Cost-effective strategies for the long-term management of diabetes mellitus

Diabetes mellitus (DM) is a significant public health problem that afflicted approximately 29.1 million Americans in 2012 (CDC, 2014). The estimated cost of diabetes in the United States in 2012 was $245 billion, including$176 billion in direct medical costs and $69 billion in reduced productivity (ADA, 2013a). To reach a diagnosis of DM, a clinician generally relies on fasting plasma glucose (FPG), the oral glucose tolerance test (OGTT), and/or the Hemoglobin A1c (HbA1c) test (ADA, 2013b). Current noninsulin antidiabetic medications include sulfonylureas, GLP-1 analogues, DPP-4 inhibitors, biguanides, thiazolidinediones, and SGLT2 inhibitors (Kaiser & Oetjen, 2014). Insulin therapies include basal (long-acting insulin analogues), biphasic (premixed insulin analogues), prandial (short-acting insulin analogues), and basal bolus (a combination of long-acting and short-acting insulin analogues) (Esposito et al., 2012). The aim of this study is to review the existing literature on the cost effectiveness of diabetes interventions to develop a standardized protocol for early type 2 diabetes care that can be delivered through primary care providers. The substantial cost effectiveness of preventative measures, including ad campaigns and outreach programs, has already been established (Mendis & Chestnov, 2013). Screening for impaired glucose tolerance early and implementing lifestyle and pharmacological changes at an early stage are also considered cost effective approaches for the long-term management of diabetes mellitus (Gillies et al., 2008). This study utilizes six cost effectiveness analyses on both clinical and non-clinical interventions to determine a standardized protocol for screening, diagnosing, and treating DM. Noninsulin antidiabetic drugs accounted for 78.4% of the 154.4 million prescriptions for antidiabetic drugs filled in 2012 (Hampp et al., 2014). Approximately half of the noninsulin antidiabetic drugs filled in 2012 was for metformin, whereas roughly a quarter of the same category was for sulfonylureas (Hampp et al., 2014). In decreasing order, long-acting human analog insulin and fast-acting human analog insulin were the most popular insulin variants in the insulin antidiabetic drug market (Hampp et al., 2014). Of the noninsulin antidiabetic drugs, the highest proportion of diabetic patients who achieved the HbA1C target of <7% were those taking sustained release exenatide (a GLP-1 analog) (63.2%) (Esposito et al., 2012). Of the insulin varieties, the highest proportion of diabetic patients who achieved the HbA1C target of <7% were those using basal bolus insulin (50.2%) (Esposito et al., 2012). While there are some concerns about the ability of diabetic patients with chronic kidney disease to clear metformin via renal excretion, extensive clinical experience supports its use in diabetic patients with mild to moderate renal impairment (Inzucchi et al., 2014). From the cost effectiveness studies, lifestyle modification (i.e., changes in diet and exercise) beginning at any age was determined to be a cost-effective approach in preventing and treating DM and may be cost saving for adults between the age of 25 to 44 (Herman et al., 2005). Screening for DM beginning at age 45 and repeating every three years if negative provides the best balance of effectiveness and cost effectiveness (Kahn et al., 2010). As a first-line clinical intervention, metformin was established to be cost-effective as well in treating DM (but less so compared to lifestyle modification) (Herman et al., 2005). Bariatric surgery for diabetics with a BMI greater than or equal to 35 kg/m2 has also been established as cost effective (Hoerger et al., 2010). Next, in considering the ideal frequency of clinical consultations, diabetics with a stable condition (assessed as HbA1c ≤7.5%, blood pressure ≤145 mmHg, and total cholesterol ≤201 mg/dL) can safely be seen by a primary care provider every six months compared to every three months with no noticeable decline in long-term health outcomes (Wermeling et al., 2014). For cases of T2D that cannot be simply controlled with metformin, sulfonylurea has shown that it is overall more cost-effective and effective as a second-line therapy when compared to DPP-4 inhibitors and GLP-1 analogs (Zhang et al., 2014). Cost effectiveness analysis of the long-acting analogue insulin detemir across different countries reveals substantially different cost effectiveness for the medication in terms of both nominal and purchasing power terms (Home et al., 2014). The results of these studies were parsed to establish a long-term clinical protocol for primary care providers in screening, diagnosing, and treating type 2 diabetes. Future studies should focus on integrating cost effectiveness and comparative effectiveness research in implementing even more nuanced clinical decisions through a structured protocol. The cost effectiveness of existing and new interventions--both clinical and non-clinical in nature--will also need to be continuously assessed to ensure that the measurements incorporate the most accurate set of assumptions on costs and effectiveness

3D - Printed Patient Specific Instrumentation in Corrective Osteotomy of the Femur and Pelvis: A Review of the Literature

Background: The paediatric patient population has considerable variation in anatomy. The use of Computed Tomography (CT)-based digital models to design three-dimensionally printed patient specific instrumentation (PSI) has recently been applied for correction of deformity in orthopedic surgery. This review sought to determine the existing application of this technology currently in use within paediatric orthopaedics, and assess the potential benefits that this may provide to patients and surgeons. Methods: A review was performed of MEDLINE, EMBASE, and CENTRAL for published literature, as well as Web of Science and clinicaltrials.gov for grey literature. The search strategy revolved around the research question: “What is the clinical impact of using 3D printed PSI for proximal femoral or pelvic osteotomy in paediatric orthopaedics?” Two reviewers, using predetermined inclusion criteria, independently performed title and abstract review in order to select articles for full text review. Data extracted included effect on operating time and intraoperative image use, as well as osteotomy and screw positioning accuracy. Data were combined in a narrative synthesis; meta-analysis was not performed given the diversity of study designs and interventions. Results: In total, ten studies were included: six case control studies, three case series and a case report. Five studies directly compared operating time using PSI to conventional techniques, with two showing a significant decrease in the number of intraoperative images and operative time. Eight studies reported improved accuracy in executing the surgical plan compared to conventional methods. Conclusion: Compared to conventional methods of performing femoral or pelvic osteotomy, use of PSI has led to improved accuracy and precision, decreased procedure times, and decreased intra-operative imaging requirements. Additionally, the technology has become more cost effective and accessible since its initial inception and use

Trend Analysis of Belief-State History with Discrete Wavelet Transform for Improved Intention Discovery

Software Product Lines (SPL) have emerged as a new paradigm of software development. By means of mass production of customized software products, SPL has the potential to significantly reduce development time and cost while improving the quality of software systems. Currently, there is still a severe shortage of tools that support the decision-making process for software clients to interactively order software products due to the difficulty of software customization, especially via dialogue in natural language. While most of the existing approaches use POMDP-based dialogue management, this thesis research proposes to introduce historical information of belief states into the POMDP model and to analyze its trend with discrete wavelet transformation (DWT). Accordingly, a new algorithm is developed to improve the accuracy of intention discovery with trend analysis, and to reduce the dialog length by switching POMDP policies between contextual control modes according to the anticipated knowledge of different users. The efficiency and accuracy of the proposed method are examined by experiments with simulation

Synthetic peripherally-restricted cannabinoid suppresses chemotherapy-induced peripheral neuropathy pain symptoms by CB1 receptor activation.

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe and dose-limiting side effect of cancer treatment that affects millions of cancer survivors throughout the world and current treatment options are extremely limited by their side effects. Cannabinoids are highly effective in suppressing pain symptoms of chemotherapy-induced and other peripheral neuropathies but their widespread use is limited by central nervous system (CNS)-mediated side effects. Here, we tested one compound from a series of recently developed synthetic peripherally restricted cannabinoids (PRCBs) in a rat model of cisplatin-induced peripheral neuropathy. Results show that local or systemic administration of 4-{2-[-(1E)-1[(4-propylnaphthalen-1-yl)methylidene]-1H-inden-3-yl]ethyl}morpholine (PrNMI) dose-dependently suppressed CIPN mechanical and cold allodynia. Orally administered PrNMI also dose-dependently suppressed CIPN allodynia symptoms in both male and female rats without any CNS side effects. Co-administration with selective cannabinoid receptor subtype blockers revealed that PrNMI's anti-allodynic effects are mediated by CB1 receptor (CB1R) activation. Expression of CB2Rs was reduced in dorsal root ganglia from CIPN rats, whereas expression of CB1Rs and various endocannabinoid synthesizing and metabolizing enzymes was unaffected. Daily PrNMI treatment of CIPN rats for two weeks showed a lack of appreciable tolerance to PrNMI's anti-allodynic effects. In an operant task which reflects cerebral processing of pain, PrNMI also dose-dependently suppressed CIPN pain behaviors. Our results demonstrate that PRCBs exemplified by PrNMI may represent a viable option for the treatment of CIPN pain symptoms

Combining Organocatalysis with Transitionmetal Catalysis

The use of transition metals or small organic molecules established as catalysts powerful technique in organic synthesis. In recent years combining transition metal with organocatalysis (dual catalysis) has gained considerable attention. The advantage of the dual catalysis is the ability to access pharmaceutically relevant frameworks or building blocks, which is not possible by single catalytic systems. To explore this dual catalytic strategy we initiated a program to use tether technology to combine the transition metal catalysis and organocatalysis for library development. Chapter I deals with combining the organocatalysis with Hg(II) salts for direct alkylation of aldehydes with unactivated alkenes. In chapter II focus is on using a disiloxane linker to combine gold catalysis with enamine catalysis. In chapter III deals with the synthesis of dihydropyridines, which are found in many natural products and biologically active molecules. We attempted to develop titanium promoted reductive coupling of pi-unsaturated substrates with pyridinium salts to access highly substituted dihydropyridines.Chemistr