Background: Primary medication non-adherence (PMN), defined as failure to obtain newly prescribed medications, results in adverse clinical and economic outcomes.We aimed to (a) assess the prevalence of PMN in six common chronic diseases: asthma and/ or chronic obstructive pulmonary disease, depression, diabetes mellitus, hyperlipidaemia, hypertension and osteoporosis; (b) identify and categorise factors associated with PMN; (c) explore characteristics that contributed to heterogeneity between studies. Methods:We performed a systematic search in MEDLINE, Embase, Cochrane Library, CINAHL and PsycINFO. Studies published in English between January 2008 and August 2018 assessing PMN in subjects aged ≥18 years were included. We used the Cochrane risk of bias tool, Newcastle-Ottawa Scale and National Heart, Lung and Blood Institute Quality Assessment Tool to assess the quality of randomised controlled trials, cohort and cross-sectional studies, respectively. Findings were reported using the PRISMA checklist. PMN rates were pooled using a random effects model. We summarised factors associated with PMN descriptively. Subgroup analysis was performed to explore sources of heterogeneity. Results:We screened 3083 articles and included 33 (5 randomised controlled trials, 26 cohort and 2 cross-sectional studies, n = 539 156), of which 31 (n = 519 971) were used in meta-analysis. The pooled PMN rate was 17% (95% CI: 15%-20%). Pooled PMN rates were highest in osteoporosis (25%, 95% CI: 7%-44%) and hyperlipidaemia (25%, 95% CI: 18%-32%) and lowest in diabetes mellitus (10%, 95% CI: 7%-12%).Factors commonly associated with PMN include younger age, number of concurrent medications, practitioner specialty and higher co-payment. Type of chronic disease, age, study setting and PMN definition contributed to heterogeneity between studies (all P < 0.001). Conclusion:Primary medication non-adherence is common among patients with chronic diseases and more needs to be done to address this issue in order to improve patient outcomes. Future PMN studies could benefit from greater standardisation to enhance comparability.

Raman microspectroscopy is a non-destructive, label-free optical technique that offers information-rich molecular analysis of living cells. We report here the first Raman spectral study of human induced pluripotent stem cells (hiPSCs), and compare their Raman features to those of human embryonic stem cells (hESCs) and differentiated progeny of hESCs. Raman spectra from 687 cm(-1) to 1073 cm(-1) were collected from living hiPSCs, hESCs and hESCs non-specifically differentiated for 20 days. Spectra of hiPSCs and hESCs were found to be highly similar, and both were distinguishable from differentiated hESCs in terms of relative Raman peak intensities and variances. Principal component analysis (PCA) of the spectra demonstrated a clear discrimination between hiPSCs and differentiated hESCs. These results suggested that reprogramming returned human somatic cells to a state where the overall cellular composition was similar to that of human embryonic stem cells. Some metabolic differences between the two groups of pluripotent cells could be inferred, however it was unclear whether or not these differences were related to reprogramming.

Highlights• Medication utilization trends for type 2 diabetes have changed significantly over the years with a shift towards newer agents, and in line with prevailing treatment guidelines. • Metformin is currently the most commonly prescribed glucose-lowering agent, while the use of insulin has increased tremendously in our institution. Use of sulfonylureas decreased, but to a lesser extent than other studies. • Glycemic control has remained largely stable throughout the 11-year study period, but the rate of severe hypoglycemia has increased. AbstractBackground: Use of glucose-lowering agents is a cornerstone in combating type 2 diabetes (T2DM). Treatment guidelines have changed significantly over the past decade. We report temporal trends in medication utilization, glycemic control and rate of severe hypoglycemia in T2DM patients at a tertiary referral center in Singapore. Methods: We analyzed data of 36 924 T2DM patients seen at Singapore General Hospital from 2007 to 2017. Annual age-, sex-and racially-standardized proportions of patients (a) prescribed with each class of glucose-lowering agent, (b) on various glucose-lowering regimens, and (c) had an HbA 1c of less than 6%, 6% to less than 7%, 7% to less than 8%, 8% to less than 9%, or 9% or more were estimated using logistic regression. Poisson regression was used to estimate standardized rate of severe hypoglycemia. Results: From 2007 to 2017, use of metformin (45.9% to 59.6%) and insulin (24.4% to 57.9%) increased, while utilization of sulfonylureas (52.0% to 44.9%) decreased (all P < 0.001). Utilization of dipeptidyl peptidase-4 inhibitors (1.2% to 31.2%) and sodium-glucose cotransporter-2 inhibitors (0.5% to 7.4%) increased from 2008 to 2017 and 2012 to 2017, respectively (all P < 0.001). More patients were prescribed a combination of insulin and oral agents (17.3% to 46.0%, P < 0.001). The proportion of patients with HbA 1c of 8% or more increased (33.7% to 36.0%, P < 0.001). Rates of severe hypoglycemia (5.0 to 8.4 per 100 patient-years, P < 0.001) also rose. Conclusion: Medication utilization patterns have changed significantly over the past 11 years with a shift towards newer agents. Glycemic control has remained *Co-first author

This is the first study comparing the use of desflurane and TIVA showing that both anesthetic regimens allowed successful intraoperative monitoring useage throughout the procedures. For MEP recording, the AH was the preferred muscle with a desflurane anesthetic regimen.