, shortages were estimated to affect more patients during the pandemic than before the pandemic. An estimated 330,872 patient-level shortage events were observed, and 98.5% were associated with shortages of generic ASM brands. Shortages occurred at a rate of 41.06 shortages per 100 person-years in patients on generic ASM brands versus 0.83 shortages per 100 person-years in patients on originator ASM brands. In patients taking a formulation of levetiracetam affected by a shortage, 67.6% switched to a different levetiracetam brand or formulation during shortages compared with 46.6% in non-shortage periods. CONCLUSIONS: Approximately 20% of patients on ASMs were estimated to have been impacted by an ASM shortage in Australia. The rate of patient-level shortages was approximately 50 times higher for patients on generic ASM brands versus originator brands. Shortages of levetiracetam were associated with formulation and brand switching. Improved supply chain management amongst sponsors of generic ASMs is needed to maintain the continuity of supply in Australia.

Micro-fabricated polydimethyl siloxane (PDMS) surfaces regulate the development of marine microbial biofilm communities.

This study explored an antifouling (AF) concept based on deployment of microfabricated polydimethyl siloxane (PDMS) surfaces with 1-10 µm periodicity corrugated topographies in temperate marine waters. The effect of the surfaces on the development of microbial biofilms over 28 days and during different seasons, including both summer and winter, was examined using confocal laser scanning microscopy (CLSM) as well as terminal restriction fragment (T-RF) analysis for phylogenetic fingerprinting. The microscale topography significantly impacted biofilm development by altering the attachment pattern and reducing microcolony formation on the 1, 2 and 4 µm PDMS surfaces. Also, field deployments over 28 days showed a significant reduction in biovolume on the 4 and 10 µm PDMS surfaces despite altered environmental conditions. The microfabricated PDMS surfaces further significantly impacted on the community composition of the biofilms, as revealed by changes in T-RF profiles, at different stages of development. Moreover, altered biofilm resistance was demonstrated by exposing pre-established biofilms on 10 µm micro-fabricated surfaces to enhanced flagellate predation by a heterotrophic protist, Rhynchomonas nasuta. Pronounced changes in the overall marine microbial biofilm development as well as community composition warrant exploring substratum modification for marine AF applications.