In vitro and Computational Modelling of Drug Delivery across the Outer Blood-Retinal Barrier

The ability to produce rapid, cost-effective and human-relevant data has the potential to accelerate development of new drug delivery systems. Intraocular drug delivery is an area undergoing rapid expansion due to the increase in sight-threatening diseases linked to increasing age and lifestyle factors. The outer bloodretinal barrier (OBRB) is important in this area of drug delivery, as it separates the eye from the systemic blood flow. This study reports the development of complementary in vitro and in silico models to study drug transport from silicone oil across the outer blood-retinal barrier. Monolayer cultures of a human retinal pigmented epithelium cell line, ARPE-19, were added to chambers and exposed to a controlled flow to simulate drug clearance across the OBRB. Movement of dextran molecules and release of ibuprofen from silicone oil in this model were measured. Corresponding simulations were developed using COMSOL Multiphysics computational fluid dynamics (CFD) software and validated using independent in vitro data sets. Computational simulations were able to predict dextran movement and ibuprofen release, with all of the features of the experimental release profiles being observed in the simulated data. Simulated values for peak concentrations of permeated dextran and ibuprofen released from silicone oil were within 18% of the in vitro results. This model could be used as a predictive tool of drug transport across this important tissue

The stigma and self-stigma scales for attitudes to mental health problems: psychometric properties and its relationship to mental health problems and absenteeism

The Stigma and Self-Stigma scales (SASS) measure multiple aspects of stigmatic beliefs about mental health problems, including cognitive aspects of stigma towards others (Stigma to Others) and emotional stigma toward others (Social Distance), anticipated stigma by others, self-stigma, avoidant coping strategies, and help-seeking intentions, alongside an index of social desirability. The properties of the SASS were investigated by employees of a large UK government organization. With minor exceptions, each of the SASS scales had strong psychometric properties, good internal reliability, and test-retest reliability. Social Distance, Anticipated Stigma, Self-Stigma, and Avoidant Coping were all strongly associated with a lack of help-seeking for mental health problems. Similarly, Stigma to Others, Self-Stigma, and Avoidant Coping were all associated with current mental health problems. Finally, absenteeism from the workplace was found to be negatively related to Stigma to Others, and positively related to Avoidant Coping and Anticipated Stigma. In conclusion, the SASS was able to measure several different forms of stigma about mental health simultaneously in people both with and without a history of mental health problems. The SASS can be used to monitor changes in mental health attitudes outcomes following intervention programs to investigate stigmatic attitudes to mental health problems across different samples

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research