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Objective We evaluated the cost-effectiveness of wireless spinal cord stimulation (Wireless SCS) with single stage "direct to permanent" implantation vs. screening with temporary electrodes and an external pulse generator followed by implantation of a system for long-term use (IPG SCS). Materials and methods We created a cost model that takes a 2019 United States (U.S.) payer perspective and is based on IPG SCS cost models for subjects with chronic back and/or leg pain. Our six-month decision tree includes the screening trial period (success ≥50% relief) and leads to various levels of pain relief with or without complications for IPG SCS and Wireless SCS and without complications for conventional medical management (CMM). Every three months in the follow-on 15-year Markov model (with costs and quality-adjusted life years discounted 3.5% annually), subjects remain stable or transition to deteriorated health or death. Subjects who fail SCS receive CMM. After 60 Markov cycles, a 100,000-sample simulation reveals the impact of maximum willingness-to-pay (WTP) from $10,000 to $100,000 per quality-adjusted life year on net monetary benefit (NMB). Sensitivity analyses considered the impact of the Wireless SCS screening success rate, Wireless SCS device cost, and IPG SCS device longevity. Results Compared with IPG SCS, Wireless SCS offers higher clinical effectiveness at a lower cost and a higher NMB for our WTP thresholds and is, thus, dominant. Wireless SCS is also cost-effective compared with CMM. Results remain robust with 1) Wireless SCS screening success rates as low as 85% (dominant), 2) the cost of the Wireless SCS devices as high as $55,000 (cost-effective), and 3) IPG SCS devices lasting 12 years (dominant). Conclusions In this model, compared with IPG SCS or with CMM, Wireless SCS is a superior strategy.

Hepatocyte to biliary transdifferentiation has been documented in various models of bile duct injury. In this process, mature hepatocytes transform into mature biliary epithelial cells by acquiring biliary phenotypic markers. Several signaling pathways including PI3 kinase, Notch, Hes1, Sox9, and Hippo are shown to be involved in the process. However, whether Oct4 is involved in hepatocyte to biliary transdifferentiation is unknown. We investigated the role of Oct4 in hepatocyte to biliary transdifferentiation utilizing an in vitro organoid culture system as a model of transdifferentiation. Oct4 was inhibited using adenovirus containing Oct4 shRNA. Hepatocyte-specific HNF-4α and biliary-specific HNF-1β and CK19 expression were assessed to gauge the extent of transdifferentiation. Oct4 was induced during hepatocyte to biliary transdifferentiation. Oct4 inhibition significantly downregulated the appearance of biliary cells from hepatocytes. This was accompanied by a significant downregulation of signaling pathways including Notch, Sox9, and Hippo. Our findings suggest that Oct4 is crucial for hepatocyte to biliary transdifferentiation and maturation and that it acts upstream of Notch, Sox9, and Hippo signaling in this model. This finding identifies new signaling through Oct4 in plasticity between hepatocytes and biliary epithelial cells, which can be potentially utilized to identify new strategies in chronic biliary diseases.

Gestational diabetes mellitus (GDM) is diabetes that is diagnosed during the second or third trimester of pregnancy and is not clearly overt diabetes (1). Diagnosis is defined by severity of carbohydrate intolerance. The upper end of the GDM diagnostic glucose range is the same as would be indicative of diabetes outside of pregnancy, whereas the lower end of the GDM range is only slightly above normal and asymptomatic but still associated with increased risk of fetal morbidity (1,2). Diabetes during pregnancy is diagnosed by either a one-step approach involving a 75-g oral glucose tolerance test (OGTT) or a two-step approach starting with a 50-g (nonfasting) screen followed by a 100-g OGTT for those who initially screen positive (1). Glycemic goals for patients with a GDM diagnosis are as follows: preprandial ≤95 mg/dL and either 1-hour postprandial ≤140 mg/dL or 2-hour postprandial ≤120 mg/dL. Hyperglycemia throughout pregnancy carries increased risk for adverse fetal and maternal outcomes (3–8). Treatment of diabetes during pregnancy is aimed at decreasing the risk of perinatal outcomes such as macrosomia, birth trauma, neonatal metabolic abnormalities, and cesarean section (4,9–12). Lifestyle modification is first-line treatment and includes medical nutrition therapy (MNT), exercise, and glucose monitoring (13). Pharmacological therapy generally consists of insulin, glyburide, or metformin, and agents may be used adjunctly to MNT depending on presence and severity of hyperglycemia (13). Insulin is the preferred pharmacological treatment for management of diabetes in pregnancy if lifestyle modification is insufficient in achieving euglycemia (13). The setting of this review is the diabetes clinic located within the Hall County Health Department (HCHD) prenatal clinic in Gainesville, Ga. The population of Gainesville is ∼187,000 and includes a large percentage of Latino immigrants (14). The proportion of Latinos in the diabetes clinic has grown …

Depression is one of the most common mental illnesses characterized by loss of pleasure, whereas diabetes is a metabolic disorder which leads to high serum glucose levels. Current literature supports the development of depressive symptoms in patients with chronic illnesses including diabetes. However, depression as a potential risk factor for diabetes has attracted a lot of attention for clinicians and researchers. It has been hypothesized that both diabetes and depression may be bidirectional in nature, and each may exacerbate the symptoms or play an important role in the development of the other. The most common association between them is the diagnosis of depression in Type 1 or Type 2 diabetes. As the matter of fact, diabetes has been reported to double the risk of depression. In this review article, we have summarized various scientific studies to evaluate the potential of depression as a risk factor for diabetes. MEDLINE search identified various articles assessing this hypothesis. Our review of literature indicate some support for depression as a risk factor for Type 2 diabetes however more clinical studies need to be performed to clarify the contribution of depression as an independent risk factor for diabetes and to check the diabetes epidemic from escalating at a higher rate.

The AMCP Managed CareSpecialty Pharmacy Annual Meeting 2018 in Boston, Massachusetts, is expected to attract more than 3,800 managed care pharmacists and other health care professionals who manage and evaluate drug therapies, develop and manage networks, and work with medical managers and information specialists to improve the care of all individuals enrolled in managed care programs. The AMCP Abstracts program provides a forum through which authors can share their insights and outcomes of advanced managed care practice. Abstracts are presented as posters on Wednesday, April 25, from 12:30 pm to 2:30 pm. Posters will also be displayed on Tuesday, April 24, from 5:45 pm to 7:30 pm, and on Thursday, April 26, from 9:30 am to 11:00 am. Podium presentations for the Platinum award-winning abstracts are Thursday, April 26, from 8:00 am to 9:15 am. Professional abstracts that have been reviewed are published in the Journal of Managed CareSpecialty Pharmacy's Meeting Abstracts supplement.

Background: Currently, various phone apps have been developed to assist patients. Many of these apps are developed to assist patients in the self-management of chronic diseases such as diabetes. It is essential to analyze these various apps to understand the key features that would potentially be instrumental in helping patients successfully achieve goals in disease self-management. Objective: The objective of this study was to conduct a review of all the available diabetes-related apps in the iOS App Store to evaluate which diabetic app is more interactive and offers a wide variety of operations such as monitoring glucose, water, carbohydrate intake, weight, body mass index (BMI), medication, blood pressure (BP) levels, reminders or push notifications, food database, charts, exercise management, email, sync between devices, syncing data directly to the prescribers, and other miscellaneous functions such as (Twitter integration, password protection, retina display, barcode scanner, apple watch functionality, and cloud syncing). Methods: Data was gathered using the iOS App Store on an iPad. The search term “diabetes” resulted in 1209 results. Many of the results obtained were remotely related to diabetes and focused mainly on diet, exercise, emergency services, refill reminders, providing general diabetes information, and other nontherapeutic options. We reviewed each app description and only included apps that were meant for tracking blood glucose levels. All data were obtained in one sitting by one person on the same device, as we found that carrying out the search at different times or on different devices (iPhones) resulted in varying results. Apps that did not have a feature for tracking glucose levels were excluded from the study. Results: The search resulted in 1209 results; 85 apps were retained based on the inclusion criteria mentioned above. All the apps were reviewed for average customer ratings, number of reviews, price, and functions. Of all the apps surveyed, 18 apps with the highest number of user ratings were used for in-depth analysis. Of these 18 apps, 50% (9/18) also had a medication adherence function. Our analysis revealed that the Diabetes logbook used by the mySugr app was one of the best; it differentiated itself by introducing fun as a method of increasing adherence. Conclusions: A large variation was seen in patient ratings of app features. Many patient reviewers desired simplicity of app functions. Glucose level tracking and email features potentially helped patients and health care providers manage the disease more efficiently. However, none of the apps could sync data directly to the prescribers. Additional features such as graph customization, availability of data backup, and recording previous entries were also requested by many users. Thus, the use of apps in disease management and patient and health-care provider involvement in future app refinement and development should be encouraged. [JMIR Diabetes 2017;2(2):e12]

Background Depression is a prevalent mental health disorder and the fourth leading cause of disability in the world as per the World Health Organization. Use of antidepressants can lead to adverse drug events (ADEs), defined as any injury resulting from medication use. This study aimed to examine changes in hospital admissions due to antidepressant-related ADEs (ArADEs) among different socio-demographic groups and changes in lengths of stay (LOS) and hospital charges in ArADE admissions from 2001 to 2011. Methods The Healthcare Cost and Utilization Project database was used. ArADE admissions in different socio-demographic groups were examined including characteristics such as age, gender, rural/urban, and income. LOS and hospital charges for ArADE cases were compared between 2001 and 2011. Chi-square test and t test were used for statistical analyses. Results There were 17,375 and 20,588 ArADE related admissions in 2001 and 2011, respectively. There was a 17.6% increase among the group of 18 to 64 years old and a 64.8% increase among the group of 65 years or older while the other age groups experienced decreased admission rates. Males and females had similar increases. Patients from the lower income areas experienced a two-fold increase while those from the higher income areas experienced a decrease. The mean LOS for all ArADE related admissions increased from 2.18 to 2.81 days and mean hospital charges increased from $8,456.2 to $21,572.5. Conclusions There was an increase in ArADE hospital admissions. The greater increase in ArADE admissions among elderly, urban or low-income patients should be noted and addressed by practitioners and policy makers. The large increase in hospital charges needs further research.

Objective: To review the epidemiology, clinical features, proposed mechanisms, risk factors, and management of statin-associated myopathy. Data Sources: Literature searches were conducted in PubMed (1948 to April 2013), TOXLINE, International Pharmaceutical Abstracts (1970 to April 2013), and Google Scholar using the terms statin, hydroxymethylglutaryl-coenzyme A reductase inhibitors, myopathy, myalgia, safety, and rhabdomyolysis. Results were limited to English publications. Study Selection and Data Extraction: All relevant original studies, guidelines, meta-analyses, and reviews of statin-associated myopathy and safety of statins were assessed for inclusion. References from selected articles were reviewed to identify additional citations. Data Synthesis: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors remain one of the most effective medications for reducing low-density-lipoprotein cholesterol. Statins are well tolerated by most patients; however, it is estimated that 10% to 15% of patients develop statin-related muscle adverse effects known as statin-associated myopathy. Although clinicians may be aware of statin-associated myopathy, they may not be aware of its clinical presentation. Providers should assess individual patient risk factors before choosing the appropriate statin. A variety of skeletal muscle aches that may not present as a danger to the patient, may affect patient adherence and quality of life. There are several steps that providers can take to properly treat and manage patients with myalgia complaints. Conclusions: Statin-associated myopathy is a clinical problem that contributes to statin therapy discontinuation. Patients who are statin intolerant may be treated with alternative treatment options such as low-dose statins, switching statins, using alternative dosing strategies in statins with longer half-lives, non-statin lipid-lowering agents, and complementary therapies.

Tumor hypoxia, or low oxygen concentration, is a result of disordered vasculature that lead to distinctive hypoxic microenvironments not found in normal tissues. Many traditional anti-cancer agents are not able to penetrate into these hypoxic zones, whereas, conventional cancer therapies that work by blocking cell division are not effective to treat tumors within hypoxic zones. Under these circumstances the use of magnetic nanoparticles as a drug delivering agent system under the influence of external magnetic field has received much attention, based on their simplicity, ease of preparation, and ability to tailor their properties for specific biological applications. Hence in this review article we have reviewed current magnetic drug delivery systems, along with their application and clinical status in the field of magnetic drug delivery.

Autoimmune vasculitis is an endothelial inflammatory disease that results from the deposition of immune-complexes (ICs) in blood vessels. The interaction between Fcgamma receptors (FcγRs) expressed on inflammatory cells with ICs is known to cause blood vessel damage. Hence, blocking the interaction of ICs and inflammatory cells is essential to prevent the IC-mediated blood vessel damage. Thus we tested if uncoupling the interaction of FcγRs and ICs prevents endothelium damage. Herein, we demonstrate that dimeric FcγR-Igs prevented nitric oxide (NO) mediated apoptosis of human umbilical vein endothelial cells (HUVECs) in an in vitro vasculitis model. Dimeric FcγR-Igs significantly inhibited the IC-induced upregulation of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) release by murine monocytic cell line. However, FcγR-Igs did not affect the exogenously added NO-induced upregulation of pro-apoptotic genes such as Bax (15 fold), Bak (35 fold), cytochrome-C (11 fold) and caspase-3 (30 fold) in HUVECs. In conclusion, these data suggest that IC-induced NO could be one of the major inflammatory mediator promoting blood vessel inflammation and endothelial cell death during IC-mediated vasculitis which can be effectively blocked by dimeric decoy FcγRs.

In the current chapter, adverse reactions to thyroid hormones, thyroid hormone analogue eprotirome, octreotide, iodine, radioactive iodine, and antithyroid drugs thionamides which were reported from January 2015 to May 2016 have been reviewed. PUBMED was used as the major search index.

In this chapter we have reviewed side effects reported for Vitamin A (carotenoids), vitamins of the B group (cobalamins, folic acid and folinic acid, hopantenic acid, pyridoxine, riboflavin, tetrahydrobiopterin and sapropterin and thiamine), vitamin C (ascorbic acid), vitamin D analogues, vitamin E (tocopherol), vitamin K analogues, amino acids (arginine and glutamine), and eternal and parental nutrition. Our Search was restricted from January 2015 to January 2016. PUBMED, EMBASE and International Pharmaceutical Abstracts (IPA) were used as our search engines.

As currently diagnosed, gestational diabetes mellitus (GDM) affects 5–9% of all pregnancies in the United States and is growing in prevalence.1 It is defined as carbohydrate intolerance of variable severity that is first recognized during pregnancy. Although GDM has been recognized for decades, the potential significance of the condition, as well as criteria for screening and diagnosis, remain debatable.1 Historically, GDM has been treated with lifestyle modifications and insulin, and oral antihyperglycemic agents have been used infrequently because of concerns regarding neonatal hypoglycemia and teratogenicity. Most recent studies suggest that oral hypoglycemic agents, specifically metformin, are safe to use during pregnancy (Table 1).2–13 Risk for developing GDM has been noted in women who are overweight before pregnancy, have had GDM in a previous pregnancy, or have a family history of diabetes. Poorer outcomes have been seen in both pregnant women and their developing fetuses, including induction of labor and caesarean delivery in women and death, shoulder dystocia, bone fracture, and nerve palsy in fetuses.1 Moreover, recent studies show that diagnosis and management of this disorder will have beneficial effects on both maternal and neonatal outcomes.14,15 According to the American College of Obstetrics and Gynecology, comprehensive screening techniques have been implemented by > 90% of practices in the United States.16 Reasons for the implementation of screening programs were developed from the evidence obtained in the Hyperglycemia and Adverse Pregnancy Outcomes study.17 This large, prospective, observational study found possible adverse effects associated with even mild maternal hyperglycemia. It included a cohort of women with glucose levels at the upper end of the normal range, as well as women with mild GDM. The investigators found a linear correlation between higher levels of maternal glucose and adverse outcomes, including increased birth weight, …

This article is a revision of the previous edition article by Sharmilee P. Sawant and Harihara M. Mehendale, volume 2, pp 457–460, © 2005, Elsevier Inc.

This article is a revision of the previous edition article by Sharmilee P. Sawant and Harihara M. Mehendale, volume 1, pp 206–207, © 2005, Elsevier Inc.

The design, synthesis, and use of lerisetron-based molecular probes to investigate the 5-HT 3 R binding site are described. A SAR study, which involved distance and electronic parameter modifications of lerisetron's N -benzyl group, resulted in the discovery of a partial agonist.

To create a capstone course that provides a comprehensive and integrated review of the pharmacy curriculum with a broad range of assessment tools to evaluate student knowledge and skills as a final preparation prior to beginning fourth-year advanced pharmacy practice experiences (APPEs).The capstone course was a 4 credit-hour, case-based course. Eight comprehensive cases were assigned to students over the course of the term. The cases were designed to mimic complex clinical scenarios that students were likely to encounter during an APPE. Students were required to prepare a written and oral presentation for each case and were assessed on material covered during the cases. Faculty members presented weekly reviews on selected topics such as calculations, pharmacokinetics, and pharmaceutical compounding. At the end of the course, students took an observed structured clinical examination (OSCE), which simulated the Georgia Board of Pharmacy Practical Examination, and a comprehensive examination designed to mimic the NAPLEX (North American Pharmacy Licensure Examination).Evaluation of student outcomes was based on written and verbal presentations of the cases, multiple-choice examinations, a short-answer calculations examination, an "Errors and Omissions" examination, a standardized patient encounter, and pharmaceutical compounding examinations. Ninety-five percent of students successfully passed the course on their first attempt. Student feedback indicated satisfaction with the depth, breadth, and organization of material covered and felt that the course helped prepare them for APPEs.The culminating experience of the capstone course gave students a thorough review of practical, clinical, and communication skills and provided faculty members with feedback regarding the curriculum through robust assessment.

Electrostatic potential surface mapping of various aromatic ring systems contained in 5-HT3R agonists indicate that some agonists contain an aromatic moiety capable of a favorable cation–π interaction next to the e-face of pyridine (or its bioisostere). A pharmacophore model has been proposed based on superimposition of two distinct ‘aryl’ interactions.

Background Lerisetron, a competitive serotonin type 3 receptor (5-HT3R) antagonist, contains five functional groups capable of interacting with amino acids in the 5-HT3R binding site. Site directed mutagenesis studies of the 5-HT3AR have revealed several amino acids that are thought to form part of the binding domain of this receptor. The specific functional groups on the ligand that interact with these amino acids are, however, unknown. Using synthetic analogs of lerisetron as molecular probes in combination with site directed mutagenesis, we have identified some of these interactions and have proposed a model of the lerisetron binding site.