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Biomedical subjects

Margo A Denke

Publications and source records attributed to Margo A Denke.

10 recordsLinked to original sources
PubMed2004

Subclinical thyroid disease: scientific review and guidelines for diagnosis and management.

CONTEXT: Patients with serum thyroid-stimulating hormone (TSH) levels outside the reference range and levels of free thyroxine (FT4) and triiodothyronine (T3) within the reference range are common in clinical practice. The necessity for further evaluation, possible treatment, and the urgency of treatment have not been clearly established. OBJECTIVES: To define subclinical thyroid disease, review its epidemiology, recommend an appropriate evaluation, explore the risks and benefits of treatment and consequences of nontreatment, and determine whether population-based screening is warranted. DATA SOURCES: MEDLINE, EMBASE, Biosis, the Agency for Healthcare Research and Quality, National Guideline Clearing House, the Cochrane Database of Systematic Reviews and Controlled Trials Register, and several National Health Services (UK) databases were searched for articles on subclinical thyroid disease published between 1995 and 2002. Articles published before 1995 were recommended by expert consultants. STUDY SELECTION AND DATA EXTRACTION: A total of 195 English-language or translated papers were reviewed. Editorials, individual case studies, studies enrolling fewer than 10 patients, and nonsystematic reviews were excluded. Information related to authorship, year of publication, number of subjects, study design, and results were extracted and formed the basis for an evidence report, consisting of tables and summaries of each subject area. DATA SYNTHESIS: The strength of the evidence that untreated subclinical thyroid disease is associated with clinical symptoms and adverse clinical outcomes was assessed and recommendations for clinical practice developed. Data relating the progression of subclinical to overt hypothyroidism were rated as good, but data relating treatment to prevention of progression were inadequate to determine a treatment benefit. Data relating a serum TSH level higher than 10 mIU/L to elevations in serum cholesterol were rated as fair but data relating to benefits of treatment were rated as insufficient. All other associations of symptoms and benefit of treatment were rated as insufficient or absent. Data relating a serum TSH concentration lower than 0.1 mIU/L to the presence of atrial fibrillation and progression to overt hyperthyroidism were rated as good, but no data supported treatment to prevent these outcomes. Data relating restoration of the TSH level to within the reference range with improvements in bone mineral density were rated as fair. Data addressing all other associations of subclinical hyperthyroid disease and adverse clinical outcomes or treatment benefits were rated as insufficient or absent. Subclinical hypothyroid disease in pregnancy is a special case and aggressive case finding and treatment in pregnant women can be justified. CONCLUSIONS: Data supporting associations of subclinical thyroid disease with symptoms or adverse clinical outcomes or benefits of treatment are few. The consequences of subclinical thyroid disease (serum TSH 0.1-0.45 mIU/L or 4.5-10.0 mIU/L) are minimal and we recommend against routine treatment of patients with TSH levels in these ranges. There is insufficient evidence to support population-based screening. Aggressive case finding is appropriate in pregnant women, women older than 60 years, and others at high risk for thyroid dysfunction.

Humans↗
PubMed2004

Utility of currently available modes of therapy in reaching lipid goals.

The National Cholesterol Education Program Adult Treatment Panel III lipid management guidelines emphasize the importance of matching the intensity of lipid modification therapy to each patient's risk of coronary heart disease. For many patients who are at low risk, nonpharmacologic interventions such as diet, exercise, and smoking cessation can be effective lipid-lowering strategies. However, many patients require the addition of drug therapy to achieve lipid targets. Currently available lipid-modifying drugs include bile acid sequestrants, fibrates, nicotinic acid, cholesterol absorption inhibitors, and statins. In addition, nonprescription agents such as plant stanols and sterols are available to modify plasma lipid levels. These agents can be used individually or coadministered to achieve lipid goals.

Anticholesteremic Agents↗
PubMed2004

Coadministration of multidrug therapy to achieve lipid goals.

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are the drug of first choice for lowering low-density lipoprotein cholesterol (LDL-C) levels and reducing risk of coronary heart disease (CHD). Current therapeutic use of statins, however, has resulted in only a small percentage of patients reaching their LDL-C treatment goal. Despite the clinical trial data supporting early aggressive use of statins, prescribing physicians are more likely to use lower doses of statins, leaving many patients at high risk of CHD short of goals. The barrier to achieving cholesterol treatment goals does not appear to be the decision to initiate statin therapy, but the failure of prescribers to titrate statin therapy to a dose sufficient to achieve goals. An alternative to statin monotherapy is coadministration of a statin and a second agent that has a different mechanism of action. This approach can increase the likelihood of achieving target lipid levels and may be more acceptable to physicians. The coadministration of ezetimibe and simvastatin reduces cholesterol derived from both endogenous and exogenous sources. Simvastatin reduces the hepatic production of cholesterol, and ezetimibe decreases the intestinal absorption of dietary and biliary free cholesterol. The coadministration of low doses of these agents has been proved to be as effective as high-dose statin therapy in reducing LDL-C levels and assisting patients achieve their treatment goals.

Anticholesteremic Agents↗
PubMed2002

Metabolic syndrome.

The metabolic syndrome is like an elephant, and any literary review of its importance is shamefully reduced to an examination of tusks, trunk, and tail. Evidence continues to mount that this diminutive approach is an incorrect management strategy for such a large problem. Diet and lifestyle are effective strategies, but they must effectively compete with behaviors that have instant gratification. Our society has turned its focus away from the long-term rewards of good sustainable behaviors and has instead focused on short-term rewards of unsustainable behaviors. To tame the behaviors that promote the metabolic syndrome, simple answers from diet and drug therapy will require support from society to be effective.

Humans↗
PubMedDate not supplied

A novel therapeutic approach.

Since 1988, the National Cholesterol Education Program has identified low-density lipoprotein cholesterol (LDL-C) as the target of therapy; the new Adult Treatment Panel III (ATP III) guidelines continue the tradition of matching the aggressiveness of LDL-lowering therapy according to the risk of coronary heart disease (CHD). A significant change in the new guidelines is the definition of.CHD risk equivalents. and the inclusion of a modified Framingham global risk score. These revisions significantly raise the number of patients who qualify for lipid-lowering therapy. ATP III recognizes statins as the drug of first choice for LDL-C lowering. Statins are proven to be safe and effective for LDL-C reduction and are proven to reduce CHD event rates and mortality. Some patients are not candidates for statin therapy, however, and must rely on nonstatin agents that are less effective in reducing LDL-C, less safe, or poorly tolerated. Consequently, new cholesterol-lowering therapies are needed. Ezetimibe, approved by the U.S. Food and Drug Administration (FDA) in October 2002, is the first in a new class of selective cholesterol absorption inhibitors and offers a novel approach to the treatment of dyslipidemia. Phase 2 data demonstrated that ezetimibe lowers LDL-C by 18% and has a tolerability and short-term safety profile similar to placebo. This paper reviews the cholesterol metabolic pathways and the mechanism of action of the currently available lipid-modifying agents and introduces ezetimibe, the first selective cholesterol absorption inhibitor.

Anticholesteremic Agents↗
PubMedDate not supplied

Combination therapy.

Adult Treatment Panel III (ATP III) guidelines recommend specific treatment targets for low-density lipoprotein cholesterol (LDL-C) levels according to an individual.s short-term and long-term risk for coronary heart disease (CHD). Therapeutic lifestyle changes are recommended for all patients at any level of risk for CHD. Although most patients will achieve some LDL-C lowering with lifestyle modification, ATP III recognizes that a majority of patients with dyslipidemia will require drug therapy to reach their LDL goal. Surveys of physicians. practices suggest that only a small percentage of patients enrolled in an active treatment program actually achieve their LDL-C target. In addition, other surveys suggest that not all patients who are treatment candidates are receiving assessment. From a medication perspective, either up-titration of statin dose or the use of drug combinations should further enhance the likelihood of achieving target lipid levels. Combination therapies that target both the endogenous and exogenous pathways of cholesterol synthesis are particularly attractive. This paper reviews the pharmacotherapeutic effects of combination therapy, summarizes the strengths and weaknesses of current lipid-lowering drug combinations, and identifies the potential contribution of the novel cholesterol absorption inhibitor, ezetimibe, to the LDL-C treatment algorithm.

Anticholesteremic Agents↗