Treatment patterns and related clinical consequences in adults with asthma.

OBJECTIVE: A stepwise therapeutic management is recommended for asthma patients by the Global Initiative for Asthma (GINA). Little is known about the recommendations applied in real world settings. This study aims to associate Treatment step with clinical events in patients with mild or severe asthma. METHODS: A retrospective claims database analysis included adult patients with mild (GINA step 1) or severe asthma (GINA step 4). Maximum Treatment Step was measured within the first and second 90-day period after index date (the first date of asthma diagnosis during the inclusion period). Step-down was defined as a Treatment Step change from a higher to lower step, while Step-up was defined as a Treatment Step change from a lower to higher step. The primary outcome was a composite endpoint of asthma-related clinical events, measured at the third 90-day period. RESULTS AND CONCLUSIONS: A total of 6,354 mild-asthma patients and 5,695 severe-asthma patients were included. In mild-asthma, when compared with No Change in Treatment Step, Step-down was associated with a lower risk of future clinical events [adjusted odds ratio (OR) 0.80, 95% confidence interval (95% CI); 0.69-0.94], while Step-up was not associated with a change in clinical events [OR 0.98, 95% CI: 0.77-1.27]. In severe-asthma patients, Step-down was not associated with a change in clinical events [OR 0.94, 95% CI: 0.81-1.10], while Step-up was associated with a higher risk of future clinical events [OR 2.07, 95% CI: 1.29-3.33]. Our findings reassure the appropriateness of stepping-down treatment in mild-asthma patients. Clinicians should closely monitor and/or provide detailed asthma action plans for severe-asthma patients who are stepping-up treatment.

Factors influencing the acceptance of referrals for clinical pharmacist managed disease states in primary care.

OBJECTIVE: Clinical pharmacists use population health methods to generate chronic disease management referrals for patients with uncontrolled chronic conditions. The purpose of this study was to compare primary care providers' (PCPs) referral responses for 4 pharmacist-managed indications and to identify provider and patient characteristics that are predictive of PCP response. DESIGN: Retrospective cohort study. SETTING: This study occurred in an academic internal medicine clinic. PARTICIPANTS: Clinical pharmacy referrals generated through a population health approach between 2012 and 2016 for hypertension, chronic pain, depression, and benzodiazepine management were included. MAIN OUTCOME MEASURES: Proportion of referrals accepted, left pending, or rejected and influencing provider and patient characteristics. RESULTS: Of 1769 referrals generated, PCPs accepted 869 (49%), left pending 300 (17%), and rejected 600 (34%). Compared with referrals for hypertension, benzodiazepine management, and depression, chronic pain referrals had the lowest likelihood of rejection (odds ratio [OR] 0.31; 95% CI 0.19-0.49). Depression referrals had an equal likelihood of being accepted or rejected (OR 1.04; 95% CI 0.66-1.64). Provider characteristics were not significantly associated with referral response, but residents were more likely to accept referrals. Patient characteristics associated with lower referral rejection included black race (OR 0.39; 95% CI 0.18-0.87), higher systolic blood pressure (OR 0.98; 95% CI 0.97-0.99), and missed visits (OR 0.24; 95% CI 0.07-0.81). CONCLUSION: The majority of referrals for clinical pharmacists in primary care settings were responded to, varying mostly between acceptance and rejection. There was variability in referral acceptance across indications, and some patient characteristics were associated with increased referral acceptance.

Semaglutide: The Newest Once-Weekly GLP-1 RA for Type 2 Diabetes.

OBJECTIVE: To review efficacy and safety of the glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide for type 2 diabetes (T2D). DATA SOURCES: A literature search of PubMed/MEDLINE and EMBASE using the term semaglutide was completed through April 2018. A search of clinicaltrials.gov was also conducted. STUDY SELECTION AND DATA EXTRACTION: English-language studies assessing the efficacy and/or safety of semaglutide were evaluated. DATA SYNTHESIS: Semaglutide is a newly approved GLP-1 RA for the treatment of T2D. Administered once weekly at a dose of 0.5 or 1 mg, it has been compared with placebo, sitagliptin, insulin glargine, a combination of oral antidiabetic therapies, and 2 GLP-1 RAs, exenatide ER and dulaglutide, and demonstrated greater efficacy compared with these therapies. Published data from studies ranging from 30 to 104 weeks duration demonstrate efficacy with decreases in hemoglobin A1C (A1C) ranging from 1.1% to 2.2%. Studies show reductions in weight from 1.4 to 6.5 kg. Semaglutide demonstrated a reduction in the composite outcome of cardiovascular (CV) death, nonfatal myocardial infarction, or nonfatal stroke compared with placebo in patients at high risk of CV events (hazard ratio = 0.74; P = 0.02). Common adverse effects include nausea, vomiting, and diarrhea as seen with other GLP-1 RAs. Relevance to Patient Care and Clinical Practice: Semaglutide represents an attractive GLP-1 RA considering its A1C and weight reduction. It provides patient convenience and high patient satisfaction. CONCLUSIONS: Semaglutide is an appealing option for the treatment of T2D as a once-weekly GLP-1 RA with established glycemic, CV, and weight benefits.

Dulaglutide: the newest GLP-1 receptor agonist for the management of type 2 diabetes.

OBJECTIVE: To review the pharmacology, pharmacokinetics, safety, and efficacy of the glucagon-like peptide-1 receptor agonist (GLP-1 RA), dulaglutide, in the treatment of type 2 diabetes mellitus (T2D). DATA SOURCES: A PubMed search was completed to identify publications from 1947 to October 2014 using the search terms dulaglutide and LY2189265. References were reviewed to identify additional resources. STUDY SELECTION AND DATA EXTRACTION: Articles were included if they evaluated the pharmacology, pharmacokinetics, safety, or efficacy of dulaglutide. DATA SYNTHESIS: Dulaglutide reduces both glycosylated hemoglobin (A1C) and weight by stimulating insulin secretion and suppressing glucagon in a glucose-dependent manner, delaying gastric emptying, and promoting satiety. Dulaglutide consists of 2 GLP-1 analogues that have been modified to make it a long-acting, once-weekly agent. Dulaglutide has been studied as monotherapy and in combination with metformin, glimepiride, pioglitazone, and insulin lispro. It has demonstrated superior A1C reduction compared with placebo, metformin, insulin glargine, sitagliptin, and twice-daily exenatide. It demonstrated noninferiority in A1C reduction to liraglutide. Dulaglutide changed A1C by -0.78% to -1.51%, and it changed weight by -0.35 kg to -3.03 kg. The most common adverse effects in clinical studies were nausea, vomiting, and diarrhea. CONCLUSIONS: Dulaglutide is the fifth GLP-1 RA approved for T2D in the United States. It is an attractive option because it is dosed once-weekly, provides A1C lowering similar to liraglutide, weight reduction similar to exenatide, and has an adverse effect profile similar to exenatide and liraglutide.

Sport and exercise as contributors to the health of nations.

Self-reported rates of participation in sport vary by country. In the UK, about 40% of men and women aged 16 years or older participate in at least one sport every week. Although few data exist to assess trends for participation in sport, there is little evidence of change in the past decade among adults. Large cohort studies suggest that such participation in sport is associated with a 20-40% reduction in all-cause mortality compared with non-participation. Randomised trials and crossover clinical studies suggest that playing sport is associated with specific health benefits. Some sports have relatively high injury risk although neuromuscular training programmes can prevent various lower extremity injuries. Clinicians can influence a large number of patients through brief interventions that promote physical activity, and encouragement toward participation in sport for some physically inactive patients qualifies as evidence-based therapy. Exercise might also be considered as a fifth vital sign and should be recorded in patients' electronic medical records and routine histories.

Complementary effects of multivitamin and omega-3 fatty acid supplementation on indices of cardiovascular health in individuals with elevated homocysteine.

Homocysteine (HCY), C-reactive protein (hsCRP), and triglycerides (TG) are risk factors for cardiovascular disease (CVD). While multivitamins (MVit) may reduce HCY and hsCRP, omega-3 fatty acids (N3) reduce TG; yet, they are seldom studied simultaneously. We randomly assigned 100 participants with baseline HCY (> 8.0 umol/L) to the daily ingestion of: (1) placebo, (2) MVit (VitC: 200 mg; VitE: 400 IU; VitB6: 25 mg; Folic Acid: 400 ug; VitB12: 400 ug) + placebo, (3) N3 (2 g N3, 760 mg EPA, 440 mg DHA)+placebo, or (4) MVit + N3 for 12 weeks. At follow-up, we observed significant reductions in HCY (umol/L) for the MVit (- 1.43, 95 %CI, - 2.39, - 0.47) and MVit + N3 groups (- 1.01, 95 %CI, - 1.98, - 0.04) groups, both being significant (p < 0.05) vs. placebo (- 0.57, 95 %CI, - 1.49, 0.35) and N3 (1.11, 95 % CI, 0.07, 2.17). hsCRP (nmol/L) was significantly reduced in the MVit (- 6.00, 95 %CI, - 1.04, - 0.15) and MVit + N3 (- 0.98, 95 %CI, - 1.51, - 0.46) groups, but not vs. placebo (- 0.15, 95 %CI, - 0.74, 0.43) or N3 (- 0.53, 95 %CI, - 1.18, 0.12). Lastly, we observed significant reductions in TG for the N3 (- 0.41, 95 %CI, - 0.69, - 0.13) and MVit + N3 (- 0.71, 95 %CI, - 0.93, - 0.46) groups, both significant vs. placebo (- 0.10, 95 %CI, - 0.36, 0.17) and MVit groups (0.15, 95 %CI, - 12, 0.42). The co-ingestion of MVit + N3 provides synergistic affects on HCY, hsCRP, and plasma TG.

Dietary intake of Nova Scotia youth in grades 7 and 11.

PURPOSE: We examined dietary intakes among Nova Scotia youth, and analyzed whether these intakes met existing dietary guidelines. METHODS: Data from 1469 students in grades 7 and 11 from randomly selected schools were collected via a web-based dietary assessment tool, including a 24-hour recall. Nutrient analysis products were subjected to descriptive and inferential statistical analyses. RESULTS: Reported dietary intakes across sexes and grades showed the vast majority of youth did not meet minimum recommendations for fibre (96% to 98%) or vegetable and fruit servings (83.3% to 90.7%). Girls in grade 11 reported greater intakes of folate and lower intakes of saturated fat, and were less likely to report iron intakes at or above the Estimated Average Requirement than were grade 7 girls. Across ages, more than 75% of girls reported low calcium and folate intakes. Boys in both grades reported consuming more energy than did girls, and older boys reported consuming more than did younger boys. Foods outside the four main food groups contributed about 25% of total reported energy intake. Students in grade 7 consumed pop, salty snacks, and french fries more frequently than did students in grade 11. CONCLUSIONS: Adolescents' self-reported dietary intakes may not meet current dietary recommendations. Continued efforts are needed to develop innovative strategies to ensure healthy eating patterns.

Association of inflammation and endothelial dysfunction with metabolic syndrome, prediabetes and diabetes in adults from Inner Mongolia, China.

BACKGROUND: We examined the association of biomarkers of inflammation and endothelial dysfunction with diabetes and metabolic syndrome (MetS) in persons from Inner Mongolia. METHODS: A cross-sectional study was conducted among 2,536 people aged 20 years and older from Inner Mongolia, China. Overnight fasting blood samples were obtained to measure plasma concentrations of high sensitivity C-reactive protein (hsCRP), soluble inter-cellular adhesion molecule-1 (sICAM-1), sE-selectin, angiotensin II, high density lipoprotein cholesterol, triglycerides, and blood glucose. Waist circumference and blood pressure were measured by trained staff. MetS was defined according to the modified ATP III definition for Asians. Elevated level of the biomarker was defined as values in the upper tertile of the distribution. Participants were categorized into one of four groups based on the presence or absence of metabolic and glycemic abnormalities: 1) free of prediabetes, diabetes and MetS (reference group), 2) prediabetes or diabetes only, 3) MetS without prediabetes or diabetes, and 4) MetS plus prediabetes or diabetes. The multivariable models are adjusted for age, gender, smoking, drinking, family history of hypertension, and body mass index. RESULTS: Among study participants, 18.5% had prediabetes, 3.6% had diabetes, and 27.4% of the entire study population had 3 or more components of the MetS. Elevated hsCRP was associated with an increased odds of prediabetes or diabetes only, MetS without prediabetes or diabetes, and MetS plus prediabetes or diabetes with multivariable adjusted odds ratios (95% confidence intervals) of 2.3 (1.7-3.1), 3.0 (2.4-3.8), and 5.8 (4.5-7.5), respectively. Elevated sICAM-1 was associated with increased odds (95% CI) of prediabetes or diabetes only (2.1, 1.6-2.9) and MetS plus prediabetes or diabetes (4.2, 3.2-5.3) but was not associated with MetS alone. Elevated sE-selectin was associated with a modestly increased risk of MetS (OR 1.7, 95% CI 1.4-2.2). Elevated levels of Angiotensin II were not associated with the MetS plus prediabetes or diabetes in this study. CONCLUSIONS: Diabetes and the MetS are common in the Inner Mongolia population. The biomarkers of inflammation and endothelial dysfunction are associated with increased risk for diabetes and MetS in this population. These results are consistent with results from other populations.

Antihypertensive treatment and secondary prevention of cardiovascular disease events among persons without hypertension: a meta-analysis.

CONTEXT: Cardiovascular disease (CVD) risk increases beginning at systolic blood pressure levels of 115 mm Hg. Use of antihypertensive medications among patients with a history of CVD or diabetes and without hypertension has been debated. OBJECTIVE: To evaluate the effect of antihypertensive treatment on secondary prevention of CVD events and all-cause mortality among persons without clinically defined hypertension. DATA SOURCES: Meta-analysis with systematic search of MEDLINE (1950 to week 3 of January 2011), EMBASE, and the Cochrane Collaboration Central Register of Controlled Clinical Trials and manual examination of references in selected articles and studies. STUDY SELECTION: From 874 potentially relevant publications, 25 trials that fulfilled the predetermined inclusion and exclusion criteria were included in the meta-analysis. DATA EXTRACTION: Information on participant characteristics, trial design and duration, treatment drug, dose, control, and clinical events were extracted using a standardized protocol. Outcomes included stroke, myocardial infarction (MI), congestive heart failure (CHF), composite CVD outcomes, CVD mortality, and all-cause mortality. RESULTS: Compared with controls, participants receiving antihypertensive medications had a pooled relative risk of 0.77 (95% confidence interval [CI], 0.61 to 0.98) for stroke, 0.80 (95% CI, 0.69 to 0.93) for MI, 0.71 (95% CI, 0.65 to 0.77) for CHF, 0.85 (95% CI, 0.80 to 0.90) for composite CVD events, 0.83 (95% CI, 0.69 to 0.99) for CVD mortality, and 0.87 (95% CI, 0.80 to 0.95) for all-cause mortality from random-effects models. The corresponding absolute risk reductions per 1000 persons were -7.7 (95% CI, -15.2 to -0.3) for stroke, -13.3 (95% CI, -28.4 to 1.7) for MI, -43.6 (95% CI, -65.2 to -22.0) for CHF events, -27.1 (95% CI, -40.3 to -13.9) for composite CVD events, -15.4 (95% CI, -32.5 to 1.7) for CVD mortality, and -13.7 (95% CI, -24.6 to -2.8) for all-cause mortality. Results did not differ according to trial characteristics or subgroups defined by clinical history. CONCLUSIONS: Among patients with clinical history of CVD but without hypertension, antihypertensive treatment was associated with decreased risk of stroke, CHF, composite CVD events, and all-cause mortality. Additional randomized trial data are necessary to assess these outcomes in patients without CVD clinical recommendations.

Patient Outreaches for Clinical Pharmacy Services: A Population Health Management Program Assessment.

BACKGROUND: Pharmacists in ambulatory care can utilize population health approaches to identify patients needing disease management and improve outcomes. However, population health is only effective when identified patients are successfully outreached and show to appointments. OBJECTIVE: Describe a population health approach utilized by pharmacists in primary care, report outcomes of outreach attempts and scheduled appointments, and determine whether patient and referral characteristics predict no-show appointments. METHODS: Retrospective cohort study of patients referred for pharmacist management of hypertension or chronic pain through population health between 2013-2016. Outreach attempt and appointments outcomes were collected. Patient and referral characteristics were analyzed to determine whether predictive of no-show appointments using logistic regression. RESULTS: Of 450 outreach attempts, 250 (56%) patients were not reached, 164 (36%) scheduled appointments, and 36 (8%) were reached but declined an appointment. Of 164 patients with appointments, 71 (43%) no-showed. Patients with higher systolic blood pressure were more likely to no-show (OR: 1.02, 95% CI: 1.00-1.04). Other characteristics were not predictive of no-show appointments. CONCLUSION: Successful outreach and showed appointments are essential components of successful population health programs. Using multiple outreach modalities and further identifying factors predictive of no-show appointments to refine the current approach may lead to increased efficiency.

Physical activity of children and youth in Nova Scotia from 2001/02 and 2005/06.

OBJECTIVES: This paper reports on physical activity of students in grades 3, 7, and 11 from two surveillance studies (from 2001 and 2005). METHODS: Randomly selected students (Study1 n=1730; Study2 n=2341) from randomly selected schools in Nova Scotia participated. Physical activity was measured for seven consecutive days using Actigraph accelerometers. Descriptive statistics were calculated for moderate, hard, and very hard intensity, and total minutes of physical activity. Between study, grade, and sex differences were determined using univariate Analyses of Variance. RESULTS: Students in Study2 were significantly less active (mean [SD]=531.0 [392.3] min/week) than Study1 (662.2 [495.1] min/week). Girls were significantly less active (525.4 [419.1] min/week) than boys (657.1 [460.3] min/week). Students in grade 11 were significantly less active (225.2 [171.1] min/week) than students in grade 7 (457.5 [227.2] min/week) who were significantly less active than students in grade 3 (1038.4 [387.6] min/week). A significant study-grade interaction indicated that compared to students in grades 7 and 11, the level of physical activity in students in grade 3 was considerably lower in Study2 compared to Study1. CONCLUSIONS: Given the lower level of physical activity found in Study2, efforts at informing public policy and strategies that promote physical activity in children and youth should be made.

Integration of Community Pharmacists in Transition of Care (TOC) Services: Current Trends and Pharmacist Perceptions.

BACKGROUND:: Barriers exist for patients transitioning from one health-care setting to another, or to home, and health-care systems are falling short of meeting patient needs during this time. Community pharmacist incorporation poses a solution to the current communication breakdown and high rates of medication errors during transitions of care (TOC). The purpose of this study was to determine community pharmacists' involvement in and perceptions of TOC services. METHODS:: Cross-sectional study using electronic surveys nationwide to pharmacists employed by a community pharmacy chain. RESULTS:: Of 7236 pharmacists surveyed, 546 (7.5%) responded. Only 33 (6%) pharmacists reported their pharmacy participates in TOC services. Most pharmacists (81.5%) reported receiving discharge medication lists. The most common reported barrier to TOC participation is lack of electronic integration with surrounding hospitals (51.1%). Most pharmacists agreed that (1) it is valuable to receive discharge medication lists (83.3%), (2) receiving discharge medication lists is beneficial for patients' health (89.1%), (3) discharge medication list receipt improves medication safety (88.8%). CONCLUSIONS:: Most pharmacists reported receiving discharge medication lists and reported discharge medication lists are beneficial, but less than half purposefully used medication lists. To close TOC gaps, health-care providers must collaborate to overcome barriers for successful TOC services.

Overweight Nova Scotia children and youth: the roles of household income and adherence to Canada's Food Guide to Healthy Eating.

OBJECTIVE: Poor diet quality has been observed in Nova Scotia children and youth, characterized by low intake from the traditional four food groups and a high intake from the Other Foods category. In this study, we addressed how household income and adherence to Canada's Food Guide to Healthy Eating influenced weight status category in Nova Scotia children and youth. METHODS: During the 2005-06 school year, data were collected from 2,296 students and their parents, across Nova Scotia. Questionnaires and anthropometric measurements were obtained from grades 3, 7 and 11 students. The grade 3 students were excluded from the dietary intake assessment. The information collected from the online 24-hour food recalls and food frequency questionnaires were analyzed for adherence to Canada's Food Guide to Healthy Eating recommendations. A general linear model was employed to examine the relationships between household income, food group and weight status category. RESULTS: Overall adherence to Canada's Food Guide to Healthy Eating was low among grades 7 and 11 students. Fewer servings from Grain Products, Milk Products and Vegetables and Fruit were observed in at risk of overweight and overweight students. At risk of overweight and overweight were significantly related to lower household income in grades 3 and 11. Our results show that the rates of overweight in Nova Scotia students are double those reported by the 2004 Canadian Community Health Survey. CONCLUSION: Household income and dietary intake play significant roles in weight status among Nova Scotia children and youth.

Clinical pharmacy academic career transitions: Viewpoints from the field.

The six authors of this commentary series, who have recently transitioned into or within an academic career, discuss challenging aspects of an academic career change. This is a three-part commentary series that explores select challenges: 1) feedback, evaluation, and advancement; 2) understanding and balancing of distribution of effort; 3) learning how and when to say yes. Faculty, or those interested in pursuing a career in pharmacy academia, can refer to this commentary series as a reference. Schools of pharmacy may utilize this as a tool for new faculty members during orientation in order to ensure smooth integration into the academic environment.

Clinical pharmacy academic career transitions: Viewpoints from the fieldPart 1: Understanding feedback, evaluation, and advancement.

The six authors of this commentary series, who have recently transitioned into or within an academic career, discuss challenging aspects of an academic career change. This is a three-part commentary series that explores select challenges: 1) feedback, evaluation and advancement; 2) understanding and balancing of distribution of effort; 3) learning how and when to say yes. Faculty, or those interested in pursuing a career in pharmacy academia, can refer to this commentary series as a reference. Schools of pharmacy may utilize this as a tool for new faculty members during orientation in order to ensure smooth integration into the academic environment.

Clinical pharmacy academic career transitions: Viewpoints from the field part 3: Learning when and how to say yes.

The six authors of this commentary series, who have recently transitioned into or within an academic career, discuss challenging aspects of an academic career change. This is Part 3 of a three-part commentary series that focuses on when and how to say yes to the multitude of opportunities available to pharmacy practice faculty. Part 1 discusses feedback, evaluation, and advancement. Part 2 explains distribution of effort (DOE) and how to marry the different components of teaching, research, and service. While the entire series is intended to be read in continuity, faculty, or those interested in pursuing a career in pharmacy academia, can refer to Part 3 as a reference on how to screen opportunities within academia to maximize professional and personal growth and minimize career burnout. Schools of pharmacy may utilize this as a tool for new faculty members during orientation to help ensure faculty success.

Efficacy and safety of twice- vs once-daily dosing of lisinopril for hypertension.

This retrospective cohort study compared administration of lisinopril twice daily and once daily for hypertension. Data were collected from an ambulatory electronic health record between 2011 and 2014. Patients previously receiving lisinopril 20 mg were placed into the once-daily cohort if changed to 40 mg once daily or into the twice-daily cohort if changed to 20 mg twice daily. Efficacy outcome measures were change in systolic blood pressure and diastolic blood pressure and achievement of blood pressure control (<140/90 mm Hg). Of 90 patients included (45 per cohort), the mean age was 61.8 years and 17.8% were black. Once- and twice-daily administrations were associated with blood pressure reductions of 6.2/1.5 mm Hg and 16.5/5.9 mm Hg, with a 10.2/4.3 mm Hg greater reduction with twice-daily administration (systolic blood pressure, P=.016; diastolic blood pressure, P=.068). Twice-daily lisinopril dosing was associated with greater systolic blood pressure reductions compared with the same total daily dose administered once daily.

Antihypertensive Therapy in Females: A Clinical Review Across the Lifespan.

Hypertension affects one-third of all females in the United States, with the prevalence increasing over a female's lifespan. The approach to treating females with hypertension varies depending on a female's age, race, comorbidities, and whether she is of child-bearing age or pregnant. It is important to factor in the safety and effectiveness of antihypertensive medications across these populations of females. Blood pressure target goals are the same in females as in males regardless of comorbidities or stage of life, with the exception of those females who are pregnant. Recommendations for antihypertensive medication do not differ between females and males based on disease state or stage of life, with the exception of females who are pregnant, breastfeeding, or of child-bearing age. Multiple guidelines recommend avoiding renin-angiotensin system blockers during pregnancy and suggest balancing the risk versus benefit in females of child-bearing age. Further, multiple guidelines provide race-based therapy recommendations for the use of calcium channel blockers and thiazide diuretics in black versus nonblack patients, irrespective of sex. Future research is needed to evaluate whether there are sex differences relative to blood pressure and cardiovascular event-lowering relative to specific antihypertensive medications with a focus on pharmacogenomic differences.

Advances in the treatment of type 2 diabetes: impact of dulaglutide.

The purpose of this review is to provide a review of current data of the most recently approved glucagon-like peptide (GLP)-1-receptor agonist, dulaglutide, in the treatment of type 2 diabetes. To complete this, a PubMed search was performed to identify manuscripts published from 1947 to July 2015. The search terms "Trulicity", "dulaglutide", and "LY2189265" were utilized, and publications were included if they evaluated the pharmacology, pharmacokinetics, efficacy, safety, or patient-reported outcomes of dulaglutide. Dulaglutide is a GLP-1 receptor agonist that mimics endogenous GLP-1, the hormone produced in response to food intake. Modifications have been made to the molecule to delay breakdown and allow for once-weekly dosing. Dulaglutide has been studied as monotherapy and in combination with several agents, including metformin, glimepiride, pioglitazone, and insulin lispro. Dulaglutide has demonstrated superior efficacy compared to placebo, metformin, insulin glargine, sitagliptin, and twice-daily exenatide. It was found to be noninferior to liraglutide. The most common adverse effects in clinical studies were gastrointestinal-related adverse events, and patient satisfaction was high with the use of dulaglutide. Dulaglutide is an appealing option for the treatment of type 2 diabetes, based on its once-weekly dosing, A1c lowering comparable to liraglutide, weight reduction comparable to exenatide, and a similar adverse-effect profile to other GLP-1 receptor agonists.

Cocaine-induced modulation of long-term potentiation in the CA1 region of rat hippocampus.

In order to further characterize the actions of cocaine on synaptic activity in the hippocampus, recordings of field excitatory postsynaptic potentials in the CA1 region of the rat hippocampal slice preparation were used to monitor drug effects on long-term potentiation (LTP) evoked in response to stimulation of the Schaffer collateral pathway. Cocaine had dose-dependent, biphasic effects on the magnitude of LTP at these excitatory synapses in the stratum radiatum ranging from a significant enhancement of LTP at intermediate drug concentrations (5-10 microM), to an inhibition of LTP at a relatively high drug concentration (30 microM). The local anesthetic lidocaine had only inhibitory effects on the induction of LTP at all concentrations examined (10-75 microM), whereas the monoamine transporter antagonists, WIN 35348 (1 microM) or GBR 12935 (5 microM) significantly enhanced the magnitude of LTP. The D(2)-like dopamine receptor antagonist, eticlopride was effective in preventing this action of cocaine, whereas pretreatment with the D(1/5) antagonist, SCH 23390 was ineffective. These results suggest that endogenously released dopamine, in the presence of cocaine (5-10 microM), can act via D(2)-like receptors to significantly increase the magnitude of LTP in the CA1 region of the hippocampus.