Rate of achievement of therapeutic outcomes and factors associated with control of non-communicable diseases in rural east Malaysia: implications for policy and practice.

Non-communicable diseases (NCDs) are an increasing problem worldwide, including in Malaysia. National surveys have been performed by the government but had poor coverage in east Malaysia, particularly in rural regions. This study aimed to describe the achievement of target therapeutic outcomes in the control of diabetes mellitus (DM), hypertension (HPT), and dyslipidemia (DLP) among diabetic patients in rural east Malaysia. A cross-sectional study was conducted among DM patients who visited the NCDs clinic in Lundu Hospital, Sarawak, Malaysia, from Jan to March 2016. In total, 214 patients (male, 37.9%; female, 62.1%) were recruited using a systemic sampling method. Multiple logistic regression models were applied to estimate the adjusted odds ratio (AOR) and confidence interval (CI) for the target therapeutic achievement in the control of DM, HPT, and DLP. Compared to the national average, therapeutic target achievement in Lundu was higher for DM (43.0% vs. 23.8%), equal for DLP (35.8% vs. 37.8%) but lower for HPT (30.9% vs. 47.9%). DM patients who had at least yearly HbA1c monitoring (AOR 2.30, 95% CI 1.04-5.06, P = 0.039), and those 58.7 years or older (AOR 2.50, 95% CI 1.32-4.74, P = 0.005) were more likely to achieve the therapeutic target for DM. Health promotion and public education regarding HPT needs to be emphasized in rural Malaysia. HbA1c monitoring at least once a year was one of the important factors associated with achieving DM control in rural east Malaysia. Accessibility to HbA1c tests and monitoring should be ensured for diabetic patients.

Immuno-oncological Efficacy of RXDX-106, a Novel TAM (TYRO3, AXL, MER) Family Small-Molecule Kinase Inhibitor.

Expression of the TAM (TYRO3, AXL, MER) family of receptor tyrosine kinases (RTK) has been associated with cancer progression, metastasis, and drug resistance. In immune cells, TAM RTKs can dampen inflammation in favor of homeostatic wound-healing responses, thus potentially contributing to the evasion of cancer cells from immune surveillance. Here we characterize the small-molecule RXDX-106 as a selective and potent pan-TAM RTK inhibitor with slow dissociation kinetics and significant antitumor activity in multiple syngeneic tumor models. Expression of AXL and MER on both immune and tumor cells increased during tumor progression. Tumor growth inhibition (TGI) following treatment with RXDX-106 was observed in wild-type mice and was abrogated in immunodeficient mice, suggesting that the antitumor activity of RXDX-106 is, in part, due to the presence of immune cells. RXDX-106-mediated TGI was associated with increased tumor-infiltrating leukocytes, M1-polarized intratumoral macrophages, and activation of natural killer cells. RXDX-106 proportionally increased intratumoral CD8+ T cells and T-cell function as indicated by both IFNγ production and LCK phosphorylation (pY393). RXDX-106 exhibited its effects via direct actions on TAM RTKs expressed on intratumoral macrophages and dendritic cells, leading to indirect activation of other immune cells in the tumor. RXDX-106 also potentiated the effects of an immune checkpoint inhibitor, α-PD-1 Ab, resulting in enhanced antitumor efficacy and survival. Collectively, these results demonstrate the capacity of RXDX-106 to inhibit tumor growth and progression and suggest it may serve as an effective therapy against multiple tumor types. SIGNIFICANCE: The pan-TAM small-molecule kinase inhibitor RXDX-106 activates both innate and adaptive immunity to inhibit tumor growth and progression, indicating its clinical potential to treat a wide variety of cancers.