SafeMed: Using pharmacy technicians in a novel role as community health workers to improve transitions of care.

OBJECTIVES: To describe the design, implementation, and early experience of the SafeMed program, which uses certified pharmacy technicians in a novel expanded role as community health workers (CPhT-CHWs) to improve transitions of care. SETTING: A large nonprofit health care system serving the major medically underserved areas and geographic hotspots for readmissions in Memphis, TN. PRACTICE INNOVATION: The SafeMed program is a care transitions program with an emphasis on medication management designed to use low-cost health workers to improve transitions of care from hospital to home for superutilizing patients with multiple chronic conditions and polypharmacy. EVALUATION: CPhT-CHWs were given primary responsibility for patient outreach after hospital discharge with the use of home visits and telephone follow-up. SafeMed program CPhT-CHWs served as pharmacist extenders, obtaining medication histories, assisting in medication reconciliation and identification of potential drug therapy problems (DTPs), and reinforcing medication education previously provided by the pharmacist per protocol. RESULTS: CPhT-CHW training included patient communication skills, motivational interviewing, medication history taking, teach-back techniques, drug disposal practices, and basic disease management. Some CPhT-CHWs experienced difficulties adjusting to an expanded scope of practice. Nonetheless, once the Tennessee Board of Pharmacy affirmed that envisioned SafeMed CPhT-CHW roles were consistent with Board rules, additional responsibilities were added for CPhT-CHWs to enhance their effectiveness. Patient outreach teams including CPhT-CHWs achieved increases in home visit and telephone follow-up rates and were successful in helping identify potential DTPs. CONCLUSION: The early experience of the SafeMed program demonstrates that CPhT-CHWs are well suited for novel expanded roles to improve care transitions for superutilizing populations. CPhT-CHWs can identify and report potential DTPs to the pharmacist to help target medication therapy management. Critical success factors include strong CPhT-CHW patient-centered communication skills and strong pharmacist champions. In collaboration with state pharmacy boards and pharmacist associations, the SafeMed CPhT-CHW model can be successfully scaled to serve superutilizing patients throughout the country.

PRDX6 Promotes the Differentiation of Human Mesenchymal Stem (Stromal) Cells to Insulin-Producing Cells.

Mesenchymal stem cells (MSCs) can be differentiated in vitro to form insulin-producing cells (IPCs). However, the proportion of induced cells is modest. Extracts from injured pancreata of rodents promoted this differentiation, and three upregulated proteins were identified in these extracts. The aim of this study was to evaluate the potential benefits of adding these proteins to the differentiation medium alone or in combination. Our results indicate that the proportion of IPCs among the protein(s)-supplemented samples was significantly higher than that in the samples with no added proteins. The yield from samples supplemented with PRDX6 alone was 4-fold higher than that from samples without added protein. These findings were also supported by the results of fluorophotometry. Gene expression profiles revealed higher levels among protein-supplemented samples. Significantly higher levels of GGT, SST, Glut-2, and MafB expression were noted among PRDX6-treated samples. There was a stepwise increase in the release of insulin and c-peptide, as a function of increasing glucose concentrations, indicating that the differentiated cells were glucose sensitive and insulin responsive. PRDX6 exerts its beneficial effects as a result of its biological antioxidant properties. Considering its ease of use as a single protein, PRDX6 is now routinely used in our differentiation protocols.

Differentiation Potential of Nestin (+) and Nestin (-) Cells Derived from Human Bone Marrow Mesenchymal Stem Cells into Functional Insulin Producing Cells.

The feasibility of isolating and manipulating mesenchymal stem cells (MSCs) from human patients provides hope for curing numerous diseases and disorders. Recent phenotypic analysis has shown heterogeneity of MSCs. Nestin progenitor cell is a subpopulation within MSCs which plays a role in pancreas regeneration during embryogenesis. This study aimed to separate nestin (+) cells from human bone marrow MSCs, and differentiate these cells into functional insulin producing cells (IPCs) compared with nestin (-) cells. Manual magnetic separation was performed to obtain nestin (+) cells from MSCs. Approximately 91±3.3% of nestin (+) cells were positive for anti-nestin antibody. Pluripotent genes were overexpressed in nestin (+) cells compared with nestin (-) cells as revealed by quantitative real time-PCR (qRT-PCR). Following in vitro differentiation, flow cytometric analysis showed that 2.7±0.5% of differentiated nestin (+) cells were positive for anti-insulin antibody in comparison with 0.08±0.02% of nestin (-) cells. QRT-PCR showed higher expression of insulin and other endocrine genes in comparison with nestin (-) cells. While immunofluorescence technique showed the presence of insulin and C-peptide granules in nestin (+) cells. Therefore, our results introduced nestin (+) cells as a pluripotent subpopulation within human MSCs which is capable to differentiate and produce functional IPCs.

Effects of polyethylene glycol molecular weight and concentration on lactate dehydrogenase activity in solution and after freeze-thawing.

Lactate dehydrogenase (LDH) is a tetrameric enzyme that has been used as a model for labile protein drugs. Polyethylene glycols (PEGs) have been proposed as excipients to stabilize labile proteins in solution and during the freezing portion of the lyophilization cycle. The aim of this study was to determine the effects of PEG molecular weight and concentration on the activity of LDH. In general, PEG protection increases with PEG molecular weight and concentration. PEGs slow the loss of activity in LDH solutions stored at 4 degrees C, but are not sufficiently effective to allow for a solution product. PEGs 8000, 10,000, and 20,000 show full freezing protection at less than 0.01%, while lower molecular weight PEGs need higher concentrations to produce protection upon freezing. Circular dichroism (CD) studies of LDH solutions before and after freezing with PEG 400 and PEG 8000 confirm the activity studies. The CD spectrum of LDH before freezing shows the classic alpha helix pattern. After unprotected LDH solution is frozen and thawed, the CD spectrum erodes. Low concentrations of PEG 8000 (1% or less) preserve the alpha helix profile after freezing of the samples. PEG 400 preserves the alpha helix CD profile in a stepwise fashion with increasing concentrations. The CD and activity data suggest that PEGs can protect alpha helix structures and activity of LDH through the freezing process.

ß2-Adrenoreceptor Polymorphisms in Asthmatic Patients.

ß2-adrenergic receptors (ß2AR) are GTP-binding protein (G-protein) coupled receptors widely distributed in human tissue. Inhaled ß2-agonist drugs exert their primary effect on the ß2AR of bronchial smooth muscles, causing relaxation and bronchial dilatation. Polymorphisms in the ß2AR gene have been identified, which may affect responsiveness to ß2-agonists and disease severity in asthmatics. Nine single nucleotide polymorphisms (SNPs) within the coding region and eight SNPs within in the 5' upstream region of the ß2AR gene have been identified. The two most studied polymorphisms are mutations in the coding region at codon 16, Arg to Gly (Arg16Gly) and at codon 27, Gln to Glu (Gln27Glu). Evidence suggests that carriers of Gly16, as well as carriers of Gln27, are prone to down-regulation of ß2AR. Patients who are homozygous for Arg16 and/or Glu 27 may be more susceptible to tachyplaxis with chronic use of ß2-agonists. Although ß2AR polymorphism is not related to the severity of asthma, patients with nocturnal asthma have higher frequency of Gly16. A polymorphism in the 5' upstream region, 5' leader cistron (5'LC), encodes for a protein that regulates mRNA transcription. The Cys19 polymorphism in the 5'LC is associated with higher expression of ß2AR. More recent studies have focused on combinations of polymorphisms across the gene region (haplotypes). The interaction of multiple SNPs within a haplotype may control ß2AR function resulting in different phenotypic response in patients with asthma. ß2AR polymorphism may have a significant implication in the pathophysiology of asthma and therapeutic response.

Chemical compatibility of depacon(®) with medications frequently administered by intravenous y-site delivery in patients with epilepsy or head trauma.

OBJECTIVES: Intravenous Y-site administration of more than one medication through the same in-line catheter is a common practice used in the management of acute seizures. The objective of this study was to determine the compatibility of valproate sodium (Depacon(®); 2 or 20 mg/mL) with 13 medications that are frequently administered to manage seizures or are given to patients with an acute head injury who are at risk for developing post-traumatic epilepsy. METHODS: The study medications included atracurium, dexamethasone, diazepam, fosphenytoin, lorazepam, magnesium sulfate, mannitol, methyl-prednisolone, midazolam, pentobarbital, phenytoin, ranitidine, and thiopental. Equal volumes of valproate and each of the study drugs were admixed and immediately examined using several physiochemical criteria: Tyndall effect, color and pH change, gas evolution, and particle formation (HIAC/Royco liquid particle counter). Samples were also evaluated using HPLC analysis (C(18) column; methanol/tetrahydrofuran/ phosphate buffer; 44/1/55% v/v, at 1.5 mL/min; 50°C) with UV (190-400 nm) photodiode detection. The valproate peak (220 nm) was quantified by both peak area and height. Samples were analyzed within 5 minutes of admixture and were reassessed at 15 and 30 minutes. RESULTS: With the exception of diazepam, midazolam, and phenytoin, all of the remaining drugs were chemically compatible with valproate, both in 5% Dextrose Injection, USP(D5W) and in 0.9% Sodium Chloride Injection, USP (Normal Saline -NS). None of the compatible medications produced a significant pH change, discernible gas, particle formation, reduced valproate titer by HPLC analysis (coefficient of variability < 1.5%), or the temporal formation of unidentified UV absorbing (190-400 nm) peaks. CONCLUSIONS: Intravenous valproate is compatible with most agents employed in seizure management or used in patients at risk for seizures following head injury and is safe for concurrent Y-site drug administration.

Type 2 diabetes mellitus in children and adolescents: the new challenge.

The epidemic increase in the incidence of type 2 diabetes mellitus (T2DM) in children and adolescents is presenting enormous challenges to the medical profession. The combination of factors such as obesity, ethnicity, puberty, and genetic predisposition has contributed to the development of T2DM in younger ages. These factors affect the regulatory mechanism of insulin secretion, insulin action, and hepatic gluconeogenesis. In contrast to adults, children appear to have a shorter latency to disease, a more rapid development of symptoms, and an increased ketoacidosis. There are limited therapeutic options to prevent or manage T2DM in children. Although the role of diet and exercise (lifestyle intervention) has not been adequately evaluated in children, they will remain important adjuncts in the prevention and treatment of T2DM. Insulin and metformin are currently the only approved medications for the treatment of T2DM in children. Clinical trials involving other oral agents used in adults are currently being conducted to evaluate their safety and efficacy in children.