Stroke thrombolysis in a middle-income country: A case study exploring the determinants of its implementation

Introduction: Translation of evidence into clinical practice for use of intravenous thrombolysis in acute stroke care has been slow, especially across low- and middle-income countries. In Malaysia where the average national uptake was poor among the public hospitals in 2018, one hospital intriguingly showed comparable thrombolysis rates to high-income countries. This study aimed to explore and provide in-depth understanding of factors and explanations for the high rates of intravenous stroke thrombolysis in this hospital. Methods: This single case study sourced data using a multimethod approach: (1) semi-structured in-depth interviews and focus group discussions, (2) surveys, and (3) review of medical records. The Tailored Implementation of Chronic Diseases (TICD) framework was used as a guide to understand the determinants of implementation. Twenty-nine participants comprising the Hospital Director, neurologists, emergency physicians, radiologists, pharmacists, nurses and medical assistants (MAs) were included. Thematic analyses were conducted inductively before triangulated with quantitative analyses and document reviews. Results: Favorable factors contributing to the uptake included: (1) cohesiveness of team members which comprised of positive interprofessional team dynamics, shared personal beliefs and values, and passionate leadership, and (2) facilitative work process through simplification of workflow and understanding the rationale of the sense of urgency. Patient factors was a limiting factor. Almost two third of ischemic stroke patients arrived at the hospital outside the therapeutic window time, attributing patients' delayed presentation as a main barrier to the uptake of intravenous stroke thrombolysis. One other barrier was the availability of resources, although this was innovatively optimized to minimize its impact on the uptake of the therapy. As such, potential in-hospital delays accounted for only 3.8% of patients who missed the opportunity to receive thrombolysis. Conclusions: Despite the ongoing challenges, the success in implementing intravenous stroke thrombolysis as standard of care was attributed to the cohesiveness of team members and having facilitative work processes. For countries of similar settings, plans to improve the uptake of intravenous stroke thrombolysis should consider the inclusion of interventions targeting on these modifiable factors

Integration of an On-Axis General Sun-Tracking Formula in the Algorithm of an Open-Loop Sun-Tracking System

A novel on-axis general sun-tracking formula has been integrated in the algorithm of an open-loop sun-tracking system in order to track the sun accurately and cost effectively. Sun-tracking errors due to installation defects of the 25 m2 prototype solar concentrator have been analyzed from recorded solar images with the use of a CCD camera. With the recorded data, misaligned angles from ideal azimuth-elevation axes have been determined and corrected by a straightforward changing of the parameters' values in the general formula of the tracking algorithm to improve the tracking accuracy to 2.99 mrad, which falls below the encoder resolution limit of 4.13 mrad

Identifying factors in the provision of intravenous stroke thrombolysis in Malaysia: a multiple case study from the healthcare providers’ perspective

Background: Translation into clinical practice for use of intravenous thrombolysis (IVT) for the management of ischemic stroke remains a challenge especially across low- and middle-income countries, with regional inconsistencies in its rate. This study aimed at identifying factors that influenced the provision of IVT and the variation in its rates in Malaysia. Methods: A multiple case study underpinning the Tailored Implementation for Chronic Diseases framework was carried out in three public hospitals with differing rates of IVT using a multiple method design. Twenty-five in-depth interviews and 12 focus groups discussions were conducted among 89 healthcare providers, along with a survey on hospital resources and a medical records review to identify reasons for not receiving IVT. Qualitative data were analysed using reflective thematic method, before triangulated with quantitative findings. Results: Of five factors identified, three factors that distinctively influenced the variation of IVT across the hospitals were: 1) leadership through quality stroke champions, 2) team cohesiveness which entailed team dynamics and its degree of alignment and, 3) facilitative work process which included workflow simplification and familiarity with IVT. Two other factors that were consistently identified as barriers in these hospitals included patient factors which largely encompassed delayed presentation, and resource constraints. About 50.0 – 67.6% of ischemic stroke patients missed the opportunity to receive IVT due to delayed presentation. Conclusions: In addition to the global effort to explore sustainable measures to improve patients’ emergency response for stroke, attempts to improve the provision of IVT for stroke care should also consider the inclusion of interventions targeting on health systems perspectives such as promoting quality leadership, team cohesiveness and workflow optimisation

Combination of Talazoparib and Calcitriol Enhanced Anticancer Effect in Triple−Negative Breast Cancer Cell Lines

Monotherapy for triple−negative breast cancer (TNBC) is often ineffective. This study aimed to investigate the effect of calcitriol and talazoparib combination on cell proliferation, migration, apoptosis and cell cycle in TNBC cell lines. Monotherapies and their combination were studied for (i.) antiproliferative effect (using real−time cell analyzer assay), (ii.) cell migration (CIM−Plate assay), and (iii.) apoptosis and cell cycle analysis (flow cytometry) in MDA−MB−468 and BT−20 cell lines. The optimal antiproliferative concentration of talazoparib and calcitriol in BT−20 was 91.6 and 10 µM, respectively, and in MDA−MB−468, it was 1 mM and 10 µM. Combined treatment significantly increased inhibition of cell migration in both cell lines. The combined treatment in BT−20 significantly increased late apoptosis (89.05 vs. control 0.63%) and S and G2/M populations (31.95 and 24.29% vs. control (18.62 and 12.09%)). Combined treatment in MDA−MB−468 significantly increased the S population (45.72%) and decreased G0/G1 (45.86%) vs. the control (26.79 and 59.78%, respectively). In MDA−MB−468, combined treatment significantly increased necrosis, early and late apoptosis (7.13, 33.53 and 47.1% vs. control (1.5, 3.1 and 2.83%, respectively)). Talazoparib and calcitriol combination significantly affected cell proliferation and migration, induction of apoptosis and necrosis in TNBC cell lines. This combination could be useful as a formulation to treat TNBC

Demonstration lithography using plasma focus soft x-ray source

To demonstrate the soft x-ray source(SXR) developed and to gain experience in handling SXR masks and resists.RG 12/9

Plasma radiation sources for X-ray lithography and neutron analysis applications

The main aim of this project was to develop soft x-ray point sources of sufficient power for application in SXR microelectronics lithography. The stated objective was to deliver l00-200W of SXR power, averaged over several minutes of burst duration, from a point source into 47~. The source was to be based on a plasma focus. The second aim of this project was to carry out a feasibility study of the use of plasma fusion neutrons for activation analysis applications.ARC 5/9

Development of the lithographic sources and processes for device fabrication

The aim of this project was to develop lithographic sources and processes for device fabrication. The NX2 was developed to become a reliable x-ray source for operation in neon.RGM 1/9

Familial Young-Onset Diabetes, Pre-Diabetes and Cardiovascular Disease Are Associated with Genetic Variants of DACH1 in Chinese

In Asia, young-onset type 2 diabetes (YOD) is characterized by obesity and increased risk for cardiovascular disease (CVD). In a genome-wide association study (GWAS) of 99 Chinese obese subjects with familial YOD diagnosed before 40-year-old and 101 controls, the T allele of rs1408888 in intron 1 of DACH1(Dachshund homolog 1) was associated with an odds ratio (OR) of 2.49(95% confidence intervals: 1.57-3.96, P = 8.4610(-5)). Amongst these subjects, we found reduced expression of DACH1 in peripheral blood mononuclear cells (PBMC) from 63 cases compared to 65 controls (P = 0.02). In a random cohort of 1468 cases and 1485 controls, amongst top 19 SNPs from GWAS, rs1408888 was associated with type 2 diabetes with a global P value of 0.0176 and confirmation in a multiethnic Asian case-control cohort (7370/7802) with an OR of 1.07(1.02-1.12, P-meta = 0.012). In 599 Chinese non-diabetic subjects, rs1408888 was linearly associated with systolic blood pressure and insulin resistance. In a case-control cohort (n = 953/953), rs1408888 was associated with an OR of 1.54(1.07-2.22, P = 0.019) for CVD in type 2 diabetes. In an autopsy series of 173 non-diabetic cases, TT genotype of rs1408888 was associated with an OR of 3.31(1.19-9.19, P = 0.0214) and 3.27(1.25-11.07, P = 0.0184) for coronary heart disease (CHD) and coronary arteriosclerosis. Bioinformatics analysis revealed that rs1408888 lies within regulatory elements of DACH1 implicated in islet development and insulin secretion. The T allele of rs1408888 of DACH1 was associated with YOD, prediabetes and CVD in Chinese

Association of SNPs with familial young-onset Type 2 diabetes and obesity in Hong Kong Chinese in a genome-wide association study using Illumina HumanHap550 chip with <i>P</i> values less than 10⁻⁴.

*<p><b>Nearest Entrez genes within 250 Kb.</b></p><p>Stage 1 (genome scan) included 99 young-onset familial T2D patients and 101 controls. Stage 2 (replication stage) included 1468 T2D patients and 1485 controls. <i>P</i>_Allelic and <i>P</i>_permutation represent <i>P</i> values of allelic test and after permutation of 10,000 times based on 19 SNPs in stage 2, respectively.</p><p>Risk allele refers to the allele with a higher frequency in T2D patients than in controls in stage 1.</p><p>RAF (T2D) and RAF (Controls), risk allele frequencies in T2D patients and controls, respectively.</p><p>OR, odds ratio are reported with respect to the risk allele.</p

Clinical profiles of discovery, replication and validation cohorts in a 3-stage genome wide association study in Asian populations.

<p>Clinical profiles of discovery, replication and validation cohorts in a 3-stage genome wide association study in Asian populations.</p