Search

Major histocompatibility (MHC) class II molecules are strongly associated with many autoimmune disorders. In type 1 diabetes (T1D), the DQ8 molecule is common, confers significant disease risk, and is involved in disease pathogenesis. We hypothesized that blocking DQ8 antigen presentation would provide therapeutic benefit by preventing recognition of self-peptides by pathogenic T cells. We used the crystal structure of DQ8 to select drug-like small molecules predicted to bind structural pockets in the MHC antigen–binding cleft. A limited number of the predicted compounds inhibited DQ8 antigen presentation in vitro, with 1 compound preventing insulin autoantibody production and delaying diabetes onset in an animal model of spontaneous autoimmune diabetes. An existing drug with a similar structure, methyldopa, specifically blocked DQ8 in patients with recent-onset T1D and reduced inflammatory T cell responses to insulin, highlighting the relevance of blocking disease-specific MHC class II antigen presentation to treat autoimmunity.

Uricosuria and crystallization are increasingly recognized risk factors for diabetic tubulopathy. This pilot clinical trial aimed to determine the acute effect of urinary alkalinization using oral sodium bicarbonate (NaHCO3 ) on UA crystals in adults with type 1 diabetes (T1D). Adults with T1D, ages 18 to 65 years (n = 45, 60% female, HbA1c, 7.5 ± 1.2%, 20.2 ± 9.3 years duration) without chronic kidney disease (eGFR ≥60 mL/min/1.73 m2 and albumin-to-creatinine ratio < 30 mg/g) received 2 doses of 1950 mg oral NaHCO3 over 24 hours. Fasting urine and serum were collected pre- and post-intervention. UA crystals were identified under polarized microscopy. Urine measurements included: osmolality, pH, UA, creatinine and kidney injury molecule-1 (KIM-1). NaHCO3 therapy increased mean ± SD urine pH from 6.1 ± 0.7 to 6.5 ± 0.7 (P < .0001). Prior to therapy, 31.0% of participants had UA crystals vs 6.7% post therapy (P = .005). Change in urine pH inversely correlated with change in urine KIM-1 (r:-0.51, P = .0003). In addition, change in urine UA over 24 hours correlated with change in urine KIM-1 (r:0.37, P = .01). In conclusion, oral NaHCO3 normalized urine pH and decreased UA crystals, and may hold promise as an inexpensive and safe tubulo-protective intervention in individuals with T1D.

Introduction In 2014, vaccination was included within the scope of practice for Australian pharmacists. A number of Australian pharmacy schools have either commenced or are planning to incorporate vaccination training into pharmacy curricula. The primary objective of this article is to articulate the process undertaken to develop an Australian vaccination training program with nested injection skills training for pharmacy students. Material and methods A set of learning outcomes, assessable knowledge, and assessable skills were developed following a critical review of relevant literature, guided by the Australian Pharmacy Council Standards for the Accreditation of Programs to Support Pharmacist Administration of Vaccines. This ensures that the modules will enable students to demonstrate competency required for vaccination, similar to that of current Australian vaccinators: doctors, nurses, and pharmacists. Results A vaccination training program with nested injection skills training was developed and validated. The new teaching and learning concepts will be integrated and delivered via spiral curriculum. Knowledge and skills should progressively improve as students advance through the pharmacy course. Core skills will be assessed on a number of occasions. Integrated modules are embedded into the first year, third year, and fourth year of the pharmacy program. Conclusion A vaccination training program with nested injection skills training was developed for Australian pharmacy students.

To summarize recent studies about obesity, insulin resistance, and type 1 diabetes mellitus (T1DM).Overweight and obesity continue to be prevalent among individuals with T1DM. Obesity rates appear to have reached a plateau among children with T1DM in some parts of the world. The risk for development of T1DM is increased by obesity and may occur at an earlier age among obese individuals with a predisposition. Obesity increases the risk for comorbidities among individuals with T1DM, especially metabolic syndrome, and microvascular and macrovascular diseases. Metformin, glucagon-like peptide-1 agonist therapy, sodium glucose cotransporter-2 inhibitor therapy, and bariatric surgery may be beneficial therapies for glucose control, comorbidity management, and obesity among adults with T1DM. Insulin resistance may be improved among obese individuals with T1DM by biguanides (metformin) and glucagon-like peptide-1 agonists (exenatide).We review the last 18 months of literature on obesity, insulin resistance, and T1DM to highlight new epidemiologic results and treatments.

Objective: To review the pharmacology, pharmacokinetics, safety, and efficacy of Technosphere insulin (TI), a new inhaled insulin product. Data Sources: Searches were conducted in PubMed/MEDLINE, Scientific Citation Index, and abstracts from both the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) meetings from 2005 to August 2014, utilizing the search terms Afrezza, Technosphere, Afresa, and inhaled insulin. References were reviewed to identify additional sources. Study Selection and Data Extraction: Studies with adequate sample sizes, evaluating clinically relevant end points were included. Data Synthesis: TI is approved by the Food and Drug Administration as a bolus insulin to treat patients with type 1 and type 2 diabetes. Its glucose-lowering properties are less than that of rapid-acting insulins, but it does demonstrate less hypoglycemia. TI’s kinetics make it the fastest absorbed of any insulin available, although its overall onset of action appears similar to insulin lispro. It represents an alternative to bolus injections but would likely be used concomitantly with injected basal insulin. Major adverse effects are respiratory in nature, with cough being the most prominent. There is a small decrease in the forced expiratory volume in 1 s (FEV1) with TI; this appears to be consistent, nonprogressive, and reversible. Patients using TI must receive pulmonary function tests periodically throughout therapy. TI is contraindicated in patients with chronic lung disease and should be used with caution in patients who smoke. Conclusion: TI is a novel inhaled insulin that provides prandial coverage to patients with diabetes, representing an alternative to bolus insulin injections.

To estimate the frequency of continuous glucose monitoring (CGM) use and change in hemoglobin A1c (HbA1c) compared to self-monitoring of blood glucose (SMBG) alone in adults with type 1 diabetes in a clinical practice setting.We retrospectively identified 66 adult type 1 diabetes patients at the Barbara Davis Center for Diabetes (BDC) who first initiated CGM between 2006 and 2011 and 67 controls using SMBG. The frequency of CGM use was estimated from survey recall and defined as the mean number of days/month of CGM use during a maximum follow-up of 10 months. Change in HbA1c was calculated as the difference between the baseline value and the lowest follow-up value.The mean change in HbA1c for CGM users was -0.48% (95% confidence interval [CI]: -0.67, -0.28) and for SMBG users was -0.37% (95% CI: -0.56, -0.18). The between-group mean difference in change in HbA1c, adjusted for patient characteristics, was -0.11% (95% CI: -0.38, 0.16), whereas the subgroup with a baseline HbA1c ≥7.0% and users of CGM ≥21 days/month was -0.36% (95% CI: -0.78, 0.05). Nearly half (n = 32, 48%) used CGM21 days/month. The reasons for low frequency of CGM use or discontinuation included sensor costs, frequency of alarms, inaccuracy, and discomfort.These CGM data from clinical practice suggest a trend toward decreasing HbA1c for adults with type 1 diabetes, especially in patients with higher baseline HbA1c and higher frequency of CGM use. Future studies are needed to assess the use of CGM in larger populations of clinical practice adult type 1 diabetes patients.

Aims Improved early diagnostic methods are needed to identify risk for kidney disease in people with type 1 diabetes. We hypothesized that glomerular filtration rate (GFR) measured by iohexol clearance in dried blood spots (DBS) on filter paper would be comparable to plasma (gold-standard) and superior to estimated GFR (eGFR) and, second, that adjustment for ambient blood glucose would improve accuracy and precision of GFR measurement. Methods GFR was measured by iohexol clearance in plasma, DBS, and as estimated by the CKD-Epidemiology Collaboration equations in 15 adults with type 1 diabetes at two visits, one euglycemic and one hyperglycemic. Results GFR measured by DBS was more comparable and less biased than GFR cystatin C, serum creatinine, and both combined. GFR was higher during hyperglycemia. Correction for between visit glycemia statistically significantly reduced bias and mean squared error for GFR measured by DBS as compared to gold-standard during euglycemia. Conclusions Iohexol clearance measured with DBS performed better than eGFR methods. Correction for ambient blood glucose improved precision and accuracy of GFR measurement. This method is more convenient than the gold-standard GFR method and may improve screening and diagnostic capabilities in people with type 1 diabetes, especially when GFR is >60ml/min/1.73m 2 .

Cardiovascular (CV) disease remains the leading cause of death in people with diabetes, highlighting the importance of using treatment options that do not increase CV risk or possibly decrease CV outcomes. Since 2008, the Food and Drug Administration has required demonstration of CV safety for all new medications developed for the glycemic management of diabetes. Seven trials have been published that have established CV safety for three DPP-4 inhibitors (alogliptin, saxagliptin, and sitagliptin), three GLP-1 receptor agonists (liraglutide, lixisenatide, and semaglutide), and one sodium-glucose cotransporter-2 inhibitor (empagliflozin). Three of those studies also established superiority with liraglutide, empagliflozin, and semaglutide at reducing the composite primary endpoint of major CV events (CV death, nonfatal myocardial infarction, and nonfatal stroke). In addition, one trial found an increase in heart failure hospitalizations with saxagliptin. The findings of these trials must be compared and contrasted cautiously given the differences in patient populations and trial designs, but together they provide important information that can be used to shape our treatment guideline recommendations and patient-specific treatment decisions.

Objective To assess the impact of a diabetes-focused advanced pharmacy practice experience on students' diabetes-related confidence and knowledge. Methods A survey tool was created, including 22 confidence and 30 knowledge questions centered on diabetes care. Students entering into a diabetes-focused advanced pharmacy practice experience (APPE) during rotation 7 served as the intervention group, whereas students without this experience were the control group. Both groups completed the survey before and after rotation 7. Results Twenty-two students (13 intervention, 9 control) completed the baseline survey and 14 students (9 intervention, 5 control) completed the follow-up. The intervention group showed a significant improvement in total confidence compared with control (3.92–5.52, p = 0.002). Within-group analyses showed a significant improvement in knowledge in the intervention group (18.6–22.4, p = 0.04) compared with no difference in the control group (17.8–18.3, p = 0.85). Conclusions This pilot study suggests that a diabetes-focused APPE improves students' diabetes-related confidence and knowledge.

Diabet. Med. 28, 1176–1181 (2011) Abstract Aims Patients with Type 1 diabetes have significantly elevated postprandial glucagon secretion. Dipeptidyl peptidase IV inhibitors improve HbA1c by several mechanisms, including increasing glucagon-like peptide 1 and glucose-dependent insulinotropic peptide concentrations, which decreases postprandial rises in glucagon in both Type 1 and Type 2 diabetes. This study evaluates the clinical implications of sitagliptin in adult patients with Type 1 diabetes. Methods This investigator-initiated, double-blind, randomized, crossover, 8-week, pilot study enrolled 20 adult subjects with Type 1 diabetes. Subjects received sitagliptin 100 mg/day or placebo for 4 weeks and then crossed over. Outcomes included 2-h postprandial blood glucose and 24-h area under the curve changes in glucose measurements from continuous glucose monitoring, HbA1c, fructosamine and insulin dose. Results Sitagliptin significantly reduced blood glucose (2-h postprandial and 24-h area under the curve) despite reduced total and prandial insulin dose. Based on continuous glucose monitor findings, sitagliptin improved measures of glycaemic control, including mean blood glucose (−0.6 mmol/l; P = 0.012) and time in euglycaemic range 4.4–7.8 mmol/l (0.4 ± 0.2 h; P = 0.046). Significant reductions were also observed in M100, Glycemic Risk Assessment Diabetes Equation (GRADE) and J-index. After controlling for period, treatment and insulin dose, the HbA1c was also significantly reduced [−0.27 ± 0.11% (−2.91 ± 1.16 mmol/mol); P = 0.025] when patients were taking sitagliptin. Conclusions Sitagliptin significantly improved overall glucose control, including postprandial and 24-h glucose control, in adult patients with Type 1 diabetes, while significantly reducing prandial insulin requirements. Further investigation is warranted in patients with Type 1 diabetes in a larger cohort designed to assess both clinical outcomes and mechanism of action.

The Distributed Ambulatory Research in Therapeutics Network (DARTNet) is a federated network of electronic health record (EHR) data, designed as a platform for next-generation comparative effectiveness research in real-world settings. DARTNet links information from nonintegrated primary care clinics that use EHRs to deliver ambulatory care to overcome limitations with traditional observational research.Test the ability to conduct a remote, electronic point of care study in DARTNet practices by prompting clinic staff to obtain specific information during a patient encounter.Prospective survey of patients identified through queries of clinical data repositories in federated network organizations. On patient visit, survey is triggered and data are relinked to the EHR, de-identified, and copied for evaluation.Adult patients diagnosed with diabetes mellitus that scheduled a clinic visit for any reason in a 2-week period in DARTNet primary care practices.Survey on hypoglycemic events (past month) and over-the-counter and herbal supplement use.DARTNet facilitated point of care data collection triggered by an electronic prompt for additional information at a patient visit. More than one-third of respondents (33% response rate) reported either mild (45%) or severe hypoglycemic events (5%) in the month before the survey; only 3 of those were also coded using the ICD-9 (a significant difference in detection rates 37% vs. 1%). Nearly one-quarter of patients reported taking an OTC/herbal, 4% specifically for the treatment of symptoms of diabetes.Prospective data collection is feasible in DARTNet and can enable comparative effectiveness and safety research.

The prevalence of type 1 diabetes continues to increase worldwide at a rate higher than previously projected, while the number of patients achieving American Diabetes Association (ADA) glycated hemoglobin (A1c) goals remains suboptimal. There are numerous barriers to patients achieving A1c targets including increased frequency of severe hypoglycemia associated with lowering plasma glucose as measured by lower A1c values. Continuous glucose monitoring (CGM) was first approved for retrospective analysis and now has advanced to the next step in diabetes management with the approval of real-time glucose sensing. Real-time CGM, in short term studies, has been shown to decrease A1c values, improve glucose variability (GV), and minimize the time and number of hypoglycemic events in patients with type 1 diabetes. These products are approved for adjunctive use to self-monitoring of blood glucose (SMBG), but future long-term studies are needed to document their safety, efficacy, ability to replace SMBG as a tool of monitoring, and ultimately utility into closed-loop insulin delivery systems. New algorithms will need to be developed that account for rapid changes in the glucose values, so that accuracy of the sensor data can be maintained. In addition, for better clinical care and usage, algorithms also need to be developed for both patients and the providers to guide them for their ongoing diabetes care.

Evidence suggests that stopping oral anticoagulation with warfarin is not necessary in patients requiring low-risk dental procedures and may actually increase thrombosis risk. However, widespread belief remains among dentists that stopping oral anticoagulation for dental procedures is necessary. The purpose of this study was to investigate the teaching practice of U.S. dental faculty responsible for providing education to dental students about anticoagulation. Surveys were mailed in 2003 and 2004 to fifty-five U.S. dental faculties to assess their teaching practice regarding anticoagulation and dental procedures. Twenty-eight (50.9 percent) of the schools returned surveys. Contrary to evidence indicating anticoagulation does not need to be altered, many dental faculty responded that they teach dental students to discuss with medical providers/patients about altering warfarin therapy for several routine procedures: 21.4 percent (cleaning), 14.3 percent (restorative treatment), 46.4 percent (single simple extraction), 64.3 percent (multiple simple extractions), and 17.9 percent (root canal). However, 67.9 percent stated an International Normalized Ratio (INR) of 2.0-3.0 would be acceptable prior to dental procedures. A discrepancy was also found between the number of faculty recommending altering warfarin in intermediate- to high-risk individuals compared to those recommending heparin bridging for the same patients. Overall, this study identified inconsistencies between teaching practices in U.S. dental schools and medical evidence. Dental faculty should consider comparing their teaching material with evidence regarding anticoagulation and dental procedures. Continuing education may be necessary for practicing dentists regarding this topic.

Anticoagulation therapy with warfarin is widely considered the standard of care for stoke prophylaxis in patients with atrial fibrillation who are at high risk of stroke. Community-based studies in the US have reported that the effectiveness of anticoagulation varies by management approach and that patients receiving warfarin have international normalised ratio (INR) values within the target therapeutic range less than half the time.To estimate the lifetime societal costs and health benefits of warfarin therapy to prevent strokes, specifically in elderly patients (mean age 70 years) with atrial fibrillation who are at high risk of stroke, when anticoagulation is managed through usual care versus anticoagulation management services, where dedicated anticoagulation professionals (e.g. physician or pharmacist) monitor and oversee patients.Semi-Markov decision model with a 30-day cycle length and 10-year time horizon (to reflect the mean life expectancy of the study population). Univariate sensitivity analyses and Bayesian second-order multivariate probabilistic sensitivity analysis using Monte Carlo simulation were performed. Outcomes measures were costs and QALYs. Most of the probability and outcome estimates included were derived from the recent SPORTIF (Stroke Prevention using ORal Thrombin Inhibitor in atrial Fibrillation) V trial. Utility values were derived from a large, nationally representative sample of individuals in the Medical Expenditure Panel Survey and were adjusted for age, sex, race, ethnicity, income, education and co-morbidity. Resource utilisation was based on experience at the University Medicine Group Practice Anticoagulation Clinic (University of Colorado, Denver, CO, USA) and costs ($US; 2004 values) included were for warfarin and aspirin (acetylsalicylic acid) use and those associated with major bleeding, treatment of primary events, routine INR and biochemistry monitoring, ECGs, and clinic visits. Costs and outcomes were discounted by 3% per annum.The anticoagulation management service improved effectiveness by 0.057 (95% credible interval 0, 0.36) QALYs and reduced costs by $US2100 (95% credible interval -$US19,800, $US300) [2004 values] compared with usual care. Results were sensitive to the extent of the increase in risk of primary events (all strokes and systemic embolic events attributable to usual care, but were robust to variation in other input variables). The anticoagulation management service was the dominant strategy in 91% of Monte Carlo simulations.The anticoagulation management service appears to cost less and provide greater effectiveness than usual care. To enhance stroke prophylaxis among high-risk patients with atrial fibrillation, physicians and Medicare plans may wish to consider augmenting 'usual care' by the addition of patient-monitoring technology strategies such as formally organised anticoagulation monitoring programmes.

OBJECTIVE—Hypoglycemia and wide glucose excursions continue to be major obstacles to achieving target HbA1c values and the associated reductions in long-term complications (and economic costs) in people with insulin-treated diabetes. In this study we evaluated the accuracy, safety, and clinical effectiveness of a continuous glucose-sensing device. RESEARCH DESIGN AND METHODS—A total of 91 insulin-requiring patients with type 1 (n = 75) and type 2 (n = 16) diabetes were enrolled in this multicenter randomized study. Subjects wore a transcutaneous, 3-day, continuous glucose-sensing system for three consecutive 72-h periods. Subjects were randomly assigned (1:1 ratio) to either a control group (continuous glucose data not provided) or a display group (continuous glucose data not provided during period 1 but displayed during periods 2 and 3). During periods 2 and 3, patients in the display group had real-time access to sensor glucose values, could review glucose trends over the preceding 1, 3, and 9 h, and were provided with high (≥200 mg/dl) and low (≤80 mg/dl) alerts and a low (≤55 mg/dl) alarm. Sensors were inserted by patients, and both groups used (or wore) the system during daily activities. Device accuracy was assessed by comparing continuous glucose values to paired self-monitoring of blood glucose (SMBG) meter readings. Clinical effectiveness was evaluated by analyzing between-group (control vs. display, periods 2 and 3) and within-group (display, period 1 vs. period 3) differences in time spent in high, low, and target (81–140 mg/dl) glucose zones. RESULTS—When prospective, real-time sensor values were compared with SMBG values, 95.4% of 6,767 paired glucose values fell within Clarke error grid A and B zones. Pearson’s correlation coefficient was 0.88, and mean and median absolute relative differences were 21.2 and 15.9%, respectively. No systematic bias was detected at any of the prespecified glucose levels (50, 80, 100, 150, and 200 mg/dl). When compared with control subjects, the display group spent 21% less time as hypoglycemic ( CONCLUSIONS—We conclude that real-time continuous glucose monitoring for periods up to 72 h is accurate and safe in insulin-requiring subjects with type 1 and type 2 diabetes. This study demonstrates that availability of real-time, continuously measured glucose levels can significantly improve glycemic excursions by reducing exposure to hyperglycemia without increasing the risk of hypoglycemia, which may reduce long-term diabetes complications and their associated economic costs.

We examined the impact of ambulatory care clinical pharmacist interventions on clinical and economic outcomes of 208 patients with dyslipidemia and 229 controls treated at nine Veterans Affairs medical centers. This was a randomized, controlled trial involving patients at high risk of drug-related problems. Only those with dyslipidemia are reported here. In addition to usual medical care, clinical pharmacists were responsible for providing pharmaceutical care for patients in the intervention group. The control group did not receive pharmaceutical care. Seventy-two percent of the intervention group and 70% of controls required secondary prevention according to the National Cholesterol Education Program guidelines. Significantly more patients in the intervention group had a fasting lipid profile compared with controls (p=0.021). The absolute change in total cholesterol (17.7 vs 7.4 mg/dl, p=0.028) and low-density lipoprotein (23.4 vs 12.8 mg/dl, p=0.042) was greater in the intervention than in the control group. There were no differences in patients achieving goal lipid values or in overall costs despite increased visits to pharmacists. Ambulatory care clinical pharmacists can significantly improve dyslipidemia in a practice setting designed to manage many medical and drug-related problems.

Study Objective. To determine if clinical pharmacists could affect economic resource use and humanistic outcomes in an ambulatory, high-risk population. Design. Prospective, randomized, controlled study. Setting. Nine Veterans Affairs medical centers. Patients. Patients who were at high risk for medication-related problems. Intervention. Patients were randomized to usual medical care with input from a clinical pharmacist (intervention group) or just usual medical care (control group). Measurements and Main Results. Of 1054 patients enrolled, 523 were randomized to the intervention group and 531 to the control group. The number of clinic visits increased in the intervention group (p=0.003), but there was no difference in clinic costs. Mean increases in total health care costs were $1020 for the intervention group and $1313 for the control group (p=0.06). Conclusion. Including the cost of pharmacist interventions, overall health care expenditures were similar for patients randomized to see a clinical pharmacist versus usual medical care.

The purpose of this study was to describe and evaluate the activities and interventions provided by ambulatory care clinical pharmacists during the IMPROVE (Impact of Managed Pharmaceutical Care on Resource Utilization and Outcomes in Veterans Affairs Medical Centers) study. A total of 523 patients were randomized into the intervention arm at nine Veterans Affairs medical centers if they were considered to be at high risk for drug-related problems. Patients randomized to the control group had no interventions and they are not reported. Using a standard form, pharmacists were asked to document the length of visit, method of contact, medical conditions addressed, and drug-related problems addressed and resolved during each contact. Seventy-eight ambulatory care clinical pharmacists documented 1855 contacts over 12 months, an average of 3.54 +/- 2.31/patient. The length of visits was 15 minutes or more for 73% of contacts. In-person contacts accounted for 1421 visits (76.6%), with the remainder being telephone contacts. During each contact the average number of drug-related problems addressed and resolved were 1.64 +/- 1.16 and 1.14 +/- 0.98, respectively. More drug-related problems were addressed and resolved when visits were 15 minutes or longer (p=0.001) and when the contact was in person (p=0.001). These data may provide information to clinical pharmacists developing pharmacy-managed clinics for patients at high risk for drug-related problems. The information may be a benchmark for types of interventions that can be made, as well as the time commitments required to make them.

OBJECTIVE:To describe and inform pharmacists of a rarely reported occurrence of facial palsy in an elderly patient with uncontrolled hypertension resulting from nonadherence to blood pressure medications.CASE SUMMARY:A 62-year-old Hispanic woman presented to the hypertension clinic with left facial weakness, mild eyelid lag, and auricular pain for two days. The patient self-discontinued fosinopril and minoxidil six days and two days prior to developing these symptoms, respectively. A diagnosis of idiopathic peripheral VII cranial nerve lesion was made after ruling out other possible causes. Corticosteroids were not initiated because of this patient's labile hypertension. Palliative therapy was initiated and the left facial paralysis continuously improved during the six months after discharge.DISCUSSION:Patients have rarely presented with facial paralysis as the initial feature of severe hypertension. The relationship between facial paralysis and hypertension has been reported in a small number of cases, including several reports of recurrence of paralysis during acute exacerbations of hypertension. A variety of physiologic theories to explain the relationship between facial paralysis and hypertension have been published, including small hemorrhages into the facial canal which have been confirmed by two autopsies. However, the true etiology remains unknown.CONCLUSIONS:The possible relationship between facial paralysis and uncontrolled hypertension has not been reported in pharmacy literature and has been reported only twice in subspecialty medical journals since 1990. Pharmacists should be aware of the complications of hypertension and should question patients about signs and symptoms at each visit. While Bell's palsy complicating hypertension does not appear to be a serious complication, pharmacists must appreciate that the patient should be immediately evaluated to rule out a more serious neurologic event.

Improving metabolic control reduces micro- and macrovascular complications of diabetes. However, intensive insulin therapy increases severe hypoglycemia more than threefold (1–3). Continuous glucose monitoring (CGM) is being introduced into routine clinical care despite a lack of reimbursement. Registration studies for the Food and Drug Administration (FDA) documented that subjects using real-time CGM improve glucose excursions, reduce variability, decrease time spent in hypoglycemia and hyperglycemia, and improve A1C values (4–9). Despite these reports, there are data unsupportive of new technologies such as CGM (10) or personal digital assistants (11) for reducing hypoglycemia. This study evaluates glucose control and its relationship with glucose target ranges with continuous home monitoring of glucose (CHMG). Inclusion criteria limited analysis to subjects with A1C values and downloaded CHMG data at baseline and 3 months, as well as software to download receivers (not available for the first 9 months). Patients who were pregnant or planning a pregnancy were excluded. A total of 24 subjects on CHMG were included in this analysis. All patients in this study used the DexCom STS sensor (DexCoM, San Diego, CA). Subjects were computer matched for baseline A1C (± 0.3%), sex, age, and duration of diabetes except for one subject in the CHMG group, who had diabetes for 57 years. Baseline demographics were similar between groups (Table 1). This protocol was institutional review board approved. Subjects initiating CHMG attended a session on glucose trends, features of the CHMG …

Cost-effectiveness models for diabetes link glycated hemoglobin (HbA1c) to diabetes-related complications. Independent of diabetes-related complications, there is little known on the association between HbA1c and health utility scores. This link can alter the cost effectiveness of interventions designed to improve HbA1c. The cross-sectional relationship between HbA1c and health utility scores in adult type 1 diabetes patients was estimated after adjusting for diabetes-related complications. The EuroQoL-5 dimension (EQ-5D) questionnaire and an ad hoc survey requesting demographic information and adherence to glucose monitoring therapies was administered to adult type 1 diabetes patients during a clinic visit and combined with clinical medical record data. Health utility scores were derived using the US time-tradeoff valuation of the EQ-5D. Linear regression was used to estimate the relationship between HbA1c and utility, adjusting for treatments, demographics, and diabetes-related complications. Among 176 patients, mean (standard deviation [SD]) age was 38 (12.2) years, duration of disease was 22 (12.1) years, and number of chronic conditions other than type 1 diabetes was 2.7 (2.0). Unadjusted mean (SD) utility was 0.94 (0.09) for those with HbA1c levels

Herein, we describe recruitment efforts for a trial of lipid-lowering medications in adolescents with type 1 diabetes, age 12–21 years. Based on our experience, future studies will require multiple centers to enroll a sufficient number of participants for adequate data to direct dyslipidemia medication treatment guidelines for adolescents with type 1 diabetes.

Objective. To further develop and evaluate a diabetes disease state management (DSM) program that provided direct patient care responsibilities to advanced pharmacy practice experience (APPE) students as members of healthcare teams. Design. Nine new clinics and 3 established sites that provide self-care management education to patients with diabetes were established and maintained in rural Colorado pharmacies and supported by students in APPE training for 48 weeks per year. Evaluation. The 12 clinics provided 120 APPE student placements in 2010-2011. Students’ perceptions of their experiences were positive. Patients who completed the student-supported diabetes self-management education program had improvements in blood glucose, blood pressure, and lipid values. Conclusions. Twelve diabetes DSM clinics provided direct patient care opportunities to APPE students working as part of healthcare teams while expanding healthcare resources in underserved communities in Colorado.

To assess outcomes from a rural, community pharmacy-based diabetes care and education program involving collaboration between local pharmacists and physicians, fourth-year pharmacy students, and University of Colorado Denver School of Pharmacy faculty members.Fourth-year pharmacy students provided education and testing (hemoglobin A1c, blood glucose, blood pressure, and lipid profiles) to diabetes patients, once a month for 6 months. Clinical notes with medication recommendations were faxed to each patient's physician following each visit.Twelve pharmacy students made 533 recommendations to 29 physicians for 52 patients over 18 months. Overall, 32% of the recommendations were accepted based on subsequent medication orders and patient reports. Three of the physicians accepted 50%-60% of the recommendations they received while 4 did not accept any recommendations.Physician acceptance of pharmacy students' medication recommendations for patients attending a rural community pharmacy-based diabetes management clinic varied. Further study is needed to determine the reasons for this.

Evidence suggests that stopping oral anticoagulation with warfarin is not necessary in patients requiring low-risk dental procedures and may actually increase thrombosis risk. However, widespread belief remains among dentists that stopping oral anticoagulation for dental procedures is necessary. The purpose of this study was to investigate the teaching practice of U.S. dental faculty responsible for providing education to dental students about anticoagulation. Surveys were mailed in 2003 and 2004 to fifty-five U.S. dental faculties to assess their teaching practice regarding anticoagulation and dental procedures. Twenty-eight (50.9 percent) of the schools returned surveys. Contrary to evidence indicating anticoagulation does not need to be altered, many dental faculty responded that they teach dental students to discuss with medical providers/patients about altering warfarin therapy for several routine procedures: 21.4 percent (cleaning), 14.3 percent (restorative treatment), 46.4 percent (single simple extraction), 64.3 percent (multiple simple extractions), and 17.9 percent (root canal). However, 67.9 percent stated an International Normalized Ratio (INR) of 2.0-3.0 would be acceptable prior to dental procedures. A discrepancy was also found between the number of faculty recommending altering warfarin in intermediate- to high-risk individuals compared to those recommending heparin bridging for the same patients. Overall, this study identified inconsistencies between teaching practices in U.S. dental schools and medical evidence. Dental faculty should consider comparing their teaching material with evidence regarding anticoagulation and dental procedures. Continuing education may be necessary for practicing dentists regarding this topic.

To determine whether diabetes mellitus (DM) with minor depression is associated with poorer levels of mental and physical functioning compared with DM without depression.Retrospective database study.US adults participating in the 2001 Medical Expenditure Panel Survey were included in these analyses. Main outcome measures were differences in health status, physical and cognitive limitations, and the Short-Form 12 (SF-12) Mental Component Summary (MCS) and Physical Component Summary (PCS) for US adults with DM stratified by minor depression status and evaluated using univariate and multivariate analyses to control for demographic, behavioral, and clinical covariates.A total of 1572 respondents with DM were included (1443 without depression, 129 with depression). Compared with people with DM and without depression, those with DM and minor depression were younger (P = .04); were more likely to be female, white, and smokers; and to have physical and cognitive limitations and lower SF-12 MCS and PCS scores (all P.01). In multivariate analyses, minor depression was independently associated with lower self-reported health status, MCS scores, and more cognitive limitations.People with DM and minor depression have lower mental functional scores, more cognitive limitations, and lower self-reported health status scores compared with people with DM and without depression, differences that may adversely affect self-care activities. Primary and DM care providers should screen for and be aware of depression in their patients with DM.

Insulin glulisine (Apidra, Sanofi-Aventis), a new and recently approved rapid-acting insulin analogue, mimics the pharmacokinetic and pharmacodynamic profiles of physiological human insulin, but has a rapid onset, peak effect at 1h, and a shorter duration of action (approximately 4 h). Its rapid-action properties are maintained across subject types. Formal clinical evaluations show that insulin glulisine can be administered safely and effectively pre- and postmeal. When injected immediately premeal, insulin glulisine provides superior postprandial blood glucose control compared with regular human insulin (RHI) injected 30 min premeal. These data highlight the flexibility in the dosing schedule with insulin glulisine. Clinical trials have demonstrated that insulin glulisine elicits a greater reduction in glycosylated haemoglobin at end point than RHI, in both type 1 and 2 diabetes mellitus. In addition, the safe administration of insulin glulisine by continuous subcutaneous insulin infusion has been demonstrated in patients with type 1 diabetes. In conclusion, insulin glulisine is an effective, safe and well-tolerated rapid-acting insulin analogue.

The American Diabetes Association recommends that individuals with type 2 diabetes should utilize self-monitoring of blood glucose (SMBG) as a means of assessing the efficacy of their medication to monitor for and prevent asymptomatic hypoglycemia, though the optimal frequency of SMBG and its impact in insulin-treated type 2 diabetes subjects have not been clearly defined. Only a minority of patients with type 2 diabetes performs SMBG, and there are several barriers to the increasing use of SMBG. In this article, we have reviewed some of the recently published studies looking at the relationship between the SMBG compliance and the glycosylated hemoglobin levels that emphasize that SMBG is an important determinant of glycemic control in insulin-treated type 2 diabetes.

To establish statewide medication, disease management, and other clinical programs to serve as advanced pharmacy practice experience (APPE) training sites for the University of Colorado at Denver and Health Sciences Center School of Pharmacy, and to guarantee year-round support for the programs by providing pharmacy students with the necessary competencies to carry a significant proportion of each program's workload.Partnerships with pharmacies willing to use students to expand their scope of clinical practice or support existing programs were established. Partners were asked to choose the clinical program(s) they wished implemented or supported and were guaranteed that APPE students would contribute to carrying each program's clinical service workload for 48 week/year under the supervision of the partners' pharmacists. In addition, partners implementing new programs were offered other support, including equipment, supplies, and training and mentoring for their pharmacists.Twenty-two partnerships involving anticoagulation, diabetes, immunization, medication reconciliation, and other clinical programs were established with hospital, community, and community health center pharmacies. The partnerships provided 213 APPE placements in the 2006-2007 academic year.This work demonstrates that by using innovative approaches, a pharmacy school can form new partnerships with hospital, community health center, and community pharmacies, as well as work with existing clinical programs, to create a variety of medication, disease management, and other APPEs to meet its increasing placement needs and evolving accreditation standards.

To introduce a requirement for second-professional year (P2) and third-professional year (P3) students to administer vaccinations to adults in community pharmacy-based immunization clinics.Second-professional year students were trained to administer influenza, pneumococcal, and other vaccinations to adults following the American Pharmacists Association's standards. All P2 students in fall 2004 and all P2 and P3 students in fall 2005 were assigned to 2 community pharmacy-based immunization clinics in the metropolitan Denver area under the supervision of immunization-certified staff pharmacists. An evaluation of the experience was conducted using retrospective preceptor and student-based survey data.In 2004 and 2005, the students administered approximately 5,000 (30-50 immunizations per student) and 15,000 (60-70 per student) immunizations, respectively. Students and preceptors agreed that the requirement to administer vaccinations was an appropriate activity for students and that it increased the students' self-confidence. When asked to rate the value of the students' work administering adult immunizations in the fall 2004 semester, the mean score given by the P2 students' immunization-certified preceptors was 9.2 on a 10-point Likert scale (1 = no value and 10 = great value).Consistent with accreditation standards for students to have direct patient care responsibilities in introductory pharmacy practice experience courses, a requirement for P2 and P3 students to administer vaccines to adult patients in community pharmacies was successfully introduced.

Insulin therapy is underutilized in the treatment of diabetes mellitus for many reasons, including both patient and provider resistance. Targeting postprandial blood glucose control in patients with either type 1 or type 2 diabetes has been demonstrated to improve overall glycemic control, but the reluctance to use injectable insulin demonstrates the need for the development of alternative routes for insulin delivery. The development of inhaled insulin systems was designed to improve the ease of insulin use for patients and help alleviate fears they may have with injectable insulin. Human insulin inhalation powder (HIIP) (Eli Lilly, Indianapolis, IN/Alkermes, Cambridge, MA) has been demonstrated in Phase 2 studies to have similar effects on glycemic profiles compared to both insulin lispro and regular insulin. Hypoglycemia during HIIP was similar to that of regular insulin but was associated with greater hypoglycemic risk compared to insulin lispro. In addition, the AIR Inhaled Insulin system (Lilly/Alkermes), which delivers HIIP, has been demonstrated to be easy to use and requires minimal patient education, which may improve overall medication compliance. Phase 3 studies are ongoing to further evaluate safety and efficacy of HIIP.

Background Our objective was to determine the cost-effectiveness of Continuous Glucose Monitoring (CGM) technology with intensive insulin therapy compared to self-monitoring of blood glucose (SMBG) in adults with type 1 diabetes in the United States. Methods A Markov cohort analysis was used to model the long-term disease progression of 12 different diabetes disease states, using a cycle length of 1 year with a 33-year time horizon. The analysis uses a societal perspective to model a population with a 20-year history of diabetes with mean age of 40. Costs are expressed in $US 2007, effectiveness in quality-adjusted life years (QALYs). Parameter estimates and their ranges were derived from the literature. Utility estimates were drawn from the EQ-5D catalogue. Probabilities were derived from the Diabetes Control and Complications Trial (DCCT), the United Kingdom Prospective Diabetes Study (UKPDS), and the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Costs and QALYs were discounted at 3% per year. Univariate and Multivariate probabilistic sensitivity analyses were conducted using 10,000 Monte Carlo simulations. Results Compared to SMBG, use of CGM with intensive insulin treatment resulted in an expected improvement in effectiveness of 0.52 QALYs, and an expected increase in cost of $23,552, resulting in an ICER of approximately $45,033/QALY. For a willingness-to-pay (WTP) of $100,000/QALY, CGM with intensive insulin therapy was cost-effective in 70% of the Monte Carlo simulations. Conclusions CGM with intensive insulin therapy appears to be cost-effective relative to SMBG and other societal health interventions.