187 results on '"Sacks HS"'
Search Results
52. A Multidimensional Analysis of Prostate Surgery Costs in the United States: Robotic-Assisted versus Retropubic Radical Prostatectomy.
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Bijlani A, Hebert AE, Davitian M, May H, Speers M, Leung R, Mohamed NE, Sacks HS, and Tewari A
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- Costs and Cost Analysis, Health Care Costs, Humans, Laparoscopy economics, Male, Meta-Analysis as Topic, Models, Economic, Postoperative Complications economics, Robotic Surgical Procedures methods, Treatment Outcome, United States, Hospital Costs statistics & numerical data, Prostatectomy economics, Prostatectomy methods, Prostatic Neoplasms economics, Prostatic Neoplasms surgery, Robotic Surgical Procedures economics
- Abstract
Background: The economic value of robotic-assisted laparoscopic prostatectomy (RALP) in the United States is still not well understood because of limited view analyses., Objectives: The objective of this study was to examine the costs and benefits of RALP versus retropubic radical prostatectomy from an expanded view, including hospital, payer, and societal perspectives., Methods: We performed a model-based cost comparison using clinical outcomes obtained from a systematic review of the published literature. Equipment costs were obtained from the manufacturer of the robotic system; other economic model parameters were obtained from government agencies, online resources, commercially available databases, an advisory expert panel, and the literature. Clinical point estimates and care pathways based on National Comprehensive Cancer Network guidelines were used to model costs out to 3 years. Hospital costs and costs incurred for the patients' postdischarge complications, adjuvant and salvage radiation treatment, incontinence and potency treatment, and lost wages during recovery were considered. Robotic system costs were modeled in two ways: as hospital overhead (hospital overhead calculation: RALP-H) and as a function of robotic case volume (robotic amortization calculation: RALP-R). All costs were adjusted to year 2014 US dollars., Results: Because of more favorable clinical outcomes over 3 years, RALP provided hospital ($1094 savings with RALP-H, $341 deficit with RALP-R), payer ($1451), and societal ($1202) economic benefits relative to retropubic radical prostatectomy., Conclusions: Monte-Carlo probabilistic sensitivity analysis demonstrated a 38% to 99% probability that RALP provides cost savings (depending on the perspective). Higher surgical consumable costs are offset by a decreased hospital stay, lower complication rate, and faster return to work., (Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)
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- 2016
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53. Antibiotic prophylaxis and risk of Clostridium difficile infection after coronary artery bypass graft surgery.
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Poeran J, Mazumdar M, Rasul R, Meyer J, Sacks HS, Koll BS, Wallach FR, Moskowitz A, and Gelijns AC
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- Anti-Bacterial Agents administration & dosage, Cephalosporins administration & dosage, Cephalosporins adverse effects, Clostridioides difficile pathogenicity, Clostridium Infections diagnosis, Clostridium Infections epidemiology, Clostridium Infections microbiology, Databases, Factual, Drug Administration Schedule, Drug Therapy, Combination, Humans, Logistic Models, Multivariate Analysis, Odds Ratio, Practice Patterns, Physicians', Prevalence, Retrospective Studies, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, United States, Vancomycin administration & dosage, Vancomycin adverse effects, Anti-Bacterial Agents adverse effects, Antibiotic Prophylaxis adverse effects, Clostridioides difficile drug effects, Clostridium Infections chemically induced, Coronary Artery Bypass
- Abstract
Objective: Antibiotic use, particularly type and duration, is a crucial modifiable risk factor for Clostridium difficile. Cardiac surgery is of particular interest because prophylactic antibiotics are recommended for 48 hours or less (vs ≤24 hours for noncardiac surgery), with increasing vancomycin use. We aimed to study associations between antibiotic prophylaxis (duration/vancomycin use) and C difficile among patients undergoing coronary artery bypass grafting., Methods: We extracted data on coronary artery bypass grafting procedures from the national Premier Perspective claims database (2006-2013, n = 154,200, 233 hospitals). Multilevel multivariable logistic regressions measured associations between (1) duration (<2 days, "standard" vs ≥2 days, "extended") and (2) type of antibiotic used ("cephalosporin," "cephalosporin + vancomycin," "vancomycin") and C difficile as outcome., Results: Overall C difficile prevalence was 0.21% (n = 329). Most patients (59.7%) received a cephalosporin only; in 33.1% vancomycin was added, whereas 7.2% received vancomycin only. Extended prophylaxis was used in 20.9%. In adjusted analyses, extended prophylaxis (vs standard) was associated with significantly increased C difficile risk (odds ratio, 1.43; confidence interval, 1.07-1.92), whereas no significant associations existed for vancomycin use as adjuvant or primary prophylactic compared with the use of cephalosporins (odds ratio, 1.21; confidence interval, 0.92-1.60, and odds ratio, 1.39; confidence interval, 0.94-2.05, respectively). Substantial inter-hospital variation exists in the percentage of extended antibiotic prophylaxis (interquartile range, 2.5-35.7), use of adjuvant vancomycin (interquartile range, 4.2-61.1), and vancomycin alone (interquartile range, 2.3-10.4)., Conclusions: Although extended use of antibiotic prophylaxis was associated with increased C difficile risk after coronary artery bypass grafting, vancomycin use was not. The observed hospital variation in antibiotic prophylaxis practices suggests great potential for efforts aimed at standardizing practices that subsequently could reduce C difficile risk., Competing Interests: Statement Authors have nothing to disclose with regard to commercial support., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)
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- 2016
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54. Correction: Micronutrients in HIV: A Bayesian Meta-Analysis.
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Carter GM, Indyk D, Johnson M, Andreae M, Suslov K, Busani S, Esmaeili A, and Sacks HS
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[This corrects the article DOI: 10.1371/journal.pone.0120113.].
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- 2016
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55. ACP Journal Club. Preexposure tenofovir-emtricitabine reduced HIV infection in men who have unprotected anal sex with men.
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Sacks HS
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- Humans, Male, Anti-HIV Agents therapeutic use, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination therapeutic use, HIV Infections prevention & control, Pre-Exposure Prophylaxis methods, Unsafe Sex
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- 2016
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56. Inhaled Cannabis for Chronic Neuropathic Pain: A Meta-analysis of Individual Patient Data.
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Andreae MH, Carter GM, Shaparin N, Suslov K, Ellis RJ, Ware MA, Abrams DI, Prasad H, Wilsey B, Indyk D, Johnson M, and Sacks HS
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- Administration, Inhalation, Adult, Aged, Bayes Theorem, Chronic Pain epidemiology, Female, Humans, Male, Medical Marijuana administration & dosage, Middle Aged, Pain epidemiology, Peripheral Nervous System Diseases epidemiology, Randomized Controlled Trials as Topic, Young Adult, Cannabis, Chronic Pain drug therapy, Medical Marijuana therapeutic use, Pain drug therapy, Peripheral Nervous System drug effects, Peripheral Nervous System Diseases drug therapy
- Abstract
Unlabelled: Chronic neuropathic pain, the most frequent condition affecting the peripheral nervous system, remains underdiagnosed and difficult to treat. Inhaled cannabis may alleviate chronic neuropathic pain. Our objective was to synthesize the evidence on the use of inhaled cannabis for chronic neuropathic pain. We performed a systematic review and a meta-analysis of individual patient data. We registered our protocol with PROSPERO CRD42011001182. We searched in Cochrane Central, PubMed, EMBASE, and AMED. We considered all randomized controlled trials investigating chronic painful neuropathy and comparing inhaled cannabis with placebo. We pooled treatment effects following a hierarchical random-effects Bayesian responder model for the population-averaged subject-specific effect. Our evidence synthesis of individual patient data from 178 participants with 405 observed responses in 5 randomized controlled trials following patients for days to weeks provides evidence that inhaled cannabis results in short-term reductions in chronic neuropathic pain for 1 in every 5 to 6 patients treated (number needed to treat = 5.6 with a Bayesian 95% credible interval ranging between 3.4 and 14). Our inferences were insensitive to model assumptions, priors, and parameter choices. We caution that the small number of studies and participants, the short follow-up, shortcomings in allocation concealment, and considerable attrition limit the conclusions that can be drawn from the review. The Bayes factor is 332, corresponding to a posterior probability of effect of 99.7%., Perspective: This novel Bayesian meta-analysis of individual patient data from 5 randomized trials suggests that inhaled cannabis may provide short-term relief for 1 in 5 to 6 patients with neuropathic pain. Pragmatic trials are needed to evaluate the long-term benefits and risks of this treatment., (Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.)
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- 2015
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57. ACP Journal Club: review: some TNF inhibitors increase adverse events in patients with rheumatoid arthritis.
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Sacks HS
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- Humans, Antirheumatic Agents adverse effects, Arthritis, Rheumatoid drug therapy, Tumor Necrosis Factor-alpha antagonists & inhibitors
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- 2015
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58. Micronutrients in HIV: a Bayesian meta-analysis.
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Carter GM, Indyk D, Johnson M, Andreae M, Suslov K, Busani S, Esmaeili A, and Sacks HS
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- Bayes Theorem, Dietary Supplements adverse effects, Disease Progression, HIV Infections mortality, Humans, Micronutrients adverse effects, HIV Infections diet therapy, Micronutrients pharmacology
- Abstract
Background: Approximately 28.5 million people living with HIV are eligible for treatment (CD4<500), but currently have no access to antiretroviral therapy. Reduced serum level of micronutrients is common in HIV disease. Micronutrient supplementation (MNS) may mitigate disease progression and mortality., Objectives: We synthesized evidence on the effect of micronutrient supplementation on mortality and rate of disease progression in HIV disease., Methods: We searched MEDLINE, EMBASE, the Cochrane Central, AMED and CINAHL databases through December 2014, without language restriction, for studies of greater than 3 micronutrients versus any or no comparator. We built a hierarchical Bayesian random effects model to synthesize results. Inferences are based on the posterior distribution of the population effects; posterior distributions were approximated by Markov chain Monte Carlo in OpenBugs., Principal Findings: From 2166 initial references, we selected 49 studies for full review and identified eight reporting on disease progression and/or mortality. Bayesian synthesis of data from 2,249 adults in three studies estimated the relative risk of disease progression in subjects on MNS vs. control as 0.62 (95% credible interval, 0.37, 0.96). Median number needed to treat is 8.4 (4.8, 29.9) and the Bayes Factor 53.4. Based on data reporting on 4,095 adults reporting mortality in 7 randomized controlled studies, the RR was 0.84 (0.38, 1.85), NNT is 25 (4.3, ∞)., Conclusions: MNS significantly and substantially slows disease progression in HIV+ adults not on ARV, and possibly reduces mortality. Micronutrient supplements are effective in reducing progression with a posterior probability of 97.9%. Considering MNS low cost and lack of adverse effects, MNS should be standard of care for HIV+ adults not yet on ARV.
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- 2015
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59. Isoniazid prevented active tuberculosis in patients with HIV treated with antiretroviral therapy.
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Sacks HS
- Subjects
- Female, Humans, Male, AIDS-Related Opportunistic Infections prevention & control, Anti-Retroviral Agents therapeutic use, Antitubercular Agents therapeutic use, HIV Infections drug therapy, Isoniazid therapeutic use, Tuberculosis, Pulmonary prevention & control
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- 2014
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60. Epicardial adipose excision slows the progression of porcine coronary atherosclerosis.
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McKenney ML, Schultz KA, Boyd JH, Byrd JP, Alloosh M, Teague SD, Arce-Esquivel AA, Fain JN, Laughlin MH, Sacks HS, and Sturek M
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- Animals, Atherosclerosis diagnosis, Coronary Angiography, Coronary Artery Disease diagnosis, Disease Models, Animal, Disease Progression, Male, Swine, Swine, Miniature, Ultrasonography, Interventional, Adipose Tissue surgery, Atherosclerosis surgery, Cardiac Surgical Procedures methods, Coronary Artery Disease surgery, Pericardium surgery
- Abstract
Background: In humans there is a positive association between epicardial adipose tissue (EAT) volume and coronary atherosclerosis (CAD) burden. We tested the hypothesis that EAT contributes locally to CAD in a pig model., Methods: Ossabaw miniature swine (n=9) were fed an atherogenic diet for 6 months to produce CAD. A 15 mm length by 3-5 mm width coronary EAT (cEAT) resection was performed over the middle segment of the left anterior descending artery (LAD) 15 mm distal to the left main bifurcation. Pigs recovered for 3 months on atherogenic diet. Intravascular ultrasound (IVUS) was performed in the LAD to quantify atheroma immediately after adipectomy and was repeated after recovery before sacrifice. Coronary wall biopsies were stained immunohistochemically for atherosclerosis markers and cytokines and cEAT was assayed for atherosclerosis-related genes by RT-PCR. Total EAT volume was measured by non-contrast CT before each IVUS., Results: Circumferential plaque length increased (p<0.05) in the proximal and distal LAD segments from baseline until sacrifice whereas plaque length in the middle LAD segment underneath the adipectomy site did not increase. T-cadherin, scavenger receptor A and adiponectin were reduced in the intramural middle LAD. Relative to control pigs without CAD, 11β-hydroxysteroid dehydrogenase (11βHSD-1), CCL19, CCL21, prostaglandin D2 synthase, gp91phox [NADPH oxidase], VEGF, VEGFGR1, and angiotensinogen mRNAs were up-regulated in cEAT. EAT volume increased over 3 months., Conclusion: In pigs used as their own controls, resection of cEAT decreased the progression of CAD, suggesting that cEAT may exacerbate coronary atherosclerosis.
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- 2014
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61. Exercise training does not increase muscle FNDC5 protein or mRNA expression in pigs.
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Fain JN, Company JM, Booth FW, Laughlin MH, Padilla J, Jenkins NT, Bahouth SW, and Sacks HS
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- Animals, Citrate (si)-Synthase metabolism, Gene Expression genetics, Male, Muscle Proteins genetics, Muscle Proteins metabolism, Subcutaneous Fat metabolism, Swine genetics, Swine metabolism, Fibronectins genetics, Fibronectins metabolism, Muscle, Skeletal metabolism, Myocardium metabolism, Physical Conditioning, Animal, RNA, Messenger genetics, Swine physiology
- Abstract
Background: Exercise training elevates circulating irisin and induces the expression of the FNDC5 gene in skeletal muscles of mice. Our objective was to determine whether exercise training also increases FNDC5 protein or mRNA expression in the skeletal muscles of pigs as well as plasma irisin., Methods: Castrated male pigs of the Rapacz familial hypercholesterolemic (FHM) strain and normal (Yucatan miniature) pigs were sacrificed after 16-20 weeks of exercise training. Samples of cardiac muscle, deltoid and triceps brachii muscle, subcutaneous and epicardial fat were obtained and FNDC5 mRNA, along with that of 6 other genes, was measured in all tissues of FHM pigs by reverse transcription polymerase chain reaction. FNDC protein in deltoid and triceps brachii was determined by Western blotting in both FHM and normal pigs. Citrate synthase activity was measured in the muscle samples of all pigs as an index of exercise training. Irisin was measured by an ELISA assay., Results: There was no statistically significant effect of exercise training on FNDC5 gene expression in epicardial or subcutaneous fat, deltoid muscle, triceps brachii muscle or heart muscle. Exercise-training elevated circulating levels of irisin in the FHM pigs and citrate synthase activity in deltoid and triceps brachii muscle. A similar increase in citrate synthase activity was seen in muscle extracts of exercise-trained normal pigs but there was no alteration in circulating irisin., Conclusion: Exercise training in pigs does not increase FNDC5 mRNA or protein in the deltoid or triceps brachii of FHM or normal pigs while increasing circulating irisin only in the FHM pigs. These data indicate that the response to exercise training in normal pigs is not comparable to that seen in mice., (Copyright © 2013 Elsevier Inc. All rights reserved.)
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- 2013
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62. Adult epicardial fat exhibits beige features.
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Sacks HS, Fain JN, Bahouth SW, Ojha S, Frontini A, Budge H, Cinti S, and Symonds ME
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- Aged, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Female, Gene Expression, Humans, Ion Channels genetics, Male, Middle Aged, Mitochondrial Proteins genetics, PPAR gamma genetics, PPAR gamma metabolism, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Transcription Factors genetics, Transcription Factors metabolism, Tumor Necrosis Factor Receptor Superfamily, Member 9 genetics, Tumor Necrosis Factor Receptor Superfamily, Member 9 metabolism, Uncoupling Protein 1, Adipose Tissue, Brown metabolism, Intra-Abdominal Fat metabolism, Ion Channels metabolism, Mitochondrial Proteins metabolism, Pericardium metabolism
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Context: Human epicardial fat has been designated previously as brown-like fat. The supraclavicular fat depot in man has been defined as beige coexistent with classical brown based on its gene expression profile., Objective: The aim of the study was to establish the gene expression profile and morphology of human epicardial and visceral paracardial fat compared with sc fat., Setting: The study was conducted at a tertiary care hospital cardiac center., Patients: Epicardial, visceral paracardial, and sc fat samples had been taken from middle-aged patients with severe coronary atherosclerosis or valvular heart disease., Interventions: Gene expression was determined by reverse transcription-quantitative PCR and relative abundance of the mitochondrial uncoupling protein-1 (UCP-1) by Western blotting. Epicardial tissue sections from patients were examined by light microscopy, UCP-1 immunohistochemistry, and cell morphometry., Main Outcome Measures: We hypothesized that epicardial fat has a mixed phenotype with a gene expression profile similar to that described for beige cell lineage., Results: Immunoreactive UCP-1 was clearly measurable in each epicardial sample analyzed but was undetectable in each of the 4 other visceral and sc depots. Epicardial fat exhibited high expression of genes for UCP-1, PRDM16, PGC-1α, PPARγ, and the beige adipocyte-specific marker CD137, which were also expressed in visceral paracardial fat but only weakly in sternal, upper abdominal, and lower extremity sc fat. Histology of epicardial fat showed small unilocular adipocytes without UCP-1 immunostaining., Conclusion: UCP-1 is relatively abundant in epicardial fat, and this depot possesses molecular features characteristic of those found in vitro in beige lineage adipocytes.
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- 2013
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63. ACP Journal Club. Adding procalcitonin-guided therapy to standard care did not reduce mortality in critically ill patients.
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Sacks HS
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- 2012
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64. Depot-specific overexpression of proinflammatory, redox, endothelial cell, and angiogenic genes in epicardial fat adjacent to severe stable coronary atherosclerosis.
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Sacks HS, Fain JN, Cheema P, Bahouth SW, Garrett E, Wolf RY, Wolford D, and Samaha J
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- Adipose Tissue pathology, Aged, Angiogenesis Inducing Agents metabolism, Case-Control Studies, Coronary Artery Disease metabolism, Coronary Artery Disease pathology, Disease Progression, Endothelial Cells pathology, Female, Gene Expression Regulation, Humans, Inflammation metabolism, Inflammation Mediators metabolism, Male, Middle Aged, Oxidation-Reduction, Severity of Illness Index, Up-Regulation genetics, Adipose Tissue metabolism, Coronary Artery Disease genetics, Endothelial Cells metabolism, Inflammation genetics, Neovascularization, Physiologic genetics, Pericardium metabolism
- Abstract
Background: Pro- and antiinflammatory genes are expressed in epicardial adipose tissue (EAT). Our objectives were to characterize genes in EAT that may contribute specifically to coronary atherogenesis and to measure circulating adipokines matched to their messenger RNAs (mRNAs) in EAT. We hypothesized that severe coronary atherosclerosis (CAD) would preferentially affect gene expression in EAT as compared to substernal fat or subcutaneous thoracic adipose tissue (SAT), as well as circulating levels of adipokines., Methods: Fat mRNA was quantified using reverse transcription polymerase chain reaction (RT-PCR), and circulating adipokines were measured by enzyme-linked immunosorbent assays (ELISAs) in patients with severe stable CAD and controls without severe CAD undergoing open heart surgery., Results: A total of 39 of 70 mRNAs in EAT were significantly increased in CAD. Only 4 and 3 of these mRNAs were increased in substernal fat and SAT, respectively. Of the mRNAs increased in EAT, 17 were either inflammatory adipokines or proteins known to be involved in inflammatory processes, 7 were involved in oxidative stress and or oxygen species regulation, whereas 15 were proteins involved in metabolism and regulation of gene transcription or proteins unique to fat cells. The largest increases, over three-fold, were seen in GPX3, gp91 phox, p47phox, heme oxygenase, and interleukin-8 (IL-8). Tpl2 mRNA was uniquely elevated in all three fat depots from CAD patients, and its expression in SAT, but not in EAT or substernal fat, was directly correlated with homeostasis model assessment of insulin resistance (HOMA-IR) values. Compared to controls, there were no associations between circulating levels of IL-8, lipocalin-2, nerve growth factor (NGF), RANTES, CD-163, GPX-3, monocyte chemotactic protein-1 (MCP-1)/CCL2, leptin, soluble vascular endothelial growth factor receptor-1 (sFLT1), fatty acid binding protein-4 (FABP-4), and plasminogen activator inhibitor-1 (PAI-1) and increases in their gene expression in EAT adjacent to CAD., Conclusions: Expression of proinflammatory, redox, endothelial cell, and angiogenic genes in EAT is depot specific and supports the hypothesis that pathophysiologically EAT contributes locally to CAD. CAD links with these fat depots might involve Tpl2 as a primary response indicator.
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- 2011
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65. Human epicardial fat: what is new and what is missing?
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Sacks HS and Fain JN
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- Adipokines metabolism, Adipose Tissue diagnostic imaging, Adipose Tissue metabolism, Animals, Body Temperature Regulation physiology, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease immunology, Coronary Artery Disease metabolism, Coronary Artery Disease physiopathology, Coronary Vessels immunology, Coronary Vessels metabolism, Coronary Vessels physiology, Female, Heart diagnostic imaging, Heart innervation, Heart physiology, Humans, Male, Mice, Obesity metabolism, Obesity physiopathology, Pericardium diagnostic imaging, Pericardium metabolism, Radiography, Rats, Weight Loss physiology, Adipose Tissue physiology, Pericardium physiology
- Abstract
1. Putative physiological functions of human epicardial adipose tissue (EAT) include: (i) lipid storage for the energy needs of the myocardium; (ii) thermoregulation, whereby brown fat components of EAT generate heat by non-shivering thermogenesis in response to core cooling; (iii) neuroprotection of the cardiac autonomic ganglia and nerves; and (iv) regulation of vasomotion and luminal size of the coronary arteries. Under pathophysiological circumstances, EAT may play an adverse paracrine role in cardiac arrhythmias and in lipotoxic cardiomyopathy, but of major current interest is its hypothetical role as an immunological organ contributing to inflammation around coronary artery disease (CAD). 2. The amount of EAT measured either by echocardiographic thickness over the free wall of the right ventricle or as volume by computed tomography expands in patients with obesity both without and with CAD. The mechanisms other than obesity governing the increase in EAT volume in CAD are unknown, but EAT around CAD is infiltrated by chronic inflammatory cells and overexpresses genes for adipokines that have pro- or anti-inflammatory actions and regulate oxidative stress plus angiogenesis. 3. Many cross-sectional studies have shown positive associations between increased EAT mass and stable CAD burden. One prospective population-based epidemiological study suggested that EAT volume at baseline is a predictor of acute myocardial infarction, but was without significant incremental predictive value after adjustment for established cardiovascular risk factors. However, strategies are needed to obtain robust epidemiological, interventional and experimental evidence to prove or disprove the hypothesis that EAT is a cardiovascular risk factor locally contributing to CAD., (© 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.)
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- 2011
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66. ACP Journal Club. Influenza vaccination reduced cardiovascular events in patients hospitalized with an acute coronary syndrome.
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Sacks HS
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- Female, Humans, Male, Acute Coronary Syndrome prevention & control, Influenza Vaccines administration & dosage, Influenza, Human prevention & control
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- 2011
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67. Response to Dr. Reich's letter: "'Sarcoid-like' granulomatous pulmonary disease in world trade center disaster responders: influence of incidence computation methodology in inferring airborne dust causation": "Sarcoid-like" granulomatous pulmonary disease in World Trade Center disaster responders.
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Crowley LE, Herbert R, Moline JM, Wallenstein S, Shukla G, Schechter C, Skloot GS, Udasin I, Luft BJ, Harrison D, Shapiro M, Wong K, Sacks HS, Teirstein AS, and Landrigan PJ
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- History, 21st Century, Humans, Incidence, Lung Diseases epidemiology, United States epidemiology, Air Pollutants, Occupational adverse effects, Dust, Lung Diseases etiology, Occupational Exposure adverse effects, Relief Work history, September 11 Terrorist Attacks history
- Published
- 2011
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68. De minimis risk: a proposal for a new category of research risk.
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Rhodes R, Azzouni J, Baumrin SB, Benkov K, Blaser MJ, Brenner B, Dauben JW, Earle WJ, Frank L, Gligorov N, Goldfarb J, Hirschhorn K, Hirschhorn R, Holzman I, Indyk D, Jabs EW, Lackey DP, Moros DA, Philpott S, Rhodes ME, Richardson LD, Sacks HS, Schwab A, Sperling R, Trusko B, and Zweig A
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- Ethics, Research, Humans, Mental Competency, Quality Assurance, Health Care ethics, Quality Assurance, Health Care legislation & jurisprudence, Quality Improvement ethics, Quality Improvement legislation & jurisprudence, Tissue Banks legislation & jurisprudence, United States, Informed Consent ethics, Research legislation & jurisprudence, Research Subjects, Risk, Specimen Handling ethics, Tissue Banks ethics
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- 2011
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69. ACP Journal Club. Dexamethasone reduced length of hospital stay in patients with community-acquired pneumonia.
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Sacks HS
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- 2011
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70. "Sarcoid like" granulomatous pulmonary disease in World Trade Center disaster responders.
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Crowley LE, Herbert R, Moline JM, Wallenstein S, Shukla G, Schechter C, Skloot GS, Udasin I, Luft BJ, Harrison D, Shapiro M, Wong K, Sacks HS, Landrigan PJ, and Teirstein AS
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- Adolescent, Adult, Aged, Aged, 80 and over, Case-Control Studies, Female, Health Surveys, Humans, Incidence, Male, Middle Aged, Occupational Diseases etiology, Occupational Diseases pathology, Respiratory Function Tests, Risk Factors, Sarcoidosis, Pulmonary etiology, Sarcoidosis, Pulmonary pathology, Surveys and Questionnaires, United States epidemiology, Young Adult, Lung pathology, Occupational Diseases epidemiology, Occupational Exposure adverse effects, Rescue Work, Sarcoidosis, Pulmonary epidemiology, September 11 Terrorist Attacks statistics & numerical data
- Abstract
Background: More than 20,000 responders have been examined through the World Trade Center (WTC) Medical Monitoring and Treatment Program since September 11, 2001. Studies on WTC firefighters have shown elevated rates of sarcoidosis. The main objective of this study was to report the incidence of "sarcoid like" granulomatous pulmonary disease in other WTC responders., Methods: Cases of sarcoid like granulomatous pulmonary disease were identified by: patient self-report, physician report and ICD-9 codes. Each case was evaluated by three pulmonologists using the ACCESS criteria and only "definite" cases are reported., Results: Thirty-eight patients were classified as "definite" cases. Six-year incidence was 192/100,000. The peak annual incidence of 54 per 100,000 person-years occurred between 9/11/2003 and 9/11/2004. Incidence in black responders was nearly double that of white responders. Low FVC was the most common spirometric abnormality., Conclusions: Sarcoid like granulomatous pulmonary disease is present among the WTC responders. While the incidence is lower than that reported among firefighters, it is higher than expected., (Copyright © 2010 Wiley-Liss, Inc.)
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- 2011
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71. Epicardial fat gene expression after aerobic exercise training in pigs with coronary atherosclerosis: relationship to visceral and subcutaneous fat.
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Company JM, Booth FW, Laughlin MH, Arce-Esquivel AA, Sacks HS, Bahouth SW, and Fain JN
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- Adipokines genetics, Animals, Castration, Coronary Artery Disease pathology, Coronary Artery Disease physiopathology, Disease Models, Animal, Gene Expression Regulation, Hyperlipoproteinemia Type II pathology, Hyperlipoproteinemia Type II physiopathology, Inflammation pathology, Inflammation physiopathology, Inflammation prevention & control, Inflammation Mediators metabolism, Intra-Abdominal Fat metabolism, Male, Oxidative Stress genetics, Pericardium, Polymerase Chain Reaction, RNA, Messenger metabolism, Subcutaneous Fat metabolism, Swine, Adiposity genetics, Coronary Artery Disease genetics, Hyperlipoproteinemia Type II genetics, Inflammation genetics, Intra-Abdominal Fat physiopathology, Physical Exertion, Subcutaneous Fat physiopathology
- Abstract
Epicardial adipose tissue (EAT) is contiguous with coronary arteries and myocardium and potentially may play a role in coronary atherosclerosis (CAD). Exercise is known to improve cardiovascular disease risk factors. The purpose of this study was to investigate the effect of aerobic exercise training on the expression of 18 genes, measured by RT-PCR and selected for their role in chronic inflammation, oxidative stress, and adipocyte metabolism, in peri-coronary epicardial (cEAT), peri-myocardial epicardial (mEAT), visceral abdominal (VAT), and subcutaneous (SAT) adipose tissues from a castrate male pig model of familial hypercholesterolemia with CAD. We tested the hypothesis that aerobic exercise training for 16 wk would reduce the inflammatory profile of mRNAs in both components of EAT and VAT but would have little effect on SAT. Exercise increased mEAT and total heart weights. EAT and heart weights were directly correlated. Compared with sedentary pigs matched for body weight to exercised animals, aerobic exercise training reduced the inflammatory response in mEAT but not cEAT, had no effect on inflammatory genes but preferentially decreased expression of adiponectin and other adipocyte-specific genes in VAT, and had no effect in SAT except that IL-6 mRNA went down and VEGFa mRNA went up. We conclude that 1) EAT is not homogeneous in its inflammatory response to aerobic exercise training, 2) cEAT around CAD remains proinflammatory after chronic exercise, 3) cEAT and VAT share similar inflammatory expression profiles but different metabolic mRNA responses to exercise, and 4) gene expression in SAT cannot be extrapolated to VAT and heart adipose tissues in exercise intervention studies.
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- 2010
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72. Human epicardial adipokine messenger RNAs: comparisons of their expression in substernal, subcutaneous, and omental fat.
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Fain JN, Sacks HS, Bahouth SW, Tichansky DS, Madan AK, and Cheema PS
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- Adipokines genetics, Adipose Tissue chemistry, Adult, Female, Humans, Obesity, Morbid genetics, RNA, Messenger analysis, RNA, Messenger genetics, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, Tissue Distribution, Adipokines metabolism, Adipose Tissue metabolism, Gene Expression, Obesity, Morbid metabolism
- Abstract
We compared the gene expression of inflammatory and other proteins by real-time quantitative polymerase chain reaction in epicardial, substernal (mediastinal) and subcutaneous sternal, upper abdominal, and leg fat from coronary bypass patients and omental (visceral) fat from extremely obese women undergoing bariatric surgery. We hypothesized that (1) epicardial fat would exhibit higher expression of inflammatory messenger RNAs (mRNAs) than substernal and subcutaneous fat and (2) epicardial mRNAs would be similar to those in omental fat. Epicardial fat was clearly different from substernal fat because there was a far higher expression of haptoglobin, prostaglandin D(2) synthase, nerve growth factor beta, the soluble vascular endothelial growth factor receptor (FLT1), and alpha1 glycoprotein but not of inflammatory adipokines such as monocyte chemoattractant protein-1, interleukin (IL)-8, IL-1beta, tumor necrosis factor alpha, serum amyloid A, plasminogen activator inhibitor-1, or adiponectin despite underlying coronary atherosclerosis. However, the latter inflammatory adipokines as well as most other mRNAs were overexpressed in epicardial fat as compared with the subcutaneous depots except for IL-8, fatty acid binding protein 4, the angiotensin II receptor 1, IL-6, and superoxide dismutase-2. Relative to omental fat, about one third of the genes were expressed at the same levels, whereas monocyte chemoattractant protein-1, cyclooxygenase-2, plasminogen activator inhibitor-1, IL-1beta, and IL-6 were expressed at far lower levels in epicardial fat. In conclusion, epicardial fat does not appear to be a potentially more important source of inflammatory adipokines than substernal mediastinal fat. Furthermore, the expression of inflammatory cytokines such as IL-6 and IL-1beta is actually higher in omental fat from obese women without coronary atherosclerosis. The data do not support the hypothesis that most of the inflammatory adipokines are expressed at high levels in epicardial fat of humans., (Copyright 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
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73. Uncoupling protein-1 and related messenger ribonucleic acids in human epicardial and other adipose tissues: epicardial fat functioning as brown fat.
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Sacks HS, Fain JN, Holman B, Cheema P, Chary A, Parks F, Karas J, Optican R, Bahouth SW, Garrett E, Wolf RY, Carter RA, Robbins T, Wolford D, and Samaha J
- Subjects
- Aged, Coronary Artery Disease metabolism, Diabetes Mellitus drug therapy, Diabetes Mellitus metabolism, Female, Humans, Male, Middle Aged, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, RNA, Messenger analysis, Uncoupling Protein 1, Adipose Tissue metabolism, Adipose Tissue, Brown metabolism, DNA-Binding Proteins genetics, Heat-Shock Proteins genetics, Ion Channels genetics, Mitochondrial Proteins genetics, Pericardium metabolism, Transcription Factors genetics
- Abstract
Context: Uncoupling protein-1 (UCP-1) is the inner mitochondrial membrane protein that is a specific marker for and mediator of nonshivering thermogenesis in brown adipocytes., Objective: This study was performed to better understand the putative thermogenic function of human epicardial fat., Design: We measured the expression of UCP-1 and brown adipocyte differentiation transcription factors PR-domain-missing 16 (PRDM16) and peroxisome-proliferator-activated receptor gamma co-activator-1 alpha (PGC-1 alpha) in epicardial, substernal, and sc thoracic, abdominal, and leg fat., Setting: The study was conducted at a tertiary care hospital cardiac center., Patients: Forty-four patients had coronary artery bypass surgery, and six had heart valve replacement., Interventions: Fat samples were taken at open heart surgery., Results: UCP-1 expression was 5-fold higher in epicardial fat than substernal fat and barely detectable in sc fat. Epicardial fat UCP-1 expression decreased with age, increased with body mass index, was similar in women and men and patients on and not on statin therapy, and showed no relationship to epicardial fat volume or waist circumference. UCP-1 expression was similar in patients without and with severe coronary atherosclerosis and metabolic syndrome or type 2 diabetes. PRDM16 and PGC-1 alpha expression was 2-fold greater in epicardial than sc fat. Epicardial fat UCP-1, PRDM16, and PGC1-alpha mRNAs were similar in diabetics treated with thiazolidinediones compared to diabetics not treated with thiazolidinediones., Conclusion: Because UCP-1 is expressed at high levels in epicardial fat as compared to other fat depots, the possibility should be considered that epicardial fat functions like brown fat to defend the myocardium and coronary vessels against hypothermia. This process could be blunted in the elderly.
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- 2009
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74. Weight loss in obesity reduces epicardial fat thickness; so what?
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Sacks HS
- Subjects
- Adipose Tissue diagnostic imaging, Coronary Angiography, Echocardiography, Heart Ventricles pathology, Humans, Intra-Abdominal Fat pathology, Magnetic Resonance Angiography, Obesity pathology, Obesity physiopathology, Pericardium diagnostic imaging, Subcutaneous Fat pathology, Tomography, X-Ray Computed, Treatment Outcome, Adipose Tissue pathology, Exercise Therapy, Obesity therapy, Pericardium pathology, Weight Loss
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- 2009
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75. Identification of omentin mRNA in human epicardial adipose tissue: comparison to omentin in subcutaneous, internal mammary artery periadventitial and visceral abdominal depots.
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Fain JN, Sacks HS, Buehrer B, Bahouth SW, Garrett E, Wolf RY, Carter RA, Tichansky DS, and Madan AK
- Subjects
- Biomarkers analysis, Female, GPI-Linked Proteins, Humans, Male, Mammary Arteries chemistry, Middle Aged, Pericardium chemistry, Adipose Tissue chemistry, Cytokines analysis, Lectins analysis, Nicotinamide Phosphoribosyltransferase analysis, RNA, Messenger analysis
- Abstract
Objective: The purpose of this study was to determine the relative distribution of omentin and visfatin mRNA in human epicardial, peri-internal mammary, upper thoracic, upper abdominal and leg vein subcutaneous adipose tissue as well as the distribution of omentin in the nonfat cells and adipocytes of human omental adipose tissue., Background: Omentin is found in human omentum but not subcutaneous fat. Omentin and visfatin are considered markers of visceral abdominal fat., Research Design and Methods: The mRNA content of omentin and visfatin was measured by qRT-PCR analysis of fat samples removed from humans undergoing cardiac or bariatric surgery., Results: Omentin mRNA in internal mammary fat was 3.5%, that in the upper thoracic subcutaneous fat was 4.7% while that in the other subcutaneous fat depots was less than 1% of omentin in epicardial fat. The distribution of visfatin mRNA did not vary between the five depots. Omentin mRNA was preferentially expressed in the nonfat cells of omental adipose tissue since the omentin mRNA content of isolated adipocytes was 9% of that in nonfat cells, and similar results were seen for visfatin. The amount of omentin mRNA in differentiated adipocytes was 0.3% and that of visfatin 4% of that in nonfat cells. The amount of omentin mRNA in preadipocytes was virtually undetectable while that of visfatin was 3% of that in freshly isolated nonfat cells from omental adipose tissue., Conclusion: Omentin mRNA is predominantly found in epicardial and omental human fat whereas visfatin mRNA is found to the same extent in epicardial, subcutaneous and omental fat.
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- 2008
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76. Human epicardial adipose tissue: a review.
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Sacks HS and Fain JN
- Subjects
- Adiponectin metabolism, Adipose Tissue diagnostic imaging, Adipose Tissue pathology, Aged, Animals, Disease Models, Animal, Female, Humans, Male, Pericardium diagnostic imaging, Pericardium pathology, Radiography, Adipose Tissue metabolism, Coronary Artery Disease etiology, Coronary Artery Disease metabolism, Obesity complications, Pericardium metabolism
- Abstract
We discuss the anatomy, physiology, and pathophysiology of epicardial adipose tissue and its relationship to coronary atherosclerosis. Epicardial fat stores triglyceride to supply free fatty acids for myocardial energy production and produces adipokines. It shares a common embryological origin with mesenteric and omental fat. Like visceral abdominal fat, epicardial fat thickness, measured by echocardiography, is increased in obesity. Epicardial fat could influence coronary atherogenesis and myocardial function because there is no fibrous fascial layer to impede diffusion of free fatty acids and adipokines between it and the underlying vessel wall as well as the myocardium. Segments of coronary arteries lacking epicardial fat or separated from it by a bridge of myocardial tissue are protected against the development of atherosclerosis in those segments. However, when epicardial fat is totally absent in congenital generalized lipodystrophy, coronary atherosclerosis can still occur. Macrophages are more numerous and densely packed in the periadventitial fat of human atherosclerotic coronary arteries with lipid cores than in that of fibrocalcific or nonatherosclerotic coronary arteries. In obese patients with multiple cardiovascular risk factors, epicardial fat around atheromatous coronaries secretes several proinflammatory cytokines and is infiltrated by macrophages, lymphocytes, and basophils. Epicardial adipokine expression in obesity without coronary atherosclerosis has not been determined. In nonobese patients, epicardial fat around atheromatous coronary arteries expresses proinflammatory cytokines but produces either less adiponectin, a vasoprotective adipokine, than fat around nonatheromatous coronaries or a similar amount compared with thoracic subcutaneous fat. Further studies should be done to test the hypothesis that adipokines produced by and released from human epicardial adipose tissue might contribute locally to the pathogenesis of coronary atherosclerosis.
- Published
- 2007
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77. Aging and HIV infection.
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Kohli R, Klein RS, Schoenbaum EE, Anastos K, Minkoff H, and Sacks HS
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- Aging psychology, Anti-Retroviral Agents therapeutic use, Endocrine System Diseases etiology, Humans, Mental Disorders complications, Metabolic Diseases etiology, Middle Aged, Risk-Taking, Aging physiology, HIV Infections complications, HIV Infections diagnosis, HIV Infections drug therapy
- Abstract
With the advent of highly active antiretroviral therapy (HAART) in mid-1995, the prognosis for HIV-infected individuals has brightened dramatically. However, the conjunction of potent antiviral therapy and longer life expectancy may engender a variety of health risks that, heretofore, HIV specialists have not had to confront. The long-term effects of HIV infection itself and exposure to antiretroviral agents is unknown. Several aspects of aging, including psychiatric disease, neurocognitive impairment, and metabolic and hormonal disorders, may be influenced by chronic exposure to HIV and/or HIV therapeutics. In this paper, we discuss the health issues confronting HIV-infected older adults and areas for future research.
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- 2006
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78. Validity of clinical prediction rules for isolating inpatients with suspected tuberculosis. A systematic review.
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Wisnivesky JP, Serebrisky D, Moore C, Sacks HS, Iannuzzi MC, and McGinn T
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- Humans, Odds Ratio, Predictive Value of Tests, Radiography, Thoracic, Reproducibility of Results, Tuberculosis diagnosis, Tuberculosis therapy
- Abstract
Objective: Declining rates of tuberculosis (TB) in the United States has resulted in a low prevalence of the disease among patients placed on respiratory isolation. The purpose of this study is to systematically review decision rules to predict the patient's risk for active pulmonary TB at the time of admission to the hospital., Data Sources: We searched MEDLINE (1975 to 2003) supplemented by reference tracking. We included studies that reported the sensitivity and specificity of clinical variables for predicting pulmonary TB, used Mycobacterium TB culture as the reference standard, and included at least 50 patients., Review Method: Two reviewers independently assessed study quality and abstracted data regarding the sensitivity and specificity of the prediction rules., Results: Nine studies met inclusion criteria. These studies included 2,194 participants. Most studies found that the presence of TB risk factors, chronic symptoms, positive tuberculin skin test (TST), fever, and upper lobe abnormalities on chest radiograph were associated with TB. Positive TST and a chest radiograph consistent with TB were the predictors showing the strongest association with TB (odds ratio: 5.7 to 13.2 and 2.9 to 31.7, respectively). The sensitivity of the prediction rules for identifying patients with active pulmonary TB varied from 81% to 100%; specificity ranged from 19% to 84%., Conclusions: Our analysis suggests that clinicians can use prediction rules to identify patients with very low risk of infection among those suspected for TB on admission to the hospital, and thus reduce isolation of patients without TB.
- Published
- 2005
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79. Cancer risk among participants in the women's interagency HIV study.
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Hessol NA, Seaberg EC, Preston-Martin S, Massad LS, Sacks HS, Silver S, Melnick S, Abulafia O, and Levine AM
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- Adult, Anti-HIV Agents therapeutic use, Antiretroviral Therapy, Highly Active, Drug Therapy, Combination, Female, HIV Infections drug therapy, Humans, Incidence, Lung Neoplasms epidemiology, Lung Neoplasms etiology, Lymphoma, Non-Hodgkin epidemiology, Lymphoma, Non-Hodgkin etiology, Middle Aged, Population Surveillance, Risk Factors, Sarcoma, Kaposi epidemiology, Sarcoma, Kaposi etiology, Surveys and Questionnaires, United States epidemiology, HIV Infections complications, Neoplasms epidemiology, Neoplasms etiology
- Abstract
Background: The HIV epidemic has been associated with an increased incidence of specific cancers. However, less is known about cancers occurring in HIV-infected women than men., Methods: To determine the risk of cancer among HIV-infected and at-risk HIV-uninfected women, cancer incidence data from the Women's Interagency HIV Study (WIHS) were compared with data from the population-based United States Surveillance, Epidemiology, and End Results (SEER) registry. Age- and race-adjusted standardized incidence ratios (SIRs) were computed and exact statistical tests were used to measure significance., Results: Among the 1950 women participants (1554 HIV infected, 391 HIV uninfected, and 5 HIV seroconverters), 48 cancers were diagnosed during study follow-up. Among HIV-infected women, significantly (P < 0.05) increased incidence rates were observed for all cancer types (SIR = 1.9), Kaposi sarcoma (SIR = 213.5), non-Hodgkin lymphoma (NHL) (SIR = 19.0), and lung cancer (SIR = 6.3) when compared with SEER rates. Lung cancer incidence was also elevated (P = 0.07) among the HIV-uninfected women (SIR = 6.9), when compared with SEER rates, and was similar to the SIR for HIV-infected women. While the incidence rate of NHL among HIV-infected women was significantly lower during the era of highly active antiretroviral therapy (HAART) compared with the pre-HAART era (relative risk = 0.15, P = 0.005), the incidence of NHL among HIV-infected WIHS participants remained significantly higher than in the US population (SIR = 6.4, 95% CI = 1.3-15.5)., Conclusion: In the HAART era, the higher rates of cancer among HIV-infected women, coupled with increased life expectancy, should lead to more intensive cancer screening and prevention efforts in this population.
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- 2004
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80. An evaluation of antiretroviral HIV/AIDS treatment in a Rio de Janeiro public clinic.
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Carmody ER, Diaz T, Starling P, dos Santos AP, and Sacks HS
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- Adult, Age Distribution, Aged, Antiretroviral Therapy, Highly Active, Brazil, CD4 Lymphocyte Count, Drug Monitoring standards, Female, Guideline Adherence, HIV Infections immunology, HIV Infections virology, Humans, Logistic Models, Male, Middle Aged, Patient Compliance, Pilot Projects, Practice Guidelines as Topic, Program Evaluation, Public Health Administration standards, Retrospective Studies, Viral Load, Ambulatory Care Facilities standards, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, Quality of Health Care
- Abstract
The Brazilian public health system has implemented free, universal access to antiretroviral (ARV) therapy for HIV-infected patients. To evaluate this system, we performed a pilot study to determine whether ARVs were prescribed according to Brazilian guidelines in place in 2000, and whether prescriptions were refilled in a timely manner. Year 2000 data were abstracted from all medical and pharmacy records of adult patients first registered for HIV/AIDS care in a Rio de Janeiro public clinic from January to June 2000 (n = 67). Results were analysed using frequency analyses, chi-square tests and logistic regression. The patient sample was 41.8% female and had a mean age of 34.9 years. 54 (81%) had AIDS; total sample mean baseline CD4+/viral counts were 276 cells/mm3 and 237 517 copies per millilitre, respectively. Delays between clinic request and receipt of first CD4+/viral load results ranged from 25 to 107 (mean 66) and 33 to 139 (mean 86) days, respectively. Fifty-nine patients (88.1%) were prescribed ARV treatment. Forty-two regimens (71.2%) were highly active antiretroviral therapies; 17 (28.8%) were combination regimens with two nucleoside reverse transcriptase inhibitors. No combinations were prescribed that were contraindicated in Brazilian guidelines, however 33 patients (55.9%) were prescribed ARV drugs before one or both HIV status parameters (initial CD4+ level or viral load) were recorded. Fourteen patients prescribed ARVs (23.7%) lacked a supply of medication for >1 month during the year at least once. Of these patients, 11 had treatment lapses as a result of failure to pick up medications, and three lacked medication because of drug shortages. Medication lapses were associated with female sex, being hospitalized in 2000, and having more than two drugs in regimen, but were not associated with age, CD4+ level or use of ARVs before 2000. The results from this pilot study suggest conservative prescription of HAART, high practitioner adherence to guidelines, and some problems with refilling medications in a timely manner. Monitoring delays were identified as a structural limitation to optimal adherence to practice guidelines. Better access to monitoring-laboratory facilities and greater drug availability would improve programme success.
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- 2003
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81. Adherence to antiretroviral therapy and its association with sexual behavior in a national sample of women with human immunodeficiency virus.
- Author
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Wilson TE, Barrón Y, Cohen M, Richardson J, Greenblatt R, Sacks HS, and Young M
- Subjects
- Adult, Cohort Studies, Female, HIV Infections physiopathology, HIV-1, Humans, Antiretroviral Therapy, Highly Active psychology, HIV Infections psychology, Sexual Behavior physiology
- Abstract
To delineate the relationship between adherence to human immunodeficiency virus (HIV) therapy and sexual behavior among HIV type 1-infected women in the United States, data were collected from October 1998 through March 1999 from 766 HIV-positive women on adherence to therapy, risk behavior, and disease markers. Adherence rates of >/=95% were reported by 66% of the patients. In multivariate analyses, patients with lower rates of adherence tended to be younger (odds ratio [OR], 1.69), to be active drug users (OR, 2.27), to have detectable virus load levels (OR, 2.00), and to have a lower quality of life (OR, 1.20). Among sexually active women, lower adherence rates were associated with an increased risk for inconsistent condom use (adjusted OR, 2.17). Although counseling regarding sexual behavior and adherence to treatment regimens are often addressed separately, our data highlight the importance of discussing these factors in relation to one another, particularly with regard to patients experiencing virologic failure.
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- 2002
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82. Outpatient treatment of deep venous thrombosis in diverse inner-city patients.
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Dunn AS, Schechter C, Gotlin A, Vomvolakis D, Jacobs E, Sacks HS, and Coller B
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- Adult, Aged, Aged, 80 and over, Anticoagulants adverse effects, Comorbidity, Costs and Cost Analysis, Female, Gastrointestinal Hemorrhage chemically induced, Heparin adverse effects, Humans, Insurance, Health, Length of Stay, Male, Middle Aged, Warfarin adverse effects, Warfarin therapeutic use, Ambulatory Care methods, Anticoagulants therapeutic use, Heparin therapeutic use, Urban Population, Venous Thrombosis drug therapy
- Abstract
Purpose: We sought to describe the development and outcomes of a hospital-based program designed to provide safe and effective outpatient treatment to a diverse group of patients with acute deep venous thrombosis., Methods: Patients enrolled in the program were usually discharged on the day of or the day after presentation. Low- molecular-weight heparin was administered for a minimum of 5 days and warfarin was given for a minimum of 3 months. The hospital provided low-molecular-weight heparin free of charge to patients. Patients received daily home nursing visits to monitor the prothrombin time, assess compliance, and detect complications. The inpatient and outpatient records of the first 89 consecutive patients enrolled in the program were reviewed. Patients were observed for a 3-month period after enrollment., Results: The median length of stay was 1 day. Low-molecular-weight heparin was administered for a mean (+/- standard deviation [SD]) of 4.7 +/- 2.4 days at home. Recurrent thromboembolism was noted in 1 patient (1%), major bleeding in 2 patients (2%), and minor bleeding in 2 patients (2%). No patients died or developed thrombocytopenia. Assuming that patients would have been hospitalized for the duration of treatment with low-molecular-weight heparin, the program eliminated a mean of 4.7 days of hospitalization, with an estimated reduction of $1,645 in total health care costs per patient., Conclusion: This hospital-based program to provide outpatient treatment of deep venous thrombosis to a diverse group of inner-city patients achieved a low incidence of adverse events and substantial health care cost savings. Specific strategies, including providing low-molecular-weight heparin free of charge and daily home nursing visits, can be utilized to facilitate access to outpatient treatment and ensure high-quality care.
- Published
- 2001
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83. Leukocyte-reduced red blood cell transfusions in patients with anemia and human immunodeficiency virus infection: the Viral Activation Transfusion Study: a randomized controlled trial.
- Author
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Collier AC, Kalish LA, Busch MP, Gernsheimer T, Assmann SF, Lane TA, Asmuth DM, Lederman MM, Murphy EL, Kumar P, Kelley M, Flanigan TP, McMahon DK, Sacks HS, Kennedy MS, and Holland PV
- Subjects
- AIDS-Related Opportunistic Infections complications, AIDS-Related Opportunistic Infections immunology, Adult, Anemia immunology, CD4 Lymphocyte Count, Cytokines blood, Cytomegalovirus genetics, Cytomegalovirus Infections complications, Cytomegalovirus Infections immunology, DNA, Viral analysis, Double-Blind Method, Female, HIV Infections physiopathology, Humans, Leukocytes, Lymphocyte Subsets, Male, Prospective Studies, Survival Analysis, Viral Load, Virus Activation, Anemia complications, Anemia therapy, Erythrocyte Transfusion methods, HIV Infections complications, HIV Infections immunology
- Abstract
Context: Allogeneic blood transfusions have immunomodulatory effects and have been associated with activation of human immunodeficiency virus (HIV) and cytomegalovirus (CMV) in vitro and of HIV in small pilot studies. Retrospective studies suggest that transfusions adversely affect the clinical course of HIV. Data in selected non-HIV-infected patients requiring blood transfusion have suggested clinical benefit with leukocyte-reduced red blood cells (RBCs)., Objective: To compare the effects of leukoreduced and unmodified RBC transfusions on survival, complications of acquired immunodeficiency syndrome, and relevant laboratory markers in HIV-infected patients., Design and Setting: Double-blind randomized controlled trial conducted in 11 US academic medical centers from July 1995 through June 1999, with a median follow-up of 12 months (24 months in survivors)., Patients: A total of 531 persons infected with HIV and CMV, aged 14 years or older, who required transfusions for anemia; 259 received leukoreduced transfusions and 262 received unmodified transfusions (10 did not receive the planned transfusion)., Main Outcome Measures: Survival and change in plasma HIV RNA level 7 days after transfusion, compared by type of transfusion., Results: At entry, the groups were similar in demographic, clinical, and relevant laboratory characteristics. A total of 3864 RBC units were transfused. Two hundred eighty-nine deaths occurred (151 with leukoreduced transfusion; 138 with unmodified transfusion); median survival was 13.0 and 20.5 months, respectively (relative hazard [RH], 1.20; 95% confidence interval [CI], 0.95-1.51; log-rank P =.12). Analyses adjusted for prognostic factors suggested possible worse survival with leukoreduction (RH, 1.35; 95% CI, 1.06-1.72). There was no difference in time to new opportunistic event/death or frequency of transfusion reactions. No changes in plasma HIV RNA level were seen in either group at days 7, 14, 21, or 28, even in patients not taking antiretroviral drugs. There were no differences in trends between groups in CMV DNA, CD4 cell counts, activated (CD38% or human leukocyte antigen-DR) CD8 cell counts, or plasma cytokine levels., Conclusions: We found no evidence of HIV, CMV, or cytokine activation following blood transfusion in patients with advanced HIV infection. Leukoreduction provided no clinical benefit in these patients. These data demonstrate the importance of conducting controlled studies of effects of leukoreduction in different patient populations, since smaller studies in other patient populations have suggested leukoreduction may be beneficial.
- Published
- 2001
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84. Preferential suppression of CXCR4-specific strains of HIV-1 by antiviral therapy.
- Author
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Philpott S, Weiser B, Anastos K, Kitchen CM, Robison E, Meyer WA 3rd, Sacks HS, Mathur-Wagh U, Brunner C, and Burger H
- Subjects
- Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Female, HIV-1 physiology, Humans, RNA, Viral chemistry, Receptors, CXCR4 physiology, Anti-HIV Agents pharmacology, HIV-1 drug effects
- Abstract
To initiate infection, HIV-1 requires a primary receptor, CD4, and a secondary receptor, principally the chemokine receptor CCR5 or CXCR4. Coreceptor usage plays a critical role in HIV-1 disease progression. HIV-1 transmitted in vivo generally uses CCR5 (R5), but later CXCR4 (X4) strains may emerge; this shift heralds CD4+ cell depletion and clinical deterioration. We asked whether antiretroviral therapy can shift HIV-1 populations back to R5 viruses after X4 strains have emerged, in part because treatment has been successful in slowing disease progression without uniformly suppressing plasma viremia. We analyzed the coreceptor usage of serial primary isolates from 15 women with advanced disease who demonstrated X4 viruses. Coreceptor usage was determined by using a HOS-CD4+ cell system, biological and molecular cloning, and sequencing the envelope gene V3 region. By constructing a mathematical model to measure the proportion of virus in a specimen using each coreceptor, we demonstrated that the predominant viral population shifted from X4 at baseline to R5 strains after treatment. Multivariate analyses showed that the shift was independent of changes in plasma HIV-1 RNA level and CD4+ cell count. Hence, combination therapy may lead to a change in phenotypic character as well as in the quantity of HIV-1. Shifts in coreceptor usage may thereby contribute to the clinical efficacy of anti-HIV drugs.
- Published
- 2001
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85. Observational studies and randomized trials.
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Sacks HS
- Subjects
- Cohort Studies, Humans, Treatment Outcome, Case-Control Studies, Randomized Controlled Trials as Topic, Research Design
- Published
- 2000
86. Assessing the quality of randomized controlled trials: quality of design is not the only relevant variable.
- Author
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Berk PD and Sacks HS
- Subjects
- Ethics, Medical, Humans, Multicenter Studies as Topic standards, Quality Assurance, Health Care, Randomized Controlled Trials as Topic standards, Research Design
- Published
- 1999
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87. Tuberculosis preventive therapy for HIV-infected people in sub-Saharan Africa is cost-effective.
- Author
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Bell JC, Rose DN, and Sacks HS
- Subjects
- AIDS-Related Opportunistic Infections economics, AIDS-Related Opportunistic Infections microbiology, Cost-Benefit Analysis, Decision Support Techniques, Health Care Costs, Humans, Markov Chains, Models, Statistical, Quality of Life, Survival Analysis, Tuberculin Test, Tuberculosis, Pulmonary microbiology, Uganda, AIDS-Related Opportunistic Infections prevention & control, Antitubercular Agents economics, Antitubercular Agents therapeutic use, Tuberculosis, Pulmonary economics, Tuberculosis, Pulmonary prevention & control
- Abstract
Objective: Since antiretroviral therapy is largely unavailable to HIV-infected patients in developing countries and recent clinical trials have shown that tuberculosis (TB) preventive therapy can reduce TB and HIV-associated morbidity and mortality, we studied the effectiveness and cost-effectiveness of TB preventive therapy for HIV-infected persons in sub-Saharan Africa., Methods: A Markov model that used results of clinical trials of TB preventive therapy in sub-Saharan Africa and literature-derived medical care costs was used to evaluate three preventive therapy regimens in HIV-infected, tuberculin-positive patients in Uganda: (1) daily isoniazid (INH) for 6 months, (2) daily INH and rifampin (RIF) for 3 months, and (3) twice-weekly RIF and pyrazinamide (PZA) for 2 months., Results: All three regimens extend life expectancy and reduce the number of TB cases. When only medical care costs are considered, all three preventive therapy regimens cost more than not providing preventive therapy to extend life and prevent active tuberculosis. When medical care and social costs are considered together, 6-months of daily INH treatment will save money relative to no preventive therapy and when the costs associated with treating secondary infections are included, all three preventive therapy regimens are less expensive than no preventive therapy. With the inclusion of secondary infection costs, 6 months of daily INH results in savings of $24.16 per person., Conclusions: TB preventive therapy taken by HIV-infected tuberculin reactors in sub-Saharan Africa results in extended life-expectancy, reduction of the incidence of TB and monetary savings in medical care and social costs. TB control policy in sub-Saharan Africa should include preventive therapy.
- Published
- 1999
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88. Cervicovaginal human papillomavirus infection in human immunodeficiency virus-1 (HIV)-positive and high-risk HIV-negative women.
- Author
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Palefsky JM, Minkoff H, Kalish LA, Levine A, Sacks HS, Garcia P, Young M, Melnick S, Miotti P, and Burk R
- Subjects
- AIDS-Related Opportunistic Infections complications, Adult, CD4 Lymphocyte Count, Female, HIV genetics, HIV immunology, HIV Seronegativity, Humans, Logistic Models, Prevalence, RNA, Viral analysis, Risk Factors, Uterine Cervical Neoplasms virology, Uterine Cervical Dysplasia virology, AIDS-Related Opportunistic Infections virology, HIV isolation & purification, Papillomaviridae, Papillomavirus Infections virology, Precancerous Conditions virology, Tumor Virus Infections virology, Uterine Cervicitis virology, Vaginitis virology
- Abstract
Background: Human papillomavirus (HPV) infection is associated with precancerous cervical squamous intraepithelial lesions commonly seen among women infected with human immunodeficiency virus-1 (HIV). We characterized HPV infection in a large cohort of HIV-positive and HIV-negative women participating in the Women's Interagency HIV Study to determine the prevalence of and risk factors for cervicovaginal HPV infection in HIV-positive women., Methods: HIV-positive (n = 1778) and HIV-negative (n = 500) women were tested at enrollment for the presence of HPV DNA in a cervicovaginal lavage specimen. Blood samples were tested for HIV antibody status, level of CD4-positive T cells, and HIV RNA load (copies/mL). An interview detailing risk factors was conducted. Univariate and multivariate analyses were performed., Results: Compared with HIV-negative women, HIV-positive women with a CD4+ cell count of less than 200/mm3 were at the highest risk of HPV infection, regardless of HIV RNA load (odds ratio [OR] = 10.13; 95% confidence interval [CI] = 7.32-14.04), followed by women with a CD4+ count greater than 200/mm3 and an HIV RNA load greater than 20,000 copies/mL (OR = 5.78; 95% CI = 4.17-8.08) and women with a CD4+ count greater than 200/mm3 and an HIV RNA load less than 20,000 copies/mL (OR = 3.12; 95% CI = 2.36-4.12), after adjustment for other factors. Other risk factors among HIV-positive women included racial/ethnic background (African-American versus Caucasian, OR = 1.64; 95% CI = 1.19-2.28), current smoking (yes versus no; OR = 1.55; 95% CI = 1.20-1.99), and younger age (age < 30 years versus > or = 40 years; OR = 1.75; 95% CI = 1.23-2.49)., Conclusions: Although the strongest risk factors of HPV infection among HIV-positive women were indicators of more advanced HIV-related disease, other factors commonly found in studies of HIV-negative women, including racial/ethnic background, current smoking, and age, were important in HIV-positive women as well.
- Published
- 1999
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89. Effect of antiviral drugs and hematopoietic growth factors on in vitro erythropoiesis.
- Author
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Weinberg RS, Chusid ED, Galperin Y, Thomson JC, Cheung T, and Sacks HS
- Subjects
- Adult, Anemia physiopathology, Case-Control Studies, Erythroid Precursor Cells drug effects, Female, HIV Infections complications, Humans, In Vitro Techniques, Male, Middle Aged, Anemia etiology, Antiviral Agents pharmacology, Erythropoiesis drug effects, HIV Infections drug therapy, Hematopoietic Cell Growth Factors pharmacology
- Abstract
Background: The purpose of these studies was to improve our understanding of nucleoside analog, antiviral, drug-induced anemia in HIV infection., Methods: Peripheral blood erythroid progenitor cells (BFU-E) from HIV-positive (HIV+) patients and normal donors were compared in methylcellulose cultures with erythropoietin, with and without antiviral drugs, and with and without the hematopoietic growth factors, stem cell factor (SCF), hemin, and interleukin-3 (IL-3)., Results: Normal numbers of BFU-E-derived colonies were observed in cultures from HIV+ patients (mean +/- 1 SD BFU-E/10(5) cells plated: normal = 14.1 +/- 7.9, HIV+ = 17.2 +/- 14.2, p = 0.39). The antiviral drugs zidovudine (AZT), dideoxyinosine (ddI), and didehydrodideoxythymidine (d4T) all inhibited erythroid colonies in HIV+ and normal cultures. AZT was the most erythropoietically inhibitory drug (AZT ID50, mean +/- 1 SD for normal cultures = 2.64 +/- 4.15 microM, for HIV+ cultures = 6.28 +/- 10.79 microM, p = 0.24). Hematologic toxicity was less with ddI and d4T. However, doses of ddI and d4T < or = 10 microM inhibited colony growth in 9/14 and 8/12 cultures, respectively, from HIV+ patients., Conclusions: Stem cell factor (SCF), hemin, and interleukin-3 (IL-3) increased colony growth in HIV+ and normal cultures. In control cultures, hematopoietic growth factors added singly increased growth 1.3- to 8-fold. Hematopoietic growth factors increased growth even in cultures containing antiviral drugs. In some instances growth factors restored growth to control levels. SCF, hemin, and IL-3 were most effective when combined.
- Published
- 1998
90. The relationship between study design, results, and reporting of randomized clinical trials of HIV infection.
- Author
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Ioannidis JP, Cappelleri JC, Sacks HS, and Lau J
- Subjects
- Anti-HIV Agents adverse effects, Bias, Data Collection statistics & numerical data, HIV Infections mortality, Humans, Publication Bias, Research Design, Survival Analysis, Treatment Outcome, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, Randomized Controlled Trials as Topic statistics & numerical data
- Abstract
We examined whether the study design of randomized clinical trials for medications against human immunodeficiency virus (HIV) may affect the results and whether the outcomes of these trials affect reporting and publication. We used a database of 71 published randomized HIV-related drug efficacy trials and considered the following study design factors: endpoint definition and method of analysis, masked design, sample size, and duration of follow-up. Large variation was noted in the methods of analysis for surrogate endpoints. Often statistical significance for a surrogate endpoint was not associated with statistical significance for the clinical endpoint or for survival in the same trial, although disagreements in the direction of the treatment effect for surrogate endpoints and survival within individual trials were uncommon. Open-label design seemed to affect the magnitude of the treatment effect for two treatments. The magnitude of the treatment effect in trials of zidovudine monotherapy was inversely related to their sample size, but this probably reflected the confounding effect of longer duration of follow-up in large trials (with a resulting loss of efficacy) rather than publication bias. There was, however, evidence for potential bias in reporting and publication of HIV-related trials. Meta-analyses of published trials for specific treatments demonstrated a sizable treatment benefit for all the examined medications regardless of whether these medications were officially approved, controversial, or abandoned, raising concerns about either publication bias or unjustifiable rejection of potentially useful medications. Compared with trials published in specialized journals, trials published in journals of wide readership were larger (p = 0.001) and 4.4 times more likely to report "positive" results (p = 0.01). We identified several examples of trials with "negative" results that have remained unpublished for a long time. In conclusion, study design factors may have an impact on the magnitude and significance of the treatment effect in HIV-related trials. Bias in reporting can further affect the information that these studies provide.
- Published
- 1997
- Full Text
- View/download PDF
91. Hypothalamic-pituitary axis dysfunction in critically ill patients with a low free thyroxine index.
- Author
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Mechanick JI, Sacks HS, and Cobin RH
- Subjects
- Adult, Aged, Aged, 80 and over, Critical Care, Female, Humans, Male, Middle Aged, Pituitary Function Tests, Pituitary Hormones blood, Prospective Studies, Thyroid Hormones blood, Thyroxine blood, Critical Illness, Hypothalamo-Hypophyseal System physiopathology, Thyroxine deficiency
- Abstract
The purpose of this study is to investigate the association of hypothalamic-pituitary axis abnormalities with the free thyroxine index (FTI) in critically ill patients. Fourteen critically ill patients and twenty healthy volunteers were studied using combined anterior pituitary gland testing with CRF, GHRH, TRH, and GnRH. The subjects were grouped as follows: I-healthy volunteers; II-sick/normal FTI; and III-sick/low FTI. Serial measurements of hormones were performed over a two-hour interval and the following parameters were measured: baseline level, response amplitude and time to maximal response. Response velocities and area-under-the-curves (integrated responses) were also computed. Group III had a longer mean ICU duration prior to testing than group II. Urinary cortisol, serum cortisol and serum PRL levels were elevated in groups II and III. However, group III had lower baseline ACTH levels, slower ACTH and TSH response velocities and decreased PRL integrated responses. Cortisol response parameters were similar between groups II and III. There were no differences in LH, FSH or GH response velocities or integrated responses among the 3 groups. These data confirm that critically ill patients develop hyperprolactinemia and hypothalamic-pituitary-adrenal axis activation but when a low FTI exists, a plurality of changes occur reflected by attenuated PRL, TSH and ACTH responses despite unaffected adrenal cortisol output.
- Published
- 1997
- Full Text
- View/download PDF
92. Predictors and impact of patients lost to follow-up in a long-term randomized trial of immediate versus deferred antiretroviral treatment.
- Author
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Ioannidis JP, Bassett R, Hughes MD, Volberding PA, Sacks HS, and Lau J
- Subjects
- Adult, CD4 Lymphocyte Count, Disease Progression, Double-Blind Method, Female, Follow-Up Studies, HIV Infections immunology, HIV Infections mortality, Humans, Male, Patient Compliance, Treatment Refusal, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV-1, Patient Dropouts statistics & numerical data, Zidovudine therapeutic use
- Abstract
We studied predictors for losses to follow-up and the impact of such losses in the AIDS Clinical Trials Group 019 protocol, a long-term randomized trial of immediate versus deferred antiretroviral therapy in asymptomatic HIV-1-infected patients with >500 CD4 cells/mm3. The trial was selected because of its key importance in determining guidelines for antiretroviral therapy, and because it had the longest follow-up among all antiretroviral trials and the largest percentage of patients whose vital status was unknown at study end. Younger age, a history of parenteral drug use, and nonwhite race were associated with higher rates of loss to follow-up, but race was not an important predictor after adjusting for clinical site. There was large and statistically significant variability in the rates of losses among different clinical sites (p < 0.001). Patient retention was significantly better in clinical sites that enrolled many participants, with 25% of enrollees lost to follow-up in sites enrolling >100 patients and 44% in sites enrolling <33 patients each. As a group, patients lost to follow-up after the 2nd year had steeper declines of CD4 cell counts, and a significantly larger proportion had reached a CD4 cell count <300/mm3 in the year before being lost, compared with patients remaining in the study. Losses to follow-up probably decreased substantially the observed number of primary endpoints, curtailed the power of the trial to demonstrate any difference between immediate and deferred initiation of antiretroviral therapy, and may have introduced large bias in the estimated hazard ratio for the primary endpoint and its statistical significance.
- Published
- 1997
- Full Text
- View/download PDF
93. The botulism hazard.
- Author
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Sacks HS
- Subjects
- Cost-Benefit Analysis, Food Preservatives economics, Humans, Product Labeling, Botulism prevention & control
- Published
- 1997
- Full Text
- View/download PDF
94. Cost-effectiveness of cytomegalovirus (CMV) disease prevention in patients with AIDS: oral ganciclovir and CMV polymerase chain reaction testing.
- Author
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Rose DN and Sacks HS
- Subjects
- AIDS-Related Opportunistic Infections economics, AIDS-Related Opportunistic Infections virology, Administration, Oral, Antiviral Agents economics, Cohort Studies, Cost-Benefit Analysis, Cytomegalovirus Infections complications, Cytomegalovirus Infections economics, Cytomegalovirus Infections virology, Ganciclovir economics, Humans, Survival Analysis, AIDS-Related Opportunistic Infections prevention & control, Antiviral Agents therapeutic use, Cytomegalovirus Infections prevention & control, Ganciclovir therapeutic use, Polymerase Chain Reaction economics
- Abstract
Objective: To perform a cost-effectiveness analysis of strategies to prevent cytomegalovirus (CMV) disease., Method: Markov model and published data., Patients: Hypothetical HIV-infected patients with CD4 cell counts < or = 50 x 10(6)/l and positive CMV serologies., Interventions: Oral ganciclovir daily versus plasma CMV DNA polymerase chain reaction (PCR) testing every 3 months with oral ganciclovir for patients with positive tests., Outcome Measures: The number of CMV disease cases prevented by the interventions, life expectancy, disease-free life expectancy, and the cost to extend life by 1 year., Results: Oral ganciclovir preventive therapy reduces the lifetime number of CMV disease cases by 50 per 1000 cohort, extends life expectancy by 5 days and disease-free life expectancy by 18 days, and costs US$ 1,762,517 per year of life extended. Periodic PCR testing reduces the lifetime number of CMV disease cases by eight per 1000 cohort, extends life expectancy by 1 day and disease-free life expectancy by 3 days, and costs US$ 495,158 per year of life extended. The prevention strategies could be acceptably cost effective only under a combination of optimistic assumptions and reduced costs., Conclusions: Oral ganciclovir preventive therapy and periodic plasma testing for CMV PCR with oral ganciclovir for those with positive tests result in small benefits at great cost. They are not cost-effective prevention strategies for persons with advanced HIV infection and positive CMV serologies.
- Published
- 1997
- Full Text
- View/download PDF
95. BCG vaccination to prevent tuberculosis in health care workers: a decision analysis.
- Author
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Marcus AM, Rose DN, Sacks HS, and Schechter CB
- Subjects
- Antitubercular Agents therapeutic use, Cross Infection prevention & control, Humans, Incidence, Isoniazid therapeutic use, Markov Chains, Models, Statistical, Occupational Exposure statistics & numerical data, Reference Standards, Sensitivity and Specificity, Tuberculin Test adverse effects, Tuberculin Test statistics & numerical data, BCG Vaccine adverse effects, Decision Support Techniques, Health Personnel statistics & numerical data, Occupational Exposure prevention & control, Tuberculosis prevention & control
- Abstract
Objective: To perform a decision analysis to determine the optimal strategy to prevent tuberculosis (TB) in health care workers with negative tuberculin skin tests., Methods: We used a Markov model to study the occurrence of events each year and compared BCG vaccination to annual tuberculin testing plus isoniazid (INH) preventive therapy for those who become skin test positive. The outcome measures studied were the number of cases and deaths from TB and BCG and/or INH adverse reactions over 10 years., Results: Annual tuberculin testing decreases the number of TB cases by 9% and BCG vaccination decreases the number by 49%, relative to no prevention intervention. BCG vaccination results in fewer deaths than annual tuberculin testing if the workplace incidence of Mycobacterium tuberculosis infection is greater than 0.06%, BCG vaccination effectiveness exceeds 3%, or the rate of fatal BCG adverse reactions is less than 15 times the rate reported in the literature., Conclusions: BCG vaccination results in less morbidity and mortality than annual tuberculin skin testing for health care workers in workplaces with documented TB transmission despite comprehensive infection control policies and procedures. Current policy on the prevention of TB among health care workers should be reconsidered.
- Published
- 1997
- Full Text
- View/download PDF
96. Meta-analysis: an update.
- Author
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Sacks HS, Reitman D, Pagano D, and Kupelnick B
- Subjects
- Bias, Data Collection methods, Data Interpretation, Statistical, Randomized Controlled Trials as Topic, Reproducibility of Results, Research Design, Meta-Analysis as Topic
- Abstract
A fairly new type of research, termed meta-analysis, attempts to analyze and combine the results of previous reports. In 1992 we updated our 1987 survey of 86 meta-analyses of randomized control trial reports in the english language literature with an additional 78. We evaluated the quality of these meta-analyses using a scoring method that lists 23 items in six major areas: study design, combinability, control of bias, statistical analysis, sensitivity analysis, and application of results. Of the 23 individual items, the mean number satisfactorily addressed was 7.63 +/- 2.84 (mean +/- S.D.) for 40 papers published from 1955 through 1982, 6.80 +/- 3.86 for 66 papers published from 1983 through 1986, and 11.91 +/- 4.79 for 58 papers published from 1987 through 1990 (F = 31.3, p < .001). We noted that methodology has definitely improved since our first survey of meta-analyses, but an urgent need still exists for a better search of the literature, quality evaluation of trials, and a synthesis of the results. Recently, meta-analysis has expanded to cover non-randomized studies, including evaluation of diagnostic tests and pooling of epidemiologic studies. There is growing concern for standards, and several methodologic issues remain unresolved.
- Published
- 1996
97. Synergy, activity and tolerability of zidovudine and interferon-alpha in patients with symptomatic HIV-1 infection: AIDS Clincal Trial Group 068.
- Author
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Mildvan D, Bassiakos Y, Zucker ML, Hyslop N Jr, Krown SE, Sacks HS, Zachary J, Paredes J, Fessel WJ, Rhame F, Kramer F, Fischl MA, Poiesz B, Wood K, Ruprecht RM, Kim J, Grossberg SE, Kasdan P, Bergé P, Marshak A, and Pettinelli C
- Subjects
- Administration, Cutaneous, Administration, Oral, Adult, Anti-HIV Agents administration & dosage, Antiviral Agents administration & dosage, CD4 Lymphocyte Count, Drug Synergism, Drug Therapy, Combination, Drug Tolerance, Female, HIV Core Protein p24 blood, HIV Infections blood, Humans, Interferon-alpha administration & dosage, Male, Zidovudine administration & dosage, Anti-HIV Agents therapeutic use, Antiviral Agents therapeutic use, HIV Infections drug therapy, HIV-1, Interferon-alpha therapeutic use, Zidovudine therapeutic use
- Abstract
Thirty-four subjects with symptomatic HIV-1 infection, p24 antigenaemia, and CD4 cell counts > 200/mm3 were randomly assigned to receive treatment with either zidovudine (ZDV) orally, interferon-alpha (IFN-alpha) subcutaneously, or both at respective low (200 mg ZDV/ 2 million international units IFN-alpha (MIU)), middle (400 mg/4 MIU) or high (600 mg/6 MIU) daily dose levels for 12 weeks. Thereafter, all patients received combination therapy at the initially assigned dose level to a total of 96 weeks. This design permitted analysis by the combination index (CI) method, which demonstrated antiretroviral synergy between ZDV and IFN-alpha with respect to p24 antigen suppression. Over the first 12 weeks, combination therapy was acceptably tolerated, more so than IFN-alpha monotherapy, and it was significantly more active in suppressing antigenaemia than either of the monotherapies. Similarly, the high-dose combination was the most active dose level over weeks 12 to 96. Combination ZDV/IFN-alpha at the optimal dose level defined by this trial merits further study. In addition, the CI design strategy employed here may be useful for the investigation of new antiretroviral combinations.
- Published
- 1996
98. Predictive value of viral load measurements in asymptomatic untreated HIV-1 infection: a mathematical model.
- Author
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Ioannidis JP, Cappelleri JC, Lau J, Sacks HS, and Skolnik PR
- Subjects
- CD4 Lymphocyte Count, Cohort Studies, HIV Infections physiopathology, HIV-1 genetics, Humans, Longitudinal Studies, Models, Theoretical, HIV Infections virology, HIV-1 isolation & purification, RNA, Viral blood
- Abstract
Objective: To model the predictive value of viral load measurements in asymptomatic patients with HIV-1 infection, who have CD4 cell counts > 500 x 10(6)/l and no prior antiretroviral therapy, when the time of seroconversion and the prior levels of viremia are unknown., Design: A mathematical model was constructed for the changes in HIV RNA load over time based on data from cohorts of HIV-infected patients followed since the time of seroconversion., Methods: For different values of viral load, the time to progression to AIDS or an equivalent state [progression to AIDS equivalent (PAE)] was calculated using a wide range of estimates for the time since seroconversion and the rate of change of the viral load over time., Results: In the absence of antiretroviral treatment, patients with a viral load of 10(5) copies/ml serum are at risk for PAE in less than 3 years (0-3 years) and patients with a viral load half a log higher are at risk in less than 1 year. In contrast, patients with a viral load of 10(4.5) have at least 1.9 years and may have up to 8 years before risk of PAE. Patients with a viral load of 10(4) RNA copies/ml have at least 2.8 years and may have up to 19 years before risk of PAE. The rate of change of the viral load was an important predictor of outcome; the time since seroconversion had only a minor effect., Conclusions: The viral load in the plasma or serum has predictive value even if the time of seroconversion is unknown. The rate of change of viral load over time may also be an important predictive factor. Serial measurements of viral load over time may provide therapeutic guidance.
- Published
- 1996
- Full Text
- View/download PDF
99. The efficacy of influenza vaccine in elderly persons. A meta-analysis and review of the literature.
- Author
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Gross PA, Hermogenes AW, Sacks HS, Lau J, and Levandowski RA
- Subjects
- Age Factors, Aged, Chronic Disease, Cost-Benefit Analysis, Female, Hospital Mortality, Humans, Male, Odds Ratio, Pneumonia, Viral mortality, Pneumonia, Viral prevention & control, Severity of Illness Index, Sex Factors, Influenza Vaccines economics, Influenza, Human prevention & control
- Abstract
Objective: To quantify the protective efficacy of influenza vaccine in elderly persons., Data Sources: A MEDLINE search was done using the index terms influenza vaccine, vaccine efficacy, elderly, mortality, hospitalized, and pneumonia. Appropriate references in the initially selected articles were also reviewed., Study Selection: Only cohort observational studies with mortality assessment were included in the meta-analysis. In addition, 3 recent case-control studies, 2 cost-effectiveness studies, and 1 randomized, double-blind, placebo-controlled trial were reviewed., Data Extraction: Vaccine and epidemic virus strains, age and sex of patients, severity of illness, patient status, and study design were recorded. Upper respiratory illness, hospitalization, pneumonia, and mortality were used as outcome measures., Data Synthesis: In a meta-analysis of 20 cohort studies, the pooled estimates of vaccine efficacy (1-odds ratio) were 56% (95% Cl, 39% to 68%) for preventing respiratory illness, 53% (Cl, 35% to 66%) for preventing pneumonia, 50% (Cl, 28% to 65%) for preventing hospitalization, and 68% (Cl, 56% to 76%) for preventing death. Vaccine efficacy in the case-control studies ranged from 32% to 45% for preventing hospitalization for pneumonia, from 31% to 65% for preventing hospital deaths from pneumonia and influenza, from 43% to 50% for preventing hospital deaths from all respiratory conditions, and from 27% to 30% for preventing deaths from all causes. The randomized, double-blind, placebo-controlled trial showed a 50% or greater reduction in influenza-related illness. Recent cost-effectiveness studies confirm the efficacy of influenza vaccine in reducing influenza-related morbidity and mortality and show that vaccine provides important cost savings per year per vaccinated person., Conclusion: Despite the paucity of randomized trials, many studies confirm that influenza vaccine reduces the risks for pneumonia, hospitalization, and death in elderly persons during an influenza epidemic if the vaccine strain is identical or similar to the epidemic strain. Influenza immunization is an indispensable part of the care of persons 65 years of age and older. Annual vaccine administration requires the attention of all physicians and public health organizations.
- Published
- 1995
- Full Text
- View/download PDF
100. Octreotide enhances positive calcium balance in Duchenne muscular dystrophy.
- Author
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Nutting DF, Schriock EA, Palmieri GM, Bittle JB, Elmendorf BJ, Horner LH, Edwards MC, Griffin JW, Sacks HS, and Bertorini TE
- Subjects
- Adolescent, Calcium urine, Child, Diet, Digestive System metabolism, Growth Hormone metabolism, Humans, Insulin-Like Growth Factor I metabolism, Intestinal Absorption drug effects, Male, Octreotide administration & dosage, Phosphates urine, Calcium metabolism, Muscular Dystrophies metabolism, Octreotide pharmacology
- Abstract
Although receptors for somatostatin are found in bone cells, the effect of somatostatin analogs on calcium metabolism is unknown. The authors studied, in a metabolic ward, the effect of octreotide (a long-acting somatostatin analog) and a placebo in two 6-day calcium balance periods in 8 children with Duchenne muscular dystrophy. As expected, octreotide (2 micrograms/kg, subcutaneously, every 8 hours) reduced serum growth hormone and somatomedin (IGF-1) to levels found in growth hormone deficiency. Octreotide enhanced calcium retention by 30% (96 mg daily [P < 0.04]) in 7 boys for whom complete data (diet, urine, and fecal calcium) were available. In 6 children with urinary calcium excretion (Uca) greater than 50 mg daily, octreotide markedly lowered Uca, from 114 +/- 23 mg daily to 61 +/- 9 mg daily (P < 0.03). Calcium retention occurred in patients with or without initial hypercalciuria, but the higher the basal Uca, the greater was the inhibition by octreotide (r = 0.79; P < 0.03). Inactive, nonambulatory patients had a more pronounced response of Uca to octreotide (P < 0.02). Octreotide caused a mild, nonsignificant reduction in fecal calcium, with no major changes in serum calcium, phosphorus, parathyroid hormone, urinary excretion of sodium and potassium, or in creatinine clearance. Based on the current observations and the presence of receptors for somatostatin in bone cells, this hormone may have, at least on a short-term basis, an anabolic effect on calcium, perhaps favoring its deposition in bone.
- Published
- 1995
- Full Text
- View/download PDF
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