Critical appraisal of amlodipine and olmesartan medoxomil fixed-dose combination in achieving blood pressure goals

Hypertension remains a significant health burden in the United States, with almost one in three adults affected, and is an independent risk factor for cardiovascular and renal disease. The goal of antihypertensive treatment is to reduce cardiovascular and renal morbidity and mortality by reducing blood pressure (BP). Guidelines recommend a target BP of <140/90 mmHg, with a more stringent goal of <130/80 mmHg for patients with diabetes and chronic renal disease. However, BP goal attainment rates remain low and most patients require therapy with two or more antihypertensive agents. Combination antihypertensive therapy usually employs agents from different classes, thus benefitting from complementary mechanisms of action to achieve greater BP control with fewer side effects. Patient adherence to therapy is enhanced by formulating treatments as fixed-dose (single-pill) combinations. One example is the combination of amlodipine, a dihydropyridine calcium channel blocker (CCB), with olmesartan medoxomil, an angiotensin receptor blocker (ARB). Here, the rationale for the use of CCB/ARB combination therapy is discussed, as well as the pharmacology and tolerability of the amlodipine/olmesartan medoxomil combination and its efficacy in terms of achieving BP goal in patients with hypertension. Advantages of its use from the patient’s perspective are also discussed

Increased Calcium Intake Does Not Suppress Circulating 1,25-Dihydroxyvitamin D in Normocalcemic Patients with Sarcoidosis

Ca absorption is regulated by 1,25(OH)2D, and serum values vary inversely with Ca intake. In sarcoidosis, 1,25(OH)2D is produced by alveolar macrophages in response to y-interferon, and patients may develop hypercalcemia after prolonged exposure to sunlight and increased dermal production of vitamin D3. To determine if increased Ca intake suppresses serum 1,25(OH)2D in normocalcemic patients and to identify those at risk, 17 normal subjects and 11 patients were studied on a metabolic ward for two and one-half days while receiving first 400 and then 1,000 mg/d of Ca. On the low Ca intake, serum angiotensin-converting enzyme (ACE), an index of disease activity, was higher in only three of the patients than in the controls, mean serum 1,25(OH)2D was higher in the patients, and mean serum total Ca, serum Ca , and urinary Ca were not different in the two groups. On the higher Ca intake, mean urinary Ca increased in both groups, but mean serum 1,25(OH)2D was suppressed only in the normal subjects. Thus, 1,25(OH)2D production is abnormally regulated, indicating that (a) normocalcemic patients with sarcoidosis are at risk for developing abnormal Ca metabolism, and (b) a better index of disease activity is provided by the oral Ca suppression test than by serum ACE. (J. Clin. Invest. 1993. 91:1396- 1398.

Exploring the Boundaries of Conditionality in the EU. Egmont European Policy Brief No. 51 June 2018

Conditionality in the EU comes in many forms: legally codified and enforced by the Court of Justice, or reliant on intergovernmental bargaining and expressed by means of political or economic (dis)incentives. This European Policy Brief explores the boundaries of the conditionality debate, and assesses what varying degrees of conditionality can and cannot achieve. The overarching objective of conditionality is to foster integration and cohesion amongst the peoples of Europe and their Member States. A sound logic of conditionality must therefore set incentives in such a way that their application contributes to this intended outcome. A balanced combination of political, legal and budgetary instruments can help remedy a major lacuna in the Treaties: the effective protection of the rule of law and democracy

Lipoprotein lipase SNPs rs13702 and rs301 correlate with clinical outcome in chronic lymphocytic leukemia patients

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world and is characterized by a heterogeneous clinical course. This variability in clinical course has spiked the search for prognostic markers able to predict patient evolution at the moment of diagnosis. Markers demonstrated to be of value are the mutation status of the immunoglobulin heavy chain variable region genes (IGHV) and lipoprotein lipase (LPL) expression. High LPL mRNA expression has been associated with short treatment free (TFS) and decreased overall survival (OS) in CLL. The LPL SNPs rs301 (T<C), rs328 (C<G) and rs13702 (T<C) have been associated with various metabolic disorders, but the association with CLL evolution is unknown. Here, in a cohort of 248 patients, we show that patients with the LPL SNP rs13702 wild-type T/T genotype had significantly shorter OS than patients with C/C and T/C genotypes (median time until CLL related death: 90 and 156 months respectively, p=0.008). The same was observed for LPL SNP rs301 (median time until CLL related death T/T: 102 and C/C, T/C: 144 months, p=0.03). Both SNPs rs301 and rs13702 were significantly associated with each other and notably, no association was found between IGHV status and presence of the SNP genotypes, indicating that these LPL SNPs are reliable prognostic markers that could add extra prognostic and predictive information to classical markers and help to improve the management of CLL

Prospectus, October 18, 1978

PARKLAND\u27S BOOKSTORE-- IS IT RIPPING YOU OFF?; letters to the editor One student does not want gay bars to turn into \u27freak shows\u27; Give blood today; College Cuisine; Dec. 31 is EC fellowship application deadline; Advertising Policy; Instructors attend meeting next week; Electronics \u27bugs\u27 invited to Parkland; Gammon elected charter member; Riding club has contest; Raffle winners have last day to claim prizes; Language clubs will have dinner; Nov. 5 poetry review deadline; PC defines typical student; Taiwan students to give performance at U of I; SNAP to host guest speakers; Parkland is getting ready for hard winter; PC math contest to be Saturday, April 28; Mimes visit campus; Legal clinic is Oct. 19; Farm emergency workshop to be held on Nov. 4; Women\u27s creativity honored; Parkland\u27s nursing program is Gogol\u27s first full-time job; High cost of books is common problem; DeShong attacking PC apathy; PC health service sponsors lectures; WPCD\u27s Top 15 For The Week Of Oct. 9; Final Christmas bazaar meeting; \u27I Quit Smoking\u27 draws fifteen; PC events for the week; Battered women series part 2: Battered women face struggles; Craft media in art exhibit; Free Classifieds; Informants can profit; Family Service conducts workshop; Golf team places 20th; PC still looking for wrestlers; Paxton still undefeated; \u27Spikers\u27 ready for tourney; Intramural basketball team organizing now; B-ball meeting for girls to be tuesday; Fast Freddy Contest; Fast Freddy has a winner with three wrong answershttps://spark.parkland.edu/prospectus_1978/1007/thumbnail.jp

The knowledge transfer from science to practice – a survey with EU researchers

Group members came from 12 European countries, six from new (Bulgaria, Czech Republic, Estonia, Hungary, Poland and Slovenia) and six from old EU member states (Germany, Spain, Finland, Italy, The Netherlands, Portugal). The aim of the work was to analyze the role of the scientists in a dialogue between them and the practitioners within the organic production sector. Another important aim was to find the best practice models of such dialogue as the examples to be followed by others. In order to reach this aim the survey with the scientists has been conducted by all project partners; every partner has conducted the survey with 10 selected scientists from own country. Only the scientists possessing PhD level and actively working in the organic sector could be selected. Key areas of the questionnaire were directed to the (A) person (gender, age, years of activity in teaching and/or researching), (B) number of projects, papers, trainings and interviews, (C) Examples of best practice models, (D) Estimations of potential collaboration and dialog between scientists and stakeholders, (E) Estimations about the success of personal activities with regard to the improvement of the four fields (farming, processing, trading & marketing), (F) Estimates of the improvement of communication and knowledge transfer from science to practice, (G) Estimates of potential threats for good communication and knowledge transfer among scientists and practitioners. Interviewees were finally asked for general remarks and comments. The results indicate that there is not a big difference between the scientists from the old EU member states and new EU member states in most of the analyzed areas. The main difference is that the scientists from the new EU member states provide more training sessions for practitioners outside their institutions compared to the researchers from the old EU member states. The results reveal also a relatively low level of the researchers’ activity in conducting the implementation projects and writing the popular papers, both in the old and new EU member states

Olfactory Nomenclature: An Orchestrated Effort to Clarify Terms and Definitions of Dysosmia, Anosmia, Hyposmia, Normosmia, Hyperosmia, Olfactory Intolerance, Parosmia, and Phantosmia/Olfactory Hallucination

BACKGROUND: Definitions are essential for effective communication and discourse, particularly in science. They allow the shared understanding of a thought or idea, generalization of knowledge, and comparison across scientific investigation. The current terms describing olfactory dysfunction are vague and overlapping. SUMMARY: As a group of clinical olfactory researchers, we propose the standardization of the terms "dysosmia," "anosmia," "hyposmia," "normosmia," "hyperosmia," "olfactory intolerance," "parosmia," and "phantosmia" (or "olfactory hallucination") in olfaction-related communication, with specific definitions in this text. KEY MESSAGES: The words included in this paper were determined as those which are most frequently used in the context of olfactory function and dysfunction, in both clinical and research settings. Despite widespread use in publications, however, there still exists some disagreement in the literature regarding the definitions of terms related to olfaction. Multiple overlapping and imprecise terms that are currently in use are confusing and hinder clarity and universal understanding of these concepts. There is a pressing need to have a unified agreement on the definitions of these olfactory terms by researchers working in the field of chemosensory sciences. With the increased interest in olfaction, precise use of these terms will improve the ability to integrate and advance knowledge in this field

Effects of Renal Denervation vs Sham in Resistant Hypertension after Medication Escalation:Prespecified Analysis at 6 Months of the RADIANCE-HTN TRIO Randomized Clinical Trial

IMPORTANCE: Although early trials of endovascular renal denervation (RDN) for patients with resistant hypertension (RHTN) reported inconsistent results, ultrasound RDN (uRDN) was found to decrease blood pressure (BP) vs sham at 2 months in patients with RHTN taking stable background medications in the Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN TRIO) trial. OBJECTIVES: To report the prespecified analysis of the persistence of the BP effects and safety of uRDN vs sham at 6 months in conjunction with escalating antihypertensive medications. DESIGN, SETTING, AND PARTICIPANTS: This randomized, sham-controlled, clinical trial with outcome assessors and patients blinded to treatment assignment, enrolled patients from March 11, 2016, to March 13, 2020. This was an international, multicenter study conducted in the US and Europe. Participants with daytime ambulatory BP of 135/85 mm Hg or higher after 4 weeks of single-pill triple-combination treatment (angiotensin-receptor blocker, calcium channel blocker, and thiazide diuretic) with estimated glomerular filtration rate (eGFR) of 40 mL/min/1.73 m(2 )or greater were randomly assigned to uRDN or sham with medications unchanged through 2 months. From 2 to 5 months, if monthly home BP was 135/85 mm Hg or higher, standardized stepped-care antihypertensive treatment starting with aldosterone antagonists was initiated under blinding to treatment assignment. INTERVENTIONS: uRDN vs sham procedure in conjunction with added medications to target BP control. MAIN OUTCOMES AND MEASURES: Six-month change in medications, change in daytime ambulatory systolic BP, change in home systolic BP adjusted for baseline BP and medications, and safety. RESULTS: A total of 65 of 69 participants in the uRDN group and 64 of 67 participants in the sham group (mean [SD] age, 52.4 [8.3] years; 104 male [80.6%]) with a mean (SD) eGFR of 81.5 (22.8) mL/min/1.73 m(2) had 6-month daytime ambulatory BP measurements. Fewer medications were added in the uRDN group (mean [SD], 0.7 [1.0] medications) vs sham (mean [SD], 1.1 [1.1] medications; P = .045) and fewer patients in the uRDN group received aldosterone antagonists at 6 months (26 of 65 [40.0%] vs 39 of 64 [60.9%]; P = .02). Despite less intensive standardized stepped-care antihypertensive treatment, mean (SD) daytime ambulatory BP at 6 months was 138.3 (15.1) mm Hg with uRDN vs 139.0 (14.3) mm Hg with sham (additional decreases of −2.4 [16.6] vs −7.0 [16.7] mm Hg from month 2, respectively), whereas home SBP was lowered to a greater extent with uRDN by 4.3 mm Hg (95% CI, 0.5-8.1 mm Hg; P = .03) in a mixed model adjusting for baseline and number of medications. Adverse events were infrequent and similar between groups. CONCLUSIONS AND RELEVANCE: In this study, in patients with RHTN initially randomly assigned to uRDN or a sham procedure and who had persistent elevation of BP at 2 months after the procedure, standardized stepped-care antihypertensive treatment escalation resulted in similar BP reduction in both groups at 6 months, with fewer additional medications required in the uRDN group. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0264942