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"Miller, Ross M"
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The Spectral Properties of (-)-Epigallocatechin 3-O-Gallate (EGCG) Fluorescence in Different Solvents: Dependence on Solvent Polarity
(-)-Epigallocatechin 3-O-gallate (EGCG) a molecule found in green tea and known for a plethora of bioactive properties is an inhibitor of heat shock protein 90 (HSP90), a protein of interest as a target for cancer and neuroprotection. Determination of the spectral properties of EGCG fluorescence in environments similar to those of binding sites found in proteins provides an important tool to directly study protein-EGCG interactions. The goal of this study is to examine the spectral properties of EGCG fluorescence in an aqueous buffer (AB) at pH=7.0, acetonitrile (AN) (a polar aprotic solvent), dimethylsulfoxide (DMSO) (a polar aprotic solvent), and ethanol (EtOH) (a polar protic solvent). We demonstrate that EGCG is a highly fluorescent molecule when excited at approximately 275 nm with emission maxima between 350 and 400 nm depending on solvent. Another smaller excitation peak was found when EGCG is excited at approximately 235 nm with maximum emission between 340 and 400 nm. We found that the fluorescence intensity (FI) of EGCG in AB at pH=7.0 is significantly quenched, and that it is about 85 times higher in an aprotic solvent DMSO. The Stokes shifts of EGCG fluorescence were determined by solvent polarity. In addition, while the emission maxima of EGCG fluorescence in AB, DMSO, and EtOH follow the Lippert-Mataga equation, its fluorescence in AN points to non-specific solvent effects on EGCG fluorescence. We conclude that significant solvent-dependent changes in both fluorescence intensity and fluorescence emission shifts can be effectively used to distinguish EGCG in aqueous solutions from EGCG in environments of different polarity, and, thus, can be used to study specific EGCG binding to protein binding sites where the environment is often different from aqueous in terms of polarity.
Journal Article
A path to improve colorectal cancer screening outcomes: faculty roundtable evaluation of cost-effectiveness and utility
The American Journal of Managed Care® and Exact Sciences Corporation hosted a roundtable meeting to discuss the impact of colorectal cancer (CRC) screening modalities on improving patient outcomes. The roundtable participants were a diverse panel of experts, including primary care, gastroenterology, and oncology providers; experts in health outcomes research and health policy; and managed care executives with commercial and public payer experience. Participants discussed CRC prevention and treatment strategies, screening modalities and adherence, molecular diagnostics, patient navigation, evaluation of large data sets, managed care, outcomes research, quality improvement, and reimbursement policies. They focused on developing better value-based medical policies and payment procedures, identifying knowledge, practice, and access deficits related to CRC screening. Participants also provided suggestions on how to improve care quality and patient outcomes through effective evidence-based approaches. They also discussed costeffectiveness modeling for CRC screening, specifically the advantages and the real-world limitations of these models.
Journal Article
Impact of Chiropractic Services at an On-Site Health Center
OBJECTIVE:To compare the influence of employer-sponsored, on-site chiropractic care against community-obtained care on health care utilization.
METHODS:This was a retrospective claims analysis of members of a single employee health plan receiving chiropractic care on-site or off-site from 2010 to 2012. Utilization differences were evaluated by having 1 health care event or more, including radiology or clinical visits.
RESULTS:There were 876 on-site and 759 off-site participants. The off-site group received more radiology services overall (55.5% vs 38.2%; P < 0.001) including magnetic resonance imaging, ultrasound, and radiograph (all P < 0.0001); had higher outpatient (P < 0.0001) and emergency department (P = 0.022) utilization; and demonstrated greater use of chiropractic care and physical therapy (both P < 0.0001).
CONCLUSIONS:Compared with off-site care, on-site chiropractic services are associated with lower health care utilization. These results support the value of chiropractic services offered at on-site health centers.
Journal Article
Is there an association between elevated or low serum levels of phosphorus, parathyroid hormone, and calcium and mortality in patients with end stage renal disease? A meta-analysis
Background
Biochemical markers of altered mineral metabolism have been associated with increased mortality in end stage renal disease patients. Several studies have demonstrated non-linear (U-shaped or J-shaped) associations between these minerals and mortality, though many researchers have assumed linear relationships in their statistical modeling. This analysis synthesizes the non-linear relationships across studies.
Methods
We updated a prior systematic review through 2010. Studies included adults receiving dialysis and reported categorical data for calcium, phosphorus, and/or parathyroid hormone (PTH) together with all-cause mortality. We performed 2 separate meta-analyses to compare higher-than-referent levels vs referent and lower-than-referent levels vs referent levels.
Results
A literature review showed that when a linear relationship between the minerals and mortality was assumed, the estimated associations were more likely to be smaller or non-significant compared to non-linear models. In the meta-analyses, higher-than-referent levels of phosphorus (4 studies, RR = 1.20, 95% CI = 1.15-1.25), calcium (3 studies, RR = 1.10, 95% CI = 1.05-1.14), and PTH (5 studies, RR = 1.11, 95% CI = 1.07-1.16) were significantly associated with increased mortality. Although no significant associations between relatively low phosphorus or PTH and mortality were observed, a protective effect was observed for lower-than-referent calcium (RR = 0.86, 95% CI = 0.83-0.89).
Conclusions
Higher-than-referent levels of PTH, calcium, and phosphorus in dialysis patients were associated with increased mortality risk in a selection of observational studies suitable for meta-analysis of non-linear relationships. Findings were less consistent for lower-than-referent values. Future analyses should incorporate the non-linear relationships between the minerals and mortality to obtain accurate effect estimates.
Journal Article
Value of Chiropractic Services at an On-Site Health Center
Objective: Chiropractic care offered at an on-site health center could reduce the economic and clinical burden of musculoskeletal conditions. Methods: A retrospective claims analysis and clinical evaluation were performed to assess the influence of on-site chiropractic services on health care utilization and outcomes. Results: Patients treated off-site were significantly more likely to have physical therapy (P < 0.0001) and outpatient visits (P < 0.0001). In addition, the average total number of health care visits, radiology procedures, and musculoskeletal medication use per patient with each event were significantly higher for the off-site group (all P < 0.0001). Last, headache, neck pain, and low back pain-functional status improved significantly (all P < 0.0001). Conclusions: These results suggest that chiropractic services offered at on-site health centers may promote lower utilization of certain health care services, while improving musculoskeletal function.
Journal Article
Systematic Review and Meta-analysis of Real-World Adherence to Drug Therapy for Osteoporosis
To quantify the adherence of patients to drug therapy for osteoporosis in real-world settings via a systematic review and meta-analysis of observational studies.
The PubMed and Cochrane databases were searched for English-language observational studies published from January 1, 1990, to February 15, 2006, that assessed patient adherence to drug therapy for osteoporosis using the following medical subject headings and keywords:
drug therapy, medication adherence, medication persistence, medication possession ratio, patient compliance, and
osteoporosis. Studies were stratified into 3 groups: persistence (how long a patient continues therapy), compliance (how correctly, in terms of dose and frequency, a patient takes the medication), and adherence (a combination of persistence and compliance). A random-effects model was used to pool results from the selected studies.
Twenty-four studies were included in the meta-analysis. The pooled database-derived persistence rate was 52% (95% confidence interval [CI], 44%-59%) for treatment lasting 1 to 6 months, 50% (95% CI, 37%-63%) for treatment lasting 7 to 12 months, 42% (95% CI, 20%-68%) for treatment lasting 13 to 24 months, returning to 52% (95% CI, 45%-58%) for treatment lasting more than 24 months. Pooled adherence rates decreased from 53% (95% CI, 52%-54%) for treatment lasting 1 to 6 months to 43% for treatment lasting 7 to 12 months (95% CI, 38%-49%) or 13 to 24 months (43%; 95% CI, 32%-54%). The pooled refill compliance estimate was 68% (95% CI, 63%-72%) for treatment lasting 7 to 12 months and 68% (95% CI, 67%-69%) for treatment lasting 13 to 24 months. The pooled self-reported compliance rate was 62% (95% CI, 48%-75%) for treatment lasting 1 to 6 months and 66% (95% CI, 45%-81%) for treatment lasting 7 to 12 months.
One-third to half of patients do not take their medication as directed. Nonadherence occurs shortly after treatment initiation. Terms and definitions need to be standardized to permit comparability of technologies designed to improve patient adherence. Prospective trials are needed to assess the relationship between adherence and patient outcomes.
Journal Article
Managing the Risks of On-site Health Centers
This review sought to assess compliance concerns, determine risk management strategies, and identify opportunities for future research to contribute to employers' understanding of the laws and regulations that apply to on-site care. A comprehensive review of databases, professional organizations' websites, and journals resulted in 22 publications reporting on the consequences of noncompliance among on-site health centers accepted for inclusion. None of those studies reported a study design or quantifiable outcome data. Two noncompliance themes were repeated among the publications. First, direct penalties included fines, civil actions, loss of licensure, and, potentially, criminal charges. Second, noncompliance also resulted in indirect costs such as employee mistrust and lowered standards of care, which jeopardize on-site health centers' ability to demonstrate a return on investment. Further research with rigorous methodology is needed to inform employer decisions about on-site health services and associated risk management.
Journal Article