BACKGROUND β2-adrenergic receptor (ADRB2) polymorphisms affect β2-mediated glucose production by terbutaline. Whether beta-blockers' effects on β2-mediated glucose production are affected by ADRB2 polymorphisms is unknown. This study determines the effect of ADRB2 Arg16Gly and Glu27Gln polymorphisms on β2-mediated glucose dynamics during beta-blocker titration in heart failure. METHODS From a previous heart failure cohort whose metoprolol or carvedilol were titrated to maximally tolerated doses (up to metoprolol 200mg/d or carvedilol 25mg twice daily) in 5 visits, we analyzed ADRB2 polymorphisms at codons 16 and 27, and glucose AUC0–180min upon a β2-agonist (terbutaline) infusion in nondiabetic individuals. RESULTS Glucose AUC (mmol/Lx180 min) upon terbutaline infusion decreases as beta-blocker dosages increase (p=0.0033, repeated measure ANOVA). At baseline, subjects carrying a Glu allele at codon 27 demonstrated lower glucose AUC compared to individuals homozygous for Gln, although this difference was not significant. After maximal beta-blocker titration, glucose AUC decreased from 5.5±0.2 to 4.9±0.2 in subjects carrying a Glu allele at codon 27 versus from 6.3±0.4 to 5.5±0.4 in subjects homozygous for Gln (p=0.0342, ANCOVA for comparisons between genotype groups). The ADRB2 Arg16Gly variant was not associated with differences in glucose values. CONCLUSIONS ADRB2 polymorphisms may play a role in β2-mediated glucose production in heart failure patients taking beta-blockers. Clinical Pharmacology & Therapeutics (2005) 79, P35–P35; doi: 10.1016/j.clpt.2005.12.126
A 76-year-old man with a history of myocardial infarction, Type 2 diabetes, hypertension, hypercholesterolemia, and heart failure presents with muscle pain and spasm. A number of medication-related problems are identified by the pharmacist. Prioritization of medication-related problems and therapeutic recommendations are provided. The medication-related problems described in this case reinforce the need for establishing individualized action plans and avoiding making too many changes in medication regimens at one time. In addition, the issue of nonpharmacological causes of symptoms can be overlooked when focusing on medication-induced illness.
We studied patient persistence with oral contraceptive pills (OCPs) compared to metformin for treatment of polycystic ovary syndrome (PCOS) in an urban university clinic population.We conducted a retrospective cohort study of women with PCOS who were treated in our specialty clinic between 2004 and 2006. All women with the diagnosis of PCOS, defined as oligomenorrhea or amenorrhea in conjunction with clinical or biochemical evidence of hyperandrogenism, with exclusion of other causes, were included in the study. We abstracted data on demographic characteristics, medical history, anthropometrical measures, desire for pregnancy, prescribed treatment, and patient report of persistence with treatment at 3, 6, and 12 months. The primary outcome measure was persistence with prescribed treatment.One hundred nineteen subjects were included in the study. Demographic and anthropometrical characteristics were similar between the groups. At 3 months, 57.1% were persistent with OCPs, and 57.8% were persistent with metformin (p=0.93). At 6 months, the percentages dropped to 38.1% with OCPs and 43.9% with metformin (p=0.46). At 12 months, only 21.7% continued with OCPs compared to 31.2% with metformin (p=0.19). Subjects were significantly more likely to be persistent with either OCPs or metformin at 3 months compared to either 6 or 12 months (p<0.01).Women with PCOS showed similar persistence rates with OCPs compared to metformin. Persistence with either treatment precipitously decreases over time and is modest at 12 months.
Postoperative venous thromboembolism occurs in a significant proportion of women undergoing major gynecologic surgery and cesarean delivery. Prophylactic use of sequential compression devices (SCDs) is a well-established method for prevention of venous thromboembolism in these and other surgical patients. Medical guidelines recommend continuous use of pneumatic compression devices until ambulation and discontinuation only at the time of discharge. Few studies have assessed compliance to these devices in postoperative benign gynecology surgery and cesarean delivery settings. The aim of this prospective observational study was to assess compliance to SCDs in patients who have undergone major obstetric or benign gynecologic procedures and to determine whether use of nursing and patient education about venous thromboembolism prevention would improve compliance. The study was conducted from October 2012 to April 2013 at a university medical center. Subjects were English-speaking patients who underwent cesarean delivery or benign gynecologic surgery and had been prescribed to wear SCDs throughout hospitalization. The study was divided into four 1-month segments. The first month was a period of baseline observations of compliance by a coauthor. The second month involved structured patient education, the third month involved structured nursing education, and the final month included both interventions. Observations of compliance were made twice daily. Educational interventions and observations were performed by the coauthors. Compliance was defined as ambulation or lying in bed with SCDs applied, tubing attached, and the machine powered on, or sitting in a chair (with or without SCDs applied). During the study period, 859 observations were recorded for 228 patients. The mean number of hospitalization days was 2.4 (range, 1–13 days). There was no significant difference in compliance among the 4 segments. Compliance for each consecutive month was 141 (61.3%) of 230, 106 (54.6%) of 194, 155 (56.0%) of 277, and 95 (60.1%) of 158; P = 0.44. Noncompliance increased with each successive postoperative day; the adjusted odds ratio was 1.18 per day, with a 95% confidence interval of 1.07 to 1.30. The most common reasons given by patients for noncompliance were “the nurse said I don’t need them anymore” (82/362 observations [22.6%]), “I just got back in bed, and no one has reapplied them” (n = 59 [17.1%]), and “I’ve been walking” (n = 63 [16.3%]). Overall, compliance following cesarean delivery was lower than gynecologic surgery (272/519 [52.4%] vs 225/340 [66.2%], P < 0.001). These findings show that postoperative compliance with use of SCDs is approximately 58% and is not improved with patient or nursing educational interventions.
The bridging mechanism of antithrombin inhibition of thrombin is a dominant mechanism contributing a massive approximately 2500-fold acceleration in the reaction rate and is also a key reason for the clinical usage of heparin. Our recent study of the antithrombin-activating properties of a carboxylic acid-based polymer, poly(acrylic acid) (PAA), demonstrated a surprisingly high acceleration in thrombin inhibition (Monien, B. H.; Desai, U. R. J. Med. Chem. 2005, 48, 1269). To better understand this interesting phenomenon, we have studied the mechanism of PAA-dependent acceleration in antithrombin inhibition of thrombin. Competitive binding studies with low-affinity heparin and a heparin tetrasaccharide suggest that PAA binds antithrombin in both the pentasaccharide- and the extended heparin-binding sites, and these results are corroborated by molecular modeling. The salt-dependence of the K(D) of the PAA-antithrombin interaction shows the formation of five ionic interactions. In contrast, the contribution of nonionic forces is miniscule, resulting in an interaction that is significantly weaker than that observed for heparins. A bell-shaped profile of the observed rate constant for antithrombin inhibition of thrombin as a function of PAA concentration was observed, suggesting that inhibition proceeds through the "bridging" mechanism. The knowledge gained in this mechanistic study highlights important rules for the rational design of orally available heparin mimics.
Women with polycystic ovarian syndrome (PCOS) are at increased risk for developing glucose intolerance and type 2 diabetes mellitus (DM). Recommendations for the timing and method of screening have varied. The purpose of this statement is to determine the optimal screening method, timing of screening, and treatment modalities for impaired glucose tolerance (IGT) among women with PCOS.The expert panel was appointed by the Androgen Excess Society (AES) to review the literature and make recommendations based on the available evidence. Meetings were open, and there was no funding for the panel.A systematic review was conducted of the published, peer-reviewed medical literature using MEDLINE to identify studies that addressed the prevalence, risk factors, testing, and treatment for IGT in both adults and adolescents with PCOS. Unpublished data were not considered.The panel held meetings to review the literature and draft the statement as a committee. The AES board members reviewed and critiqued the manuscript, and changes were made based on their comments.The panel recommends that all patients with PCOS be screened for IGT with a 2-h oral glucose tolerance test. A few members of the AES board recommend alternatively screening women with PCOS for IGT and type 2 DM using an oral glucose tolerance test only in patients with a body mass index of 30 kg/m2 or greater or in lean patients with additional risk factors. Patients with normal glucose tolerance should be rescreened at least once every 2 yr, or more frequently if additional risk factors are identified. Those with IGT should be screened annually for development of type 2 DM. PCOS patients with IGT should be treated with intensive lifestyle modification and weight loss and considered for treatment with insulin-sensitizing agents.
Objective. To describe the implementation and evaluation of population health management learning activities in a second-year Doctor of Pharmacy (PharmD) course. Methods. Population health learning sessions were implemented in a step-wise manner: population needs assessment activity to identify priority programs for implementation given a specific patient population; didactic materials to introduce program evaluation foundational knowledge; program evaluation design activity to evaluate implemented programs using the Centers for Disease Control and Prevention’s Program Evaluation Framework; and evaluation of program outcome data. Students’ self-rated abilities (grouped into Bloom’s Taxonomy classifications) and perceptions before and after program evaluation activities were assessed. Qualitative analyses evaluated student feedback on learning sessions. Results. Students’ self-rated abilities for all Bloom’s classifications increased after the learning sessions. Student perceptions on importance of program evaluation also improved (from 71% reporting “agree” or “strongly agree” pre-activities to 79% post-activities). Students found the application to case scenarios and the opportunity to integrate each component of program evaluation into a complete process useful. Conclusion. Step-wise population health management learning sessions were implemented, culminating in skill-based program evaluation activities. The activities improved students’ self-rated abilities and perceptions regarding program evaluation. Areas for improvement for the learning sessions were also identified and will inform future instructional design.
Insulin resistance is a central feature of the polycystic ovary syndrome (PCOS). Women with PCOS suffer both short- and long-term health consequences from insulin resistance and the compensatory hyperinsulinemia associated with PCOS. Short-term consequences include anovulation, hyperandrogenism, infertility, and early pregnancy loss. Over the long term, chronic hyperinsulinemia predisposes women with PCOS to increased risks of diabetes and cardiovascular events. Current data support the use of metformin for treatment of anovulation in women with PCOS, both in monotherapy and in combination with clomiphene in clomiphene-resistant patients. The effect of insulin sensitizers on hirsutism will also be reviewed. In addition, novel evidence, although limited, suggests that insulin sensitizers may play a role in preventing early pregnancy loss. Over the long term, insulin sensitizers may prevent cardiovascular and diabetes complications by ameliorating the metabolic syndrome associated with chronic insulin resistance in PCOS, pending further evidence. Several insulin-sensitizing agents are available commercially: metformin, rosiglitazone, and pioglitazone. Metformin has the most desirable pregnancy safety profile and is the agent that has been most frequently studied in PCOS. In conclusion, there is strong support for the use of insulin-sensitizing drugs, particularly metformin, in women with PCOS.
