Penalized maximum likelihood inference under the mixture cure model in sparse data.

INTRODUCTION: When a study sample includes a large proportion of long-term survivors, mixture cure (MC) models that separately assess biomarker associations with long-term recurrence-free survival and time to disease recurrence are preferred to proportional-hazards models. However, in samples with few recurrences, standard maximum likelihood can be biased. OBJECTIVE AND METHODS: We extend Firth-type penalized likelihood (FT-PL) developed for bias reduction in the exponential family to the Weibull-logistic MC, using the Jeffreys invariant prior. Via simulation studies based on a motivating cohort study, we compare parameter estimates of the FT-PL method to those by ML, as well as type 1 error (T1E) and power obtained using likelihood ratio statistics. RESULTS: In samples with relatively few events, the Firth-type penalized likelihood estimates (FT-PLEs) have mean bias closer to zero and smaller mean squared error than maximum likelihood estimates (MLEs), and can be obtained in samples where the MLEs are infinite. Under similar T1E rates, FT-PL consistently exhibits higher statistical power than ML in samples with few events. In addition, we compare FT-PL estimation with two other penalization methods (a log-F prior method and a modified Firth-type method) based on the same simulations. DISCUSSION: Consistent with findings for logistic and Cox regressions, FT-PL under MC regression yields finite estimates under stringent conditions, and better bias-and-variance balance than the other two penalizations. The practicality and strength of FT-PL for MC analysis is illustrated in a cohort study of breast cancer prognosis with long-term follow-up for recurrence-free survival.

Adenosine-rich extract of Ganoderma lucidum: A safe and effective lipid-lowering substance.

Ganoderma lucidum is a traditional Chinese medicine with a variety of active compounds and possesses adequate lipid-lowering and anti-atherosclerotic effects. However, its main active components and potential mechanisms still remain unclear. Here, we evaluated the anti-hyperlipidemic effect of the adenosine extract from Ganoderma lucidum (AEGL) in high-fat-diet (HFD)-induced hyperlipidemic ApoE-/- mice and explored the underlying biological mechanism by multi-omics analysis. Treatment with AEGL for 8 weeks significantly decreased the serum levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-c) by 45.59%, 41.22%, and 39.02%, respectively, as well as reduced liver TC and TG by 44.15% and 76.23%, compared with the HFD-only group. We also observed significant amelioration of hepatic steatosis without liver and kidney damage after AEGL treatment. Regulating the expression and acetylation/crotonylation of proteins involved in the PPAR signaling pathway may be one of the potential mechanisms involved in the observed lipid-lowering effects of AEGL.

Evaluating the impact of onsite diabetes education teams in primary care on clinical outcomes.

BACKGROUND: To evaluate the impact of integrating diabetes education teams in primary care on glycemic control, lipid, and blood-pressure management in type 2 diabetes patients. METHODS: A historical cohort design was used to assess the integration of teams comprising nurse and dietitian educators in 11 Ontario primary-care sites, which delivered individualized self-management education. Of the 771 adult patients with A1C ≥ 7% recruited, 487 patients attended appointments with the diabetes teams, while the remaining 284 patients did not. The intervention's primary goal was to increase the proportion of patients with A1C ≤7%. Secondary goals were to reduce mean A1C, low-density lipoprotein, total cholesterol-high density lipoprotein, and diastolic and systolic blood pressure, as recommended by clinical-practice guidelines. RESULTS: After 12 months, a higher proportion of intervention-group patients reached the target for A1C, compared with the control group. Mean A1C levels fell significantly among all patients, but the mean reduction was larger for the intervention group than the control group. Although more intervention-group patients reached targets for all clinical outcomes, the between-group differences were not statistically significant, except for A1C. CONCLUSIONS: Nurse and dietitian diabetes-education teams can have a clinically meaningful impact on patients' ability to meet recommended A1C targets. Given the study's historical cohort design, results are generalizable and applicable to day-to-day primary-care practice. Longer follow-up studies are needed to investigate whether the positive outcomes of the intervention are sustainable.

Impact of diabetes education teams in primary care on processes of care indicators.

AIMS: To evaluate the impact of the integration of onsite diabetes education teams in primary care on processes of care indicators according to practice guidelines. METHODS: Teams of nurse and dietitian educators delivered individualized self-management education counseling in 11 Ontario primary care sites. Of the 771 adult patients with HbA1c ≥7% who were recruited in a prospective cohort study, 487 patients attended appointments with the education teams, while the remaining 284 patients did not (usual care group). Baseline demographic, clinical information, and patient care processes (diabetes medical visit, HbA1c test, lipid profile, estimated glomerular filtration rate, and albumin-to-creatinine ratio, measuring blood pressure, performing foot exams, provision of flu vaccine, and referral for dilated retinal exam) were collected from patient charts one year before (pre period) and after (post period) the integration began. A multi-level random effects model was used to analyze the effect of group and period on whether the process indicators were met based on practice guidelines. RESULTS: Compared to the usual care group, patients seen by the education teams had significant improvements on indicators for semi-annual medical visit and annual foot exam. No significant improvements were found for other process of care indicators. CONCLUSIONS: Onsite education teams in primary care settings can potentially improve diabetes management as shown in two process of care indicators: medical visits and foot exams. The results support the benefits of having education teams in primary care settings to increase adherence to practice guidelines.

Functional immobilization of interferon-gamma induces neuronal differentiation of neural stem cells.

Stem cell transplantation provides significant promise to regenerative strategies after injury in the central nervous system. Neural stem/progenitor cells (NSPCs) have been studied in terms of their regenerative capacity and their ability to differentiate into neurons when exposed to various soluble factors. In this study, interferon-gamma (IFN-gamma) was compared with brain-derived neurotrophic factor (BDNF) and erythropoietin and was shown to be the best single growth factor for inducing neuronal differentiation from adult rat brain-derived NSPCs. Next, IFN-gamma was surface immobilized to a methacrylamide chitosan (MAC) scaffold that was specifically designed to match the modulus of brain tissue and neuronal differentiation of NSPCs was examined in vitro by immunohistochemistry. Bioactive IFN-gamma was successfully immobilized and quantified by ELISA. Both soluble and immobilized IFN-gamma on MAC surfaces showed dose dependent neuronal differentiation with soluble saturation occurring at 100 ng/mL and the most effective immobilized IFN-gamma dose at 37.5 ng/cm(2), where significantly more neurons resulted compared with controls including soluble IFN-gamma.