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1.
R Soc Open Sci ; 6(3): 182001, 2019 Mar.
Article in English | MEDLINE | ID: mdl-31032047

ABSTRACT

The instantaneous frequency (IF) of a signal is a well-defined quantity that is widely used for analysing non-stationary signals. However, often in practice, IF as a function of time can possess large spikes and negative values. Moreover, IF is very sensitive to noise, limiting its range of practical application. Due to these deficiencies, we introduce the concept of moment of velocity (MoV) for signal analysis. As a case study, we compare the performance of MoV to a standard Hilbert transform-based approach for R-wave identification in human electrocardiogram signals, demonstrating that our approach is more robust to noise. We examine characteristic heartbeats obtained from the MIT-BIH Arrhythmia database. A detection error rate of 0.07%, a positive predictive value of 99.97%, and a sensitivity of 99.95% are achieved against analysis results from the database.

2.
Hernia ; 23(1): 51-59, 2019 02.
Article in English | MEDLINE | ID: mdl-30446849

ABSTRACT

PURPOSE: In patients with cirrhosis, the Model for End-Stage Liver Disease Sodium (MELD-Na) score is a validated predictor of outcomes after transplant and non-transplant surgical procedures. This study investigates the association of MELD-Na score with complications following elective ventral hernia repair in non-cirrhotic patients. METHODS: The ACS NSQIP database was queried (2005-2016) for all elective laparoscopic and open ventral hernia procedures in patients without ascites or esophageal varices. Postoperative outcomes were compared by MELD-Na score using Chi-square tests. Multivariate logistic regression was used to control for potentially confounding variables. RESULTS: A total of 48,955 elective hernia repairs were identified; 68.7% were open repairs. The overall complication rate (Clavien-Dindo ≥ 1) was 14.3%, with a wound complication rate of 5.5%, and major complication rate (Clavien-Dindo ≥ 3) of 4.3%. A preoperative MELD-Na score ≥ 10 was present in 29.4%. Incremental increases in MELD-Na score (10-14, 15-19, and ≥ 20) were associated with increased overall complications (OR 1.25, CI 1.31-1.37; OR 1.53, CI 1.30-1.80; OR 1.70, CI 1.24-2.31, respectively), major complications (OR 1.42, CI 1.20-1.69; OR 1.85, CI 1.43-2.39; OR 2.13, CI 1.35-3.38, respectively), 30-day mortality (OR 1.58, CI 1.05-2.37; OR 2.34, CI 1.39-3.96; OR 3.16, CI 1.37-7.28, respectively), and return to the operating room (OR 1.19, CI 1.01-1.41; OR 1.38, CI 1.05-1.81; OR 1.78, CI 1.10-2.90, respectively). CONCLUSION: MELD-Na score is independently associated with postoperative complications in ventral hernia repair. As an objective and simple predictive model, it may be useful in preoperative risk calculations for complex patients.


Subject(s)
Hernia, Ventral/surgery , Herniorrhaphy/adverse effects , Postoperative Complications/epidemiology , Aged , Elective Surgical Procedures/adverse effects , Female , Humans , Incidence , Laparoscopy/methods , Liver Cirrhosis , Male , Middle Aged , United States/epidemiology
3.
J Hum Hypertens ; 30(9): 549-54, 2016 09.
Article in English | MEDLINE | ID: mdl-26791477

ABSTRACT

African Americans have the highest prevalence of hypertension in the United States. Blood pressure (BP) control is important to reduce cardiovascular disease-related morbidity and mortality in this ethnic group. Genetic variants have been found to be associated with BP response to treatment. Previous pharmacogenetic studies of BP response to treatment in African Americans suffer limitations of small sample size as well as a limited number of candidate genes, and often focused on one antihypertensive treatment. Using 1131 African-American treatment-naive participants from the Genetics of Hypertension Associated Treatment Study, we examined whether variants in 35 candidate genes might modulate BP response to four different antihypertensive medications, including an angiotensin-converting enzyme inhibitor (lisinopril), a calcium channel blocker (amlodipine), and an a-adrenergic blocker (doxazosin) as compared with a thiazide diuretic (chlorthalidone) after 6 months of follow-up. Several suggestive gene by treatment interactions were identified. For example, among participants with two minor alleles of renin rs6681776, diastolic BP response was much improved on doxazosin compared with chlorthalidone (on average -9.49 mm Hg vs -1.70 mm Hg) (P=0.007). Although several suggestive loci were identified, none of the findings passed significance criteria after correction for multiple testing. Given the impact of hypertension and its sequelae in this population, this research highlights the potential for genetic factors to contribute to BP response to treatment. Continued concerted research efforts focused on genetics are needed to improve treatment response in this high-risk group.


Subject(s)
Antihypertensive Agents/therapeutic use , Black or African American/genetics , Blood Pressure/drug effects , Blood Pressure/genetics , Hypertension/drug therapy , Hypertension/genetics , Pharmacogenomic Variants , Adrenergic alpha-1 Receptor Antagonists/therapeutic use , Aged , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Calcium Channel Blockers/therapeutic use , Diuretics/therapeutic use , Double-Blind Method , Female , Genetic Predisposition to Disease , Humans , Hypertension/ethnology , Hypertension/physiopathology , Male , Middle Aged , North America/epidemiology , Pharmacogenetics , Phenotype , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/genetics , Treatment Outcome
4.
Pharmacogenomics J ; 13(4): 330-4, 2013 Aug.
Article in English | MEDLINE | ID: mdl-22664477

ABSTRACT

Nearly one-third of adults in the United States have hypertension, which is associated with increased cardiovascular disease (CVD) morbidity and mortality. The goal of antihypertensive pharmacogenetic research is to enhance understanding of drug response based on the interaction of individual genetic architecture and antihypertensive therapy to improve blood pressure control and ultimately prevent CVD outcomes. In the context of the Genetics of Hypertension Associated Treatment study and using a case-only design, we examined whether single-nucleotide polymorphisms in RYR3 interact with four classes of antihypertensive drugs, particularly the calcium channel blocker amlodipine versus other classes, to modify the risk of coronary heart disease (CHD; fatal CHD and non-fatal myocardial infarction combined) and heart failure (HF) in high-risk hypertensive individuals. RYR3 mediates the mobilization of stored Ca(+2) in cardiac and skeletal muscle to initiate muscle contraction. There was suggestive evidence of pharmacogenetic effects on HF, the strongest of which was for rs877087, with the smallest P-value=0.0005 for the codominant model when comparing amlodipine versus all other treatments. There were no pharmacogenetic effects observed for CHD. The findings reported here for the case-only analysis of the antihypertensive pharmacogenetic effect of RYR3 among 3058 CHD cases and 1940 HF cases show that a hypertensive patient's genetic profile may help predict which medication(s) might better lower CVD risk.


Subject(s)
Antihypertensive Agents/administration & dosage , Cardiovascular Diseases/genetics , Hypertension/drug therapy , Ryanodine Receptor Calcium Release Channel/genetics , Adult , Amlodipine/administration & dosage , Blood Pressure/genetics , Calcium Channel Blockers/administration & dosage , Cardiovascular Diseases/complications , Cardiovascular Diseases/physiopathology , Diuretics/administration & dosage , Female , Humans , Hypertension/complications , Hypertension/genetics , Male , Polymorphism, Single Nucleotide , Treatment Outcome , United States
5.
Antimicrob Agents Chemother ; 52(2): 446-51, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18025116

ABSTRACT

The increased incidence of methicillin-resistant Staphylococcus aureus (MRSA), the emergence of community-acquired MRSA, and the continued high incidence of methicillin-resistant Staphylococcus epidermidis have required that certain institutions choose vancomycin for surgical prophylaxis. However, the data supporting the use of vancomycin for surgical prophylaxis are controversial. The purpose of this project was to assess the effect of the change from cefuroxime to vancomycin for surgical site infection (SSI) rates in patients undergoing coronary artery bypass graft (CABG) surgery. The monthly rates of SSIs from 2001 to 2005 were analyzed before and after a change from cefuroxime to vancomycin antibiotic prophylaxis in patients undergoing CABG by using an interrupted time series analysis. Patients who underwent cardiac valve replacement surgery and who had received vancomycin during the entire study period were used as a comparator group. A total of 6,465 patients underwent CABG surgery (n = 4,239) or valve replacement surgery (n = 2,226) during the study period. On average, the monthly SSI incidence rate in patients undergoing CABG surgery decreased by 2.1 cases per 100 surgeries after the switch from cefuroxime to vancomycin (P = 0.042) when patients undergoing valve replacement were used as a comparator group. The change in SSI rates was associated with a decrease in the incidence of infections caused by coagulase-negative Staphylococcus and MRSA isolates, with little change in the incidence of SSIs due to other gram-positive organisms or gram-negative organisms. In institutions with a high incidence of methicillin-resistant Staphylococcus species, this study provides evidence for the clinical efficacy of vancomycin prophylaxis for the prevention of postoperative SSIs in patients undergoing CABG surgery.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis , Cefuroxime/therapeutic use , Coronary Artery Bypass/adverse effects , Surgical Wound Infection , Vancomycin/therapeutic use , Aged , Coagulase/metabolism , Female , Humans , Incidence , Male , Methicillin Resistance , Middle Aged , Staphylococcal Infections/epidemiology , Staphylococcal Infections/microbiology , Staphylococcal Infections/prevention & control , Staphylococcus/enzymology , Staphylococcus/isolation & purification , Staphylococcus aureus/drug effects , Staphylococcus aureus/isolation & purification , Surgical Wound Infection/epidemiology , Surgical Wound Infection/microbiology , Surgical Wound Infection/prevention & control
6.
Ann Hum Genet ; 71(Pt 6): 735-45, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17608790

ABSTRACT

Research suggests pulse pressure (PP) is a predictor of cardiovascular disease, and genes likely influence PP levels. Additionally, gender may be an effect modifier between PP and cardiovascular disease. This study addresses whether two renin-angiotensin-aldosterone system (RAAS) variants are associated with PP in a sex-specific manner (genotype-by-sex interaction). Subjects comprised 35,048 GenHAT study participants over 55 years old, approximately half were women and half non-Hispanic white. Blood pressure measurements were obtained 6 months after randomization to one of four antihypertensive medications. The polymorphisms considered were AGT-6 and ACE-I/D. We employed linear regression to assess the interaction. AGT-6 showed a significant (p < 0.001) genotype-by-sex interaction. Men with the 'G/G' genotype had a higher PP (0.6 mm HG) than men carrying an 'A' allele, while 'G/G' women had a lower PP (0.7 mm Hg) than women carrying an 'A' allele. Three of the four treatment groups (chlorthalidone, amlodipine and lisinopril) suggested a consistent interaction in sub-group analyses (only amlodipine was statistically significant, p < 0.001), whereas doxazosin did not. The interaction was evident among non-Hispanic participants but not among Hispanic participants. For ACE-I/D no evidence for a genotype-by-sex interaction was detected. This finding of genotype-by-sex interaction on PP helps our understanding of the complexity of genetic effects on blood pressure.


Subject(s)
Angiotensinogen/genetics , Antihypertensive Agents/therapeutic use , Blood Pressure/genetics , Peptidyl-Dipeptidase A/genetics , Polymorphism, Genetic , Aged , Blood Pressure/drug effects , Blood Pressure/physiology , Double-Blind Method , Female , Genotype , Humans , Hypertension/drug therapy , Hypertension/genetics , Hypertension/physiopathology , Male , Middle Aged , Polymorphism, Single Nucleotide , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/genetics , Renin-Angiotensin System/physiology , Sequence Deletion , Sex Characteristics
7.
Pharmacogenomics J ; 7(2): 112-22, 2007 Apr.
Article in English | MEDLINE | ID: mdl-16702981

ABSTRACT

In a double-blind, outcome trial conducted in hypertensive patients randomized to chlorthalidone (C), amlodipine (A), lisinopril (L), or doxazosin (D), the alpha-adducin Gly460Trp polymorphism was typed (n=36 913). Mean follow-up was 4.9 years. Relative risks (RRs) of chlorthalidone versus other treatments were compared between genotypes (Gly/Gly+Gly/Trp versus Trp/Trp). Primary outcome was coronary heart disease (CHD). Coronary heart disease incidence did not differ among treatments or genotypes nor was there any interaction between treatment and genotype (P=0.660). Subgroup analyses indicated that Trp allele carriers had greater CHD risk with C versus A+L in women (RR=1.31) but not men (RR=0.91) with no RR gender differences for non-carriers (gender-gene-treatment interaction, P=0.002). The alpha-adducin gene is not an important modifier of antihypertensive treatment on cardiovascular risk, but women Trp allele carriers may have increased CHD risk if treated with C versus A or L. This must be confirmed to have implications for hypertension treatment.


Subject(s)
Antihypertensive Agents/therapeutic use , Calmodulin-Binding Proteins/genetics , Coronary Disease/genetics , Coronary Disease/prevention & control , Hypertension/drug therapy , Hypertension/genetics , Polymorphism, Genetic , Aged , Amlodipine/therapeutic use , Antihypertensive Agents/pharmacology , Blood Pressure/drug effects , Chlorthalidone/therapeutic use , Coronary Disease/epidemiology , Double-Blind Method , Doxazosin/therapeutic use , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Glycine , Humans , Hypertension/complications , Hypertension/physiopathology , Incidence , Kaplan-Meier Estimate , Lisinopril/therapeutic use , Male , Middle Aged , Patient Selection , Proportional Hazards Models , Risk Assessment , Risk Factors , Sex Factors , Time Factors , Treatment Outcome , Tryptophan
8.
Int J Oral Maxillofac Surg ; 34(8): 871-6, 2005 Dec.
Article in English | MEDLINE | ID: mdl-15955668

ABSTRACT

"Free-grafting" of the superior segment, either alone or in combination with a posterior ramus osteotomy, is occasionally required when managing displaced condylar neck fractures. This allows ideal reduction and fixation, but carries the risk of proximal segment resorption, possibly requiring secondary reconstruction. The purpose of this study was to evaluate the clinical and radiographic outcomes of this technique in all patients who underwent this procedure during a seven-year period at a tertiary care centre. Ten patients who had undergone 11 free graft procedures were included in the study. Three patients required secondary costochondral reconstruction due to advanced resorption of the free-grafted condylar segment, this occurring from 3 to 9 months following the initial trauma surgery. All but one of the remaining patients exhibited varying degrees of condylar resorption/flattening radiographically, occurring within the first year only. However, no occlusal changes occurred in this group either objectively or subjectively during this year or during the subsequent follow-up period. The mean inter-incisal opening was 47mm (range 40-56). With the exception of one patient that had a non-painful reciprocal click of the treated side, no patients demonstrated either objective or subjective signs of TMJ pathology. No patients reported dietary limitations, and all reported satisfaction with treatment to date. Based on objective and subjective evaluation, free grafting of the fractured condylar segment in this patient population had a 70% success rate. All failures occurred within 9 months and required secondary costochondral reconstruction.


Subject(s)
Bone Transplantation/methods , Mandibular Condyle/injuries , Mandibular Condyle/surgery , Mandibular Fractures/surgery , Oral Surgical Procedures/methods , Adolescent , Adult , Bone Resorption/etiology , Bone Transplantation/adverse effects , Female , Humans , Male , Mandibular Condyle/transplantation , Middle Aged , Osteotomy/methods , Range of Motion, Articular , Retrospective Studies , Treatment Outcome , Young Adult
9.
J Laryngol Otol ; 119(2): 161-3, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15829075

ABSTRACT

A 19-year-old farmer was referred by his general practitioner as an emergency to our otolaryngology department complaining of marked breathlessness of a few hours duration. He gave a three-day history of painful swelling and hair loss in the beard area of the right side of the neck. His upper airway was compromised unless extension of the neck was maintained. Larynx and pharynx were normal. The acute symptoms settled with intravenous antibiotics and hydrocortisone. Culture of skin scrapings revealed a growth of Tricophyton verrucosum. The neck swelling subsided after a course of oral griseofulvin followed by terbinafine. Difficulty in breathing due to fungal infection of the neck has not been previously reported in the English literature.


Subject(s)
Agricultural Workers' Diseases/diagnosis , Airway Obstruction/microbiology , Tinea/diagnosis , Adult , Agricultural Workers' Diseases/drug therapy , Antifungal Agents/therapeutic use , Humans , Male , Neck , Tinea/complications , Tinea/drug therapy
10.
Pharmacogenomics J ; 2(5): 309-17, 2002.
Article in English | MEDLINE | ID: mdl-12439737

ABSTRACT

The Genetics of Hypertension Associated Treatment (GenHAT) study will determine whether variants in hypertension susceptibility genes interact with antihypertensive medication to modify coronary heart disease (CHD) risk in hypertensives. GenHAT is an ancillary study of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial, ALLHAT, a double-blind, randomized trial of 42 418 hypertensives, 55 years of age or older, with systolic or diastolic hypertension and one or more risk factors for cardiovascular disease. About 50% are non-white, and about half are female. ALLHAT completes follow-up in March 2002. GenHAT is typing variants in hypertension genes; completion of genotyping is scheduled for 2003. Analysis of gene-treatment interactions in relation to outcomes include CHD, stroke, heart failure, and blood pressure lowering. To our knowledge, GenHAT is the largest pharmacogenetic study ever conducted. An added strength is its ability to link gene-treatment interactions with important clinical outcomes across diverse ethnic and gender groups.


Subject(s)
Hypertension/drug therapy , Hypertension/genetics , Pharmacogenetics/methods , Randomized Controlled Trials as Topic/methods , Humans , Pharmacogenetics/trends , Randomized Controlled Trials as Topic/statistics & numerical data , Randomized Controlled Trials as Topic/trends
11.
Gene Ther ; 9(11): 691-4, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12032689

ABSTRACT

Gene therapy treatment of disease will be greatly facilitated by the identification of genetic mutations through the Human Genome Project. The specific treatment will ultimately depend on the type of mutation as different genetic lesions will require different gene therapies. For example, large rearrangements and translocations may call for complementation with vectors containing the cDNA for the wild-type (wt) gene. On the other hand, smaller lesions, such as the reversion, addition or deletion of only a few base pairs, on single genes, or monogenic disorders, lend themselves to gene targeting. The potential for one gene targeting technique, small fragment homologous replacement (SFHR) to the gene therapy treatment of sickle cell disease (SCD) is presented. Successful conversion of the wt-beta-globin locus to a SCD genotype of human lymphocytes (K562) and progenitor/stem hematopoietic cells (CD34(+) and lin-CD38-) was achieved by electroporation or microinjection small DNA fragments (SDF).


Subject(s)
Gene Targeting/methods , Genetic Therapy/methods , Sickle Cell Trait/therapy , Antigens, CD34 , Cells, Cultured , Electroporation , Globins/genetics , Hematopoietic Stem Cells , Humans , Lymphocytes/immunology , Lymphocytes/metabolism , Microinjections , Plasmids/administration & dosage
12.
Gene Ther ; 9(2): 118-26, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11857070

ABSTRACT

Chimeric oligonucleotides have been used successfully to correct point and frameshift mutations in several cell types, as well as in animal and plant models. However, their application to primitive human blood cells has been limited. In this investigation, chimeric oligonucleotides designed to direct a site-specific nucleotide exchange in the human beta-globin gene (an A to T substitution within codon 6) were introduced into normal human CD34(+) and Lin(-)CD38(-) cells via microinjection. This A to T nucleotide exchange introduces the single site mutation responsible for sickle cell anemia. In 23% of experimental samples, gene conversion was detected in the progeny of microinjected CD34(+) and Lin(-)CD38(-) cells that were cultured for at least 4 weeks. In addition, gene conversion was detected in the erythroid progeny of Lin(-)CD38(-) cells at the mRNA level. Conversion rates as high as 10-15% in 11% (five of 44) of experimental samples were confirmed by allele-specific PCR and sequence analysis of genomic DNA from the progeny of microinjected Lin(-)CD38(-) cells. Given that as few as 10% normal hematopoietic cells are sufficient to keep patients free of sickle cell disease, the level of conversion we have achieved in some samples may well be of therapeutic benefit in patients with sickle cell disease.


Subject(s)
Anemia, Sickle Cell/genetics , Antigens, CD , Gene Conversion , Gene Targeting/methods , Genetic Therapy/methods , Globins/genetics , ADP-ribosyl Cyclase , ADP-ribosyl Cyclase 1 , Antigens, CD34/analysis , Antigens, Differentiation/analysis , Cells, Cultured , Hematopoietic Stem Cells/pathology , Humans , Membrane Glycoproteins , Microinjections , NAD+ Nucleosidase/analysis , Point Mutation
13.
Eur Heart J ; 23(3): 207-15, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11792135

ABSTRACT

AIMS: To assess the effects of pravastatin on all-cause mortality and cause-specific mortality and to compare the effects for patients with prior coronary heart disease with those for patients without, using pooled data from the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study, the Cholesterol and Recurrent Events (CARE) study, and the West of Scotland Coronary Prevention Study (WOSCOPS). METHODS AND RESULTS: 13 173 patients with coronary heart disease and 6595 men with elevated cholesterol and no prior coronary disease received pravastatin, 40 mg daily, or placebo for an average of 5 to 6 years. Data were analysed according to a pre-specified, published protocol. For all three trials combined, the mortality among patients assigned pravastatin was significantly lower, at 7.9%, than the 9.8% among those assigned placebo, a relative risk reduction of 20% (95% confidence interval (CI) 12-27%, P<0.0001). Active treatment was associated with a reduction in coronary mortality (24%, 95% CI 14-33%). Larger reductions in absolute risk were estimated in those with prior coronary heart disease than in those without. CONCLUSION: Treatment with pravastatin over 5 years reduces all-cause mortality and coronary mortality in patients with and those without a history of coronary heart disease. The size of the benefit was related principally to the baseline risk.


Subject(s)
Cholesterol/blood , Coronary Disease/blood , Coronary Disease/mortality , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Pravastatin/therapeutic use , Aged , Coronary Disease/drug therapy , Double-Blind Method , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prevalence , Risk Factors , Sensitivity and Specificity , Survival Analysis , Time Factors , Treatment Outcome
14.
Control Clin Trials ; 22(6): 659-73, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11738122

ABSTRACT

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a randomized clinical outcome trial of antihypertensive and lipid-lowering therapy in a diverse population (including substantial numbers of women and minorities) of 42,419 high-risk hypertensives aged > or = 55 years with a planned mean follow-up of 6 years. In this paper, we describe our experience in the identification, recruitment, and selection of clinical centers for this large simple trial capable of meeting the recruitment goals outlined for ALLHAT, and we highlight factors associated with clinical center performance. Over 135,000 recruitment brochures were mailed to physicians. Requests for information and application packets were received from 9351 (6.8%) interested investigators. A total of 1053 completed applications were received and 909 sites (86%) were eventually approved to join the trial. Of the approved sites, 278 either later declined participation or were never activated, and 8 were closed within a year for lack of enrollment. The final 623 randomizing centers exceeded the trial's recruitment goal to enroll at least 40,000 participants into the trial, although the recruitment period was extended 1.5 years longer than planned. Fewer than a quarter of the sites (22.6%) were recruited from academic medical centers or Department of Veterans Affairs Medical Centers. More than half of the sites (54.7%) were private solo or group practices, which contributed 53% of randomized participants. Community health centers comprised about 8% of the ALLHAT sites and 2.9% were part of health maintenance organizations. More than 22% of the principal investigators reported that they had no previous clinical research experience. In summary, ALLHAT was successful in recruiting a diverse group of clinical centers to achieve its patient recruitment goals.


Subject(s)
Antihypertensive Agents/therapeutic use , Hypolipidemic Agents/therapeutic use , Myocardial Infarction/prevention & control , Personnel Selection/methods , Randomized Controlled Trials as Topic , Black People , Female , Humans , Male , Middle Aged , Multicenter Studies as Topic , United States
15.
Control Clin Trials ; 22(6): 674-86, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11738123

ABSTRACT

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a practice-based, randomized, multicenter clinical trial in 42,419 high-risk hypertensive patients aged 55 years and older; 10,356 of these patients are also in a lipid-lowering trial component. The purpose of the antihypertensive component is to determine whether the occurrence of fatal coronary heart disease and/or nonfatal myocardial infarction differs between patients randomized to diuretic (chlorthalidone) and those randomized to either calcium antagonist (amlodipine), angiotensin-converting enzyme inhibitor (lisinopril), or alpha-adrenergic blocker (doxazosin) therapy. (The doxazosin arm has been discontinued.) The purpose of the lipid-lowering component is to determine whether lowering low-density lipoprotein cholesterol with a 3-hydroxymethyl-glutaryl coenzyme A reductase inhibitor (pravastatin) in moderately hypercholesterolemic patients will reduce all-cause mortality compared to a control group receiving "usual care." ALLHAT recruited patients from a variety of practice settings from February 1994 through January 1998. Sites were paid for randomizations and are paid for completed follow-up visits and documented study events. Communication and monitoring were facilitated by nine regional coordinator teams. It was recognized from the outset that patient recruitment would be a very large task because of the number of participants (> 40,000) needed, the ambitious nature of the goal for recruitment of African-Americans (> 55%), and the knowledge that many investigators had limited experience recruiting participants for clinical trials. Multiple adjustments in the initial ALLHAT overall recruitment plan facilitated achievement of sample size goals for both components of the trial. The experience obtained from this large trial should be valuable for the planning and implementation of successful recruitment in future trials.


Subject(s)
Antihypertensive Agents/therapeutic use , Hypolipidemic Agents/therapeutic use , Myocardial Infarction/prevention & control , Personnel Selection/methods , Randomized Controlled Trials as Topic/methods , Aged , Female , Goals , Humans , Male , Middle Aged , Multicenter Studies as Topic , Personnel Selection/economics , Randomized Controlled Trials as Topic/statistics & numerical data , Time Factors , United States
16.
Nature ; 411(6841): 992, 2001 Jun 28.
Article in English | MEDLINE | ID: mdl-11429570
17.
Diabetes Care ; 24(4): 654-8, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11315826

ABSTRACT

OBJECTIVE: Hypertension (HTN) is a major risk factor for cardiovascular disease (CVD) in the setting of diabetes. There is no consensus on how best to treat hypertension among those with diabetes. Here we describe the characteristics of a cohort of hypertensive adults with diabetes who are part of a large prospective blood pressure study. This study will help clarify the treatment of HTN in the setting of diabetes. RESEARCH DESIGN AND METHODS: The Antihypertensive and Lipid-Lowering high-risk hypertensive participants, ages > or = 55 years, designed to determine whether the incidence of fatal and nonfatal coronary heart disease (CHD) and combined cardiovascular events (fatal and nonfatal CHD, revascularization surgery, angina pectoris, congestive heart failure, and stroke) differs between diuretic (chlorthalidone) treatment and three alternative antihypertensive therapies: a calcium channel blocker (amlodipine), an ACE inhibitor (lisinopril), and an alpha-adrenergic blocker (doxazosin). The planned follow-up is an average of 6 years, to be completed March 2002. RESULTS: There are 15,297 diabetic individuals in the ALLHAT study (36.0% of the entire cohort). Of these individuals, 50.2% are male, 39.4% are African-American, and 17.7% are Hispanic. Demographic and laboratory characteristics of the cohort are similar to those of other studies of the U.S. elderly population with HTN. The sample size has 42 and 93% confidence, treatments for the two study outcomes. CONCLUSIONS: The diabetic cohort in ALLHAT wil be able to provide valuable information about the treatment of hypertension in older diabetic patients at risk for incident CVD.


Subject(s)
Antihypertensive Agents/therapeutic use , Cholesterol, Dietary , Coronary Disease/prevention & control , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypercholesterolemia/diet therapy , Hypercholesterolemia/drug therapy , Hypertension/drug therapy , Myocardial Infarction/prevention & control , Pravastatin/therapeutic use , Adrenergic alpha-Antagonists/therapeutic use , Adult , Aged , Amlodipine/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Blood Pressure , Calcium Channel Blockers/therapeutic use , Cohort Studies , Coronary Disease/epidemiology , Coronary Disease/mortality , Double-Blind Method , Doxazosin/therapeutic use , Ethnicity , Female , Humans , Hypercholesterolemia/complications , Hypertension/complications , Lisinopril/therapeutic use , Male , Middle Aged , Myocardial Infarction/epidemiology , Myocardial Infarction/mortality , Racial Groups , Risk Factors , United States
18.
Circulation ; 103(3): 387-92, 2001 Jan 23.
Article in English | MEDLINE | ID: mdl-11157690

ABSTRACT

BACKGROUND: Stroke is a leading cause of death and disability. Although clinical trials of the early lipid-lowering therapies did not demonstrate a reduction in the rates of stroke, data from recently completed statin trials strongly suggest benefit. METHODS AND RESULTS: The effect of pravastatin 40 mg/d on stroke events was investigated in a prospectively defined pooled analysis of 3 large, placebo-controlled, randomized trials that included 19 768 patients with 102 559 person-years of follow-up. In all, 598 participants had a stroke during approximately 5 years of follow-up. The 2 secondary prevention trials (CARE [Cholesterol And Recurrent Events] and LIPID [Long-term Intervention with Pravastatin in Ischemic Disease]) individually demonstrated reductions in nonfatal and total stroke rates. When the 13 173 patients from CARE and LIPID were combined, there was a 22% reduction in total strokes (95% CI 7% to 35%, P:=0.01) and a 25% reduction in nonfatal stroke (95% CI 10% to 38%). The beneficial effect of pravastatin on total stroke was observed across a wide range of patient characteristics. WOSCOPS (West of Scotland Coronary Prevention Study, a primary prevention trial in hypercholesterolemic men) exhibited a similar, although smaller, trend for a reduction in total stroke. Among the CARE/LIPID participants, pravastatin was associated with a 23% reduction in nonhemorrhagic strokes (95% CI 6% to 37%), but there was no statistical treatment group difference in hemorrhagic or unknown type. CONCLUSIONS: Pravastatin reduced the risk of stroke over a wide range of lipid values among patients with documented coronary disease. This effect was due to a reduction in nonfatal nonhemorrhagic strokes.


Subject(s)
Anticholesteremic Agents/therapeutic use , Coronary Disease/drug therapy , Pravastatin/therapeutic use , Stroke/prevention & control , Humans , Male , Proportional Hazards Models , Prospective Studies , Stroke/mortality , Time Factors
19.
Control Clin Trials ; 22(1): 29-41, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11165421

ABSTRACT

The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a randomized, practice-based trial sponsored by the National Heart, Lung, and Blood Institute (NHLBI). The double-blind, active-controlled component of ALLHAT was designed to determine whether the rate of the primary outcome-a composite of fatal coronary heart disease and nonfatal myocardial infarction-differs between diuretic (chlorthalidone) treatment and each of three other classes of antihypertensive drugs: a calcium antagonist (amlodipine), an angiotensin-converting enzyme inhibitor (lisinopril), and an alpha-adrenergic blocker (doxazosin) in high-risk hypertensive persons ages 55 years and older. In addition, 10,377 ALLHAT participants with mild to moderate hypercholesterolemia were also enrolled in a randomized, open-label trial designed to determine whether lowering serum LDL cholesterol with an HMG CoA reductase inhibitor (pravastatin) will reduce all-cause mortality as compared to a control group receiving "usual care." In January 2000, an independent data review committee recommended discontinuing the doxazosin treatment arm. The NHLBI director promptly accepted the recommendation. This article discusses the steps involved in the orderly closeout of one arm of ALLHAT and the dissemination of trial results. These steps included provisional preparations; the actual decision process; establishing a timetable; forming a transition committee; preparing materials and instructions; informing 65 trial officers and coordinators, 628 active clinics and satellite locations, 313 institutional review boards, over 42,000 patients, and the general public; reporting detailed trial results; and monitoring the closeout process. Control Clin Trials 2001;22:29-41


Subject(s)
Adverse Drug Reaction Reporting Systems , Antihypertensive Agents/adverse effects , Coronary Disease/prevention & control , Doxazosin/adverse effects , Hypercholesterolemia/prevention & control , Hypertension/drug therapy , Myocardial Infarction/prevention & control , Antihypertensive Agents/therapeutic use , Cause of Death , Coronary Disease/mortality , Databases, Factual , Double-Blind Method , Doxazosin/therapeutic use , Female , Heart Failure/chemically induced , Heart Failure/mortality , Humans , Hypercholesterolemia/mortality , Hypertension/mortality , Male , Middle Aged , Myocardial Infarction/mortality , Pravastatin/adverse effects , Pravastatin/therapeutic use , Risk Assessment , Survival Rate , Treatment Outcome , United States
20.
Chaos ; 11(3): 747-754, 2001 Sep.
Article in English | MEDLINE | ID: mdl-12779513

ABSTRACT

In this paper we describe an apparent paradox concerning a moving plate capacitor driven by thermal noise from a resistor. The plates are attracted together, but a demon restores the plates of the capacitor to their original position when the voltage across the capacitor is small-hence only small forces are present for the demon to work against. The demon has to work harder than this to avoid the situation of perpetual motion, but the open question is how? This is unsolved, however we explore the concept of a moving plate capacitor by examining the case where it is still excited by thermal noise, but where the restoring force on the capacitor plates is provided by a simple spring rather than some unknown demon. We display simulation results with interesting behavior, particularly where the capacitor plates collide with each other. (c) 2001 American Institute of Physics.

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