Tablet Scorings

Selected summaries of published journal articles

The Peer Reviewers Say “Yes”: Eight Papers Published or Accepted in First Quarter of 2009, Including Four on the Management of Attention-Deficit/Hyperactivity Disorder (ADHD)


APRIL 6, 2009 WYCKOFF, NJ—With the posting of the Integrated Data Exploratory Analysis (IDEA) study report (on management of ADHD) to the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP) website on March 23, 2009, eight articles have been published or accepted by top-tier peer-reviewed medical journals with editorial support from Rete Biomedical Communications Corp.   More…



Chemical structure of atomoxetine HCl (Strattera®;
Eli Lilly and Co., Indianapolis, IN)
Source: www.chemblink.com

 

Rete Com Reaches Publication Milestone

With the posting of a review article on the American Journal of Cardiology website in August, 20 papers have now been published in top-tier peer-reviewed journals with assistance from Rete Biomedical Communications Corp. in 2008. Three manuscripts have recently been accepted, including one each by the Archives of Ophthalmology and the Journal of Sexual Medicine. One of these reports resulted from pooled analyses of clinical trials, and the company is also involved in other, related “data-mining” projects. A total of 24 papers are projected to have been accepted and/or published by the end of 2008―an average of two each month. Rete Com was also recently awarded a contract to provide editorial support in 2008-2009 to Eli Lilly Canada (Ontario; www.lilly.ca) as scientists with the company prepare to submit study reports on two CNS medications to peer-reviewed journals.

Supplement on Aortic Stenosis Published

Hot topics in aortic stenosis. Eur Heart J 2008;10:E4-E40.

Proceedings from a December 6, 2007 satellite symposium to EUROECHO 2007, the 11th Annual Meeting of the Association of Echocardiography, a registered branch of the European Society of Cardiology, have been published as a supplement to the European Heart Journal.

The symposium and supplement were supported by Merck/Schering-Plough, and the supplement is available online at http://eurheartjsupp.oxfordjournals.org/current.dtl

Publication of this supplement brings to 19 the number of articles published in top-tier peer-reviewed journals with editorial assistance from Rete Biomedical Communications Corp. in 2008 (or nearly one article per week from January through June).

Rete Com collaborated with an internationally renowned faculty, including Nalini M. Rajamannan, MD, Valve Director, Bluhm Cardiovascular Institute, Division of Cardiology and Department of Pathology, Northwestern University, Feinberg School of Medicine (Chicago), on her article entitled “Update on the pathophysiology of aortic stenosis”; Nikolaus Jander, MD, Internist/Kardiologe, Oberarzt und Leiter der Echokardiographie Herz-Zentrum, Bad Krozingen, Germany, on his article entitled “Low-gradient ‘severe’ aortic stenosis with preserved ejection fraction: new entity, or discrepant definitions?”; Kristian Wachtell, MD, PhD, FESC, Department of Medicine B, The Heart Center, Rigshospitalet, Copenhagen, on his article entitled “Left ventricular systolic performance in asymptomatic aortic stenosis”; Eva Gerdts, MD, PhD, Professor of Medicine, Institute of Medicine, University of Bergen, Director, Noninvasive Imaging Unit, Department of Heart Disease, Haukeland University Hospital, Bergen, Norway, on her article entitled “Left ventricular structure in different types of chronic pressure overload”; and Terje R. Pedersen, MD, Centre for Preventive Medicine, Ullevål University Hospital, Oslo, Norway on his article entitled “Overview of clinical trials on calcific aortic stenosis.”

This is the second journal supplement published in 2008 with editorial assistance from Rete Com. The other was published in the journal Diabetes, Obesity and Metabolism and concerned management of type 2 diabetes mellitus with an incretin enhancer (DPP-IV inhibitor). Diabetes, Obesity and Metabolism is published by Blackwell Publishing (http://www.blackwellpublishing.com/journal.asp?ref=1462-8902&site=1).  

The Gila Monster (Heloderma suspectum) Strikes Again:
Review of Incretin Mimetics and Analogues for Type 2 Diabetes Mellitus (DM2)

Van Gaal LF, Gutkin SW, Nauck MA. Exploiting the antidiabetic properties of incretins to treat type 2 diabetes mellitus: glucagon-like peptide 1 receptor agonists or insulin for patients with inadequate glycemic control. Eur J Endocrinol 2008;158(6):773-784.

 Peptide hormones secreted into the saliva of the venomous Gila monster, a slow-moving nocturnal predator indigenous to the American Southwest that can survive for months without food, were found by Eng and Raufman to be long-lived agonists of the glucagon-like protein (GLP-1) receptor in mammals. These findings spawned pharmaceutical research to synthesize compounds sharing these properties. One such agent, exenatide (Byetta®; Amylin/Eli Lilly), was initially termed “exendin” because it was secreted by an exocrine gland (in the Gila) but also exerted endocrine effects in mammals. In human beings, GLP-1 is secreted by entero-endocrine cells—hormone-secreting cells within the distal small intestine (ileum)—in response to meal intake.
 
These compounds were the objects of intense scrutiny at the recent 68th Scientific Sessions of the American Diabetes Association, June 6-10, 2008, in San Francisco, CA
(http://professional.diabetes.org/Congress_Display.aspx?TYP=9&CID=58000).

A review of the topic that was researched, drafted, and edited with assistance from
Rete Com was published in the June 2008 issue of European Journal of Endocrinology. Through a uniquely balanced therapeutic attack on both components of Unger’s “bihormonal hypothesis,” which involves the counter-regulatory hormone glucagon secreted by α-cells and insulin secreted by β-cells in the pancreatic Islets of Langerhans, these compounds can delay gastric emptying, promote a sense of satiety, and exert glucose-dependent insulinotropic effects. Consequently, treatment with some of these agents can help to normalize the endocrine and metabolic disturbances of DM2 without inducing weight gain (or even promoting weight loss in overweight or obese patients) or increasing the risk of hypoglycemia when administered as monotherapy.

The review focused on injectable incretin mimetics and analogues. Oral agents that enhance circulating levels of endogenous incretins (GLP-1 and GIP) have also been developed (DPP-IV inhibitors). After discussing the biology of incretins, as well as the efficacy, safety, and tolerability profiles of certain incretin mimetics and analogues, the review considered patient factors consistent with incretin mimetics or insulin.

Stephen W. Gutkin of Rete Com collaborated with Prof. Drs. Luc F. Van Gaal, Department of Diabetology, Metabolism and Clinical Nutrition, Antwerp (Belgium) University Hospital, and Michael A. Nauck, Diabeteszentrum, Bad Lauterberg IM Harz, Germany, on the paper, which was supported by Eli Lilly. The article is available online at www.eje-online.org.

Cholesterol Goal Attainment Rate No Better Than Chance in Largest Pan-Asian Pharmacoepidemiologic Study Published to Date

Kim H-S, Wu Y, Lin S-J, Deerochanawong C, Zambahari R, Zhao L, Zhang Q, Yan P. Current status of cholesterol goal attainment after statin therapy among patients with hypercholesterolemia in Asian countries and region: the Return on Expenditure Achieved for Lipid Therapy in Asia (REALITY-Asia) study. Curr Med Res Opin 2008;24(7):1951-1963.

 Less than half (48%) of 2,622 patients with hypercholesterolemia in the People’s Republic of China, Korea, Malaysia, Singapore, Taiwan, and Thailand achieved consensus cholesterol treatment targets, according to this study report from the international Return on Expenditure Achieved for Lipid Therapy (REALITY) program.

Approximately 9 of every 10 patients in the study population had coronary heart disease (CHD) or at least two CHD risk factors. Echoing previous findings in other pharmacoepidemiologic studies, including the Lipid Treatment Assessment Program (LTAP), the likelihood of goal achievement in Asian patients varied inversely with their absolute cardiovascular risk: only 38% of those at highest risk, individuals with CHD and/or diabetes mellitus, followed by 62% of those with at least two risk factors but no CHD, and 81% in those with less than two CHD risk factors.

With urbanization and economic development in many regions of Asia over the past 20 years, residents have become more susceptible to “the diseases of affluence,” including CHD. As in other populations, rising mean levels of serum total cholesterol and LDL cholesterol have been associated with increasing incidences of CHD morbidity and mortality in Asia, although there is considerable regional variation, particularly between rural and urban populations. Despite solid evidence from clinical trials showing that therapeutic lifestyle modification and lipid-modifying therapy help to limit atherosclerotic progression and reduce cardiovascular risk in Asian patients, published data on cholesterol goal attainment in Asia had been fairly scant before this study report.

Collaborating with corresponding author Dr. Peter Yan, Gleneagles Medical Centre (Singapore) and other Asian investigators, Rete Com assisted in researching, drafting, editing, and proofreading the manuscript. The findings are also consistent with data from other study reports supported editorially by Rete Com, including the REALITY-Europe program, the FINRISK trial in Finland, the Hong Kong Hospital Audit Study, and the ASACT trial in Singapore. These studies were supported by Merck & Co., the Merck/Schering Plough joint venture, and/or their affiliates. 

The REALITY-Asia study report is available online at www.cmrojournal.com.

Effects of modifying triglycerides and triglyceride-rich lipoproteins on cardiovascular outcomes

Abdel Maksoud M, Sazonov V, Gutkin SW, Hokanson JE. J Cardiovasc Pharmacol 2008 Apr;51(4):331-351.

Although treatment with HMG-CoA reductase inhibitors (statins) significantly reduces cardiovascular risk compared with placebo in patients at elevated risk, such treatment alone does not prevent the majority of cardiovascular events in such patients. Other lipid and lipoprotein abnormalities, including elevated serum triglycerides and low HDL-cholesterol (HDL-C; “good” cholesterol), are also rational targets for lifestyle modification and/or pharmacotherapy.

Published as the first paper in the April issue of the Journal of Cardiovascular Risk, this
>8,000-word review focuses on the published literature concerning the effects on cardiovascular events and coronary arterial atherosclerotic progression of treatment with agents having more profound effects on triglycerides (and HDL-C) compared with statins, including fibric-acid derivatives (fibrates) and nicotinic acid (niacin).

In collaboration with senior author Dr. John E. Hokanson (University of Colorado Denver & Health Sciences Center) and Dr. Madiha Abdel-Maksoud (Tanta University, Egypt), whose previous work on the topic has been cited widely, Stephen W. Gutkin of Rete Com assisted in researching the topic and preparing the manuscript, which covers data from nearly 200 published references. Included among the papers reviewed are the Veterans Affairs HDL Intervention Trial (VA-HIT), Helsinki Heart Study (including 18-year mortality data recently published), Bezafibrate Infarction Prevention (BIP) study (clinical trial and registry), and Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT), all of which involved fibrates; the Coronary Drug Project involving niacin; as well as consensus guidelines from the National Cholesterol Education Program (NCEP).

The review was supported by Merck & Co., Inc., Whitehouse Station, NJ (www.merck.com), and is available online at http://www.cardiovascularpharm.com.

 
Comprehensive Review of the Effects of Niacin on Glycemic Regulation Published in April 2008 Issue of Mayo Clinic Proceedings

Goldberg RB, Jacobson TA. Effects of niacin on glucose control in patients with dyslipidemia. Mayo Clin Proc 2008 Apr;83(4):470-8.

Potentially through an effect on peripheral insulin sensitivity secondary to a rebound rise in circulating free fatty acids, nicotinic acid (niacin) treatment of dyslipidemia may result in modest, typically transient and/or reversible increases in indices of glycemic control, including hemoglobin A1c and fasting glucose. Accordingly, consensus treatment guidelines issued by the National Lipid Association, National Cholesterol Education Program, and other health authorities include recommendations for the use of this treatment in patients with and/or at elevated risk of type 2 diabetes mellitus. This review considers such guideline recommendations in the context of a risk:benefit analysis weighing the potential effects of niacin on glucose control against the potential long-term benefits of such treatment, which has been shown in published subgroup analyses of the Coronary Drug Project to confer significant long-term cardioprotective effects (vs placebo) even in patients with insulin-resistance syndromes at baseline.

Collaborating with Drs. Ronald Goldberg of the University of Miami Leonard M. Miller School of Medicine, Miami, FL (www.med.miami.edu), and Terry A. Jacobson of Emory University School of Medicine, Atlanta, GA (www.med.emory.edu), Rete Com assisted in researching the topic and preparing the manuscript. Rete Com has been collaborating with Dr. Jacobson since 1993, including papers previously published in the Journal of the American Medical Association (JAMA), Annals of Internal Medicine, Archives of Internal Medicine, American Journal of Cardiology, Drug Safety, and Expert Opinion in Drug Safety.  

The article was supported by Merck & Co., Inc., Whitehouse Station, NJ (www.merck.com), and is available online at www.mayoclinicproceedings.com.

Recent Meta-Analysis Suggests Superiority of Infliximab Over Other Biological Therapies for Induction Treatment of Psoriasis

Reich K, Sinclair R, Roberts G, Griffiths CE, Tabberer M, Barker J. Comparative effects of biological therapies on the severity of skin symptoms and health-related quality of life in patients with plaque-type psoriasis: a meta-analysis. Curr Med Res Opin 2008 Mar 19 [Epub ahead of print]

The pooled relative risk for achieving a 75% reduction of baseline Psoriasis Area Severity Index (PASI 75) scores using biological response modifiers (vs placebo) was 3.37 for alefacept, 7.47 for efalizumab, 11.92 for etanercept, and 25.48 for infliximab. Studies involving all therapies demonstrated more pronounced improvements (vs placebo) in health-related quality of life (HRQOL). Proportions of patients discontinuing treatment were similar in patients randomly assigned to each active treatment compared with placebo. These findings resulted from a systematic review of Medline and other databases evaluating the effects on PASI, HRQOL, and other endpoints of induction therapy with alefacept, efalizumab, etanercept, or infliximab in patients with active but chronic stable plaque psoriasis vulgaris. Data extracted from all randomized clinical trials were pooled by outcome and dose using both fixed- and random-effects statistical models.

Rete Com collaborated with Dr. Kristian Reich of Dermatologikum Hamburg, Hamburg, Germany, and other investigators and scientists across three continents to provide assistance in researching the topic and preparing the manuscript. Supported by Schering-Plough Pharmaceuticals, Kenilworth, NJ (www.schering-plough.com), the study report is available online at www.cmrojournal.com.

Tadalafil Effective, Well Tolerated in Elderly Men: Findings of the
MOMENTUS study

Sharlip ID, Shumaker BP, Hakim LS, Goldfischer E, Natanegara F, Wong DG. Tadalafil is efficacious and well tolerated in the treatment of erectile dysfunction (ED) in men over 65 years of age: results from the Multiple Observations in Men with ED in National Tadalafil Study in the United States [MOMENTUS]. J Sex Med 2008 Mar;5(3):716-725.

Advancing age is arguably the most salient risk factor for the development of erectile dysfunction (ED) in male species, human or rodent. In this multicenter trial,
188 men ages > 65 (mean = 71.6 )years were treated open-label with “on-demand” tadalafil 20 mg (not more than once daily) for up to 12 weeks. Men receiving tadalafil experienced significant improvement in erectile function according to multiple measures of the International Index of Erectile Function and also by their diary entries of sexual encounters for the Sexual Encounter Profile. A total of 40% of patients with ED at baseline experienced normalization of erectile function, and 81% reported improved erections, following tadalafil treatment. More than 50% of sexual-intercourse attempts were completed successfully for up to 36 hours after elderly men took tadalafil. After such treatment, men also rated their sexual self-confidence higher than at baseline (before treatment). Tadalafil was also well tolerated, with proportions of elderly men discontinuing because of adverse events (<5%) being similar to data from more heterogeneous populations.

Rete Com collaborated with Dr. Ira D. Sharlip of the University of California, San Francisco (www.ucsf.edu), and other investigators to research the topic and prepare the manuscript.
The study report was supported by Eli Lilly and Company, Indianapolis, IN (www.lilly.com), and published in the March issue of the Journal of Sexual Medicine, The Official Journal of the International Society for Sexual Medicine and the International Society for the Study of Women's Sexual Health. It is available online at http://www.jsm.issir.org.
The above-referenced study provides context for a prior review of the topic for which Rete Com provided research and editorial assistance:

Seftel AD. From aspiration to achievement: assessment and noninvasive treatment of erectile dysfunction in aging men. J Am Geriatr Soc 2005 Jan;53(1):119-130.

The above-referenced review is also available online, at http://www.blackwell-synergy.com/loi/JGS.

Atomoxetine Effective in Management of ADHD Within Usual-Care
Clinical Settings

Bakken RJ, Paczkowski M, Kramer HP, Axelson AA, Williams DW, Malcolm SK, Sumner CR, Kelsey DK. Effects of atomoxetine on attention-deficit/hyperactivity disorder [ADHD] in clinical pediatric treatment settings: a naturalistic study. Curr Med Res Opin. 2008 Feb;24(2):449-460.

This open-label observational study demonstrated that once-daily atomoxetine treatment for, on average, 21 weeks was effective in reducing ADHD symptom severity among children and adolescents treated in a clinical pediatric treatment setting. Most (59%-69%) youngsters experienced control of their ADHD symptoms throughout the day and into the evening hours while using atomoxetine. Other positive effects included decreases in academic, emotional, behavioral, and relationship problems.

Study participants (N=627) included children and adolescents ranging between 6 and 17 (mean=11) years of age. All patients had a current or prior diagnosis of ADHD and were eligible for atomoxetine treatment.  The average duration of treatment was 21.2 (range 0-89) weeks. These results obtained in naturalistic outpatient treatment settings support findings from randomized, controlled trials in children, adolescents, and adults demonstrating that atomoxetine is an effective nonstimulant medication for the management of ADHD.

To research the topic and provide editorial assistance in preparing the manuscript,
Rete Biomedical Communications collaborated with Drs. Hal P. Kramer of the Nemours  Children’s Clinic, Wilmington, DE (www.nemours.org), Alan A. Axelson of InterCare Health Systems, Ltd., Pittsburgh, PA, and Calvin R. Sumner, who was with Eli Lilly when the study was conducted and the manuscript prepared but is now chief medical officer with Biobehavioral Diagnostics Company, Cambridge, MA (www.biobdx.com), as well as investigators and other scientists with Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN (www.lilly.com). The article is available online at www.cmrojournal.com.

 

Study on the Effects of Ezetimibe and Statins on Noncholesterol Sterols Confirms Their Complementary Mechanisms of Action

Assmann G, Kannenberg F, Ramey DR, Musliner TA, Gutkin SW, Veltri EP. Effects of ezetimibe, simvastatin, atorvastatin, and ezetimibe-statin therapies on noncholesterol sterols in patients with primary hypercholesterolemia.  Curr Med Res Opin 2008 Jan;24(1):249-259.

In this post-hoc analysis, ezetimibe monotherapy significantly reduced plasma levels of phytosterols (sitosterol and campesterol), which are considered markers of cholesterol absorption, whereas statin (atorvastatin and simvastatin) monotherapy significantly reduced plasma levels of the cholesterol precursor sterols (lathosterol and desmosterol), which are regarded as markers of endogenous cholesterol biosynthesis. When ezetimibe was taken in combination with either statin, levels of all of these sterols were significantly decreased.  Ezetimibe alone lowered LDL-cholesterol (LDL-C; “bad cholesterol”) by a least-squares (LS) mean value of 18.5% and total cholesterol (TC) by 13.5% from baseline while raising HDL-cholesterol (HDL-C; “good cholesterol”) by 5.5%.  Statin monotherapy lowered LDL-C by a LS mean value of 37.1% to 43.6% and TC 26.8% to 33.0%, while raising HDL-C by 5.2% to 7.2%. Co-administration of ezetimibe with a statin resulted in a decrease of 51.4% to 56.4% in LDL-C and 37.8% to 43.9% in TC, as well as an increase of 8.8% to 9.8% in HDL-C. For LDL-C, TC, and HDL-C, the changes from baseline to study end were significantly greater for the combination ezetimibe-statin therapy than either component monotherapy. It is most probable that these favorable effects of ezetimibe-statin combination therapy on surrogate endpoints is due to dual inhibition of both cholesterol absorption and synthesis.

The above findings derived from a pooled analysis of two randomized controlled trials involving 975 patients with primary hypercholesterolemia (LDL-C = 145–250 mg/dL; triglycerides ≤ 350 mg/dL). Patients were treated for 12 weeks with ezetimibe 10 mg in combination with the HMG-CoA reductase inhibitor simvastatin 10-80 mg or atorvastatin 10-80 mg.

Stephen W. Gutkin and Rete Biomedical Communications collaborated with Drs. Gerd Assmann and Frank Kannenberg of the Leibniz-Institute of Arteriosclerosis Research in Münster, Germany; as well as Dena Ramey of Merck Research Laboratories, Rahway, NJ (www.merck.com); and Dr. Enrico Veltri of Schering-Plough Pharmaceuticals, Kenilworth, NJ (www.schering-plough.com) to research, draft, and edit the study report.

The article is available online at www.cmrojournal.com.