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By B. Murat. The McGregor School of Antioch University.

Statins Page 87 of 128 Final Report Update 5 Drug Effectiveness Review Project 58 buy discount valtrex 500mg line. Comparison of efficacy and safety of atorvastatin and simvastatin in patients with dyslepidemia with and without coronary heart disease generic 1000mg valtrex overnight delivery. Comparison of effects of simvastatin versus atorvastatin on high density lipoprotein cholesterol and apolipoprotein A I levels. Efficacy and tolerability of simvastatin 20 mg vs pravastatin 20 mg in patients with primary hypercholesterolemia. Efficacy and tolerability of simvastatin and pravastatin in patients with primary hypercholesterolemia (multicountry comparative study). Treating hypercholesterolaemia with HMG CoA reductase inhibitors a direct comparison of simvastatin and pravastatin. Lucasko P, Walters EJ, Cullen EI, Niecestro R, Friedhoff LT. Efficacy of once-daily extended-release lovastatin compared to immediate-release lovastatin in patients with cholesterolemia. Malini PL, Ambrosioni E, De Divitiis O, Di Somma S, Rosiello G, Trimarco B. Simvastatin versus pravastatin efficacy and tolerability in patients with primary hypercholesterolemia. Marz W, Wollschlager H, Klein G, Neiss A, Wehling M. Safety of low density lipoprotein cholestrol reduction with atorvastatin versus simvastatin in a coronary heart disease population (the TARGET TANGIBLE trial). Comparison of the short term efficacy and tolerability of lovastatin and pravastatin in the management of primary hypercholesterolemia. Meeting national cholesterol education goals in clinical practice a comparison of lovastatin and fluvastatin in primary prevention. A 52-week, multicenter, randomized, parallel- group, double-blind, double-dummy study to assess the efficacy of atorvastatin and simvastatin in reaching low-density lipoprotein cholesterol and triglyceride targets: The Treat-to-Target (3T) Study. Effects of rosuvastatin and atorvastatin compared over 52 weeks of treatment in patients with hypercholesterolemia. Double blind comparison of the efficacy and tolerability of simvastatin and fluvastatin in patients with primary hypercholesterolaemia. Paoletti R, Fahmy M, Mahla G, Mizan J, Southworth H. Rosuvastatin demonstrates greater reduction of low-density lipoprotein cholesterol compared with pravastatin and simvastatin in hypercholesterolaemic patients: a randomized, double-blind study. Comparison of the efficacy and tolerability of simvastatin and atorvastatin in the treatment of hypercholesterolemia. Statins Page 88 of 128 Final Report Update 5 Drug Effectiveness Review Project 73. Time as a variable with niacin extended-release/lovastatin vs. Comparison of efficacy and safety of rosuvastatin versus atorvastatin in African-American patients in a six-week trial. The DISCOVERY PENTA study: a DIrect Statin COmparison of LDL-C Value--an Evaluation of Rosuvastatin therapY compared with atorvastatin. Jukema JW, Liem A-H, Dunselman PHJM, van der Sloot JAP, Lok DJA, Zwinderman AH. LDL-C/HDL-C ratio in subjects with cardiovascular disease and a low HDL-C: results of the RADAR (Rosuvastatin and Atorvastatin in different Dosages And Reverse cholesterol transport) study. The beneficial effects of lipid-lowering drugs beyond lipid-lowering effects: a comparative study with pravastatin, atorvastatin, and fenofibrate in patients with type IIa and type IIb hyperlipidemia. Wolffenbuttel BHR, Franken AAM, Vincent HH, Dutch Corall Study G. Cholesterol- lowering effects of rosuvastatin compared with atorvastatin in patients with type 2 diabetes -- CORALL study. Effects of switching statins on achievement of lipid goals: Measuring Effective Reductions in Cholesterol Using Rosuvastatin Therapy (MERCURY I) study. Comparison of the effect of lipophilic and hydrophilic statins on serum adiponectin levels in patients with mild hypertension and dyslipidemia: Kinki Adiponectin Interventional (KAI) Study. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta- analysis. A comparative study of atorvastatin and simvastatin as monotherapy for mixed hyperlipidaemia in Type 2 diabetic patients. Effect of short term treatment with simvastatin and atorvastatin on lipids and paraoxonase activity in patients with hyperlipoproteinaemia. Comparisons of effects of statins (atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin) on fasting and postprandial lipoproteins in patients with coronary heart disease versus control subjects. Bots A, Kastelein J, on behalf of the Dutch DISCOVERY study group.

Statins Page 127 of 128 Final Report Update 5 Drug Effectiveness Review Project Appendix E generic valtrex 500 mg with amex. Black box warnings for US Food and Drug Administration-approved drugs No boxed warnings were found for any of the included drugs cheap valtrex 1000mg on line. Statins Page 128 of 128 Drug Class Review HMG-CoA Reductase Inhibitors (Statins) and Fixed-dose Combination Products Containing a Statin Final Report Update 5 Evidence Tables November 2009 This report reviews information about the comparative effectiveness and safety of drugs within a pharmaceutical class. The report is neither a usage guideline nor an endorsement or recommendation of any drug, use, or approach. Oregon Health & Science University does not endorse any guideline or recommendation developed by users of this report. Update 4: August 2006 Update 3: September 2005 Update 2: March 2004 Update 1: July 2003 Original Report: April 2002 The literature on this topic is scanned periodically. Lee, PharmD, BCPS Elizabeth Haney, MD Susan Carson, MPH Original authors: Mark Helfand, MD, MPH Cathy Kelley, PharmD Drug Effectiveness Review Project Marian McDonagh, PharmD, Principal Investigator Oregon Evidence-based Practice Center Mark Helfand, MD, MPH, Director Oregon Health & Science University Copyright © 2009 by Oregon Health & Science University Portland, Oregon 97239. Final Report Update 5 Drug Effectiveness Review Project TABLE OF CONTENTS Evidence Table 1. Trials comparing low-density lipoprotein cholesterol lowering and high- density lipoprotein cholesterol raising abilities of 2 or more statins........................................... Trials with primary coronary heart disease endpoints.............................. Placebo-controlled trials of patients with atherosclerosis........................ Trials comparing low-density lipoprotein cholesterol lowering and high- density lipoprotein cholesterol raising abilities of fixed-dose combination products.............. Trials comparing efficacy and safety of statins in children..................... Internal validity of trials evaluating statins in children............................ Prior versions of this report can be accessed at the DERP website. Statins Page 2 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 1. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Inclusion Criteria/ Patient Clinical Trial Population Exclusion criteria Intervention Atorvastatin vs. No numbers provided for 16 weeks, then aorta 10 mg qd or lova 20 exclusion. Doses doubled at 22 1,049 patients Mean baseline LDL-c weeks if LDL-c goals (based upon their risk randomized 189-192 mg/dl factors) not achieved. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Clinical Trial Results (mean changes in lipoprotein levels) Harms/Comments Davidson et al. Only those ADEs R (3:1), DB, MC, PC, not LDL-c reduction from baseline at week 16: occurring >2% were reported. Withdrawal due to ADEs occurred in 3% of ITT aorta 10 mg: 36% aorta vs. No patient experienced an increase in creatine (n= 789 aorta, 260 lova) LDL-c reduction from baseline at week 52: kinase (CK) of >10 times ULN. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Clinical Trial Funding Source Davidson et al. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Inclusion Criteria/ Patient Clinical Trial Population Exclusion criteria Intervention Atorvastatin vs. NCEP R (3:1), DB, MC, not ITT LDL-c 160-250 mg/dl during dietary function, CK elevation, more than 14 alcoholic drinks per week, s/p step 1 diet. MI, PTCA, CABG within the last 3 months or severe or unstable Mild to moderate CHD risk (dose level 1: 297 patients randomized angina, uncontrolled hypertension. No numbers provided for LDL-c goal <130 mg/dl): 10 mg qd aorta (n= 224 aorta, 73 parva) Mean baseline LDL-c exclusion. Severe CHD risk (dose level 2: LDL-c goal <115 mg/dl): aorta 20 mg qd (n=79) vs. If goal not reached, dose doubled at week 4, and again at week 8 and week 16. If renal function, more than 14 alcoholic drinks per week, taking a drug LDL-c remained >130 mg/dl at weeks 4 305 patients randomized Mean baseline LDL-c with the potential for interaction with statins. No numbers provided for and 10, doses were doubled at week 16. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Clinical Trial Results (mean changes in lipoprotein levels) Harms/Comments Assman et al.

This renders them an important component with regard to therapeu- tic and prophylactic vaccines purchase valtrex 1000mg on-line. Natural killer (NK) cells NK cells are lymphocytes not considered T or B lymphocytes nor do they express antigen-specific receptors buy discount valtrex 500mg on-line. They are important in the control of viruses and malig- nant tumors and belong to the innate immune system. NK cells express many different receptors, toll-like receptors (TLR) and killer immunoglobulin-like recep- tors (KIR) among them. KIR recognize HLA class I molecules on healthy cells which protect these cells against NK cell attack. NK cells can eliminate HIV-infected cells rapidly either via direct cytolysis or via secretion of cytokines (Walker 2013). Population-wide genetic studies show an impor- tant influence of NK cells on disease progression (Jost 2013). Certain parts of the HLA class I alleles (mainly Bw4) lead to a slower disease progression (Flores-Villanueva 2001). This effect is even stronger when combined with KIR3DL1 (Martin 2007). In addition, single nucleotide polymorphisms (SNP) within the HLA-C allele have been identified which influence disease progression. The HLA-C molecule is the ligand for the KIR2D receptor and thereby influences the function of NK cells (Jost 2013). NK cells put selective pressure on the virus which can lead to escape mutations (Alter 2011). In HIV infection, different functional and phenotypical changes of NK cells have been found. Most of those are induced by a high viral load and consequently strong immune activation (Walker 2013). Interestingly, the antiviral activity of NK cells of elite controllers is relatively weak which implies that the contribution of NK cells to the control of viremia in these patients is rather low (O’Connell 2009). T cells T cells belong to the family of T cells, but they separate in the early phases of T cell development (before maturation in the thymus) (Fig. Instead of the classic TCR- these primitive thymocytes bear a TCR- , representing a heterodimer of a and chain. In humans, there are only three different V chains and seven V chains to form a mature TCR. These receptors recognize a unique repertoire of non- peptidic antigens and do not need presentation by the classical HLA class I or II 34 The Basics molecules (Pauza 2011). These cells are therefore associated with the innate immune system. Typically, the number of V 2V 2 TCR-bearing T cells is reduced in early HIV infection. Both the extent of the loss of these cells and their loss of function corre- late with disease progression (Wallace 1997). Surprisingly, these cells are maintained in the peripheral blood of EC in high numbers and comparable to healthy controls (Riedel 2009). It was also shown that V 2V 2 T cells were reduced in EC in the early disease phase. However, the cells were able to recover numerically with a normal function. This is a phenomenon that distinguishes EC of other people living with HIV. However, the authors tested only 21 individuals in this study. Therefore, it is worthwhile to pursue this in larger cohorts and to develop mechanisms that lead to the recovery of these cell types. Adaptive immunity In contrast to the innate immune system, the adaptive immune response cannot directly eliminate microorganisms. The adaptive immune system has to learn to recognize foreign pathogens und represents the second line of defense in our body. Others, the T cell recep- tors among them, are formed individually by rearrangement. The HLA system The system of human leukocyte antigens (HLA) comprises a group of membrane- bound receptors which present antigens for the TCR of the adaptive immune system. The HLA genes that are immuno- logically important are divided into two classes, namely class I and II, which differ structurally and functionally (review: Klein 2000). The HLA class I alleles A, B and C are expressed on all somatic cells and present antigens for CD8 T cells.

Active-control trial: A trial comparing a drug in a particular class or group with a drug outside of that class or group buy 500 mg valtrex free shipping. Allocation concealment: The process by which the person determining randomization is blinded to a study participant’s group allocation 1000 mg valtrex overnight delivery. Applicability: see External Validity Before-after study: A type nonrandomized study where data are collected before and after patients receive an intervention. Before-after studies can have a single arm or can include a control group. Bias: A systematic error or deviation in results or inferences from the truth. Several types of bias can appear in published trials, including selection bias, performance bias, detection bias, and reporting bias. Bioequivalence: Drug products that contain the same compound in the same amount that meet current official standards, that, when administered to the same person in the same dosage regimen result in equivalent concentrations of drug in blood and tissue. Black box warning: A type of warning that appears on the package insert for prescription drugs that may cause serious adverse effects. It is so named for the black border that usually surrounds the text of the warning. A black box warning means that medical studies indicate that the drug carries a significant risk of serious or even life-threatening adverse effects. The US Food and Drug Administration (FDA) can require a pharmaceutical company to place a black box warning on the labeling of a prescription drug, or in literature describing it. Blinding: A way of making sure that the people involved in a research study — participants, clinicians, or researchers —do not know which participants are assigned to each study group. Blinding usually is used in research studies that compare two or more types of treatment for an illness. Targeted immune modulators 142 of 195 Final Update 3 Report Drug Effectiveness Review Project Case series: A study reporting observations on a series of patients receiving the same intervention with no control group. Case study: A study reporting observations on a single patient. Case-control study: A study that compares people with a specific disease or outcome of interest (cases) to people from the same population without that disease or outcome (controls). Clinical diversity: Differences between studies in key characteristics of the participants, interventions or outcome measures. Clinically significant: A result that is large enough to affect a patient’s disease state in a manner that is noticeable to the patient and/or a caregiver. Cohort study: An observational study in which a defined group of people (the cohort) is followed over time and compared with a group of people who were exposed or not exposed to a particular intervention or other factor of interest. A prospective cohort study assembles participants and follows them into the future. A retrospective cohort study identifies subjects from past records and follows them from the time of those records to the present. Combination Therapy: The use of two or more therapies and especially drugs to treat a disease or condition. Confidence interval: The range of values calculated from the data such that there is a level of confidence, or certainty, that it contains the true value. The 95% confidence interval is generally used in Drug Effectiveness Review Project reports. If the report were hypothetically repeated on a collection of 100 random samples of studies, the resulting 95% confidence intervals would include the true population value 95% of the time. Confounder: A factor that is associated with both an intervention and an outcome of interest. Controlled clinical trial: A clinical trial that includes a control group but no or inadequate methods of randomization. Control group: In a research study, the group of people who do not receive the treatment being tested. The control group might receive a placebo, a different treatment for the disease, or no treatment at all. Convenience sample: A group of individuals being studied because they are conveniently accessible in some way. Convenience samples may or may not be representative of a population that would normally be receiving an intervention. Crossover trial: A type of clinical trial comparing two or more interventions in which the participants, upon completion of the course of one treatment, are switched to another. Direct analysis: The practice of using data from head-to-head trials to draw conclusions about the comparative effectiveness of drugs within a class or group. Results of direct analysis are the preferred source of data in Drug Effectiveness Review Project reports. Dosage form: The physical form of a dose of medication, such as a capsule, injection, or liquid. The route of administration is dependent on the dosage form of a given drug.