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- Analgesics for Osteoarthritis: An Update of the 2006 Comparative Effectiveness Review
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Executive Summary – Oct. 24, 2011
Analgesics for Osteoarthritis: An Update of the 2006 Comparative Effectiveness Review
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Table of Contents
- Background
- Objectives
- Analytic Framework
- Methods
- Results
- Discussion and Future Research
- Glossary
- References
- Full Report
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Osteoarthritis is a chronic condition involving degeneration of cartilage within the joints. It is the most common form of arthritis and is associated with pain, substantial disability, and reduced quality of life.1 Surveys indicate that 5 to 17 percent of United States (U.S.) adults have symptomatic osteoarthritis of the knee, and 9 percent have symptomatic osteoarthritis of the hip.2 Osteoarthritis is more common with older age. The total costs for arthritis, including osteoarthritis, may be greater than 2 percent of the gross domestic product, with more than half of these costs related to work loss.3, 4
Common oral medications for osteoarthritis include nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen. Patients with osteoarthritis also use topical agents, and over-the-counter oral supplements not regulated by the U.S. Food and Drug Administration (FDA) as pharmaceuticals, including glucosamine and chondroitin.5 Opioid medications are also used for selected patients with refractory, chronic pain but are associated with special considerations related to their potential for addiction and abuse and were not included in this review.6-8 Each class of medication or supplement included in this review is associated with a unique balance of risks and benefits. In addition, benefits and harms may vary for individual drugs within a class. Nonpharmacologic interventions (such as physical therapy, weight reduction, and exercise) also help improve pain and functional status in patients with osteoarthritis, but were outside the scope of this review.5
A challenge in treating osteoarthritis is deciding which medications will provide the greatest symptom relief with the least harm. NSAIDs decrease pain, inflammation, and fever by blocking cyclooxygenase (COX) enzymes. NSAIDs are thought to exert their effects primarily through blocking different COX isoenzymes, in particular COX-1 and COX-2. COX-1 mediates the mucosal protection of the gastrointestinal mucosa, including protection from acid and platelet aggregation. COX-2 is found throughout the body, including joint and muscle, and mediates effects on pain and inflammation. By blocking COX-2, NSAIDs reduce pain compared with placebo in patients with arthritis,9 low back pain,10 minor injuries, and soft-tissue rheumatism. However, NSAIDs that also block the COX-1 enzyme (also called "nonselective NSAIDs") can cause gastrointestinal (GI) bleeding. The number of deaths in the United States due to use of non-aspirin NSAIDs is not known with certainty. One study estimated the number at 3,200 annually in the 1990s11, though other studies have reported higher estimates. Theoretically, NSAIDs that block only the COX-2 enzyme (also called "coxibs," "COX-2 selective NSAIDs," or "selective NSAIDs") should be safer with regard to GI bleeding, but were found to increase the risk of serious cardiovascular (CV) and other adverse events.
For this report, we defined the terms "selective NSAIDs" or "COX-2 selective NSAIDs" as drugs in the "coxib" class (celecoxib, rofecoxib, valdecoxib, etoricoxib, and lumiracoxib). We defined "partially selective NSAIDs" as other drugs shown to have partial in vitro COX-2 selectivity (meloxicam, etodolac, and nabumetone). However, whether partially selective NSAIDs are truly different from nonselective NSAIDs is unclear because COX-2 selectivity may be lost at higher doses and the effects of in vitro COX-2 selectivity on clinical outcomes are uncertain. Aspirin differs from other NSAIDs because it irreversibly inhibits platelet aggregation, and we considered the salicylic acid derivatives (aspirin and salsalate) a separate subgroup. We defined "non-aspirin, nonselective NSAIDs" or simply "nonselective NSAIDs" as "all other NSAIDs."
The Agency for Healthcare Research and Quality (AHRQ) funded a comparative effectiveness review (CER) of analgesics for osteoarthritis that was published in 2006.12 Since that time, additional research has become available to better understand the comparative efficacy and safety of oral and topical medications for osteoarthritis, and a study13 commissioned by AHRQ on the need to update CERs assigned high priority to the previous report on analgesics for osteoarthritis based on an assessment of the number of potentially outdated conclusions and ongoing issues related to safety.
The purpose of this comparative effectiveness review is to update the previous report12 that assessed the comparative efficacy and safety of nonopioid oral medications (selective and nonselective non-aspirin NSAIDs, aspirin, salsalate, and acetaminophen), over-the-counter supplements (chondroitin and glucosamine), and topical agents (NSAIDs and rubefacients, including capsaicin) for osteoarthritis.
The following Key Questions are the focus of our report:
Key Question 1
What are the comparative benefits and harms of treating osteoarthritis with oral medications or supplements?
- How do these benefits and harms change with dosage and duration of treatment?
The only benefits considered here are improvements in osteoarthritis symptoms. Evidence of harms associated with the use of NSAIDs includes studies of these drugs for treating osteoarthritis or rheumatoid arthritis and for cancer prevention.
Oral agents include:
COX-2 selective NSAIDs:
- celecoxib
Partially selective NSAIDs:
- etodolac
- meloxicam
- nabumetone
Non-aspirin, nonselective NSAIDs:
- diclofenac
- diflunisal
- fenoprofen
- flurbiprofen
- ibuprofen
- indomethacin
- ketoprofen
- ketorolac
- meclofenamate sodium
- mefenamic acid
- naproxen
- oxaprozin
- piroxicam
- sulindac
- tolmetin
Aspirin and salsalate:
- aspirin
- salsalate
Acetaminophen and supplements
- acetaminophen
- chondroitin
- glucosamine
Key Question 2
Do the comparative benefits and harms of oral treatments for osteoarthritis vary for certain demographic and clinical subgroups of patients?
- Demographic subgroups: age, sex, and race
- Coexisting diseases: cardiovascular conditions, such as hypertension, edema, ischemic heart disease, heart failure, peptic ulcer disease, history of previous gastrointestinal bleeding (any cause), renal disease, hepatic disease, diabetes, obesity
- Concomitant medication use: antithrombotics, corticosteroids, antihypertensives, selective serotonin reuptake inhibitors (SSRIs).
Key Question 3
What are the comparative effects of coprescribing H2 receptor antagonists, misoprostol, or proton pump inhibitors (PPIs) on the gastrointestinal harms associated with NSAID use?
Key Question 4
What are the comparative benefits and harms of treating osteoarthritis with oral medications compared with topical preparations, or of different topical medications compared with one another?
For this comparative effectiveness review update, changes have been made to clarify the Key Questions, but these changes do not alter the meaning of each Key Question. Additional coexisting diseases and concomitant medications were included.
Analytic Framework
The analytic framework (Figure A) depicts the Key Questions within the context of the populations, interventions, comparators, outcomes, timing, and setting (PICOTS). In general, the figure illustrates how the nonopioid oral medications, over-the-counter supplements, and topical agents may result in outcomes such as improvements in osteoarthritis symptoms. Also, adverse events may occur at any point after the treatment is received.
Figure A. Analytic framework
Input From Stakeholders
The topic for the original 2006 report12 was nominated in a public process. The Key Questions for that report were developed by investigators from the Evidence-based Practice Center (EPC) with input from a Technical Expert Panel (TEP), which helped to refine Key Questions, identify important issues, and define parameters for the review of evidence.
For the present report update, AHRQ proposed the same scope and Key Questions to the EPC. The EPC modified the Key Questions and list of included drugs after receiving input from a new TEP convened for this report update. Before participating in official TEP activities for this report, the TEP members disclosed all financial or other potential conflicts of interest with the topic and included drugs. The authors and the AHRQ Task Order Officer reviewed these conflicts and determined whether the disclosed potential conflicts of interest would compromise the report. The final TEP panel consists of individuals who did not have significant conflicts of interest.
Data Sources and Selection
We replicated the comprehensive search of the scientific literature conducted for the original CER, with an updated date range of 2005 to present to identify relevant studies addressing the Key Questions. We searched the Cochrane Database of Systematic Reviews (through January 2011) the Cochrane Central Register of Controlled Trials (through fourth quarter 2010) and Ovid MEDLINE (2005– January 2011). We used relatively broad searches, combining terms for drug names with terms for relevant research designs, limiting to those studies that focused on osteoarthritis and rheumatoid arthritis. Other sources include selected grey literature provided to the EPC by the Scientific Resource Center librarian, reference lists of review articles, and citations identified by public reviewers of the Key Questions. Pharmaceutical manufacturers were invited to submit scientific information packets, including citations and unpublished data.
We developed criteria for inclusion and exclusion of studies based on the Key Questions and the PICOTS approach. Abstracts were reviewed using abstract screening criteria and a two-pass process to identify potentially relevant studies. For the first pass, the abstracts were divided between three investigators. In the second pass, a fourth investigator reviewed all abstracts not selected for inclusion in the first pass. Two investigators then independently reviewed all potentially relevant full text using a more stringent set of criteria for inclusion and exclusion.
As specified in the Key Questions, this review focuses on adults with osteoarthritis. We included studies that evaluate the safety, efficacy, or effectiveness of the included medications in adults with osteoarthritis. We also included studies that report safety in patients with rheumatoid arthritis or who were taking the drug for cancer or Alzheimer's prevention.
We considered studies that compared any of the oral and topical analgesics listed above to another included drug or placebo. For this report, we categorized NSAIDs as "COX-2 selective," "partially selective," salicylic acid derivatives, and "non-aspirin, nonselective" NSAIDs as described on p. ES-5. We excluded evidence on NSAIDs unavailable in the United States, leaving celecoxib as the only COX-2 selective NSAID included in this update.
We included studies that evaluate the safety, efficacy, or effectiveness of the previously mentioned medications. Primary outcomes include improvements in osteoarthritis symptoms and adverse events. Adverse events were evaluated from studies of the drugs used for osteoarthritis, rheumatoid arthritis, or cancer treatment. Specific adverse events evaluated include CV [stroke, myocardial infarction, congestive heart failure, hypertension, and angina]; GI [perforations, symptomatic gastroduodenal ulcers and upper GI bleeding (PUBs), obstructions, and dyspepsia]; renal toxicity; and hepatotoxicity. Other outcomes of interest were quality of life and sudden death.
We defined "benefits" as relief of pain and osteoarthritic symptoms and improved functional status. The main outcome measures for this review were pain, functional status, and discontinuations due to lack of efficacy. Frequently used outcome measures include visual and categorical pain scales.14
We included systematic reviews15 and controlled trials pertinent to the Key Questions. We retrieved and evaluated for inclusion and exclusion any blinded or open, parallel, or crossover randomized controlled trial that compared one included drug to another, another active comparator, or placebo. We also included cohort and case-control studies with at least 1,000 cases or participants that evaluated serious GI and CV endpoints that were inadequately addressed by randomized controlled trials. We excluded non-English language studies unless they were included in an English language systematic review, in which case we relied on the data abstraction and results as reported in the systematic review. All 1,183 citations from these sources and the original report were imported into an electronic database (EndNote X3) and considered for inclusion.
Data Extraction and Quality Assessment
After studies were selected for inclusion based on the Key Questions and PICOTS, the following data were abstracted and used to assess applicability (see discussion below) (and quality of the study: study design; inclusion and exclusion criteria; population and clinical characteristics (including sex, age, ethnicity, diagnosis, comorbidities, concomitant medications, GI bleeding risk, CV risk); interventions (dose and duration); method of outcome ascertainment, if available; the number of patients randomized relative to the number of patients enrolled, and how similar those patients were to the target population; whether a run in period was used; the funding source; and results for each outcome, focusing on efficacy and safety. We recorded intention-to-treat results if available. Data abstraction for each study was completed by two investigators: the first abstracted the data, and the second reviewed the abstracted data for accuracy and completeness.
We assessed the quality of systematic reviews, randomized trials, and cohort and case control studies based on predefined criteria. We adapted criteria from the Assessment of Multiple Systematic Reviews (AMSTAR) tool (systematic reviews),16 methods proposed by Downs and Black (observational studies),17 and methods developed by the U.S. Preventive Services Task Force.18 The criteria used are similar to the approach AHRQ recommended in the draft Methods Reference Guide for Effectiveness and Comparative Effectiveness Reviews.19
Individual studies were rated as "good," "fair" or "poor."18 Studies rated "good" have the least risk of bias and results are considered valid. Good quality studies include clear descriptions of the population, setting, interventions, and comparison groups; a valid method for allocation of patients to treatment; low dropout rates, and clear reporting of dropouts; appropriate means for preventing bias; appropriate measurement of outcomes, and reporting results.
Studies rated "fair" are susceptible to some bias, but it is not sufficient to invalidate the results. These studies do not meet all the criteria for a rating of good quality because they have some deficiencies, but no flaw is likely to cause major bias. The study may be missing information, making it difficult to assess limitations and potential problems. The "fair" quality category is broad, and studies with this rating vary in their strengths and weaknesses: the results of some fair-quality studies are likely to be valid, while others are only probably valid.
Studies rated "poor" have significant flaws that imply biases of various types that may invalidate the results. They have a serious or "fatal" flaw in design, analysis, or reporting; large amounts of missing information; or discrepancies in reporting. The results of these studies are at least as likely to reflect flaws in the study design as the true difference between the compared drugs. We did not a priori exclude studies rated poor quality, but poor quality studies were considered to be less reliable than higher quality studies when synthesizing the evidence, particularly when discrepancies between studies were present.
Studies could receive one rating for assessment of efficacy and a different rating for assessment of harms. Study quality was assessed by two independent investigators, and disagreements were resolved by consensus.
The applicability of trials and other studies was assessed based on whether the publication adequately described the study population, how similar patients were to the target population in whom the intervention will be applied, whether differences in outcomes were clinically (as well as statistically) significant, and whether the treatment received by the control group was reasonably representative of standard practice.20 We also recorded the funding source and role of the sponsor. We did not assign a rating of applicability (such as "high" or "low") because applicability may differ based on the user of this report.
We assessed the overall strength of evidence for a body of literature about a particular Key Question in accordance with AHRQ's Methods Guide for Comparative Effectiveness Reviews,19 based on evidence included in the original CER,12 as well as new evidence identified for this update. We considered the risk of bias (based on the type and quality of studies); the consistency of results within and between study designs; the directness of the evidence linking the intervention and health outcomes; the precision of the estimate of effect (based on the number and size of studies and the confidence intervals for the estimates); strength of association (magnitude of effect); and the possibility for publication bias.
We rated the strength of evidence for each Key Question using the four categories recommended in the AHRQ guide:19 A "high" grade indicates high confidence that the evidence reflects the true effect and that further research is very unlikely to change our confidence in the estimate of effect; a "moderate" grade indicates moderate confidence that the evidence reflects the true effect and further research may change our confidence in the estimate of effect and may change the estimate; a "low" grade indicates low confidence that the evidence reflects the true effect and further research is likely to change the confidence in the estimate of effect and is likely to change the estimate; an "insufficient" grade indicates evidence either is unavailable or does not permit a conclusion.
Table A provides a summary of the strength of evidence and brief results from this review, based on the evidence included in the original CER and new evidence identified for this update. Overall, we found no clear differences in efficacy of different NSAIDs, but there were potentially important differences in risk of serious harms. Celecoxib may be associated with decreased risk of serious GI events and a number of NSAIDs (selective and nonselective) appear to be associated with increased risk of serious CV risks. Furthermore, individuals are likely to differ in how they prioritize the importance of the various benefits and harms of treatment. Adequate pain relief at the expense of an increase in CV risk, for example, could be an acceptable tradeoff for some patients. Others may consider even a marginal increase in CV risk unacceptable. Factors that should be considered when weighing the potential effects of an analgesic include age (older age being associated with increased risks for bleeding and CV events), comorbid conditions, and concomitant medication use (such as aspirin and anticoagulation medications). As in other medical decisions, choosing the optimal analgesic for an individual with osteoarthritis should always involve careful consideration and thorough discussion of the relevant tradeoffs.
|Key Question
|Strength of Evidence
|CHF = congestive heart failure; CI = confidence interval; CLASS = Celecoxib Long-term Arthritis Safety Study; COX = cyclooxygenase; CV = cardiovascular; FDA = U.S. Food and Drug Administration; GI = gastrointestinal; H2 = histamine 2; HR = hazard ratio; HTN = hypertension; INR = international normalized ratio; NIH = National Institutes of Health; NNT = number needed to treat; NSAID = non-steroidal anti-inflammatory drug; OR = odds ratio; PPI = proton pump inhibitor; PUD = peptic ulcer disease; RR = relative risk; VAS = visual analogue scale
|1. What are the comparative benefits and harms of treating osteoarthritis with oral medications or supplements?
|Benefits: Celecoxib vs. nonselective NSAIDs
|High (consistent evidence from many randomized trials)
|No clear difference in efficacy for pain relief, or withdrawals due to lack of efficacy.
|Benefits: Partially selective NSAIDs vs. nonselective NSAIDs
|High for meloxicam and etodolac (many randomized trials), low for nabumetone (2 short-term randomized trials)
|Meloxicam was associated with no clear difference in efficacy compared to nonselective NSAIDs in 11 head-to-head trials of patients with osteoarthritis, but a systematic review that included trials of patients with osteoarthritis or rheumatoid arthritis found lesser effects on pain compared to nonselective NSAIDs (difference 1.7 points on a 10 point VAS pain scale) and withdrawals due to lack of efficacy (RR 1.5, 95% CI 1.2 to 1.7).
Etodolac and nonselective NSAIDs were associated with no statistically significant differences on various efficacy outcomes in several systematic reviews of patients with osteoarthritis, with consistent results reported in 7 trials not included in the systematic reviews.
Nabumetone was similar in efficacy to nonselective NSAIDs in two trials.
|Benefits: Nonselective NSAID vs. nonselective NSAID
|High (consistent evidence from many randomized trials)
|No difference in efficacy between various non-aspirin, nonselective NSAIDs.
|Benefits: Aspirin or salsalate vs. other NSAIDs
|Low (one randomized trial)
|No difference in efficacy between aspirin and salsalate in one head-to-head trial. No trial compared aspirin or salsalate vs. other NSAIDs.
|GI and CV harms: Celecoxib
|High for GI harms vs. nonselective NSAIDs (multiple systematic reviews and meta-analyses of mostly short-term trials, multiple observational studies; limited long-term data on serious GI harms)
Moderate for CV harms vs. nonselective NSAIDs (multiple systematic review and meta-analyses of longer-term trials; some inconsistency between randomized trials and observational studies)
Moderate for CV harms vs. placebo (multiple systematic reviews and meta-analyses; mostly from trials of colon polyp prevention)
|GI harms: Celecoxib was associated with a lower risk of ulcer complications (RR 0.23, 95% CI 0.07 to 0.76) and ulcer complications or symptomatic ulcers (RR 0.39, 95% CI 0.21-0.73) compared with nonselective NSAIDs in a systematic review of randomized trials. The systematic review included the pivotal, large, long-term CLASS study, in which celecoxib was superior to diclofenac or ibuprofen for ulcer complications or symptomatic ulcers at 6-month followup (2.1% vs. 3.5%, p=0.02), but not at 12-month followup. However, CLASS found difference in rates of ulcer complications alone at either 6 or 12 months. Other long-term followup data from randomized trials is lacking. A systematic review found celecoxib associated with a lower risk of upper GI bleeding or perforation compared to various nonselective NSAIDs based on 8 observational studies, though confidence interval estimates overlapped in some cases.
CV harms: There was no increase in the rate of cardiovascular events with celecoxib vs. ibuprofen or diclofenac in CLASS (0.5% vs. 0.3%). In three systematic reviews of randomized trials, celecoxib was associated with increased risk of cardiovascular events compared to placebo (risk estimates ranged from 1.4 to 1.9). A systematic review of placebo-controlled trials with at least 3 years of planned followup found celecoxib associated with an increased risk of cardiovascular events (CV death, myocardial infarction, stroke, heart failure, or thromembolic event) compared to placebo (OR 1.6, 95% CI 1.1-2.3). About 3.7 additional cardiovascular events occurred for every 1,000 patients treated for one year with celecoxib instead of placebo, or 1 additional cardiovascular event for every 270 patients treated for 1 year with celecoxib instead of placebo. The risk was highest in patients prescribed celecoxib 400 mg twice daily compared to celecoxib 200 mg twice daily or 400 mg once daily. Much of the evidence for increased risks comes from two large colon polyp prevention trials. A network analysis of randomized trials and three large observational studies found celecoxib associated with no clear difference in risk of myocardial infarction compared to naproxen, ibuprofen, or diclofenac; a fourth observational study found celecoxib associated with lower risk than ibuprofen or naproxen. 11 of 13 large observational studies found celecoxib associated with no increased risk of myocardial infarction compared to nonuse of NSAIDs.
An analysis of all serious adverse events in CLASS based on FDA data found no difference between celecoxib (12/100 patient-years), diclofenac (10/100 patient-years), and ibuprofen (11/100 patient-years). A retrospective cohort study found celecoxib and ibuprofen associated with neutral risk of hospitalization for acute myocardial infarction or GI bleeding compared to use of acetaminophen, but naproxen was associated with increased risk (HR 1.6, 95% CI 1.3 to 1.9).
|GI and CV harms: Partially selective NSAIDs
|GI harms: Moderate for meloxicam and etodolac (fewer trials with methodological shortcomings), low for nabumetone (sparse data)
CV harms: Insufficient for all (no trials, few large observational studies)
|GI harms: Meloxicam (primarily at a dose of 7.5 mg/day) was associated with a lower risk of ulcer complications or symptomatic ulcers compared to various nonselective NSAIDs in 6 trials included in a systematic review (RR 0.53, 95% CI 0.29 to 0.97), but the difference in risk of ulcer complications alone did not reach statistical significance (RR 0.56, 95% CI 0.27 to 1.2). Etodolac (primarily at a dose of 600 mg/day) was associated with a lower risk of ulcer complications or symptomatic ulcer compared to various nonselective NSAIDs in 9 trials included in a systematic review (RR 0.32, 95% CI 0.15 to 0.71), but the difference in risk of ulcer complications alone did not reach statistical significance (RR 0.39, 95% CI 0.12 to 1.2) and the number of events was very small. Evidence was insufficient to make reliable judgments about GI safety of nabumetone.
CV harms: Three observational studies found meloxicam associated with no increased risk of serious CV events relative to nonuse. One observational study evaluated etodolac and nabumetone, but estimates were imprecise.
|GI and CV harms: Nonselective NSAIDs
|GI harms: High for naproxen, ibuprofen, and diclofenac (consistent evidence from many trials and observational studies); insufficient for other nonselective NSAIDs (very little evidence)
CV harms vs. placebo: Moderate for ibuprofen, diclofenac, and naproxen (almost all evidence from observational studies, few large, long-term controlled trials, indirect evidence); insufficient for other nonselective NSAIDs (very little evidence)
CV harms vs. selective NSAIDs: Moderate for ibuprofen, diclofenac, and naproxen (few large, long-term controlled trials, indirect evidence); insufficient for other nonselective NSAIDs (very little evidence)
|GI harms: COX-2 selective NSAIDs as a class were associated with a similar reduction in risk of ulcer complications vs. naproxen (RR 0.34, 95% CI 0.24 to 0.48), ibuprofen (RR 0.46, 95% CI 0.30 to 0.71), and diclofenac (RR 0.31, 95% CI 0.06 to 1.6) in a systematic review of randomized trials. Evidence from randomized trials on comparative risk of serious GI harms associated with other nonselective NSAIDs is sparse. In large observational studies, naproxen was associated with a higher risk of serious GI harms than ibuprofen in 7 studies. Comparative data on GI harms with other nonselective NSAIDs was less consistent.
CV harms: An indirect analysis of randomized trials found ibuprofen (RR 1.5, 95% CI 0.96 to 2.4) and diclofenac (RR 1.6, 95% CI 1.1 to 2.4), but not naproxen (RR 0.92, 95% CI 0.67 to 1.3) associated with an increased risk of myocardial infarction relative to placebo. 1 additional myocardial infarction occurred for about every 300 patients treated for 1 year with celecoxib instead of naproxen. A network analysis of randomized trials reported consistent results with regard to CV events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death; ibuprofen: RR 2.3, 95% CI 1.1 to 4.9; diclofenac: RR 1.6, 95% CI 0.85 to 3.0 and naproxen: RR 1.2, 955 CI 0.78 to 1.9). An Alzheimer's disease prevention trial was stopped early due to a trend towards increased risk of myocardial infarction (HR 1.5, 95% CI 0.69 to 3.2) vs. placebo, but did not employ prespecified stopping protocols. In most large observational studies, naproxen was associated with a neutral effect on risk of serious CV events.
|GI and CV harms: Aspirin
|Moderate for GI and CV harms (many trials, but almost exclusively in patients receiving aspirin for cardiovascular disease prevention, usually at lower prophylactic doses)
|GI harms: A systematic review of individual patient trial data found aspirin associated with increased risk of major GI and other extracranial bleeding when given for primary prevention of vascular events (RR 1.5, 95% CI 1.3 to 1.8, absolute risk 0.10% vs. 0.07%). Observational studies showed a similar risk of upper GI bleeding with aspirin and non-aspirin, nonselective NSAIDs.
CV harms: Aspirin reduced the risk of vascular events in a collaborative meta-analysis of individual patient data from18 randomized controlled trials (0.51% aspirin vs. 0.57% control per year, p=0.0001 for primary prevention and 6.7% vs. 8.2% per year, p<0.0001 for secondary prevention).
|GI and CV safety: Salsalate
|No randomized trial or observational study evaluated risk of serious GI or CV harms with salsalate.
|Moderate (randomized trials with few events, and observational studies)
|Large randomized trials and a meta-analysis of trials showed no difference between celecoxib and nonselective NSAIDs, but there were few events. One fair-quality cohort study found nabumetone associated with lower all-cause mortality compared with diclofenac and naproxen, but this finding has not been replicated.
|HTN, CHF, and impaired renal function
|Moderate (randomized trials and observational studies, but analyses limited by incomplete reporting of outcomes)
|All NSAIDs are associated with deleterious effects on blood pressure, edema, and renal function. No clear evidence of clinically relevant, consistent differences between celecoxib, partially selective, and nonselective NSAIDs in risk of hypertension, heart failure, or impaired renal function.
|High (many trials and large epidemiologic studies)
|Several NSAIDs associated with high rates of hepatotoxicity have been removed from the market. A systematic review found clinically significant hepatotoxicity rare with currently available NSAIDs. A systematic review of randomized trials found no difference between celecoxib, diclofenac, ibuprofen, and naproxen in clinical hepatobiliary adverse events, though diclofenac was associated with the highest rate of hepatic laboratory abnormalities (78/1000 patient-years, vs. 16 to 28/1000 patient-years for the other NSAIDs). Another systematic review found diclofenac associated with the highest rate of aminotransferase elevations compared to placebo (3.6% vs. 0.29%, compared to <0.43% with other NSAIDs).
|High for celecoxib and nonselective NSAIDs, moderate for partially selective NSAIDs (fewer trials with some methodological shortcomings)
|The most recent systematic review of randomized trials found celecoxib associated with a lower risk of GI-related adverse events (RR 0.75, 95% CI 0.70 to 0.80) and withdrawals due to GI adverse events (RR 0.45, 95% CI 0.33 to 0.56) compared to nonselective NSAIDs, but the difference in risk of any adverse event or withdrawal due to any adverse event did not reach statistical significance). Meloxicam was also associated with decreased risk of any adverse event (RR 0.91, 95% CI 0.84 to 0.99), any GI adverse events (RR 0.31, 95% CI 0.24 to 0.39), and withdrawals due to GI adverse events (RR 0.61, 95% CI 0.54 to 0.69) compared to nonselective NSAIDs, though there was no difference in risk of withdrawal due to any adverse event. Etodolac was associated with lower risk of any adverse event compared to nonselective NSAIDs (RR 0.83, 95% CI 0.70 to 0.99), but there was no difference in risk of GI adverse events, withdrawal due to adverse events, or withdrawal due to GI adverse events. A meta-analysis found nabumetone associated with similar GI adverse events (25% vs. 28%, p=0.007) compared to nonselective NSAIDs.
In a systematic review of randomized trials, the only relatively consistent finding regarding the tolerability of different nonselective NSAIDs was that indomethacin was associated with higher rates of toxicity than other NSAIDs (statistical significant unclear).
|Acetaminophen is consistently modestly inferior to NSAIDs for reducing pain and improving function in randomized trials included in multiple systematic reviews. Acetaminophen is superior to NSAIDs for GI side effects (clinical trials data) and GI complications (observational studies). Some observational studies found acetaminophen associated with modest increases in blood pressure or higher risk of renal dysfunction compared to NSAIDs, but results may be susceptible to confounding by indication. One observational study found risk of acute myocardial infarction similar in users of acetaminophen compared to users of NSAIDs. Acetaminophen may cause elevations of liver enzymes at therapeutic doses in healthy persons; comparative hepatic safety has not been evaluated.
|Glucosamine and chondroitin
|High for glucosamine vs. oral NSAIDs; (consistent evidence from multiple trials)
Low for chondroitin vs. oral NSAIDs (one trial)
High for glucosamine or chondroitin vs. placebo (consistent evidence from recent, higher quality trials)
|Seven randomized trials showed no clear difference between glucosamine vs. oral NSAIDs for pain or function. One randomized trial showed no difference between chondroitin vs. an oral NSAID.
A systematic review including recent, higher quality trials found glucosamine associated with statistically significant but clinically insignificant beneficial effects on pain (-0.4 cm on a 10 cm scale, 95% CI -0.7 to -0.1) and joint space narrowing (-0.2 mm, 95% CI -0.3 to 0.0) compared with placebo. The systematic review reported similar results for chondroitin. A recent large, good-quality NIH-funded trial found the combination of pharmaceutical grade glucosamine hydrochloride and chondroitin sulfate modestly superior to placebo only in an analysis of a small subset of patients with at least moderate baseline pain. Older trials showed a greater benefit with glucosamine or chondroitin, but were characterized by lower quality. For glucosamine, the best results have been reported in trials sponsored by the manufacturer of a European, pharmaceutical grade product (no pharmaceutical-grade glucosamine available in the United States).
|High for effects of dose and duration (many trials and observational studies with some inconsistency); low for alternative dosage strategies (1 randomized trial)
|Higher doses of NSAIDs were associated with greater efficacy for some measures of pain relief, and in some trials with greater withdrawals due to adverse events.
A meta-analysis of 41 randomized trials found no clear association between longer duration of therapy with COX-2 selective NSAIDs and increase in the relative risk of CV events. The meta-analysis found higher doses of celecoxib associated with increased risk of cardiovascular events, but most events occurred in the long-term polyp prevention trials. Almost all of the cardiovascular events in trials of celecoxib were reported in long-term trials of colon polyp prevention.
Large observational studies showed no association between higher dose and longer duration of nonselective NSAID therapy and increased risk of cardiovascular events. Many observational studies found that risk of GI bleeding increased with higher doses of nonselective NSAIDs, but no clear association with duration of therapy.
One small trial found continuous celecoxib slightly more effective than intermittent use on pain and function, and similar rates of withdrawals due to adverse events. No trial was designed to assess serious GI or CV harms associated with intermittent dosing strategies.
|2. Do the comparative benefits and harms of oral treatments for osteoarthritis vary for certain demographic and clinical subgroups?
|Demographic subgroups including age, sex, and race
|Moderate for age (consistent evidence from observational studies)
Insufficient for sex and race (most studies included a majority of women, but studies didn't evaluate whether comparative benefits and harms vary in men and women or in different racial groups)
|The absolute risks of serious GI and CV complications increase with age. Large observational studies that stratified patients by age found no clear evidence of different risk estimates for different age groups. However, because the event rates increases in older patients, even if the relative risk estimates are the same, the absolute event rates are higher.
There is insufficient evidence to determine the comparative benefits and harms of different selective and nonselective NSAIDs in men compared to women, or in different racial groups.
|Preexisting disease including history of previous bleeding due to NSAIDs or peptic ulcer disease; hypertension, edema, ischemic heart disease, and heart failure
|Moderate for previous bleeding
Moderate for hypertension, edema, ischemic heart disease, heart failure (observational studies and few randomized trials)
|The risk of GI bleeding is higher in patients with prior bleeding. Two trials found high rates of recurrent ulcer bleeding in patients randomized to either celecoxib (4.9% to 8.9% with 200 mg twice daily) or a nonselective NSAID + PPI (6.3%). One trial found celecoxib plus high dose PPI associated with lower risk of bleeding compared with celecoxib alone (0% vs. 8.9%, p=0.0004).
A systematic review of randomized trials of celecoxib found risk of CV events doubled in patients at moderate vs. low risk (HR 2.0, 95% CI 1.5 to 2.6) and doubled again in patients at high risk (HR 3.9 for high risk vs. low risk, 95% CI 2.3 to 6.7). Most large observational studies found an association between increased cardiovascular risk and increased risk of cardiovascular events in persons using NSAIDs. Following hospitalization for heart failure, one large observational study found celecoxib and diclofenac associated with a higher risk of death compared to ibuprofen or naproxen, and another large observational study found an increased risk of repeat heart failure admission with indomethacin compared to other nonselective NSAIDs, ibuprofen, acetaminophen, or celecoxib.
|Concomitant anticoagulant use
|Moderate overall: Primarily observational studies
|Concomitant use of anticoagulants and nonselective NSAIDs increases the risk of GI bleeding three- to six-fold compared with anticoagulant use without NSAIDs. The risk with concomitant celecoxib is not clear due to conflicting findings among observational studies, but may be increased in older patients. Reliable conclusions about the comparative safety of nonselective, partially selective, and COX-2 selective NSAIDs with concomitant anticoagulants could not be drawn due to small numbers of studies with methodological shortcomings. Warfarin plus low-dose aspirin increased the risk of bleeding compared with warfarin alone in patients with indications for antithrombotic prophylaxis. Acetaminophen can increase INR levels, but effects on bleeding rates have not been studied.
|Concomitant use of prophylactic-dose aspirin
|High for GI harms: Consistent evidence from clinical trials and observational studies
Moderate for CV harms: Subgroup analyses from few trials, few observational studies
|Concomitant use of aspirin appears to attenuate or eliminate the GI benefits of selective NSAIDs, resulting in risks similar to nonselective NSAIDs. Concomitant low-dose aspirin increased the rate of endoscopic ulcers by about 6% in patients on celecoxib and those on nonselective NSAIDs in one meta-analysis. Addition of a PPI may reduce the risk of GI harms associated with use of either celecoxib or nonselective NSAIDs plus low-dose aspirin.
Evidence regarding the effects of concomitant aspirin use on CV risk associated with selective or nonselective NSAIDs is limited, though three polyp prevention trials of COX-2 selective NSAIDS found that concomitant aspirin use did not attenuate the observed increased risk of CV events. Observational studies did not find increased CV risk with the addition of nonselective NSAIDs as a class to low-dose aspirin. Limited evidence suggests an increased risk of mortality with aspirin and concomitant ibuprofen compared to aspirin alone among high risk patients (HR 1.9, 95% CI 1.3 to 2.9), but studies on effects of ibuprofen added to aspirin on MI risk in average risk patients were inconsistent and did not clearly demonstrate increased risk.
|3. What are the comparative effects of coprescribing of H2-antagonists, misoprostol, or PPIs on the gastrointestinal harms associated with NSAID use?
|High: Consistent evidence from good-quality systematic reviews and numerous clinical trials
|Misoprostol was the only gastroprotective agent to reduce risk of ulcer complications compared to placebo in patients with average risk of GI bleeding prescribed nonselective NSAIDs, but was also associated with a higher rate of withdrawals due to adverse GI symptoms.
Coprescribing of PPIs, misoprostol, and H2-antagonists all reduced the risk of endoscopically detected gastric and duodenal ulcers compared to placebo in patients prescribed a nonselective NSAID.
In direct comparisons, coprescribing of PPIs in patients with increased risk of GI bleeding who were prescribed a nonselective NSAID was associated with a lower risk of endoscopically detected duodenal ulcers compared to misoprostol or H2-antagonists, a lower risk of endoscopically detected gastric ulcers compared to H2-antagonists, and a similar risk of endoscopically detected gastric ulcers compared to misoprostol. Coprescribing of misoprostol was associated with a lower risk of endoscopically detected gastric ulcers compared to ranitidine, and a similar reduction in risk of endoscopically detected duodenal ulcers.
Compared to placebo, double (full) dose H2-antagonists may be more effective than standard dose for reducing endoscopically detected gastric and duodenal ulcers.
Celecoxib alone was associated with fewer decreases in hemoglobin (> 2 g/dl) without overt GI bleeding compared with diclofenac plus a PPI. Celecoxib plus a PPI may reduce the risk of endoscopic ulcers and ulcer complications compared to celecoxib alone in average risk persons.
|4. What are the comparative benefits and harms of treating osteoarthritis with oral medications compared with topical preparations?
|Topical NSAIDs: efficacy
|Moderate (consistent evidence for topical diclofenac from three trials)
|Three head-to-head trials found topical diclofenac similar to oral NSAIDs for efficacy in patients with localized osteoarthritis.
|Topical NSAIDs: safety
|Moderate (consistent evidence for topical diclofenac from three trials)
|Topical NSAIDs were associated with a lower risk of GI adverse events and higher risk of dermatologic adverse compared to oral NSAIDs. There was insufficient evidence to evaluate comparative risks of GI bleeding or CV events. Other topical NSAIDs evaluated in head-to-head trials have not been FDA approved.
|Topical salicylates and capsaicin
|Insufficient for topical salicylates or capsaicin versus oral NSAIDs (no head-to-head trials)
|No head-to-head trials compared topical salicylates or capsaicin to oral NSAIDs for osteoarthritis.
|Low for topical salicylates or capsaicin versus placebo (some placebo-controlled trials)
|Topical salicylates were no better than placebo in two trials of patients with osteoarthritis included in a systematic review, and associated with increased risk of local adverse events when used for any acute or chronic pain condition. Topical capsaicin was superior to placebo (NNT 8.1), but associated with increased local adverse events and withdrawals due to adverse events (13% vs. 3%, RR 4.0, 95% CI 2.3 to 6.8).
Discussion and Future Research
This report provides a summary of the evidence on the comparative benefits and harms of oral NSAIDs (celecoxib, partially selective, nonselective, aspirin, and salsalate), acetaminophen, certain over-the-counter supplements (chondroitin and glucosamine), and topical agents (NSAIDs, salicylates, and capsaicin) that are commonly used for pain control and improvement of functional status in patients with osteoarthritis. At this time, no drug or supplement is known to modify the course of disease, though some data suggest potential effects of glucosamine or chondroitin on slowing progression of joint space narrowing.
Major new evidence included in this update include a large trial of celecoxib versus a PPI) plus naproxen and risk of GI bleeding, new placebo-controlled trials of glucosamine and chondroitin, and a new head-to-head trial of topical versus oral diclofenac. Other new evidence in this update includes large observational studies on serious GI and CV harms associated with NSAIDs, and a number of systematic reviews. Like the original CER, a limitation of this update is that studies have not used standardized methods for defining and assessing harms.
As in the original CER, evidence indicates that each of the analgesics evaluated in this report is associated with a unique set of risks and benefits. The role of selective, partially selective, and nonselective oral NSAIDs and alternative agents will continue to evolve as additional information emerges. At this time, although the amount and quality of evidence varies, no currently available analgesic reviewed in this report offers a clear overall advantage compared with the others, which is not surprising given the complex trade-offs between many benefits (pain relief, improved function, improved tolerability, and others) and harms (CV, renal, GI, and others). In addition, individuals are likely to differ in how they prioritize the importance of the various benefits and harms of treatment. Adequate pain relief at the expense of a small increase in CV risk, for example, could be an acceptable tradeoff for many patients. Others may consider even a marginal increase in CV risk unacceptable. Factors that should be considered when weighing the potential effects of an analgesic include age (older age being associated with increased risks for bleeding and CV events), comorbid conditions, and concomitant medication use (such as aspirin and anticoagulation). As in other medical decisions, choosing the optimal analgesic for an individual with osteoarthritis should always involve careful consideration and thorough discussion of the relevant tradeoffs.
The report identified a number of important areas for future research:
- Nearly all of the clinical trials reviewed in this report were "efficacy" trials conducted in ideal settings and selected populations. "Pragmatic" trials that allow flexible dosing or medication switches and other clinical trials of effectiveness would be very valuable for learning the outcomes of different analgesic interventions in real-world settings.
- The CV safety of nonselective NSAIDs has not been adequately assessed in large, long-term clinical trials. Naproxen in particular might have a different CV safety profile from other NSAIDs and should be investigated in long-term, appropriately powered trials.
- Large observational studies assessing the safety of NSAIDs have been helpful for assessing comparative benefits and harms, but have generally had a narrow focus on single adverse events. More observational studies that take a broader view of all serious adverse events would be more helpful for assessing the overall trade-offs between benefits and harms.
- The CV risks and GI benefits associated with different COX-2 selective NSAIDs might vary. Large, long-term trials with active and placebo-controlled arms would be needed to assess the safety and benefits of any new COX-2 selective analgesic.
- Meta-analyses of the risks associated with selective COX-2 inhibitors need to better assess for the effects of dose and duration, as most of the CV harms have only occurred with prolonged use and at higher doses.
- Large, long-term trials of the GI and CV safety associated with full-dose aspirin, salsalate, or acetaminophen compared with non-aspirin NSAIDs or placebo are lacking.
- Trials and observational studies evaluating comparative safety or efficacy should be sufficiently inclusive to evaluate whether effects differ by race or gender.
- Genetic testing could theoretically help predict patients who are at higher risk of CV complications from selective COX-2 inhibitors because of differences in the COX-2 gene promoter or other genes. This remains a promising area of future research.
- The effects of alternative dosing strategies such as intermittent dosing or drug holidays have not been well studied. Studies evaluating the benefits and risks associated with such strategies compared with conventional dosing could help clarify the effects of these alternative dosing strategies. In addition, although there is speculation that once daily versus twice daily dosing of certain COX-2 inhibitors could affect CV risk; this hypothesis has not yet been tested in a clinical trial.
- Most trials showing therapeutic benefits from glucosamine were conducted using pharmaceutical-grade glucosamine not available in the United States and may not be applicable to currently available over-the-counter preparations. Large trials comparing currently available over-the-counter preparations to oral NSAIDs are needed, as these are likely to remain available even if the FDA approves a pharmaceutical grade glucosamine. Additional long-term trials are also required to further evaluate effects of glucosamine on progression of joint space narrowing and to determine the clinical effects of any beneficial effects on radiolographic outcomes.
- Head-to-head trials of topical versus oral NSAIDs have not been large enough to evaluate the risks of serious CV and GI harms. Additional head-to-head trials and large cohort studies may be required to adequately assess serious harms.
For this report, we have defined the terms as follows:
- Selective NSAIDs or COX-2 selective NSAIDs: Drugs in the "coxib" class (celecoxib).
- Partially selective NSAIDs: Other drugs shown to have partial in vitro COX-2 selectivity (etodolac, nabumetone, meloxicam).
- Aspirin: Differs from other NSAIDs, because it irreversibly inhibits platelet aggregation; salicylic acid derivatives (aspirin and salsalate) are considered a separate subgroup.
- All other NSAIDs: Non-aspirin, nonselective NSAIDs, or simply nonselective NSAIDs.
- Towheed TE, Maxwell L, Anastassiades TP, et al. Impact of musculoskeletal disorders in Canada. Ann Roy Coll Physicians Surg Can 1998;31(5):229-32.
- Lawrence RC, Felson DT, Helmick CG, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part II. Arthritis Rheum 2008;58:26-35.
- Felson DT, Lawrence RC, Dieppe PA, et al. Osteoarthritis: New insights. Part 1: The disease and its risk factors. Ann Intern Med 2000;133:635-46.
- Felson DT, Zhang Y. An update on the epidemiology of knee and hip osteoarthritis with a view to prevention. Arthritis Rheum 1998;41(8):1343-55. PMID: 9704632
- Zhang W, Doherty M, Leeb BF, et al. EULAR evidence based recommendations for the management of hand osteoarthritis: report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2007;66(3):377-88. PMID: 17046965
- Chou R, Fanciullo GJ, Fine PG, et al. Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain. J Pain 2009;10(2):113-30.e22.
- Zhang W, Doherty M, Arden N, et al. EULAR evidence based recommendations for the management of hip osteoarthritis: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2005;64:669-81.
- Zhang W, Moskowitz RW, Nuki G, et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage 2008;16(2):137-62. PMID: 18279766
- Gotzsche PC. Musculoskeletal disorders. Non-steroidal anti-inflammatory drugs. Clin Evid 2003;(9):1292-300.
- van Tulder MW, Scholten R, Koes BW, Deyo RA. Non-steroidal anti-inflammatory drugs for low-back pain. Cochrane Database Syst Rev 2005;(3):CD000396. PMID: 00075320-100000000-00426
- Tarone RE, Blot WJ, McLaughlin JK. Nonselective nonaspirin nonsteroidal anti-inflammatory drugs and gastrointestinal bleeding: relative and absolute risk estimates from recent epidemiologic studies. Am J Therapeutics 2004;11:17-25.
- Chou R, Helfand M, Peterson K, et al. Comparative effectiveness and safety of analgesics for osteoarthritis. Comparative Effectiveness Review No.6 (Prepared by the Oregon Evidence-based Practice Center under Contract No. 290-02-0024.). 2006. PMID: 20704046
- Shekelle P, Newberry S, Maglione M, et al. Assessment of the Need to Update Comparative Effectiveness Reviews Report of an Initial Rapid Program Assessment (2005–2009). 2009. PMID: 21204320
- Strand V, Kelman A. Outcome measures in osteoarthritis: randomized controlled trials. Curr Rheumatol Rep 2004;6:20-30.
- Whitlock EP, Lin JS, Chou R, et al. Using existing systematic reviews in complex systematic reviews. Ann Intern Med 2008;148(10):776-82. PMID: 18490690
- Shea BJ, Hamel C, Wells GA, et al. AMSTAR is a reliable and valid measurement tool to assess the methodological quality of systematic reviews. J Clin Epidemiol 2009;62(10):1013-20. PMID: 19230606
- Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health. 1998;52(6):377-84. PMID: 9764259
- Harris RP, Helfand M, Woolf SH, et al. Current methods of the US Preventive Services Task Force: a review of the process. Am J Prev Med 2001;20(3 Suppl):21-35. PMID: 11306229
- Owens DK, Lohr KN, Atkins D, et al. AHRQ series paper 5: grading the strength of a body of evidence when comparing medical interventions—Agency for Healthcare Research and Quality and the Effective Health Care Program. J Clin Epidemiol 2010;63(5):513-23. PMID: 19595577
- Gartlehner G, Hansen RA, Nissman D, et al. A simple and valid tool distinguished efficacy from effectiveness studies. J Clin Epidemiol 2006;59(10):1040-8. PMID: 16980143
Full Report
This executive summary is part of the following document: Chou R, McDonagh MS, Nakamoto E, Griffin J. Analgesics for Osteoarthritis: An Update of the 2006 Comparative Effectiveness Review. Comparative Effectiveness Review No. 38. (Prepared by the Oregon Evidence-based Practice Center under Contract No. HHSA 290 2007 10057 I) AHRQ Publication No. 11-EHC076-EF. Rockville, MD: Agency for Healthcare Research and Quality. October 2011.
For More Copies
For more copies of Analgesics for Osteoarthritis: An Update of the 2006 Comparative Effectiveness Review: Comparative Effectiveness Review Executive Summary No. 38 (AHRQ Pub. No. 11-EHC076-1), please call the AHRQ Clearinghouse at 1-800-358-9295.


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This term is thrown around a lot on political forums and in the general public. Then, lefties accuse everyone else of not knowing the true meaning and saying it's not true. Let's get this settled.
Post concrete reasons/examples why or why not this term applies to our current government.
Hawaii Marijuana Dispensary

subset: commoncrawl


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Updated on 6 September 2013
Short Stay Service, also known as 'Day Surgery', involves admitting patients for a planned surgical procedure and releasing them the same day
Mumbai: PD Hinduja Hospital, which is one of India's premier healthcare providers, has inaugurated a dedicated Short Stay Service (SSS) wing.
The hospital currently performs over 120 procedures that usually require more than a day's admission. However, the launch of the dedicated SSS wing means that the lengthy procedures would now be completed in just a few hours.
Short Stay Service, also known as 'Day Surgery', involves admitting patients for a planned surgical procedure and releasing them the same day. This is being made possible by advancement in surgical technology and anaesthetic techniques.
The SSS wing offers 19 beds, four of which belong to the premium category. SSS patients will have access to quality care through state-of-the-art operation theatres, labs and qualified doctors. A team of customer service personnel will be on hand at all times, to guide patients right from admissions to check out, and keep track of patients' recovery even after discharge. The wing will also boast of a high nurse-to-bed ratio.
The benfits that the new SSS wing will offer to patients include, lower costs due to reduced length of stay; easy acceptance by insurance companies (as they favor short stay procedures); speedier return to work and community due to reduced length of stay; availability of home care service after discharge; and personalised customer care service.
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Cameron Kramer, of Chapel Hill, N.C., had finished her applications to other art schools, when her mother suggested that she look at Ringling College of Art and Design. The youthful artist was so impressed by the place and the "amazing teachers" that her other options did a fast fade to black. She moved here and is presently a sophomore majoring in illustration.
Except for her part-time job, we might not have heard about Kramer, who just turned 20 years old, for a few more years. But she wanted to work.
"I don't like asking my folks for money; they are already helping with my education," Kramer says.
So she applied at Sarasota Yogurt Co. on St. Armand's Circle, which proprietor Scott Pastor was preparing to renovate. His plans included hiring a professional artist to paint murals featuring local attractions. But, he, instead, asked to see his student employee's website (emivisuals.com/cameron-kramer.html) and gave her the job.
"I had never done a public-area project nearly as big as this," she says.
She started with sketches then drew them on the walls. (Pastor and his wife, Keely, have rescued the original drawings to display in their home.) Her medium was three primary colors of interior house paint from which she mixes her own shades.
"It was cheaper and easier," she says. She used no black to great effect — the murals virtually pop off the walls.
The artist created the first two paintings, featuring the sculpture "Unconditional Surrender" and fruits (pretty much matching what the shop offers in flavors and/or toppings), while the store was closed for renovation. She tried to work from 9 a.m. to 10 or 11 p.m., "as long as I could," for a week-and-a-half. There was still a blank wall when the shop re-opened, and Kramer "became nocturnal for a week" starting work at 11 p.m. for another week.
If you notice that most of the living creatures are sporting, spouting or sprouting frozen yogurt in some way — that's fair. These are, after all, the walls of the Sarasota Yogurt Co. the new serve-yourself specialty store at 327 Ringling Blvd. on the western spoke of St. Armands Circle.
Visit SarasotaYogurtCompany.com for more information.


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The father said to his servants, "Quick! Bring the best robe and put it on him. Put a ring on his finger and sandals on his feet. Bring the fattened calf and kill it. Let's have a feast and celebrate. For this son of mine was dead and is alive again; he was lost and is found." —Luke 15:22-24
Just as the prodigal's father was overwhelmed with joy at the return of his son, my Father God feels even more inexplicable joy when I come into His presence. He is a God who enjoys me even in my failure and immaturity, a God I don't have to strive to make happy, because He's already happy with me. He is a Father who cheers me on and enthusiastically calls me His son.
Father, Your love has changed my life and transformed my spirit. My heart is overflowing with the joy of knowing You have called me Your child.
I began my journey of understanding God's
affection for me, which powerfully changed
my life, replacing my guilt with holy
boldness and affection for Him.
Draw closer to God. Experience the presence of the Holy Spirit every month as you read Charisma magazine. Sign up now to get Charisma for as low as $1 per issue.
Get to know the Holy Spirit and how to interact with Him on a daily basis. Learn to enter God's presence and hear His voice clearly for yourself! Go deeper in your faith with Life in the Spirit and change your life and destiny. Are you ready to start your journey?


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What Kind of Housing Do I Need?
Senior Housing Listing Type Descriptions
55+ and 62 + Communities:
Age-restricted to residents at least 55 or 62 years old.
Multi-family housing; may be for all ages or seniors only.
Homes for Sale or Rent:
Single-family houses that may or may not be for seniors only.
Manufactured Homes for Sale or Rent:
Factory-built houses, on a permanent chassis, installed on site.
Independent Living:
Complexes with dining, housekeeping, transportation, activities.
Assisted Living:
For personal help with daily activities like bathing, dressing, meds.
Alzheimer's Care:
Memory care, often with medical staff, for dementia patients.
Continuing Care:
Tiered options, from independent to assisted, to age in place.
Nursing Homes:
Skilled nursing facilities that offer 24-hour medical support.
Low-Income Senior Housing:
Subsidized housing for seniors earning below set income limits.


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Wash Laundry basket. As shown, light grey. H60xØ38cm. [Wash]
Article no.: 104011029250
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Anaplastic thyroid carcinoma is a rare and aggressive form of cancer of the thyroid gland.
Anaplastic carcinoma of the thyroid
Anaplastic thyroid cancer grows very rapidly and is an invasive type of thyroid cancer. It occurs most often in people over age 60. The cause is unknown.
Anaplastic cancer accounts for only about 1% of all thyroid cancers.
A physical examination almost always show a neck growth.
Thyroid function blood tests are usually normal.
This type of cancer cannot be cured by surgery. Complete removal of the thyroid gland does not prolong most patients' life.
Of other treatment options, only radiation therapy combined with chemotherapy has a significant benefit.
Surgery to place a tube in the throat to help with breathing (tracheostomy) or in the stomach to help with eating (gastrostomy) may be needed.
For some patients, enrolling in a clinical trial of new thyroid cancer treatments may be an option.
You can often ease the stress of illness by joining a support group of people sharing common experiences and problems.
The outlook with this disease is poor. Most people do not survive longer than 6 months because the disease is aggressive and there is a lack of effective treatment options.
Call your health care provider if there is a persistent lump or mass in the neck, hoarseness, changing voice, cough, or coughing up blood.
Ladenson P, Kim M. Thyroid. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007: chap 244.
National Comprehensive Cancer Network. NCCN Guidelines in Oncology 2010: Thyroid Cancer. Version 1.2010.
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American Sociological Association
The Fund for the Advancement of the Discipline (FAD) is supported by the American Sociological Association through a matching grant from the National Science Foundation. The goal of the program is to nurture the development of scientific knowledge by funding small, groundbreaking research initiatives and other important scientific research activities such as conferences. FAD awards provide scholars with "seed money" for innovative research that has the potential for challenging the discipline, stimulating new lines of research, and creating new networks of scientific collaboration. The award is intended to provide opportunities for substantive and methodological breakthroughs, broaden the dissemination of scientific knowledge, and provide leverage for acquisition of additional research funds.
Deadlines: June 15 and Dec 15, Annually
Posted in: Social Sciences


text:
Radio Scrobbling via MQTT
Since I often listen to the most excellent Soma FM during the day (go support them, it's worth it!) I often wish that I could go and stash some similar tunes to listen to when I'm not online. To do this, I sell my soul to CBS and use last.fm to generate similar / listened to by others recommendations.
Sadly Rhythmnbox doesn't scrobble radio stations (even though the scrobble API has a flag for this
track.scrobble(chosenByUser=0) to indicate that its been chosen by a radio service), despite it updating my 'now listening' status on IM. So, in a geeky overkill solution I decided to save time in the long run and use a pub/sub system with MQTT. Oh, and use some python and twitter along the way...
The design is that I have an MQTT publisher that uses the tritter streaming api (via tweepy) and filters for all the somafm twitter streams that Rusty pushes with BigUrl. This gives me near realtime announcements of the start of the track being played (after some trivial split / strip manipulation)
justcovers Pat Boone - Enter Sandman (2012-06-25 07:20:30)
digitalis Zephyrs - Stand Round Hold Hands (Ulrich (2012-06-25 07:20:37)
secretagentsoma Eat Static - Love Truncheon (2012-06-25 07:21:02)
beatblender Kerry Chandler (Lazy Dog Ben W - Isis (2012-06-25 07:21:29)
sonicuniverse In The Country - Only The Birds Can See Us (2012-06-25 07:21:29)
Syndicated 2012-06-25 07:29:00 (Updated 2012-06-25 07:29:19) from Elwell


text:
In which I argue that the more sober treatments of Aiden Quinn's trans status were entirely appropriate, despite some of the more absurd and incendiary commentary they engendered.
Also, a correction--in the piece, I refer to Michele McPhee's FOIA request to the MBTA. As a sharp-eyed reader quickly noted, McPhee actually made a request under the Mass.


text:
You are here:
DIVISIONS » Water Permits » Offshore O&G Produced Water Discharge Permits
| Login
Petition for Judicial Review of the LAG260000 General Permit November 12, 2009
On June 10, 2011 the Louisiana First Circuit Court of Appeals remanded the LAG260000 General Permit to LDEQ.
Court of Appeals First Circuit Decision
Remanded General Permit for Discharges from oil and gas exploration, development and production facilities located within territorial seas of Louisiana (LAG260000)
Oil and Gas Exploration, Development, & Production Facilities Within Territorial Seas Individual Application
The LDEQ conducted a stakeholder meeting on February 23, 2012 at 1:30 p.m. at LDEQ headquarters, Galvez Building, Room 1051, 602 N. 5th St. Baton Rouge, LA 70802 to accept input from all stakeholders regarding the protocols and requirements for an evaluation of the effects of produced water discharges on the environment and human health.
Territorial Seas and Produced Water Discharges Presentation for stakeholder meeting held on February 23, 2012
Click here to view the timeline for issuance of the first LPDES individual permit
Click here to view the map of dischargers in the territorial seas
Click here to view the Louisiana Wildlife and Fisheries Oyster Lease Map
July 19, 2012 Meeting
Based on the input we received on stakeholder availability, we have finalized plans for the 2nd stakeholder meeting for produced water discharges in the Territorial Seas of Louisiana. The meeting will be held on Thursday, July 19, 2012 at LDEQ Headquarters in Room 1051 (same location as before) from 9:30 to 11:30 am.
The Agenda for this meeting will be:
1. To discuss comments we have received on the minimum study requirements (see revised study requirements )
2. We will hear any new comments
3. We will discuss the timeline for issuance of the first LPDES permit that will include the produced water study.
We will seek input from stakeholders on their plans for coordination/performing the study.
Click here to view the updated timeline for issuance of the first LPDES individual permit
Territorial Seas and Produced Water Discharges Presentation for stakeholder meeting held on July 19, 2012
The LDEQ, Office of Environmental Services is accepting comments on the produced water study minimum requirements for discharges of produced water into territorial seas. Click here for the proposed study requirements.
Comments can be submitted via personal delivery, U.S. Mail, email or fax. Comments are due by 4:30 PM on March 23, 2012. Delivery may be made to the drop-box at 602 North 5th Street, Baton Rouge, LA 70802. U.S. Mail may be sent to the LDEQ, Water Permits Division, Attn: Jenniffer Sheppard, P.O. Box 4313, Baton Rouge, LA 70821-4313. Emails may be submitted to email@example.com and faxes may be sent to 225-219-3309.
LDEQ is pleased to announce that the 1st individual LPDES Permit for Off Shore Oil and Gas facilities with produced water discharges for Breton Sound 53 Production Facility (LA0126250, AI 32659) was issued December 6, 2012, with an effective date of February 1, 2013. This permit includes the final study requirements and may be viewed by clicking on the following link: http://edms.deq.louisiana.gov/app/doc/view.aspx?doc=8629860&ob=yes&child=yes
The new timeline outlining the milestones for the Industry-Wide Study can be viewed by clicking here.
Various Produced Water Studies
Barium in Produced Water – Fate and Effects in the Marine Environment
Effects of Produced Water on Bottom Sediment Chemistry
Environmental Impact of Produced Water Discharges in Coastal Louisiana
EPA Definitive Component Report
EPA Executive Summaries
EPA Platform Survey Report
St. Pe Study
Fate and Effects of Drill Fluids and Cutting Discharges in Shallow, Nearshore Waters
Fate and Effects of Produced Water Discharges in Nearshore Marine Waters
Final Report – Risk Assessment for Produced Water Discharges to Louisiana Open Bays
Produced Water Impacts on Louisiana Wetlands
Produced Water Radionuclide Hazard – Risk Assessment Phase I
Produced Waters in Sensitive Coastal Habitats
Louisiana Department of Environmental Quality 602 N. Fifth Street Baton Rouge, LA 70802
Call or e-mail a hotline ·
Office Address/Phone listing · Locate a DEQ employee
Call 1-866-896-LDEQ or e-mail our Customer Service Center with questions or comments


text:
What Does Your Trash Say About You?
Posted On July 4, 2012 by Sarah van Schagen
Some people say "we are what we eat," but maybe what we throw away is just as telling.
In profiling the film "Raw Material" about the garbage pickers of Athens, writer Jennifer Hattam points out how life has changed for these scavengers now that the entire country is facing an economic crisis:
In the shadow of the Acropolis, they set off before dawn. Men and boys driving rusty trucks, pushing heavy hand-carts, towing wagons behind battered motorcycles. As the city slowly comes to life, they are already well into their day's work, scouring alleys and Dumpsters for old box-spring mattresses, appliances, car parts, anything they can salvage and sell at a scrap yard for a few dollars a day.
Many Athens residents have been struggling to get by since economic and political crisis erupted in Greece, threatening to engulf much of Europe. But the estimated 80,000 Athenians who collect and process scrap in the city's informal economy were eking out their meager livings back when the rest of the city was still living large. Continue reading »


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Category: Sponges view all from this category
Description 8" tall (20 cm) and 1" (2.5 cm) wide. Sponge produces brilliantly colored tree-like, intertwined branches in red and orange. Surface is covered with tiny, scattered pores.
Habitat Ocean or bay shallows, Tidepools.
Range Eastern Canada, Florida, New England, Mid-Atlantic, California, Texas, Northwest.
Discussion Branches of the Red Beard Sponge provide important habitats for crustaceans and juvenile fish species. Reproduces both asexually and sexually. Broken branches can regenerate into new sponges. When cells from the Red Beard Sponge are separated, they have the ability to reorganize themselves.


text:
Location: Austin, TX
Tickets: 0
Sorry, tickets are no longer available for this event.
Stubb's Bar-B-Q
801 Red River
Austin, TX
Wanee Festival, Live Oak, Fla. John Davisson
June 5, 2009 |
Karl Denson's Tiny Universe, Gomez, New Monsoon, and Trey Anastasio's band take the stage for a set of Beatles and Pink Floyd covers by jam band supergroup Brain Damaged Eggmen during the week-long Jam Cruise in the balmy Caribbean. Michael Weintrob / groovetography.com
January 7, 2006 |
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text:
Universal Fit
3 pairs 50mm Headphone Earphone Earbud Ear Pad earpad Foam Cover
50mm-55mm Headphone Earphone Earbud Ear Pad earpad Foam Cover * Brand New & high quality * Balanced density, flexibility * Elastic, comfortable and durable * enhance sound quality,Noise isolation * Fit most earbud-style earphones with 50-55 in diameter. Diameter:25mm 30mm 35mm 40mm 45mm 50mm 60mm Material: foam
Q: Electronics Noise-Isolating Ear Buds-2 Pack (Chrome)
Forget about those irritating and uncomfortable earphones that youve used to for so long and try listening to clear, unimpeded sound through the Q:Electronics Noise-Isolating Ear Buds. It features three (3) sizes of ear bud tips which come included in your purchase, in order to provide the most comfortable fit possible. This provides a meticulous sound chamber that accentuates every detail...


text:
Video: Constantin Tutu Ends 2011 With Knee KO
- Written by Rian Scalia
2011 has been a pretty good year for the Moldovan fighter Constantin Tutu. He's won all five of his fights, including a one night tournament in October where he picked up three of those wins. He's one of the better fighters in the 80kg weight range, yet to most, probably unknown. What's crazy is that for most of 2010, he was fighting at 70kg. Tutu has settled nicely into the 80kg area and established himself as one of the top players at the weight. He's only fought in Moldova this year, but let's hope in 2012 we can see him expand his horizon by fighting for some bigger organizations.
Check out his last fight from December 10 in Chisinau, Moldova. He took on Adrian Balas of Romania and didn't need much time to score an awesome KO with a jumping knee.


text:
Family: Lycaenidae, Gossamer-wing Butterflies view all from this family
Description The Silver-banded Hairstreak (Chlorostrymon simaethis) is a North and South American butterfly in the family Lycaenidae. It is also known as St. Christopher's Hairstreak and the Key Lime Hairstreak.
The upper side of the wings is dark, iridescent purple in males. Females are grayish-brown, sometimes having iridescent purple on the basal area of the wings. The underside of the wings is bright, lime green in both sexes. Both wings have a bright silvery-white postmedian band. The silver band on the hind wing juts out towards the margin and turns back in, forming a "V" shape. Beyond this band, there is a dark brownish-red patch with a variable amount of silvery-white frosting. The frosting extends across the entire edge of the hind wing. The hind wings have one pair of tails. The wingspan ranges from 2.2 to 3.2 cm.
Dimensions The wingspan ranges from 2.2 to 3.2 cm.
Habitat Scrub, shrub & brushlands.
Range Southwest, California, Florida, Texas.


text: Watching AC360 tonight David Gergen was talking with a teabagger in a round table discussion on the budget and the possible shutdown of the government. Usually the reserved Gergen is dignified and matter of fact. Tonight, much out of character, he threw his hands up in frustration over the over the comments of a teabagger who wasn't making logical arguments. Even a conservative like Gergan, who has served in three Republican administrations, finds these people impossible.


text:
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John A. Boots, 66, of Perry Park, passed away Sunday, April 21, 2013, at the King's Daughters' Hospital in Madison, Ind.
He is survived by his wife, Patricia Burgess Boots of Perry Park; a son, Joshua Aaron (April) Boots, of Carrollton; and two daughters, Mary Kathleen (Jeff) Smith, of Sparta and Kerri Lanette (Lee) Atkins, of Bagdad.
The family will receive friends Wednesday, April 24, 2013, from 5 until 8 p.m. at the Tandy-Eckler-Riley Funeral Home in Carrollton. The funeral services will be held Thursday, April 25, 2013, at 1 p.m. at the funeral home.
Ernestine (Epperson) Bauer, 88, passed away Tuesday, April 16, 2013.
She was the wife of the late Clifford E. Bauer and the mother of Susan Kay Roll (David).
The funeral service was held Saturday, April 20, 2013, at the Bolton & Lunsford Funeral Home in Westwood.
Timothy Ray Tolbert, 57, of Owenton, passed away Monday, March 25, 2013 at the St. Elizabeth Hospital in Grant County.
Born July 1, 1955, in Owenton, he was the son of the late James "Jimmy" Tolbert and was preceded by his siblings, Wayne, Chris, Pamela and Virginia.
Timmy was employed by Gotec Plus Sun in Williamstown and was a member of the Southeast Christian Church in Louisville.
Timmy was also a motorcycle enthusiast.
Dora Patton Maiden, 99, of the English community of Carrollton, passed away Monday, April 8, 2013.
She is survived by her son, Richard Pat Maiden, of Glencoe.
The funeral services were held Friday, April 12, 2013, at the English Christian Church. Burial was in the English Cemetery in Carrollton.
Arrangements were entrusted with the Tandy-Eckler-Riley Funeral Home.
Effie Ware Forte, 54, of Bowling Green, passed away Sunday, April 7, 2013, at her residence.
The Owenton native was the daughter of the late C. W. Ware and Hazel Sanders Ware.
She was the director of environmental services for The Medical Center at Bowling Green, a Mary Kay consultant and a member of Park Ridge Baptist Church in Sparta.
Christopher Bailey Ruth, 51, a native of Owen County, passed away Sunday, April 7, 2013, in Louisville.
He was preceded in death by his parents, Carl B. Ruth and Beulah Perkins Ruth.
He is survived by his wife, Bonnie Ruth of Clayvillage; his daughters, Tiffany Cook, Kristy Cook, and Jessica Ruth, all of Shelbyville; and his sons, Christopher McGarther Ruth of Lexington, James Ruth (Michelle) of Eminence, and Owen Christopher Ruth (Nicole) of Georgetown.
Nellie Blanche Toole, 88, of Sanders, passed away Friday, April 5, 2013, at the St. Elizabeth Hospital in Florence.
Survivors include her husband, Charles "Pim" Toole; and her son, Roger (Yalonda) Toole.
The funeral services were held Tuesday, April 9, 2013, at the Main Street location of McDonald & New Funeral Homes. Burial was in the Owenton Cemetery.
Danny Robb, 72, passed away April 4, 2013, at his home in Perry Park.
He is survived by his wife Linda; a daughter, Renee Mullins; and a son Scott Robb.
A memorial service will be held on Friday, April 12, 2013, at 6 p.m. at the Perry Park Community Recreation Center.
The Graham-Dunn Funeral Home of Carrollton is in charge of all arrangements.
Ileana Coates, 86, passed away April 5, 2013, at Saint Elizabeth Medical Center in Florence.
Survivors include her sister, Juanita Trusty.
The funeral services will be held Saturday, April 13, 2013, at New Liberty Baptist Church from 11 a.m. to 2 p.m. Burial will be in the Owenton IOOF Cemetery.
McDonald and New Funeral Homes is in charge of the arrangements.
Patricia Osborne, 71, of Owenton, passed away Thursday, March 14, 2013, at the Saint Elizabeth Hospital in Edgewood.
She was the daughter of the late Porter and Jennie Mullins Stamper.
Survivors include her husband, Billy Gayle Osborne; two daughters, Sandi (Bobby) O'Banion and Candi Wright; and a nephew, Bobby Harris.
The funeral services were held Saturday, March 16, 2013, at the Main Street location of the McDonald & New Funeral Homes. Burial was in the Macedonia Baptist Church Cemetery.
Copyright © 2017
The Owenton News-Herald is your source for local news, sports, events and information in Owen County and Owenton, KY, and the surrounding area.


text:
Dangerous Assignments | Colombia
Dangerous Assignments | Colombia
Dangerous Assignments | Bangladesh, Colombia, Georgia, Iraq, Philippines, Russia
Attacks on the Press | Colombia
The Colombian press remained in the cross fire of an escalating, decades-old civil conflict pitting two major leftist guerrilla groups against the Colombian army and right-wing paramilitary forces. While peace negotiations slowly moved forward at the beginning of 2002, the conflict continued to take a deadly toll on journalists and sent many into hiding. At least three journalists were killed for their work in 2001. CPJ continues to investigate the deaths of five others whose murders may have been professionally related.
Dangerous Assignments | Colombia, Peru, Spain, Switzerland
Attacks on the Press | Colombia
Alerts | Colombia, Russia, Sierra Leone
New York, January 4, 2001 --- Of the 24 journalists killed for their work in 2000, according to CPJ research, at least 16 were murdered, most of those in countries where assassins have learned they can kill journalists with impunity.
This figure is down from 1999, when CPJ found that 34 journalists were killed for their work, 10 of them in war-torn Sierra Leone.
In announcing the organization's annual accounting of journalists who lost their lives because of their work, CPJ executive director Ann Cooper noted that while most of the deaths occurred in countries experiencing war or civil strife, "The majority did not die in crossfire. They were very deliberately targeted for elimination because of their reporting." Others whose deaths were documented by CPJ appear to have been singled out while covering demonstrations, or were caught in military actions or ambushes while on assignment.
Bogotá, December 14, 2000 --- Early yesterday morning, two men on a motorcycle killed radio journalist Alfredo Abad López as he was saying goodbye to his wife outside their home in the southern Colombian city of Florencia.
Do you believe the free flow of information must be protected? Sign the #RightToReport petition and demand that President Obama immediately:
1. Issue a presidential policy directive prohibiting the hacking and surveillance of journalists and media organizations.
2. Limit aggressive prosecutions that ensnare journalists and intimidate whistleblowers.
3. Prevent the harassment of journalists at the U.S. border.
Or click here to see the full petition, and join leading journalists like Christiane Amanpour, The Guardian's Alan Rusbridger, Editor of the AP Kathleen Carroll, and Arianna Huffington in signing on.


text:
He can hide behind a medical condition all he wants, the fact is he quit on his team then let them down again getting suspended b/c he couldn't stay off drugs. I get you like him and will defend him but this is not a good guy no matter how many excuses you make.
My favorite play of Ricky Williams was in a game against KC. He broke free along the sideline and as the tackler closed on him, Ricky picked him up by the neck and threw him aside. Just awesome display of speed, power and strength.
I loved watching him and was sorry to see him go.
I cannot say I wasn't very disappointed when he retired in 04, but after 35+ carries a game in the National Football League I would smoke a lot of pot too. DW ruined what could have been the best back in the 2000's. Had HOF type skill
What an absolute beast he was that year.
On the other hand, what a disappointing year that was. I remember thinking we were headed for a huge year after that awesome game in Denver and then Ray Lucas stunk up the joint for a handful of games after Fiedler got hurt in that win.


text:
Recommend A Book
Have you read a book that you thought was really great?
Would you like other children to know about it?
If you would like to recommend a book, use this form
to tell us what makes that book so special.
Is This Entry Abusive?
| sonny from United States
School: home schooled
|Report Abusive
|I read this great book:
|angel in my backpack
|Written by:
|The book's main subject is:
|The author's main point is that:
|learn about the bible
|One of the most interesting things in this book is:
|is the angel
|In my opinion, this book is:
|I say this because:
|i love god


text:
Zack Cozart 6
Chris Heisey 8
Joey Votto 3
Brandon Phillips 4
Jay Bruce 9
Ryan Ludwick 7
Todd Frazier 5
Ryan Hanigan 2
Mat Latos 1
vs. RH Rick Porcello (3-4, 4.86)
Zack Cozart 6
Chris Heisey 8
Joey Votto 3
Brandon Phillips 4
Jay Bruce 9
Ryan Ludwick 7
Todd Frazier 5
Ryan Hanigan 2
Mat Latos 1
vs. RH Rick Porcello (3-4, 4.86)
Here @ the game and way too many Tigers fans milling about!
2017 Reds record when I'm attending: 3-12017 Dragons record when I'm attending:
"We want to be the band to dance to when the bomb drops." - Simon Le Bon of Duran Duran
I am at the game. Not sure what happened to Frazier but Cairo is starting
Injury bug starting to creep up a little bit
"Losing feels worse than winning feels good." -Vin Scully
Heisey is not nearly as fast as Stubbs. That said, he's a better overall defensive outfielder than Stubbs. (Fire away. I can take it.)
After the great catch from Heisey, Latos fans Boesch.
Latos hitting 97 on the gun tonight.
Quick 1-2-3 inning. Now let's get some runs!
Good start for Latos, and a nice job by Cairo on that slow grounder.
"Since I've been with the Reds in 1989, we've never had a farm system this loaded," Bowden said. "If we were the New York Yankees and had unlimited dollars, we could have traded for Colon, (Jeff) Weaver, Rolen, (Cliff) Floyd, (Kenny) Rogers and Finley and gotten them all -- and still held onto our top five prospects. That's an amazing statement."
Good start for Latos. He seems a bit more amped up tonight.
This will not change until the Reds win the World Series.......
April 28, 2006.
Cozart laces a single. Then goes to second on deep fly ball from Heisey.
Board Moderators may, at their discretion and judgment, delete and/or edit any messages that violate any of the following guidelines: 1. Explicit references to alleged illegal or unlawful acts. 2. Graphic sexual descriptions. 3. Racial or ethnic slurs. 4. Use of edgy language (including masked profanity). 5. Direct personal attacks, flames, fights, trolling, baiting, name-calling, general nuisance, excessive player criticism or anything along those lines. 6. Posting spam. 7. Each person may have only one user account. It is fine to be critical here - that's what this board is for. But let's not beat a subject or a player to death, please.


text: Tom Kelley is the general manager of Palo Alto, Calif.-based design and consulting firm Ideo and author of the best-seller The Art of Innovation. As a leading speaker, he addresses scores of business audiences on how to use innovation to transform a business's culture and strategic thinking, including PN's recent Executive Forum. Tom has helped manage Ideo as it has grown from 20 designers to a staff of more than 350.


text:
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Email firstname.lastname@example.com
We've negotiated prices so good, our brand partners don't allow us to share them with people who aren't members of GovX.
Join or log in to see prices and shop.
Epitomizing the art of linear design, this Jason Brous original features a multi-faceted stainless steel blade and molded plastic handle, at home on wall or belt.
All SOG products including knives, tools, gear, and packs are guaranteed against defects in workmanship and materials for the life of the item. SOG products are designed to last when used as intended and properly taken care of. In the rare, unforeseen instance when something goes south, SOG wants to make sure that you are taken care of. Any item that happens to be defective will be repaired or replaced at their discretion. All you need to do is get it back to SOG and they will take care of the rest. SOG does have lifetime warranties, but keep in mind that this warranty does not cover an item that is damaged by misuse, abuse, improper maintenance, alterations, accident, or normal wear and tear as determined at their discretion. So don't go using your knife as a screwdriver, your multi-tool to split rocks, or your pack to contain a wild hyena. In other words, use common sense and don't do stupid things. Knives, multi-tools, gear, and other sharp pointy items should be maintained properly with routine cleaning, oiling, and sharpening. Blades are cutting utensils and are not for prying or other applications outside of its intended use. Packs should be cleaned routinely to remove dirt and foreign materials and substances that may increase wear on the material. You don't want your friends or enemies smelling you before they see you. If your pack does not have a hard-molded top pocket and Hypalon MOLLE field, it was made by TORG - The Outdoor Recreation Group, a quality gear manufacturer, under the SOG license. These packs have a lifetime guarantee by TORG. More information at http://www.torgusa.com/warranty/. Take care of your SOG. SOG will take care of you. For more information or to start the warranty process please visit http://www.sogknives.com/warranty-info.html
RETURN INFORMATION GovX and SOG Knives strive to provide the best customer service possible. SOG Knives merchandise can be returned for a full refund within 30 days of the delivery date, provided the product is in new, unused condition. If you need to return an item you ordered with GovX.com, contact one of our Customer Support Team members at 888-468-5511 to obtain a Return Authorization Number and return the item within 30 days of delivery*(Do not contact manufacturer directly. All returns must be processed through GovX). ALL RETURNS MUST HAVE A RETURN AUTHORIZATION NUMBER that can only be provided by contacting Govx.com at 888-468-5511 or by emailing us at email@example.com. *Keep the following guidelines in mind: (i) all items must be returned in new, unused condition, and will undergo quality checks. All product packaging materials--including boxes, manuals, warranty cards, instructions, tags, and any other materials in the original shipment--must be returned with your returned item(s), (ii) our return policy is subject to each Manufacturer-Partner's individual return policy, which may vary from the GovX policy, in which case, the Manufacturer-Partner's policy prevails (See SOG KNIVES RETURN INFORMATION below), and, (iii) we do not cover postage expense on returned items unless there are special circumstances which will be explained when you call us to arrange for your return. SOG KNIVES RETURN INFORMATION All returns must have a return authorization number. We recommend selecting a trackable shipping method and keeping the tracking information for your records until the return/exchange is complete. Refunds/exchanges can take up to 3-4 weeks or sooner. Shipping charges are not refundable. We do not accept COD deliveries. If possible, use the original shipping package for returns and exchanges. EXCHANGES We do not process exchanges. To exchange an item, please return the item pursuant to the Return Authorization number and instructions you obtain from us, and place a new order on GovX.com.
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text: Technology law and policy is notoriously unpredictable but 2012 promises to be a busy year. My weekly technology law column offers some guesses for the coming months. January: The Supreme Court of Canada holds a hearing on whether Internet service providers can be treated as broadcasters under the Broadcasting Act.


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