Elaine Chiquette

Management of mild chronic hypertension during pregnancy: a review☆

Objective: To conduct a systematic review of evidence relating to management of mild chronic hypertension during pregnancy, including associated risks, benefits, and harms of treatment with antihypertensive agents, nonpharmacologic measures, and aspirin and benefits of various monitoring strategies. Data Sources: Using four broad search strategies, we searched English and non–English-language citations in 16 electronic databases from their inception to February 1999 and consulted relevant textbooks, references, and experts. Study Selection: Reviewers screened 6228 abstracts and found 215 articles that met multiple prespecified patient selection, study population, and design criteria. Tabulation, Integration, and Results: Forty-six studies consistently showed that chronic hypertension triples the risk for perinatal mortality (odds ratio [OR] 3.4; 95% confidence interval [CI] 3.0, 3.7) and doubles the risk for placental abruption (OR 2.1; 95% CI 1.1, 3.9). Thirteen small, randomized controlled trials had inadequate power to rule in or rule out moderate-to-large (20%–50%) benefits of antihypertensive treatment. Possible adverse effects were fetal renal failure when angiotensin-converting enzyme inhibitors are used in the second or third trimester and growth restriction when atenolol is used early in pregnancy. Trials showed that aspirin neither reduces nor increases perinatal and maternal morbidity, but they did not rule out possible small-to moderate beneficial or adverse effects. No studies provide guidance on benefits or consequences of various nonpharmacologic therapies or monitoring strategies. Conclusion: Mild chronic hypertension is associated with increased maternal and fetal risks. Beneficial treatment and monitoring regimens are not clear, but some treatments, such as angiotensin-converting enzyme inhibitors, are best avoided.

Effects of Marine Fish Oils on the Anticoagulation Status of Patients Receiving Chronic Warfarin Therapy

The purpose of this placebo-controlled, randomized, double-blinded, parallel study was to determine the existence and magnitude of effect of various doses of fish oil supplements on International Normalized Ratio (INR) determinations in patients receiving chronic warfarin therapy. Patients from anticoagulation clinics from both the Brady Green Community Health Center and Audie L. Murphy Veterans Administration in San Antonio, Texas were enrolled in the study. The enrolled subjects included 5 males and 11 females, all of whom were receiving chronic warfarin therapy for indications requiring oral anticoagulation. All enrolled patients underwent a 4-week placebo monitoring period in which INRs were determined on a weekly basis. If the INRs were found to be stable, patients were randomized to receive a 4-week treatment period of either placebo capsules (n = 6), 3 grams of fish oil daily (n = 5), or 6 grams of fish oil daily (n = 5). Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. Five patients were discontinued from the study due to noncompliance (2) and unstable INRs (3). There was no statistically significant difference in INRs between the placebo lead-in and treatment period within each group (P = 0.82). There was also no difference in INRs found between groups (P = 0.41). One bruising episode was reported, yet no major bleeding episodes were observed during the study. Fish oil supplementation in doses of 3–6 grams per day does not seem to create a statistically significant effect on the anticoagulation status of patients receiving chronic warfarin therapy.

A statistical and clinical evaluation of fingerstick and routine laboratory prothrombin time measurements

Study Objective. To compare prothrombin time measurements by fingerstick and routine laboratory methods.

Incretin Mimetics and Dipeptidyl Peptidase‐IV Inhibitors: Potential New Therapies for Type 2 Diabetes Mellitus

The emergence of the glucoregulatory hormones glucagon‐like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide has expanded our understanding of glucose homeostasis. In particular, the glucoregulatory actions of the incretin hormone GLP‐1 include enhancement of glucose‐dependent insulin secretion, suppression of inappropriately elevated glucagon secretion, slowing of gastric emptying, and reduction of food intake. Two approaches have been developed to overcome rapid degradation of GLP‐1. One is the use of agents that mimic the enhancement of glucose‐dependent insulin secretion, and potentially other antihyperglycemic actions of incretins, and the other is the use of dipeptidyl peptidase‐IV inhibitors, which reduce the inactivation of GLP‐1, increasing the concentration of endogenous GLP‐1. The development of incretin mimetics and dipeptidyl peptidase‐IV inhibitors opens the door to a new generation of antihyperglycemic agents to treat several otherwise unaddressed pathophysiologic defects of type 2 diabetes mellitus. We review the physiology of glucose homeostasis, emphasizing the role of GLP‐1, the pathophysiology of type 2 diabetes mellitus, the clinical shortcomings of current therapies, and the potential of new therapies— including the newly approved incretin mimetic exenatide—that elicit actions similar to those of GLP‐1.

Exenatide: From the Gila Monster to the Pharmacy

OBJECTIVE To explain the incretin concept and review the pharmacology and clinical utility of exenatide (Byetta-Amylin; Lilly), a new agent for the treatment of patients with type 2 diabetes mellitus, and provide pharmacists with information necessary for counseling patients in the use of exenatide. DATA SOURCES Review articles, clinical trials, and data on file with the manufacturers. STUDY SELECTION By the authors. DATA EXTRACTION By the authors. DATA SYNTHESIS Exenatide is a synthetic form of a protein found in the saliva of the Gila monster that mimics the action of glucagon-like peptide-1, an incretin important in glucose homeostasis and deficient in patients with diabetes mellitus. Three pivotal clinical trials of exenatide as an add-on therapy in patients with type 2 diabetes mellitus who were unable to achieve glycemic control with maximum doses of metformin, sulfonylurea, or these drugs in combination demonstrated significant reductions in glycosylated hemoglobin (A1C) levels following twice-daily self-injection of exenatide compared with placebo. Weight loss was observed in patients in conjunction with A1C improvement, which occurred without additional patient instruction, intentional caloric deficit, or exercise. Mild-to-moderate nausea was the most common adverse event with exenatide treatment, occurring at the beginning of therapy, lessening over time, and reduced by titration of the dose. CONCLUSION Exenatide offers a wide range of beneficial glucoregulatory effects, including enhancement of glucose-dependent insulin secretion, restoration of first-phase insulin response, suppression of inappropriately elevated glucagon secretion, slowing of gastric emptying, and reduction of food intake. These positive effects depend on the patients understanding of the proper administration technique and timing, the need for continued adherence, and what to do if adverse effects occur, all elements that can be conveyed by pharmacists in their counseling and education of patients with type 2 diabetes mellitus.

Treatment with exenatide once weekly or twice daily for 30 weeks is associated with changes in several cardiovascular risk markers.

Background Dyslipidemia and type 2 diabetes are two of the most significant risk factors for the development of cardiovascular disease. Measurement of lipoprotein subclasses provides important information about derangements in lipid metabolism and helps refine cardiovascular risk assessment. Exenatide, a glucagon-like peptide 1 receptor agonist, improved glycemic control, obesity, hypertension, and dyslipidemia in patients with type 2 diabetes in clinical trials. Methods In the DURATION-1 trial, patients with type 2 diabetes were treated with exenatide once weekly or twice daily for 30 weeks. This post hoc analysis evaluated the impact of exenatide on lipoprotein subclasses in 211 DURATION-1 patients using vertical auto profile methodology and the Statistical Package for the Social Sciences general linear model adjusted for glycosylated hemoglobin (HbA1c) and weight. Results Baseline lipids and high sensitivity C-reactive protein were normal overall based on the standard lipid panel. Once-weekly exenatide reduced apolipoprotein B and the apolipoprotein B to apolipoprotein A1 ratio (P < 0.05), independent of glycemic improvement and weight loss. A significant shift in lipoprotein pattern away from small, dense low-density lipoprotein-4 cholesterol was also observed (P < 0.05). Exenatide once weekly increased high-density lipoprotein-2 cholesterol, even after adjustment for changes in HbA1c and weight (P < 0.05). Triglycerides, very low-density lipoprotein cholesterol, and high sensitivity C-reactive protein were reduced with both the once-weekly and twice-daily exenatide regimens (P < 0.05). Conclusion In this post hoc analysis, exenatide significantly improved a number of cardiovascular risk markers. Continuous exenatide exposure with exenatide once weekly elicited a greater response than did immediate-release exenatide twice daily, generally independent of glycemic improvement and weight loss. Thus, in addition to improving glycemic control, exenatide induced favorable changes in lipid and lipoprotein metabolism and decreased systemic inflammation.

Workshop: Anticoagulation clinic care versus routine medical care: A review and interim report

The available data describing the impact of anticoagulation clinics (ACC) on complication rates is reviewed, and an interim report of an ongoing study is presented. Early reports of low complication rates with ACCs were uncontrolled descriptive reports. The findings of later controlled trials were limited because the prothrombin time ratio (PTR) rather than the International Normalized Ratio (INR) was used. Three of four INR-based studies found that the use of an ACC reduced complication rates by 70–90%. The study described in this report is an ongoing evaluation of the complication rates and associated health care costs among two inception cohorts in a university-based clinic. Patients started on warfarin during 20 months before the ACC opened are compared with patients started on warfarin (and enrolled in the ACC) after the ACC opened. Complication rates, hospitalisations, and emergency room visits appear to be reduced by 65–80% in the ACC group, and this equates to a saving in health care costs of approximately

In Silico Design of Optimal Ratio for Co-Administration of Pramlintide and Insulin in Type 1 Diabetes

1200 per patient per year.

Control of Warfarin Treatment and Problems with the International Normalized Ratio

BACKGROUND The ability to simulate in silico experiments is crucial for fast and cost-effective preliminary studies prior to clinical trials. We present an in silico approach to the design of optimal pramlintide-to-insulin (P/I) ratios, using our computer simulator of the human metabolic system, with a population of virtual adult type 1 diabetes mellitus patients and with individual parameters modified to account for the dynamic effects of pramlintide. MATERIALS AND METHODS A model of pramlintide action on gastric emptying was built using data of 15 type 1 diabetes mellitus subjects studied twice with a standardized dual-tracer meal on placebo and pramlintide, which was incorporated in our type 1 diabetes simulator. Extensive in silico experiments on 100 virtual subjects were performed to optimize the co-administration of pramlintide and insulin prior to its submission to clinical trials; several P/I ratios were tested in terms of efficacy, in attenuating postprandial hyperglycemia, and in hypoglycemia safety. RESULTS In silico experiments estimated the optimal P/I ratio to be 9 μg of pramlintide per unit (U) of insulin. Additional simulations narrowing the investigated range indicated that P/I ratios of 8 and 10 μg/U would achieve similar performance. Moreover, simulation results suggested that in clinical trials, insulin boluses should be reduced by approximately 21% at a P/I ratio of 9 μg/U to account for the effects of pramlintide and avoid postprandial hypoglycemia. CONCLUSIONS We can assert that a valid simulation model of pramlintide action was developed, leading to in silico estimation of optimal pramlintide:insulin co-administration ratio. Clinical trials will confirm (or adjust) this initial estimation.

Comparison of an anticoagulation clinic with usual medical care: Anticoagulation control, patient outcomes, and health care costs

ous or confusing data. Subsequent, the Third American College of Chest Physicians Consensus Conference published guidelines for warfarin use in International Normalized Ratio (INR) units only in 1~~~: Implementation of the INR system, however, has revealed a number of limitations which require some restrictions and modifications in the process. The INR system of reporting, however, should be used for all patients on warfarin therapy, but