ABSTRACT
The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines focus on atherosclerotic cardiovascular disease (ASCVD) risk reduction, using a Pooled Cohort Equation to calculate a patient's 10-year risk score, which is used to guide initiation of statin therapy. We identified a gap of evidence-based treatment for hyperlipidaemia in the Internal Medicine Clinic. Therefore, the aim of this study was to increase calculation of ASCVD risk scores in patients between the ages of 40 and 75 years from a baseline rate of less than 1% to 10%, within 12 months, for primary prevention of ASCVD. Root cause analysis was performed to identify materials/methods, provider and patient-related barriers. Plan-Do-Study-Act cycles included: (1) creation of customised workflow in electronic health records for documentation of calculated ASCVD risk score; (2) physician education regarding guidelines and electronic health record workflow; (3) refresher training for residents and a chart alert and (4) patient education and physician reminders. The outcome measures were ASCVD risk score completion rate and percentage of new prescriptions for statin therapy. Process measures included lipid profile order and completion rates. Increase in patient wait time, and blood test and medications costs were the balanced measures. We used weekly statistical process control charts for data analysis. The average ASCVD risk completion rate was 14.2%. The mean ASCVD risk completion rate was 4.0%. In eligible patients, the average lipid profile completion rate was 18%. ASCVD risk score completion rate was 33% 1-year postproject period. A team-based approach led to a sustainable increase in ASCVD risk score completion rate. Lack of automation in ASCVD risk score calculation and physician prompts in electronic health records were identified as major barriers. Furthermore, the team identified multiple barriers to lipid blood tests and treatment of increased ASCVD risk based on ACC/AHA guidelines.
ABSTRACT
Methamphetamine (METH) is a drug of abuse, the acute and chronic use of which induces neurotoxic responses in the human brain, ultimately leading to neurocognitive disorders. Our goals were to understand the impact of METH on microglial mitochondrial respiration and to determine whether METH induces the activation of the mitochondrial-dependent intrinsic apoptosis pathway in microglia. We assessed the expression of pro- apoptosis genes using qPCR of RNA extracted from a human microglial cell line (HTHU). We examined the apoptosis-inducing effects of METH on microglial cells using digital holographic microscopy (DHM) to quantify real-time apoptotic volume decrease (AVD) in microglia in a noninvasive manner. METH treatment significantly increased AVD, activated Caspase 3/7, increased the gene expression levels of the pro- apoptosis proteins, APAF-1 and BAX, and decreased mitochondrial DNA content. Using immunofluorescence analysis, we found that METH increased the expression of the mitochondrial proteins cytochrome c and MCL-1, supporting the activation of mitochondrion-dependent (intrinsic) apoptosis pathway. Cellular bio-energetic flux analysis by Agilent Seahorse XF Analyzer revealed that METH treatment increased both oxidative and glycolytic respiration after 3 h, which was sustained for at least 24 h. Several events, such as oxidative stress, neuro-inflammatory responses, and mitochondrial dysfunction, may converge to mediate METH-induced apoptosis of microglia that may contribute to neurotoxicity of the CNS. Our study has important implications for therapeutic strategies aimed at preserving mitochondrial function in METH abusing patients.
