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1.
Phys Rev X ; 82018.
Article in English | MEDLINE | ID: mdl-31275731

ABSTRACT

We study the dynamics of a supersonically expanding ring-shaped Bose-Einstein condensate both experimentally and theoretically. The expansion redshifts long-wavelength excitations, as in an expanding universe. After expansion, energy in the radial mode leads to the production of bulk topological excitations - solitons and vortices - driving the production of a large number of azimuthal phonons and, at late times, causing stochastic persistent currents. These complex nonlinear dynamics, fueled by the energy stored coherently in one mode, are reminiscent of a type of "preheating" that may have taken place at the end of inflation.

2.
Anaesth Intensive Care ; 45(4): 459-465, 2017 07.
Article in English | MEDLINE | ID: mdl-28673215

ABSTRACT

Chronic postsurgical pain (CPSP) is a common and debilitating complication of major surgery. We undertook a pilot study at three hospitals to assess the feasibility of a proposed large multicentre placebo-controlled randomised trial of intravenous perioperative ketamine to reduce the incidence of CPSP. Ketamine, 0.5 mg/kg pre-incision, 0.25 mg/kg/hour intraoperatively and 0.1 mg/kg/hour for 24 hours, or placebo, was administered to 80 patients, recruited over a 15-month period, undergoing abdominal or thoracic surgery under general anaesthesia. The primary endpoint was CPSP in the area of the surgery reported at six-month telephone follow-up using a structured questionnaire. Fourteen patients (17.5%) reported CPSP (relative risk [95% confidence interval] if received ketamine 1.18 [0.70 to 1.98], P=0.56). Four patients in the treatment group and three in the control group reported ongoing analgesic use to treat CPSP and two patients in each group reported their worst pain in the previous 24 hours at ≥3/10 at six months. There were no significant differences in adverse event rates, quality of recovery scores, or cumulative morphine equivalents consumption in the first 72 hours. Numeric Rating Scale pain scores (median [interquartile range, IQR]) for average pain in the previous 24 hours among those patients reporting CPSP were 17.5 [0 to 40] /100 with no difference between treatment groups. A large (n=4,000 to 5,000) adequately powered multicentre trial is feasible using this population and methodology.


Subject(s)
Chronic Pain/epidemiology , Ketamine/therapeutic use , Pain, Postoperative/epidemiology , Adult , Aged , Female , Humans , Incidence , Male , Middle Aged , Pilot Projects
3.
Article in English | MEDLINE | ID: mdl-22867562

ABSTRACT

Photoacoustic spectroscopy (PAS) has revolutionized the fields of biological, environmental, and agricultural sciences. It is a very simple, sensitive, and non-destructive technique that allows the determination of optical properties of bio-samples. The in vivo chlorophylls of the leaf have a recorded maximum absorption peak at 675 nm as against 665 nm of the in vitro chlorophylls. The intensity of purple pigmentation in leaves of Blepharocalyx salicifolius (Kunt) O. Berg, is inversely correlated to the soil moisture levels, leaf water content and leaf water potentials. The applicability of PAS to biological samples was discussed. It allows the validation of existing emission models which are important for atmospheric process. A portable device for photoacoustic spectroscopy of plants and other photosynthetic tissues, cells and organelles is provided. Further, there is provided a method to measure photosynthesis of such tissues, cells and organelles.


Subject(s)
Myrtaceae/chemistry , Photoacoustic Techniques/methods , Absorption , Plant Leaves/chemistry , Spectrophotometry, Infrared , Temperature
4.
Int J Clin Pract ; 65(1): 82-101, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21105969

ABSTRACT

Targeting elevations in low-density lipoprotein cholesterol (LDL-C) remains the cornerstone of cardiovascular prevention. However, this fraction does not adequately capture elevated triglyceride-rich lipoproteins (TRLs; e.g. intermediate-density lipoprotein, very low density lipoprotein) in certain patients with metabolic syndrome or diabetic dyslipidaemia. Many such individuals have residual cardiovascular risk that might be lipid/lipoprotein related despite therapy with first-line agents (statins). Epidemiological evidence encompassing > 100,000 persons supports the contention that non-high-density lipoprotein cholesterol (non-HDL-C) is a superior risk factor vs. LDL-C for incident coronary heart disease (CHD) in certain patient populations. In studies with clinical end-points evaluated in the current article, a 1:1 to 1:3 relationship was observed between reductions in non-HDL-C and in the relative risk of CHD after long-term treatment with statins, niacin (nicotinic acid) and fibric-acid derivatives (fibrates); this relationship increased to 1:5 to 1:10 in smaller subgroups of patients with elevated triglycerides and low HDL-C levels. Treatment with statin-, niacin-, fibrate-, ezetimibe-, and omega 3 fatty acid-containing regimens reduced non-HDL-C by approximately 9-65%. In a range of clinical trials, long-term treatment with these agents also significantly decreased the incidence of clinical/angiographic/imaging efficacy outcome variables. For patients with dyslipidaemia, consensus guidelines have established non-HDL-C treatment targets 30 mg/dl higher than LDL-C goals. Ongoing prospective randomised controlled trials should help to resolve controversies concerning (i) the clinical utility of targeting non-HDL-C in patients with dyslipidaemia; (ii) the most efficacious and well-tolerated therapies to reduce non-HDL-C (e.g. combination regimens); and (iii) associations between such reductions and clinical, angiographic, and/or imaging end-points.


Subject(s)
Cholesterol, HDL/antagonists & inhibitors , Dyslipidemias/drug therapy , Hypolipidemic Agents/therapeutic use , Adult , Azetidines/therapeutic use , Cardiovascular Diseases/blood , Cardiovascular Diseases/prevention & control , Ezetimibe , Fatty Acids, Omega-3/therapeutic use , Female , Fibric Acids/therapeutic use , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , Middle Aged , Niacin/therapeutic use , Practice Guidelines as Topic , Risk Factors , Young Adult
5.
Neurobiol Learn Mem ; 84(2): 132-7, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16054404

ABSTRACT

Estrogen's role in learning and memory may be to predispose animals to use specific cognitive strategies (Korol & Kolo, 2002). Specifically, estrogen may facilitate hippocampal-dependent learning, while at the same time attenuate striatal-dependent learning. As a stringent test of this hypothesis, place or response learning on an eight-arm radial maze was compared between ovariectomized (OVX) female Long-Evans rats and rats with chronic estrogen replacement (OVX+E; 5mg 17-beta estradiol 60-day release tablet). Reference and working memory errors were monitored separately for both place and response learning tasks. OVX+E rats learned the place task significantly faster than the response task, and faster than OVX rats. OVX rats required fewer days to reach criterion on the response task than OVX+E rats. Estrogen selectively enhanced reference memory performance, but only during place learning. The specific pattern of estrogen effects on learning suggests that future studies include verification of cognitive strategies used by animals.


Subject(s)
Association Learning/physiology , Corpus Striatum/physiology , Estradiol/physiology , Hippocampus/physiology , Maze Learning/physiology , Memory/physiology , Animals , Female , Ovariectomy , Random Allocation , Rats , Rats, Long-Evans , Space Perception/physiology
6.
Phys Rev Lett ; 93(2): 021101, 2004 Jul 09.
Article in English | MEDLINE | ID: mdl-15323893

ABSTRACT

Constraints on possible Lorentz symmetry violation (LV) of order E/M(Planck) for electrons and photons in the framework of effective field theory (EFT) are discussed. Using (i) the report of polarized MeV emission from GRB021206 and (ii) the absence of vacuum Cerenkov radiation from synchrotron electrons in the Crab Nebula, we improve previous bounds by 10(-10) and 10(-2), respectively. We also show that the LV parameters for positrons and electrons are different, discuss electron helicity decay, and investigate how prior constraints are modified by the relations between LV parameters implied by EFT.

7.
Diabetes Obes Metab ; 6(5): 353-62, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15287928

ABSTRACT

BACKGROUND: The third Adult Treatment Panel (ATP III) of the National Cholesterol Education Program defines clinical criteria for diagnosis of the metabolic syndrome, which increases cardiovascular risk and is a target for therapy. AIM: We analysed the third National Health and Nutrition Examination Survey (NHANES III; 1988-94) to determine how many US adults meet these criteria and are recommended for lipid-modifying drug therapy by ATP III. METHODS: NHANES III data were used to estimate the number of individuals with the metabolic syndrome and the number recommended for treatment by ATP III, based on 1990 census data. RESULTS: An estimated 36.3 million (23%) US adults have the metabolic syndrome. Of these, 84% met the criterion for obesity, 76% for blood pressure, 75% for HDL-C, 74% for triglycerides and 41% for glucose. Most (54%) are in the higher risk categories of ATP III, yet only 39% overall are recommended for drug therapy by ATP III cutpoints; of these, most will achieve LDL-C targets with reductions of 35-40%. Of the 15.3 million individuals with the metabolic syndrome and triglycerides > or = 2.26 mmol/l (200 mg/dl), non-HDL-C is above ATP III recommendations in 11.6 million. CONCLUSIONS: Of the large number of Americans with the metabolic syndrome, ATP III recommends drug therapy for only a minority, because LDL-C typically is not substantially elevated. Instead, high triglycerides and low HDL-C are more common; clinical trial data are needed to determine whether optimal therapy should focus on reductions in LDL-C or on comprehensive improvements to the lipid profile.


Subject(s)
Lipids/blood , Metabolic Syndrome/diagnosis , Adult , Blood Glucose/analysis , Cholesterol, HDL/blood , Female , Health Surveys , Humans , Hypertension/complications , Hypolipidemic Agents/therapeutic use , Male , Metabolic Syndrome/blood , Metabolic Syndrome/drug therapy , Obesity/complications , Patient Selection , Risk Assessment , Risk Factors , Triglycerides/blood , United States
8.
Nature ; 424(6952): 1019-21, 2003 Aug 28.
Article in English | MEDLINE | ID: mdl-12944959

ABSTRACT

Special relativity asserts that physical phenomena appear the same to all unaccelerated observers. This is called Lorentz symmetry and relates long wavelengths to short ones: if the symmetry is exact it implies that space-time must look the same at all length scales. Several approaches to quantum gravity, however, suggest that there may be a microscopic structure of space-time that leads to a violation of Lorentz symmetry. This might arise because of the discreteness or non-commutivity of space-time, or through the action of extra dimensions. Here we determine a very strong constraint on a type of Lorentz violation that produces a maximum electron speed less than the speed of light. We use the observation of 100-MeV synchrotron radiation from the Crab nebula to improve the previous limit by a factor of 40 million, ruling out this type of Lorentz violation, and thereby providing an important constraint on theories of quantum gravity.

9.
Cochrane Database Syst Rev ; (4): CD001398, 2002.
Article in English | MEDLINE | ID: mdl-12519555

ABSTRACT

BACKGROUND: Endometriosis is the presence of endometrial glands or stroma in sites other than the uterine cavity. It is variable in both its surgical appearance and clinical manifestation often with poor correlation between the two. Surgical treatment of endometriosis aims to remove visible areas of endometriosis and restore anatomy by division of adhesions. OBJECTIVES: To assess the efficacy of laparoscopic surgery in the treatment of subfertility associated with endometriosis. The review aims to compare outcomes of laparoscopic surgical interventions compared to no treatment or medical treatment with regard to improved fertility. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group's specialised register of trials (searched Feb 2000), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 2, 2000), MEDLINE (1966-July 2001), EMBASE (1980-July 2001), the National Research Register (Issue 1, 2000) and reference lists of articles. SELECTION CRITERIA: Trials were selected if they were randomised and compared the effectiveness of laparoscopic surgery in the treatment of subfertility associated with endometriosis versus other treatment modalities or placebo. DATA COLLECTION AND ANALYSIS: Two studies had data appropriate for inclusion within the review. These studies compared laparoscopic surgical treatment of minimal and mild endometriosis compared with diagnostic laparoscopy only. The recorded outcomes included live birth, pregnancy, fetal losses and complications of surgery. MAIN RESULTS: Meta-analysis of the two randomised trials show improvement in infertility associated with endometriosis with laparoscopic surgery. The largest trial (Marcoux 1997) clearly supports this outcome with an increased chance of pregnancy (OR 2.03, 95% CI 1.28 to 3.24) and ongoing pregnancy rate after 20 weeks (OR 1.95, 95% CI 1.18 to 3.22) but the smaller trial (Gruppo Italiano 1999) does not show benefit (pregnancy OR 0.76, 95% CI 0.31 to 1.88; livebirth OR 0.85, 95% CI 0.32 to 2.28). Combining ongoing pregnancy and live birth rates there was a statistically significant increase with surgery (OR 1.64, 95% CI 1.05 to 2.57). REVIEWER'S CONCLUSIONS: The use of laparoscopic surgery in the treatment of minimal and mild endometriosis may improve success rates. The relevant trials have some methodological problems and further research in this area is needed.


Subject(s)
Endometriosis/surgery , Infertility, Female/surgery , Laparoscopy , Endometriosis/complications , Female , Humans , Infertility, Female/etiology , Randomized Controlled Trials as Topic
10.
Arch Intern Med ; 161(18): 2185-92, 2001 Oct 08.
Article in English | MEDLINE | ID: mdl-11575974

ABSTRACT

Epidemiological and clinical trial evidence suggests that omega-3 polyunsaturated fatty acids (PUFAs) might have a significant role in the prevention of coronary heart disease. Dietary sources of omega-3 PUFA include fish oils rich in eicosapentaenoic acid and docosahexaenoic acid along with plants rich in alpha-linolenic acid. Randomized clinical trials with fish oils (eicosapentaenoic acid and docosahexaenoic acid) and alpha-linolenic acid have demonstrated reductions in risk that compare favorably with those seen in landmark secondary prevention trials with lipid-lowering drugs. Several mechanisms explaining the cardioprotective effect of omega-3 PUFAs have been suggested, including antiarrhythmic, hypolipidemic, and antithrombotic roles. Although official US guidelines for the dietary intake of omega-3 PUFAs are not available, several international guidelines have been published. Fish is an important source of omega-3 PUFAs in the US diet; however, vegetable sources, including grains and oils, offer an alternative source for those who are unable to regularly consume fish.


Subject(s)
Coronary Disease/prevention & control , Eicosapentaenoic Acid/analogs & derivatives , Fatty Acids, Omega-3/administration & dosage , Coronary Disease/etiology , Eicosapentaenoic Acid/administration & dosage , Fish Oils/administration & dosage , Humans , Nutrition Policy , Randomized Controlled Trials as Topic , United States , alpha-Linolenic Acid/administration & dosage
11.
Cochrane Database Syst Rev ; (4): CD001300, 2001.
Article in English | MEDLINE | ID: mdl-11687104

ABSTRACT

OBJECTIVES: To assess the efficacy of laparoscopic surgery in the treatment of pelvic pain associated with endometriosis. The review aims to compare the effectiveness of any laparoscopic procedure versus any other treatment modality, including expectant management. SEARCH STRATEGY: The search strategy of the Menstrual Disorders and Subfertility Review Group was used to identify all publications that described or might have described randomised trials of laparoscopic surgery in the treatment of symptomatic endometriosis. For a full description of the Review Group strategy see the Review Group details. SELECTION CRITERIA: Trials were selected if they were randomised and compared the effectiveness of laparoscopic surgery in the treatment of pelvic pain associated with endometriosis, with other treatment modalities or placebo. DATA COLLECTION AND ANALYSIS: One study had data appropriate for inclusion within the review. This study compared laparoscopic laser surgery with diagnostic laparoscopy. Pain relief was the primary outcome measure. The data was extracted independently by two reviewers. MAIN RESULTS: In comparison to expectant treatment there is a significant degree of pain relief at six months after surgery with laser laparoscopic surgery for minimal, mild and moderate endometriosis. Odds Ratio (OR) 4.97, 95% Confidence Interval (CI) 1.85,13.39 REVIEWER'S CONCLUSIONS: The combined surgical approach of laparoscopic laser ablation, adhesiolysis and uterine nerve ablation is likely to be a beneficial treatment for pelvic pain associated with minimal, mild and moderate endometriosis. As only one trial is included in the analysis, this conclusion should be interpreted with caution.


Subject(s)
Endometriosis/surgery , Laparoscopy , Laser Therapy , Pelvic Pain/surgery , Endometriosis/complications , Female , Humans , Pelvic Pain/etiology , Randomized Controlled Trials as Topic , Tissue Adhesions/surgery
12.
Curr Atheroscler Rep ; 3(5): 373-82, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11487448

ABSTRACT

For the care of an expanding segment of the US population with multiple coronary risk factors, combination lipid-altering therapy is emerging as a treatment imperative. The most recent National Cholesterol Education Program's consensus guidelines emphasize long-term global coronary heart disease (CHD) risk status, designate patients with CHD risk equivalents (eg, diabetes, peripheral arterial disease, 20% or more 10-year absolute CHD risk) for aggressive lipid-altering therapy, and deem the metabolic syndrome (eg, obesity, insulin resistance, hypertension, elevated triglycerides, low levels of high-density lipoprotein cholesterol, small dense low-density lipoprotein particles) as a secondary target for intervention. With the advancing age of the US population and the high prevalence of diabetes, the metabolic syndrome, and CHD, increasing numbers of patients will require a more balanced metabolic attack attainable only through combination lipid-altering regimens. Many of these patients, as well as persons at heightened risk for cardiovascular disease because of a range of heritable conditions (eg, familial hypercholesterolemia, familial combined hyperlipidemia), will undoubtedly require binary or ternary regimens involving statins in concert with niacin, fibric-acid derivatives, or bile acid resins. Such approaches enable the clinician to exploit the complementary effects of these agents, allowing them to be administered at low, optimally tolerable doses that are consistent with superior efficacy and a lower risk of adverse events as compared with escalating doses of monotherapy.


Subject(s)
Hypercholesterolemia/drug therapy , Hyperlipidemias/drug therapy , Hypolipidemic Agents/therapeutic use , Niacin/therapeutic use , Coronary Disease/drug therapy , Coronary Disease/metabolism , Coronary Disease/prevention & control , Drug Interactions , Drug Therapy, Combination , Humans , Hypercholesterolemia/metabolism , Hyperlipidemias/metabolism , Hypolipidemic Agents/adverse effects , Hypolipidemic Agents/pharmacokinetics , Metabolic Diseases/metabolism , Muscular Diseases/chemically induced , Niacin/adverse effects , Niacin/pharmacokinetics , Risk Factors , Treatment Outcome
13.
Mil Med ; 166(8): 708-10, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11515322

ABSTRACT

Chemical agent monitors (CAMs) are routinely used by the armed forces and emergency response teams of many countries for the detection of the vesicant sulfur mustard (HD) and the G series of organophosphate nerve agents. Ambient operating room isoflurane levels were found to produce strong positive signals in the "H" mode when the CAM was used to monitor the efficacy of decontamination procedures during routine surgical procedures on HD-poisoned animals requiring up to 8 hours of general anesthesia. Subsequent testing showed that isoflurane, as well as desflurane, sevoflurane, halothane and methoxyflurane, produce two ionization peaks in the CAM response. One of these peaks is interpreted by the CAM processing software as HD, resulting in a CAM "H" mode bar response. No interference was encountered with isoflurane, desflurane, and sevoflurane when the CAM was set to the "G" mode, although extremely high (nonclinical) concentrations of halothane and methoxyflurane yielded a weakly positive bar response. These findings have potentially serious ramifications for the medical management of patients resulting from terrorist, military, or chemical agent decommissioning activity when concomitant chemical injuries are also possible.


Subject(s)
Anesthetics/analysis , Chemical Warfare Agents/analysis , Environmental Monitoring/instrumentation , Operating Rooms , Animals , Environmental Monitoring/methods , False Positive Reactions , Swine
14.
Exp Physiol ; 86(1): 137-44, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11429627

ABSTRACT

We examined the effect of caffeine co-ingested with either carbohydrate or fat on metabolism and performance in eight endurance-trained subjects who performed a random order of four experimental trials consisting of 120 min of steady-state ergometer cycling at 70 % of maximal O(2) uptake (SS) followed by a time trial in which subjects completed a set amount of work (7 kJ kg-1) as quickly as possible. One hour before SS subjects ingested either 2.6 g kg-1 carbohydrate (CHO); 2.6 g kg-1 CHO + 6 mg kg-1 caffeine (CHO + CAF); 1.2 g kg-1 fat with 2000 U I.V. heparin (FAT); or 1.2 g kg-1 fat with 2000 U I.V. heparin + 6 mg kg-1 caffeine (FAT + CAF). The rate of carbohydrate oxidation was higher (micromol kg-1 min-1: CHO, 243 +/- 39 and CHO + CAF, 239 +/- 30 vs. FAT, 196 +/- 48 and FAT + CAF, 191 +/- 55; P < 0.05, values are means +/- S.D.) and the rate of fat oxidation lower (micromol kg-1 min-1: CHO, 19 +/- 8 and CHO + CAF, 22 +/- 7 vs. FAT, 35 +/- 19 and FAT + CAF, 37 +/- 17; P < 0.05) with carbohydrate than fat ingestion. Yet despite lower carbohydrate use with fat feeding, the time taken to complete the time trial was less after carbohydrate than after fat ingestion (min: CHO, 30.37 +/- 7.42 and CHO + CAF, 29.12 +/- 5.62 vs. FAT, 33.02 +/- 8.50 and FAT + CAF, 32.78 +/- 7.70; P < 0.05). We conclude that (1) caffeine co-ingested with either carbohydrate or fat meals has no additive effect on substrate utilization or exercise performance and (2) carbohydrate ingestion before exercise improves subsequent time trial performance compared with fat ingestion. Experimental Physiology (2001) 86.1, 137-144.


Subject(s)
Caffeine/pharmacology , Dietary Carbohydrates/pharmacology , Dietary Fats/pharmacology , Metabolism/drug effects , Physical Education and Training , Physical Endurance , Adult , Blood/metabolism , Energy Metabolism/drug effects , Heart Rate/drug effects , Homeostasis/drug effects , Humans , Male , Oxidation-Reduction , Physical Exertion/drug effects , Time Factors
16.
Am J Med ; 110 Suppl 6A: 3S-11S, 2001 Apr 16.
Article in English | MEDLINE | ID: mdl-11311191

ABSTRACT

Coronary heart disease (CHD) is the single greatest cause of death among adults in the United States. It is also a major cause of disability and is associated with direct and indirect costs that exceed $118 billion annually. Elevation of serum lipid levels, particularly low-density lipoprotein cholesterol (LDL-C) levels, is closely linked to the development of CHD. Lipid levels that increase the risk of CHD are present in nearly one third of the US population. Large-scale intervention studies have shown that decreasing LDL-C can significantly reduce the risk of cardiovascular mortality, adverse cardiovascular events, and the requirement for revascularization procedures. Statins are now thought the most effective agents for lowering LDL-C, and they also have positive effects on other components of the serum lipid profile. These drugs are also better tolerated than other lipid-lowering agents. Statin therapy significantly decreases the risk of cardiovascular disease and is a cost-effective cardiovascular treatment according to current standards. Because statins vary substantially in acquisition cost, using statins in the most cost-effective manner is important for controlling health-care costs. Optimizing the cost-effectiveness of statin therapy is a particular concern to managed care organizations in light of the large number of patients who are now considered candidates for this treatment.


Subject(s)
Anticholesteremic Agents/therapeutic use , Cholesterol, LDL/blood , Coronary Disease/therapy , Disease Management , Hypercholesterolemia/drug therapy , Anticholesteremic Agents/economics , Cause of Death , Cholesterol, LDL/drug effects , Coronary Disease/economics , Coronary Disease/epidemiology , Coronary Disease/mortality , Cost-Benefit Analysis , Disease Progression , Humans , Hypercholesterolemia/economics , Hypercholesterolemia/epidemiology , Hypercholesterolemia/mortality , Managed Care Programs , Morbidity , Patient Compliance , Prevalence , Primary Prevention , Risk Factors , Safety
17.
Ann Intern Med ; 133(7): 549-54, 2000 Oct 03.
Article in English | MEDLINE | ID: mdl-11015169

ABSTRACT

Since the publication of the second set of guidelines by the National Cholesterol Education Program, a solid body of data from landmark clinical studies has demonstrated that reduction in low-density lipoprotein (LDL) cholesterol with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor ("statin") therapy sharply diminishes the risk for coronary artery disease. These trials include the Scandinavian Simvastatin Survival Study, the West of Scotland Coronary Prevention Study, the Air Force/Texas Coronary Atherosclerosis Prevention Study, the Cholesterol and Recurrent Events investigation, and the Long-Term Intervention with Pravastatin in Ischaemic Disease trial. Coronary event rates and, in some cases, all-cause mortality decreased significantly after about 5 years of statin therapy in patients at risk for and those who had coronary artery disease at baseline. In contrast, recent subgroup analyses of these pivotal studies have in the aggregate challenged the premise that lower LDL cholesterol levels necessarily lead to further declines in risk for coronary artery disease, particularly among the patients most likely to be seen by the clinician: those with moderately elevated or normal cholesterol profiles. Indeed, when LDL cholesterol levels are in this range, further lowering with statin therapy elicits diminishing returns in terms of coronary event rates. These findings are readily accommodated by the curvilinear, or log-linear, model between serum cholesterol level and risk for coronary artery disease, which is predicated on data from large epidemiologic studies. In light of the current climate involving competing health care costs, the pursuit of progressively diminishing returns in terms of reductions in coronary artery disease risk through more aggressive lowering of LDL cholesterol levels appears to be unwarranted. Until data are published from ongoing randomized, clinical trials that can more effectively resolve the clinical utility of aggressive lipid-lowering strategies to improve coronary event rates, a prudent, evidence-based strategy seems warranted.


Subject(s)
Acyl Coenzyme A/antagonists & inhibitors , Anticholesteremic Agents/therapeutic use , Hypercholesterolemia/drug therapy , Practice Guidelines as Topic , Cholesterol, LDL/blood , Clinical Trials as Topic , Coronary Disease/etiology , Coronary Disease/prevention & control , Humans , Hypercholesterolemia/blood , Hypercholesterolemia/complications , Lovastatin/therapeutic use , Risk Factors , Simvastatin/therapeutic use
18.
Arch Intern Med ; 160(9): 1361-9, 2000 May 08.
Article in English | MEDLINE | ID: mdl-10809042

ABSTRACT

BACKGROUND: When the National Cholesterol Education Program Adult Treatment Panel II (ATP II) guidelines were published, National Health and Nutrition Examination Survey III data for 1988 to 1991 were used to estimate the number of Americans requiring lipid-lowering therapy based on ATP II cut points. However, the guidelines recommend using clinical judgment to determine whether to initiate drug therapy in individuals whose low-density lipoprotein cholesterol levels remain above treatment goals with diet therapy but below the initiation level for drug therapy. METHODS: We analyzed updated (1988-1994) National Health and Nutrition Examination Survey III data, based on a sample of 6796 adults aged 20 years and older, to estimate the numbers of American adults with an elevated low-density lipoprotein cholesterol level and requiring drug therapy using cut points vs clinical judgment as specified in ATP II guidelines. RESULTS: Assuming a 10% low-density lipoprotein cholesterol reduction with diet, an estimated 10.4 million American adults require drug therapy based on ATP II cut points. If we include individuals for whom the guidelines recommend clinical judgment, the estimate increases to 28.4 million. The largest increase occurs in individuals without known coronary heart disease but with 2 or more risk factors: from 5.5 to 17.5 million. These high-risk individuals have low-density lipoprotein cholesterol concentrations similar to those in patients with coronary heart disease. CONCLUSIONS: Since the ATP II guidelines were published, clinical judgment has been informed by abundant clinical trial evidence establishing the safety and benefit of lipid-lowering therapy. The large number of individuals at high risk for coronary heart disease emphasizes the need for cost-effective therapy to extend treatment to the greatest number of individuals who may benefit.


Subject(s)
Cholesterol, LDL/blood , Hypercholesterolemia/drug therapy , Hypercholesterolemia/epidemiology , Hypolipidemic Agents/therapeutic use , Adult , Evidence-Based Medicine , Female , Humans , Male , Risk Factors , United States/epidemiology
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