Dr. Mark  Grant  Md image

Dr. Mark Grant Md

225 N Michigan Ave Bcbsa
Chicago IL 60601
312 976-6216
Medical School: Other - Unknown
Accepts Medicare: No
Participates In eRX: No
Participates In PQRS: No
Participates In EHR: No
License #: 036075647
NPI: 1316219546
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Conducting quantitative synthesis when comparing medical interventions: AHRQ and the Effective Health Care Program. - Journal of clinical epidemiology
This article is to establish recommendations for conducting quantitative synthesis, or meta-analysis, using study-level data in comparative effectiveness reviews (CERs) for the Evidence-based Practice Center (EPC) program of the Agency for Healthcare Research and Quality.We focused on recurrent issues in the EPC program and the recommendations were developed using group discussion and consensus based on current knowledge in the literature.We first discussed considerations for deciding whether to combine studies, followed by discussions on indirect comparison and incorporation of indirect evidence. Then, we described our recommendations on choosing effect measures and statistical models, giving special attention to combining studies with rare events; and on testing and exploring heterogeneity. Finally, we briefly presented recommendations on combining studies of mixed design and on sensitivity analysis.Quantitative synthesis should be conducted in a transparent and consistent way. Inclusion of multiple alternative interventions in CERs increases the complexity of quantitative synthesis, whereas the basic issues in quantitative synthesis remain crucial considerations in quantitative synthesis for a CER. We will cover more issues in future versions and update and improve recommendations with the accumulation of new research to advance the goal for transparency and consistency.Copyright © 2011 Elsevier Inc. All rights reserved.
Development quality criteria to evaluate nontherapeutic studies of incidence, prevalence, or risk factors of chronic diseases: pilot study of new checklists. - Journal of clinical epidemiology
To develop two checklists for the quality of observational studies of incidence or risk factors of diseases.Initial development of the checklists was based on a systematic literature review. The checklists were refined after pilot trials of validity and reliability were conducted by seven experts, who tested the checklists on 10 articles.The checklist for studies of incidence or prevalence of chronic disease had six criteria for external validity and five for internal validity. The checklist for risk factor studies had six criteria for external validity, 13 criteria for internal validity, and two aspects of causality. A Microsoft Access database produced automated standardized reports about external and internal validities. Pilot testing demonstrated face and content validities and discrimination of reporting vs. methodological qualities. Interrater agreement was poor. The experts suggested future reliability testing of the checklists in systematic reviews with preplanned protocols, a priori consensus about research-specific quality criteria, and training of the reviewers.We propose transparent and standardized quality assessment criteria of observational studies using the developed checklists. Future testing of the checklists in systematic reviews is necessary to develop reliable tools that can be used with confidence.Copyright © 2011 Elsevier Inc. All rights reserved.
Characterization of a porcine model of chronic superficial varicose veins. - Journal of vascular surgery
Previous animal models of venous disease, while inducing venous hypertension and valvular insufficiency, do not produce superficial varicose veins. In this study, we aimed to develop and characterize a pig-based model of superficial varicose veins.Right femoral arteriovenous fistulae (AVF) were surgically fashioned in young adult pigs. Animals were examined at postoperative times up to 15 weeks to determine the development of varicose veins and measurement of both blood pressure and flow velocities within the superficial thigh veins. Histology and vascular corrosion casts were used to characterize the resulting structural venous alterations. Porcine pathophysiological features were compared with those of human primary superficial varicose veins.Gross superficial varicosities developed over the ipsilateral medial thigh region after an initial lag period of 1-2 weeks. Veins demonstrated retrograde filling with valvular incompetence, and a moderate, non-pulsatile, venous hypertension, which was altered by changes in posture and Valsalva. Venous blood flow velocities were elevated to 15-30 cm/s in varicose veins. Structurally, pig varicose veins were enlarged, tortuous, had valvular degeneration, and regions of focal medial atrophy with or without overlying intimal thickening.The superficial varicose veins, which developed within this model, have a pathophysiology that is consistent with that observed in humans. The porcine femoral AVF model is proposed as a suitable experimental model to evaluate the pathobiology of superficial venous disease. It may also be suitable for the evaluation of treatment interventions including drug therapy.
In-hospital mortality of ruptured abdominal aortic aneurysm. - ANZ journal of surgery
New Zealand, like Australia, has a widely dispersed population in towns at long distances from the main centres. We set out to estimate the in-hospital mortality rate for ruptured abdominal aortic aneurysms in New Zealand and identify factors associated with mortality.Data were gathered prospectively as part of the Vascular Society of New Zealand's continuous audit programme of all member surgeons. Data collection was validated by random record audit. In-hospital mortality of ruptured abdominal aortic aneurysms, defined as death during hospital admission irrespective of cause, was determined for the period 1993-2005. Along with other performance indicators, differences in outcomes were assessed to take into account the trend over the time period, hospital size and number of non-operative admissions.Of the 740 patients admitted with a mean age of 73.9 +/- 8.5 years, 78% were men and 17.8% were declined an operation. The in-hospital mortality was 48.3% and the operative mortality was 37.8%. With univariate analysis increasing patient age, American Society of Anesthesiology score, hospital size and female sex were predictors of in-hospital mortality. Only age and American Society of Anesthesiology score were independent predictors of operative mortality. Women were less likely to have surgery.Over the past 13 years in-hospital mortality of ruptured abdominal aortic aneurysms in New Zealand remained unchanged. In provincial hospitals the operative outcomes were satisfactory, but the reported number not offered surgery was higher.
Treatment of primary and secondary osteoarthritis of the knee. - Evidence report/technology assessment
Systematic review of outcomes of three treatments for osteoarthritis (OA) of the knee: intra-articular viscosupplementation; oral glucosamine, chondroitin or the combination; and arthroscopic lavage or debridement.We abstracted data from: 42 randomized, controlled trials (RCTs) of viscosupplementation, all but one synthesized among six meta-analyses; 21 RCTs of glucosamine/chondroitin, 16 synthesized among 6 meta-analyses; and 23 articles on arthroscopy. The search included foreign-language studies and relevant conference proceedings.The review methods were defined prospectively in a written protocol. We sought systematic reviews, meta-analyses, and RCTs published in full or in abstract. Where randomized trials were few, we sought other study designs. We independently assessed the quality of all primary studies.Viscosupplementation trials generally report positive effects on pain and function scores compared to placebo, but the evidence on clinical benefit is uncertain, due to variable trial quality, potential publication bias, and unclear clinical significance of the changes reported. The Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), a large (n=1,583), high-quality, National Institutes of Health-funded, multicenter RCT showed no significant difference compared to placebo. Glucosamine sulfate has been reported to be more effective than glucosamine hydrochloride, which was used in GAIT, but the evidence is not sufficient to draw conclusions. Clinical studies of glucosamine effect on glucose metabolism are short term, or if longer (e.g., 3 years), excluded patients with metabolic disorders. The best available evidence for arthroscopy, a single sham-controlled RCT (n=180), showed that arthroscopic lavage with or without debridement was equivalent to placebo. The main limitations of this trial are the use of a single surgeon and enrollment of patients at a single Veterans Affairs Medical Center. No studies reported separately on patients with secondary OA of the knee. The only comparative study was an underpowered, poor-quality trial comparing viscosupplementation to arthroscopy with debridement.Osteoarthritis of the knee is a common condition. The three interventions reviewed in this report are widely used in the treatment of OA of the knee, yet the best available evidence does not clearly demonstrate clinical benefit. Uncertainty regarding clinical benefit can be resolved only by rigorous, multicenter RCTs. In addition, given the public health impact of OA of the knee, research on new approaches to prevention and treatment should be given high priority.
Modeling mammary gland morphogenesis as a reaction-diffusion process. - Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference
Mammary ducts are formed through a process of branching morphogenesis. We present results of experiments using a simulation model of this process, and discuss their implications for understanding mammary duct extension and bifurcation. The model is a cellular automaton approximation of a reaction-diffusion process in which matrix metalloproteinases represent the activator, inhibitors of matrix metalloproteinases represent the inhibitor, and growth factors serve as a substrate. We compare results from the simulation model with those from in-vivo experiments as part of an assessment of whether duct extension and bifurcation during morphogenesis may be a consequence of a reaction-diffusion mechanism mediated by MMPs and TIMPs.
Human chorionic gonadotropin modulates prostate cancer cell survival after irradiation or HMG CoA reductase inhibitor treatment. - Molecular pharmacology
The impact of human chorionic gonadotropin (hCG) on prostate carcinoma viability was investigated. Treatment of LNCaP and PC-3 cells with hCG modestly reduced cell viability within 96 h. Treatment of cells with hCG followed by exposure to ionizing radiation enhanced radiosensitivity. Exposure of LNCaP cells to hCG promoted activation of epidermal growth factor receptor (ERBB1) via a Galpha(i)-, mitogen-activated protein kinase kinase (MEK)1/2-, and metalloprotease-dependent paracrine mechanism, effects that were further enhanced after radiation exposure, and that were causal in prolonged intense activation of poly(ADP-ribose) polymerase (PARP). Inhibition of ERBB1, MEK1, or PARP1 function suppressed the radiosensitizing properties of hCG. Radiosensitization was also, in part, dependent upon c-Jun NH2-terminal kinase 1/2 signaling. PARP1-dependent radiosensitization was suppressed by a pan-caspase inhibitor and by knockdown of apoptosis-inducing factor expression. Inhibition of phosphatidylinositol 3-kinase, expression of dominant-negative AKT, or treatment with the HMG CoA reductase inhibitor lovastatin suppressed AKT phosphorylation and enhanced the cytotoxic effects of hCG. The enhancing effect of lovastatin was reproduced by incubation with a geranylgeranyl transferase inhibitor and blocked by coexposure to geranylgeranyl pyrophosphate. Treatment with hCG and lovastatin decreased expression of BCL-(XL) and XIAP, and increased expression of IkappaB. The cytotoxic effects of hCG were enhanced by expression of dominant-negative IkappaB, and they were abolished by coexpression of activated AKT. Expression of activated AKT maintained BCL-(XL) levels in cells expressing dominant-negative IkappaB. The promotion of hCG lethality by lovastatin was abolished by overexpression of BCL-(XL), and was dependent upon activation of caspase-9. Thus, hCG, in combination with radiation and lovastatin, may represent a novel approach to kill prostate cancer cells.
Simulating properties of in vitro epithelial cell morphogenesis. - PLoS computational biology
How do individual epithelial cells (ECs) organize into multicellular structures? ECs are studied in vitro to help answer that question. Characteristic growth features include stable cyst formation in embedded culture, inverted cyst formation in suspension culture, and lumen formation in overlay culture. Formation of these characteristic structures is believed to be a consequence of an intrinsic program of differentiation and de-differentiation. To help discover how such a program may function, we developed an in silico analogue in which space, events, and time are discretized. Software agents and objects represent cells and components of the environment. "Cells" act independently. The "program" governing their behavior is embedded within each in the form of axioms and an inflexible decisional process. Relationships between the axioms and recognized cell functions are specified. Interactions between "cells" and environment components during simulation give rise to a complex in silico phenotype characterized by context-dependent structures that mimic counterparts observed in four different in vitro culture conditions: a targeted set of in vitro phenotypic attributes was matched by in silico attributes. However, for a particular growth condition, the analogue failed to exhibit behaviors characteristic of functionally polarized ECs. We solved this problem by following an iterative refinement method that improved the first analogue and led to a second: it exhibited characteristic differentiation and growth properties in all simulated growth conditions. It is the first model to simultaneously provide a representation of nonpolarized and structurally polarized cell types, and a mechanism for their interconversion. The second analogue also uses an inflexible axiomatic program. When specific axioms are relaxed, growths strikingly characteristic of cancerous and precancerous lesions are observed. In one case, the simulated cause is aberrant matrix production. Analogue design facilitates gaining deeper insight into such phenomena by making it easy to replace low-resolution components with increasingly detailed and realistic components.
Old fashion clinical judgment in the era of protocols: is mandatory chest X-ray necessary in injured patients? - The Journal of trauma
The ATLS Course advocates that injured patients have a chest x-ray (CXR) to identify potential injuries. The purpose of this study was to correlate clinical indications and clinician judgment with CXR results to ascertain if a selective policy would be beneficial.Patients treated at a Level I trauma center over 12 months were prospectively evaluated. Before obtaining a CXR, signs, symptoms, and history suggestive of thoracic injury were identified. Additionally, a trauma surgeon (TS) recorded whether in their judgment a CXR was clinically indicated. These findings were compared with final CXR diagnoses. The sensitivity of individual clinical indicators, combinations of clinical indicators, and TS judgment for CXR abnormalities were calculated with a 95% confidence interval.During the twelve-month study period, data were acquired on 772 patients (age 0-102 years). Seventy percent were male and 86.0% were injured by blunt force. Only 29% (N = 222) of the patients manifested one or more of the clinical indicators (signs and symptoms). The negative predictive value for the TS judgment was 98.2% which was superior to the clinical indicators. Reliance on the opinion of the TS to determine the need for a CXR would have eliminated 49.9% of CXRs and avoided hospital and radiologist reading charges totaling $100,078.22.Mandatory CXR for all trauma patients has a low yield for abnormal findings. A selective policy relying on surgical judgment guided by clinical indicators is safe and efficacious while reducing cost and conserving resources.
Dietary supplementation with safflower seeds differing in fatty acid composition differentially influences serum concentrations of prostaglandin F metabolite in postpartum beef cows. - Reproduction, nutrition, development
Synthesis and secretion of prostaglandin F2alpha (PGF2alpha) is elevated following parturition and exerts divergent effects on the re-establishment of fertile estrous cycles in cows. The objective of these experiments was to determine if oil seed supplements differing in fatty acid composition differentially influence serum concentrations of the specific PGF2alpha metabolite, PGFM. Safflower seed supplements were formulated to provide 5% of dry-matter intake as fat. In Trial 1, 24 multiparous beef cows were individually fed control (beet pulp-soybean meal) or cracked high-linoleate safflower seed (78% 18:2n-6) supplements for 80 d postpartum. Linoleate supplemented cows had greater (P < 0.001) serum concentrations of PGFM than control cows. In Trial 2, primiparous beef cows (n = 36) were individually fed control (cracked corn-soybean meal), cracked high-linoleate (76% 18:2n-6) or -oleate (72% 18:1n-9) safflower seed supplements for 92 d postpartum. As in Trial 1, serum concentrations of PGFM were greater (P < or = 0.04) in linoleate than control or oleate supplemented cows. Serum concentrations of PGFM, however, did not differ (P = 0.40) among oleate and control supplemented cows. Although potential impacts on reproductive performance remain to be proven, dietary oil supplements high in linoleate, but not oleate, increased serum concentrations of PGFM compared to control supplements.

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