Benefits Of Drug Treatment Research Articles

Discontinuation of Lipid Modifying Drugs Among Commercially Insured United States Patients in Recent Clinical Practice

Although several lipid-modifying drug (LMD) treatments and strategies are available to successfully manage patients at risk for cardiovascular events, the benefits of drug treatment can be realized only if these therapies are continued on a long-term basis. Previous observational studies examining rates of discontinuation with LMDs are not generalizable to current clinical practice in the United States. In this study, the discontinuation of newly initiated LMD classes in recent clinical practice was compared in a geographically diverse, commercially insured United States population. Administrative claims from the Ingenix Lab/Rx Database were used to identify patients aged >or=20 years who were newly prescribed statins, extended-release niacin, fibrates, bile acid sequestrants, or ezetimibe from January 1, 2001, to June 30, 2003. An LMD class was considered discontinued if a patient did not receive a prescription from the same LMD class within 180 days of the most recent prescription expiration date. The median time to discontinuation was 8.2 months in the bile acid sequestrant group, followed by 12 months in the extended-release niacin group, 17.4 months in the fibrate group, and 27.5 months in the statin group. By the end of 1 year, the adjusted cumulative incidence of discontinuation was 68.3% in bile acid sequestrant users, 55.4% in extended-release niacin users, 39.9% in fibrate users, 33.0% in ezetimibe users, and 28.9% in statin users (p <0.001 for all LMD classes vs statins). In conclusion, despite the changes in lipid treatment paradigms and the importance of long-term lipid therapy, this study found high discontinuation rates of LMD classes in recent United States clinical practice.

Edward D. Freis—A True Pioneer

but it is appropriate that a more detailed review of his major contributions be published by someone who greatly admired his work and knew of his major contributions through one of his trainees, and subsequently my mentor, Edward D. Frohlich.LIFE AND MEDICAL CAREEREdward D. Freis was born in Chicago, IL, on May 13, 1912. He earned his BS at the University of Arizona in 1936, obtained his MD in 1940 at Columbia University’s College of Physicians and Surgeons, and completed his internal medicine residency at the Boston University Hospital Program in 1942. He served as Chief of Laboratory Services in the Air Force in Nebraska from 1942 to 1944 and returned to Boston where he worked with Dr. Robert Wilkins until 1949. While in Boston, Dr. Freis authored his first article on the benefits of drug treatment of hypertension. In 1949 he went to the Veterans Administration (VA) Hospital and Georgetown University School of Medicine in Washington, DC and remained there until the end of his career in 2005. He established the Hypertension Clinic at the Medical Center and served as its chief for 10 years, from 1950 to 1960. In 1959, he was appointed one of five Senior Medical Investigators of the VA. Dr. Freis headed the VA Cooperative Study, which was the first to demonstrate the effect of antihyperten-sive drugs on cardiovascular events.Dr. Freis actively participated in professional organizations and on the editorial boards of many medical journals and was recognized by numerous organizations for his landmark research work. He received the Albert Lasker Foundation Clinical Research Award in 1971, the CIBA Award for Hypertension Research from the American Heart Association in 1981, and the first Stevo Julius Award for Education in Hypertension from the International Society of Hypertension in 2000. The National Conference on High Blood Pressure Control named an award after him in 1985. Dr. Freis continued to work as a Distinguished Physician with the VA until his death at 92 in February 2005.CONTRIBUTIONS TO CARDIOVASCULAR MEDICINEDr. Freis’s fundamental contributions to the field of cardiovascular medicine were summarized in his manuscript published in Hypertension in 2001.

Epidemiologische Studien als Teil des HTA-Bewertungsprozesses

Results of epidemiological studies should be considered as part of the available evidence when evaluating drug treatment benefits in health technology assessment (HTA). Pharmaco-epidemiological databases can provide a broader understanding of the effectiveness of drugs in populations that are frequently underrepresented in clinical trials. Such databases are also useful to investigate drug safety with regard to socio-demographic and medical care-related indicators and hereby contribute to an optimal and targeted pharmacological therapy. Using examples from pharmaco-epidemiological asthma studies, the present article discusses associated difficulties in interpreting database results against the background of various sources of bias and proposes possibilities for integrating observational data into the HTA evaluation process. Researchers are challenged to engage in considerable efforts to develop a standardized inventory of epidemiological methods, e.g. for the pooled analysis of epidemiological data.

Practical recommendations for the use of ACE inhibitors, beta‐blockers, aldosterone antagonists and angiotensin receptor blockers in heart failure: Putting guidelines into practice

Surveys of prescribing patterns in both hospitals and primary care have usually shown delays in translating the evidence from clinical trials of pharmacological agents into clinical practice, thereby denying patients with heart failure (HF) the benefits of drug treatments proven to improve well-being and prolong life. This may be due to unfamiliarity with the evidence-base for these therapies, the clinical guidelines recommending the use of these treatments or both, as well as concerns regarding adverse events. ACE inhibitors have long been the cornerstone of therapy for systolic HF irrespective of aetiology. Recent trials have now shown that treatment with beta-blockers, aldosterone antagonists and angiotensin receptor blockers also leads to substantial improvements in outcome. In order to accelerate the safe uptake of these treatments and to ensure that all eligible patients receive the most appropriate medications, a clear and concise set of clinical recommendations has been prepared by a group of clinicians with practical expertise in the management of HF. The objective of these recommendations is to provide practical guidance for non-specialists, in order to increase the use of evidenced based therapy for HF. These practical recommendations are meant to serve as a supplement to, rather than replacement of, existing HF guidelines.

Individualizing therapy - in search of approaches to maximize the benefit of drug treatment (II).

Adjusting drug therapy to the individual, a common approach in clinical practice, has evolved from 1) dose adjustments based on clinical effects to 2) dose adjustments made in response to drug levels and, more recently, to 3) dose adjustments based on deoxyribonucleic acid (DNA) sequencing of drug-metabolizing enzyme genes, suggesting a slow drug metabolism phenotype. This development dates back to the middle of the 20th century, when several different drugs were administered on the basis of individual plasma concentration measurements. Genetic control of drug metabolism was well established by the 1960s, and pharmakokinetic-based individualized therapy was in use by 1973.

Nucleoside reverse transcriptase inhibitors and HIV mutagenesis.

Potent antiretroviral therapy (ART) of HIV-1 infection with anti-retroviral drugs consisting of nucleoside reverse transcriptase inhibitors(NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs)and protease inhibitors (PIs) has dramatically reduced the rate ofHIV- and AIDS-related morbidity and mortality. The lack of patientcompliance to drug administration results in suboptimal therapy. Sub-optimal drug therapy can lead to drug resistance, which limits theclinical benefit of drug treatment and can select for new variantviruses with altered virulence and tropism.In this leading article, we discuss literature that shows a correlationbetween the evolution of drug resistance and increased HIV and otherpathogen mutation rates. In the case of HIV, NRTIs and NRTI drugresistance can increase HIV mutation rates, and can act together tofurther increase these rates. These increased mutation rates predictthat drug failure during initial treatment could increase the probabilityof subsequent drug therapy failures due to the selection of mutatorstrains. However, increased mutagenesis of HIV by NRTIs could beviewed as an advantage in therapies directed at extinguishing virusinfectivity by lethal mutagenesis.

Cholesterol, Coronary Heart Disease and Stroke: A Review of Published Evidence from Observational Studies and Randomized Controlled Trials

In observational epidemiologic studies, lower blood cholesterol is associated with a reduced risk from coronary heart disease (CHD) throughout the normal range of cholesterol values observed in most Western populations. There is a continuous positive relationship between CHD risk and blood cholesterol down to at least 3 to 4 mmol/l, with no threshold below which a lower cholesterol is not associated with a lower risk. Observational studies suggest that a prolonged difference in total cholesterol of about 1 mmol/l is associated with one-third less CHD deaths in middle age. Evidence from large-scale cholesterol lowering trials in patients at high-risk of CHD have demonstrated that much of the epidemiologically predicted difference in CHD risk associated with differences in cholesterol was achieved within a few years of treatment. Moreover, these trials have demonstrated that such therapy was not associated with increased non-CHD mortality. Total cholesterol is transported in blood as low-density lipoprotein cholesterol or LDL cholesterol (about 70%) and as high density lipoprotein cholesterol or HDL cholesterol (about 30%). Since these two cholesterol fractions have opposing effects on vascular risk, a 1 mmol/l reduction in LDL cholesterol is likely to be associated with 40 to 50% lower CHD risk. The size of the absolute reduction in CHD produced by lowering total and LDL cholesterol is determined by an individual's overall risk rather than their initial cholesterol level. Consequently, the benefits of drug treatment to lower LDL cholesterol are greater in those at higher absolute risk of CHD rather than at high cholesterol levels. Dietary saturated fat is the chief determinant of total and LDL cholesterol levels. Replacing 60% of the intake of saturated fat by other fats and reducing the intake of dietary cholesterol could reduce blood total cholesterol levels by about 0.8 mmol/l (that is by 10 to 15%), with four fifths of this reduction being in LDL cholesterol.

Are antidepressants overrated? A review of methodological problems in antidepressant trials.

There are no signs that the rapidly escalating use of antidepressants is reducing the burden of depressive disorders. This may be due to the fact that the evidence base for antidepressants is weaker than is commonly assumed. There are a number of methodological problems that may bias the results of clinical trials. Unblinding may inflate the response of people taking an active drug when compared with those taking an inert placebo. Modern measurement techniques may exaggerate the benefit of drug treatment. Excluding some randomized subjects from analysis may inflate the apparent effect of antidepressant drugs and publication bias means that published studies may not represent an accurate picture of the effects of treatment. In trials of long-term treatment discontinuation-related effects may masquerade as clinical efficacy. A brief survey of evidence from controlled trials does not present a consistently positive picture. Two of the largest and most reputable trials found only negligible differences between tricyclic antidepressants and placebo. The evidence on whether antidepressants are specific treatments is also inconclusive. Many other drugs not classed as antidepressants have shown positive effects in depression in controlled clinical trials. It is suggested that the interests of the pharmaceutical industry and the psychiatric profession have helped to establish the notion of the efficacy and specificity of antidepressant drugs.

Dementia in primary care: why the low detection rate?

Objective - The aim of the present study was to find reasons for the low detection rate of dementia in primary care. Another aim was to investigate the attitudes and knowledge on dementia among Swedish general practitioners (GPs). Design - Two-hundred-and-twenty-eight postal questionnaires were distributed to GPs in the county of Östergötland. Setting - Primary care in Sweden. Main outcome measures - The opinions of GPs on dementia management in primary care. Results - The response rate was 67%. GPs showed a good knowledge of dementia diseases but underestimated the occurrence of dementia. They presented a positive attitude towards managing patients with dementia and considered that existing drug therapy justified an active search for patients with dementia in primary care, but they believed the efficacy of the drugs to be limited. Assessing the social environment of patients and organising social support were regarded as the most difficult tasks in the management of demented patients. Conclusion ? The study indicates that the main obstacles are a lack of resources and a sceptical attitude to the benefits of drug treatment. Co-operation between the community services, specialist clinics and the primary care team should be improved.

Saving lives: Long-term morbidity and mortality trials with selective angiotensin receptor blocker therapy

Prospective randomised trials have demonstrated convincingly the benefits of drug treatment of hypertension. Treatment with conventional antihypertensive agents reduces the incidence of cardiovascular events by about that which would be expected from epidemiological data for the achieved difference in blood pressure. Newer agents, such as angiotensin II receptor blockers, have potential for benefits beyond blood pressure reduction. This rationale is under evaluation in a number of long-term morbidity and mortality trials which will report over the next few years, with the largest, VALUE, due to provide results in 2004. The findings from these trials will be decisive in determining the future role of this important new class of drugs.

Estimating the willingness to pay for drug abuse treatment

Previous economic studies of the benefits of drug treatment have limited their estimation to tangible benefits, and thus have underestimated the benefits of drug treatment. The willingness-to-pay (WTP) approach is a more encompassing benefit valuation method that captures both tangible and intangible benefits and accords with valuation concepts used by economists. In this study, we report the results of a pilot study in which we used the contingent valuation (CV) method to value drug treatment. We conducted mall intercept surveys in two communities: the Triad area in North Carolina and Brooklyn, New York. We estimated WTP models for two different drug treatment programs: a program for all drug users and a program specifically targeted to women drug users. We modeled respondents' WTP for drug treatment as a function of their demographics and to responses from attitudinal/experience questions. The mean WTP for both types of drug treatment programs was estimated to be approximately $37 per respondent. Finally, we demonstrated how the results of the CV method may be used in a benefit-cost analysis of drug treatment.

How can policy makers use available evidence on the cost benefits of drug treatement?

All the studies on the cost benefits of drug treatment reviewed by Cartwright in this issue suggest benefits outweigh costs by some margin. What lessons does this review of mainly American data have for European policy makers? Drug treatments are associated with a wide range of consequences outside the health sector and there are considerable differences in treatment regimes across countries. This could well influence results. There are also considerable differences in methodologies used across available studies and many lack strong study designs. An interesting feature is the lack of valuation of individual drug users benefits, does this imply that policy makers in the US do not care about drug misusers. Would the situation be the same in Europe or other parts of the world? There is a lot of research to be done and perhaps specific guidelines are required to ensure economic evaluations in this area can be used to guide policy decisions with more confidence.

Do vitamin E and fish oil protect against ischaemic heart disease?

Long-term outcome trials are the gold standard for establishing the benefits of drug treatments to prevent complications of a disease. However, they are notoriously expensive and their duration limits what they can tell about the efficacy and safety of drugs that may be consumed for a very long time. Dietary interventions have the advantage of the low cost of leaving the public to treat themselves, although no randomised trial of dietary advice has shown sustained, large reductions in salt or fat intake or reduction in rates of stroke or myocardial infarction. Nevertheless, the public is less likely to restrict intake of something they like than to eat more of something nutritious, so a Mediterranean diet sounds a sunnier, less proscriptive prospect than a low-fat diet. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trialDietary supplementation with n-3 PUFA led to a clinically important and satistically significant benefit. Vitamin E had no benefit. Its effects on fatal cardiovascular events require further exploration. Full-Text PDF

The role of pharmacoepidemiology in pharmacovigilance: rational drug use in pregnancy.

The most important objective of the Hungarian Case-Control Surveillance of Congenital Abnormalities is the postmarketing surveillance of the teratogenic effects of drugs. This dataset includes 22,865 pregnant women who had offspring with congenital abnormalities and 38,151 pregnant women who had healthy babies between 1980 and 1996. Their case-control analysis is appropriate to assess the risks and benefits of drug treatments during pregnancy. Of about 4000 drugs used in Hungary, 35 seemed to be human teratogens. Only a small proportion (about 1%) of congenital abnormalities is traceable to teratogenic drugs in humans. Hungarian studies were not able to confirm the teratogenicity of tetracyclines (doxycycline) and some other drugs, but indicated the beneficial effect of clotrimazole in the prevention of undescended testis related to preterm birth. Periconceptional multivitamin/folic acid supplementation can reduce the first occurrence of neural-tube defects, oral clefts, cardiovascular malformations, and urinary tract defects. At present the teratogenicity of drugs is exaggerated and the benefits of drug treatment during pregnancy are underestimated. This unbalanced risk-benefit assessment initiated disadvantageous decisions, e.g. planned pregnancies are terminated because of the supposed false teratogenic risk of drugs; pregnant women with acute or chronic diseases are not treated adequately and it causes exacerbation of the illness or fetal complications; the necessary drug treatments are connected with a permanent psychological stress. In conclusion, the anxiety and fear created by the notion that nearly all drugs cause congenital abnormalities is more harmful than the effect of proven human teratogenic drugs themselves.

Desire for Help among African-American Drug Users

We examined demographic factors, drug-problem severity indicators, and social and personal resources of African-American drug users as correlates of their self-reported desire for help with problems related to drug use. Avoiding the “ethnic gloss” of earlier research, we included ethnicity-related attitudes, perceptions, and experiences among the factors tested. Findings suggested that interpersonal problem recognition was a key determinant of desire for help in this sample. Two additional factors associated with desire for help in multivariate analysis were conventional moral beliefs and expected benefit of drug treatment. We cite implications of these findings for patterns of help-seeking and recovery among treatment-naive African-American drug users.

Treatment of benign prostatic hyperplasia. A pharmacoeconomic perspective.

Men with moderate symptoms of benign prostatic hyperplasia (BPH) are the best candidates for medical treatment, while surgery is usually indicated for patients with severe symptoms. Men with mild symptoms do not usually need treatment, but they might be re-evaluated annually if desirable. Finasteride, which produces selective hormonal deprivation, is now established as a well tolerated drug for the long term medical therapy of BPH. Recent studies suggest that finasteride is most effective in men with large prostates (> 40 ml), and the drug should probably be reserved for these patients. alpha-Blockers work in men with small or large prostates, and their rapid onset of action facilitates the identification of responders. alpha-Blockers are more effective than finasteride during the first year of treatment, but only finasteride induces regression of the prostate and offers increased efficacy over time. Even if drug therapy reduces the need for prostate surgery, the total economic cost of BPH treatment is likely to rise because of the increasing application of medical treatment. The magnitude of this increase depends largely on what percentage of the male population embark on long term therapy, at what age treatment is started, and how successful it is. At present, the answers to these questions are largely unknown. The personal economic expenses for men who begin long term medical therapy will probably be an important factor in deciding how common drug treatment for BPH will become in the future. For many men, the main benefit of drug treatment will be the relief of urinary symptoms, but whether this improvement is substantial enough to improve their overall quality of life has not yet been clearly demonstrated in controlled studies.

The benefits of reducing cholesterol levels: the need to distinguish primary from secondary prevention: 1. A meta‐analysis of cholesterol‐lowering trials

To use meta-analysis to estimate the benefits of drug treatment to lower cholesterol levels in the primary and secondary prevention of coronary heart disease (CHD) events. MEDLINE search from 1967 to 1990; bibliographies of review articles. Nine trials met the entry criteria: they were monofactorial, randomised and controlled. Two independent, unblinded observers. The odds ratio (and 95% Cl) for death from CHD was 0.85 (0.64, 1.14) in primary prevention and 0.84 (0.75, 0.95) in secondary prevention studies when calculated by the method of Peto. The event rate in the secondary prevention studies was higher than that in the primary prevention studies, and the absolute risk reduction achieved by therapy in the former (3.2%) was much higher than that in the latter (0.1%). The number of subjects needing to be treated to prevent one death from CHD was 38 in secondary prevention and 675 in primary prevention. Results with the method of DerSimonian and Laird were similar. The benefits of cholesterol lowering to prevent death from CHD are substantially greater in the secondary prevention setting than in primary prevention.

Assessing treatability in drug offenders

AbstractThe goal of this study was to describe the factors employed by clinicians in assessing treatability in offenders seeking statutory benefits of drug treatment. This goal was achieved by using descriptive principles from representative designs in the field of psychology to make explicit the decision rules or clinical policy of an Ohio forensic psychiatric center.

The Current Dilemma in the Treatment of Mild Hypertension

A number of trials evaluating drug treatment of mild hypertension are reviewed. Overall benefits and disadvantages of such treatment are discussed. In view of limited benefits of drug treatment and considerable disadvantages of side-effects, the need to evaluate non-pharmacological methods of blood pressure control is emphasized. Some of these methods are not directly aimed at the level of blood pressure but at the physiological and behavioural responses of individuals to their environments and their lifestyles. The evidence so far suggests that more holistic modes of life go a long way towards normalizing blood pressure

Chemotherapy studies in autochthonous rat tumors: Hepatomas

Diethylnitrosamine (DEN) was applied orally to a total of 250 female Wistar rats in a single dose (d) of 3 mg/kg body weight 5 times a week for a duration of 20 weeks. After approximately 150 days exploratory laparotomy was performed to all animals. By inspection of the liver they were divided into 4 stages of disease according to the extent of cancer formation. The reaction of rats with DEN induced liver tumors was tested using a 4-drug combination chemotherapy with different equitoxic doses of Adriamycin (Adm), Methotrexate (Mtx), 5-Fluorouracil (5-FU) and Cyclophosphamide (CP). No benefit of drug treatment could be noted. In drug treated animals no decrease in the development of the liver tumors, in the frequency of metastases nor in the frequency of tumors of other origin could be demonstrated. The parallels of chemotherapy in chemically induced liver cancer to clinical experience are discussed.