Towards a global partnership model in interprofessional education for cross-sector problem-solving

Objectives A partnership model in interprofessional education (IPE) is important in promoting a sense of global citizenship while preparing students for cross-sector problem-solving. However, the literature remains scant in providing useful guidance for the development of an IPE programme co-implemented by external partners. In this pioneering study, we describe the processes of forging global partnerships in co-implementing IPE and evaluate the programme in light of the preliminary data available. Methods This study is generally quantitative. We collected data from a total of 747 health and social care students from four higher education institutions. We utilized a descriptive narrative format and a quantitative design to present our experiences of running IPE with external partners and performed independent t-tests and analysis of variance to examine pretest and posttest mean differences in students’ data. Results We identified factors in establishing a cross-institutional IPE programme. These factors include complementarity of expertise, mutual benefits, internet connectivity, interactivity of design, and time difference. We found significant pretest–posttest differences in students’ readiness for interprofessional learning (teamwork and collaboration, positive professional identity, roles, and responsibilities). We also found a significant decrease in students’ social interaction anxiety after the IPE simulation. Conclusions The narrative of our experiences described in this manuscript could be considered by higher education institutions seeking to forge meaningful external partnerships in their effort to establish interprofessional global health education

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Defective TGF beta signaling in bisphosphonates associated atypical femoral fracture

INTRODUCTION: Bisphosphonates (BPs) are potent anti-resorptive agents and their therapeutic use in osteoporosis treatment and fracture prevention has been well established. However, studies investigating the association of atypical femoral fractures (AFF) and use of BPs are still inconclusive due to lack of scientific evidence. Transforming growth factor-beta (TGF-beta) is abundant in bone matrix which plays critical roles in bone remodeling, migration of bone mesenchymal stem cells to resorptive sites, osteoblastic-osteoclastic coupling in bone formation and resorption. Increase of TGF-beta1 has also been shown as the etiology of disease which exhibits diaphyseal dysplasia. PURPOSE OF STUDY: Purpose of this study was to compare expression of TGF-beta in AFF with normal control and to determine TGF-beta as possible cause of AFF. METHODS: Bone marrow supernatant was collected for active TGF-beta levels. Bone marrow stromal cells from AFF patient and control were obtained. Pluripotency of stromal cells had been demonstrated by adipogenic, chondrogenic and osteogenic differentiations. These cells were differentiated to osteoblasts and osteoclasts for in-vitro co-culture with bovine femoral cortical bone discs. Osteogenic differentiation rate was reported by ALP assay. The difference in rate of cells metabolic activities was evaluated by MTT assay. Gene and protein expressions of TGF-beta were reported by q-RT-PCR and cytokine ELISA. After initial comparison of findings between AFF and control samples, further culturing of control sample with alendronate and in-vito treatment of AFF sample by TGF-beta 1 were performed. RESULTS: In initial comparison, active TGF-beta 1 was detected as significantly decreased in bone marrow supernatant of AFF group by cytokine ELISA; higher osteogenic differentiation rate was found in AFF samples in contrary to low clinical serum ALP level in BP-treated patients. The rate of osteoblast metabolic activity was found significantly different in co-cultures with variety of spatial arrangement. Gene expressions of TGF-beta 1 and TGF-beta R1 were found down-regulated; TGF-beta 2 found up-regulated and TGF-beta R2 found down-regulated in AFF sample. ELISA results showed free release of TGF-beta 1 in medium is lower in AFF. In the follow-up culture of control sample with alendronate exhibited change of all ALP, MTT, q-RT-PCR and ELISA findings towards trends of AFF results. Whereas, in-vitro treatment of AFF sample by TGF-beta 1 demonstrated restorative effect towards control level. CONCLUSION: TGF-beta signaling pathway was found different in AFF patients from normal control. Further culture studies recommended causal relationship of defective TGF-beta signaling and BPs associated AFF. BPs affected bone marrow stromal cells which led to this defective TGF-beta signaling.published_or_final_versionOrthopaedics and TraumatologyDoctoralDoctor of Philosoph

Pattern and impact of hepatic adverse events encountered during immune checkpoint inhibitors – A territory‐wide cohort study

Abstract Background Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of cancers. We aimed to evaluate the incidence and prognostic impact of hepatic adverse events (AEs) in a territory‐wide cohort of patients who received ICIs. Methods Patients were identified from a territory‐wide database who received ICIs in 2014‐2018. Hepatic AEs were defined as any elevation of liver biochemistries including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin levels. Hepatic AEs were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results Total of 1480 patients were identified (mean age 60 years, male 65.5%) and the commonest malignancies being lung cancer (39.6%), liver cancer (16.5%), and gastrointestinal cancer (10.0%). Grade 1‐2 and grade 3‐4 hepatic AEs occurred in 41.3% and 14.9% of patients during ICI treatment, respectively. Patients with liver cancer had the highest rate of hepatic AEs (grade 1‐2:54.1%; grade 3‐4:32.8%). Among 711 patients with hepatic AEs, 383 (53.9%) had raised ALT/AST only, and 328 (46.1%) had concomitant raised ALT/AST and bilirubin levels. In the whole cohort, median overall survival of patients without any hepatic AEs, grade 1‐2 and grade 3‐4 hepatic AEs during ICI treatment was 9.0 months, 7.2 months, and 3.3 months (P < .001), respectively. Similar results on overall survival were obtained among different types of cancers. Conclusions Hepatic AEs occur in more than half of patients receiving ICIs for cancer treatment, with approximately 15% being grade 3‐4 AEs. Occurrence of hepatic AEs is associated with worse prognosis

Baveno VII criteria for recompensation predict transplant-free survival in patients with hepatitis B-related decompensated cirrhosis

Background &amp; Aims: The latest Baveno VII consensus has provided guidance for identifying patients who have truly recompensated from those with hepatic decompensation. This study aimed to evaluate patients’ transplant-free survival in three different stages of cirrhosis. Methods: All patients with chronic HBV infection and liver cirrhosis treated with oral nucleos(t)ide analogues from March 2006 to December 2022 were identified from a territory-wide database in Hong Kong. Patients with follow-up duration of <1 year were excluded. Participants were classified into three mutually exclusive groups: (1) no decompensated events (i.e. compensated group); (2) decompensated events occurred (i.e. decompensated group); or (3) decompensated events occurred followed by recompensation according to Baveno VII criteria (i.e. recompensated group). A time-dependent Cox proportional hazard model was adopted for evaluation. The follow-up period was 5 years. Results: A total of 4,701 patients with cirrhosis and HBV who were treated with entecavir, tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide fumarate (TAF) were identified. During a median follow-up of 5 years (interquartile range 3.7, 5 years), 3,327 (70.8%), 1,347 (29.2%), and 265 (5.6%) patients had compensated, decompensated, and recompensated cirrhosis, respectively, at least once before the end of the study. In the time-dependent multivariable model, the recompensated group had similar transplant-free survival compared with the compensated group (adjusted hazard ratio 1.16; 95% CI 0.72–1.86; p = 0.536). The 5-year transplant-free survival rate was 89.3% for the compensated group, whereas it was 76.0% for the recompensated group, reflecting a minimal difference between the two groups. Conclusions: The clinical significance of recompensation of cirrhosis in improving patient outcomes for individuals with CHB infection was highlighted in this study. Early identification and treatment with nucleos(t)ide analogues might promote hepatic recompensation and thus reduce mortality in patients with CHB. Impact and implications: The latest Baveno VII consensus introduces the new concept of hepatic recompensation, which refers to the reversal of the structural and functional changes of cirrhosis after removal, cure, or suppression of the aetiology of cirrhosis. It is essential to investigate the transplant-free survival rates of patients who are able to achieve hepatic recompensation, as this has significant implications for the medical resources required to manage liver failure and transplantation. This study features the clinical significance of hepatic recompensation by comparing patient outcomes of those who achieve it to those who do not. The early identification and use of antiviral treatment with nucleos(t)ide analogues is a pivotal strategy to promote hepatic recompensation, which has the potential to significantly reduce mortality rates in patients with chronic HBV infection and ultimately aid in the elimination of hepatitis

Baveno VII Criteria Is an Accurate Risk Stratification Tool to Predict High-Risk Varices Requiring Intervention and Hepatic Events in Patients with Advanced Hepatocellular Carcinoma

The Baveno VII criteria are used in patients with liver cirrhosis to predict high-risk varices in patients with liver cirrhosis. Yet its use in patients with advanced hepatocellular carcinoma (HCC) has not been validated. HCC alone is accompanied with a higher variceal bleeding risk due to its association with liver cirrhosis and portal vein thrombosis. The use of systemic therapy in advanced HCC has been thought to further augment this risk. Upper endoscopy is commonly used to evaluate for the presence of varices before initiation of treatment with systemic therapy. Yet it is associated with procedural risks, waiting time and limited availability in some localities which may delay the commencement of systemic therapy. Our study successfully validated the Baveno VI criteria with a 3.5% varices needing treatment (VNT) missed rate, also with acceptable 150 × 109/L) also revealed a low frequency (2%) of hepatic events, whilst the rule-in criteria (LSM > 25 kPa) was predictive of a higher proportion of hepatic events (14%). Therefore, our study has successfully validated the Baveno VII criteria as a non-invasive stratification of the risk of variceal bleeding and hepatic decompensation in the HCC population