What a pain in the back: a review of current treatment options with a focus on naproxen sodium.

Non-specific low back pain (LBP) represents a challenging and prevalent condition that is one of the most common symptoms leading to primary care physician visits. While established guidelines recommend prioritizing non-pharmacological approaches as the primary course of action, pharmacological treatments are advised when non-pharmacological approaches are ineffective or based on patient preference. These guidelines recommend non-steroidal anti-inflammatory drugs (NSAIDs) or skeletal muscle relaxers (SMRs) as the first-line pharmacological options for acute or subacute LBP, while NSAIDs are the exclusive first-line pharmacological option for chronic LBP. Although SMRs are generally effective for acute LBP, the available evidence does not support the view that they improve functional recovery, and their comparative efficacy to NSAIDs and other analgesics remains unknown, while studies have shown them to introduce adverse events without significantly reducing LBP. Moreover, opioids continue to be widely prescribed for LBP, despite limited evidence for effectiveness and known risks of addiction and overdose. Broader use of non-opioid pharmacotherapy, including the appropriate use of OTC options, is critical to addressing the opioid crisis. The balance of evidence indicates that NSAIDs have a favorable benefit-risk profile when compared to other available pharmacological treatment options for non-specific LBP, a condition that is primarily acute in nature and well-suited for self-treatment with OTC analgesics. While clinical guidelines do not differentiate between NSAIDs, evidence indicates that OTC naproxen sodium effectively relieves pain across multiple types of pain models, and furthermore, the 14-h half-life of naproxen sodium allows sustained, all day pain relief with reduced patient pill burden as compared to shorter acting options. Choosing the most appropriate approach for managing LBP, including non-pharmacological options, should be based on the patient's condition, severity of pain, potential risks, and individual patient preference and needs.

Primary Prevention of CVD with Aspirin: Benefits vs Risks.

Low-dose aspirin (acetylsalicylic acid [ASA]; 75 to 100 mg/d) is widely used in the prevention of cardiovascular (CV) events based on the results of large-scale studies supporting a benefit. However, questions remain regarding the benefit-risk relationship in certain settings since long-term use of ASA is not devoid of risk. Incontrovertible evidence supports the benefits of ASA treatment, which exceed the risks, in patients who have had a previous CV event (myocardial infarction, stroke, unstable angina, or transient ischemic attack). Nonetheless, the question remains for those patients who have not had a previous event (primary prevention), where the risk of CV events is lower and, consequently, the absolute benefit is also lower than in patients who have a history of a CV event or its equivalent (secondary prevention). Recent evidence from large-scale clinical trials shows that administration of low-dose ASA is associated with a reduced risk of CV events with a corresponding small absolute increase in the risk of major bleeding (eg, gastrointestinal bleeding and hemorrhagic stroke). Although the benefit and the risk of low-dose ASA in primary prevention are numerically similar, the clinical consequences of an increased risk of bleeding and a decreased risk of a CV event may not be equivalent. If these data are applied to patients with higher levels of CV outcome risk, more patients may potentially benefit from aspirin use in primary prevention.

Efficacy and Safety of Naproxen for Acute Pain.

Acute pain often is treated with over-the-counter (OTC) therapeutics, including non-steroidal anti-inflammatory drugs (NSAIDs). However, not all NSAIDs are equally effective for treating different types of acute pain. In this article, we review the data supporting the use of OTC naproxen to effectively treat a variety of types of acute pain, including dysmenorrhea, headache, and dental pain, as well as review adverse effects. This information can be used to provide appropriate treatment for patients experiencing acute pain and help prevent progression to chronic pain.

Clinical Pharmacology and Cardiovascular Safety of Naproxen.

The voluntary withdrawal of Vioxx (rofecoxib) from the market in 2004, as well as the 2005 and 2014 US FDA Advisory Committee meetings about non-steroidal anti-inflammatory drugs (NSAIDs) and cardiovascular risk, have raised questions surrounding the use of NSAIDs in at-risk populations. This paper discusses the cardiovascular safety profile of naproxen in the context of the NSAID class. The balance of evidence suggests that cardiovascular risk correlates with cyclooxygenase (COX)-2 selectivity, and the low COX-2 selectivity of naproxen results in a lower cardiovascular risk than that of other NSAIDs. The over-the-counter (OTC) use of naproxen is expected to pose minimal cardiovascular risk; however, the benefit-risk ratio and appropriate use should be considered at an individual patient level, particularly to assess underlying conditions that may increase the risk of events. Likewise, regulatory authorities should revisit label information periodically to ensure labeling reflects the current understanding of benefits and risks.

Costs and benefits of bundled community-based screening for carotid artery stenosis, peripheral artery disease, and abdominal aortic aneurysm.

PURPOSE: Perform an initial formal assessment of the costs and benefits of bundled cardiovascular screening. Primarily, determine the relative importance of data uncertainties to the integrity ofmodeled outcomes associated with bundled screening for carotid artery stenosis (CAS), peripheral artery disease (PAD), and abdominal aortic aneurysm (AAA); secondarily, establish parameters around potential costs and outcomes benefits of this screening bundle. DESIGN: A decision-analysis framework composed of four decision tree submodels with transition probabilities specific to four age- and gender-specific subgroups. Model transition probabilities for each of the four submodels are based on the prevalence of all possible combinations of the presence or absence of moderate CAS, significant CAS, PAD, and AAA, and the likelihood of appropriate or inappropriate medical follow-up. METHODOLOGY: Evaluates a hypothetical self-funded employer with 10,000 beneficiaries and who is considering whether to provide bundled cardiovascular health screenings. Screenings would be performed in addition to any other medical screenings commonly performed by physicians to assess cardiovascular risk. Determine costs and catastrophic events (death, myocardial infarction, stroke, other cardiovascular-related events, amputation events) for these self-funded hypothetical beneficiaries aged ≥ 50 years and < 65 years. RESULTS: The model predicts approximately $54 million in health care costs over 10 years for the control cohort and $51 million for the screening cohort, representing a 5.2% reduction in 10-year health care spending due to screening. CONCLUSION: This initial analysis predicts robust cost and health benefits associated with the decision to provide bundled cardiovascular health screening to a self-funded employer's beneficiaries aged ≥ 50 years and < 65 years. Further analyses are necessary to better quantify the magnitude of the cost and health benefits.

Studying women in clinical trials: scientific and legal implications.

Lack of applicable safety data has effected an ease in federal restriction on the inclusion of women in clinical trials, particularly because: (1) they consume more prescription and over-the-counter medications than do men; (2) most require some type of drug therapy during pregnancy; and (3) many drugs that have been withdrawn from the market had higher health risks for women. The desire for more women-specific data prompted the Women's Health Initiative (WHI) studies, which reported an unfavorable risk-benefit relationship for hormone replacement therapy (HRT), as well as no significant reduction in disease or fracture risk with calcium and vitamin D supplementation but possible kidney stone development. Although the health risks were minimal, physicians feared any possible litigation involved with the use of HRT and were concerned with any possible adverse effects from calcium supplementation, and therefore altered their prescribing practices. Women, fearing any long-term health risks, also began seeking alternative treatments. However, the safety of these alternative therapies may be questionable, because they often are not subjected to extensive scrutiny and do not require federal approval. Alternative prescription drug treatments may have long-term adverse consequences that will only become evident with years of use. It is important to recognize that over-generalization and extrapolation of data may deny appropriate treatment to certain subgroups of women who may benefit.

Aspirin use among adults aged 40 and older in the United States: results of a national survey.

BACKGROUND: Aspirin is effective for the primary and secondary prevention of cardiovascular events, but its use has been suboptimal. METHODS: Investigators performed a nationally representative Internet-based survey of U.S. consumers aged 40 and older using online databases maintained by Harris Interactive((R)) to measure use of aspirin for cardiovascular disease (CVD) prevention and factors associated with its use. Respondents reported whether they used aspirin therapy regularly for cardiovascular prevention; and provided information about their cardiovascular risk factors, discussions with their healthcare provider about aspirin therapy, and their perceptions about risks and benefits of aspirin. Objective risk of cardiovascular events was estimated using counts of self-reported risk factors. Survey results were weighted to be representative of the general U.S. population. Researchers performed bivariate and multivariate analyses to understand factors associated with aspirin use. RESULTS: A total of 1299 adults aged 40 or older completed the survey. Mean age was 55.9, 53% were women, 79% self-identified as white, 10% African American, and 9% Latino. Current regular aspirin use for CVD prevention was reported by 41% of respondents. The factor most strongly associated with aspirin use was reporting a previous conversation with a healthcare provider about aspirin (88% aspirin use among respondents reporting such discussion versus 17% who did not report discussion; odds ratio 36.6, 95% confidence interval 25.9-51.7). CONCLUSIONS: Aspirin use is low, even among patients at increased risk. Better provider-patient communication about aspirin prevention is associated with greater use, and should be a target for future interventions.

Calcium supplementation during pregnancy and lactation: effects on the mother and the fetus.

Calcium consumption is essential for bone development and maintenance throughout life, yet more than one half of the female population in the United States does not consume the recommended amount of calcium. Calcium intake is especially crucial during pregnancy and lactation because of the potential adverse effect on maternal bone health if maternal calcium stores are depleted. There is often a transient lowered bone mineral density and increased rate of bone resorption, with the greatest consequence during the third trimester and throughout lactation. Studies indicate that calcium consumption should be encouraged, especially during pregnancy and lactation, to replace maternal skeletal calcium stores that are depleted during these periods. Because the fetus in utero and the neonate through breast-feeding are dependent on maternal sources for the total calcium load, adequate maternal calcium intake also can affect fetal bone health positively. Proper calcium consumption can be attained through the diet by the consumption of dairy products or leafy greens (such as kale), the consumption of fortified foods, or by supplementation with widely available calcium-containing supplement products. Because many women experience heartburn during pregnancy, calcium-based antacids are ideal for providing heartburn relief, and they offer a calcium supplement to ensure maternal and fetal bone health, without the danger of adverse effects on the neonate.

Risk of hemorrhagic stroke with aspirin use: an update.

BACKGROUND: Low-dose aspirin is an important therapeutic option in the secondary prevention of myocardial infarction (MI) and ischemic stroke, especially in light of its unique cost-effectiveness and widespread availability. In addition, based on the results of a number of large studies, aspirin is also widely used in the primary prevention of MI. This review provides an update of the available data to offer greater clarity regarding the risks of aspirin with respect to hemorrhagic stroke, as well as insights regarding patient selection to minimize the risk of this complication. SUMMARY OF REVIEW: In the secondary prevention of cardiovascular, cerebrovascular, and ischemic events, the evidence supports that the benefits of aspirin treatment significantly outweigh the risk of a major hemorrhage. The evidence from primary prevention of MI studies, including that from the recent Women's Health Study evaluation of aspirin use in healthy women, demonstrate that the increased risk for hemorrhagic stroke is small, is comparable to the secondary prevention studies, and fails to achieve statistical significance. A reasonable estimate of the risk of hemorrhagic stroke associated with the use of aspirin in primary prevention patients is 0.2 events per 1000 patient-years, which is comparable to estimates of the risk associated with the use of aspirin in secondary prevention patients. CONCLUSIONS: When considering whether aspirin is appropriate, the absolute therapeutic cardiovascular benefits of aspirin must be balanced with the possible risks associated with its use, with the most serious being hemorrhagic stroke.

Potential use of biochemical markers of bone turnover for assessing the effect of calcium supplementation and predicting fracture risk.

BACKGROUND: Biochemical markers of bone remodeling have been extensively used (independent of bone mass measurements) to document the efficacy of various anticatabolic and anabolic bone-modifying medications in reducing fracture risk. Nonetheless, their usefulness in determining the effectiveness of osteoporosis prevention and treatment, particularly calcium supplementation, has not been well established. OBJECTIVE: This article reviews the use of biochemical markers of bone remodeling as a measure of the effect of calcium supplementation and the implications for prediction of fracture risk. METHODS: A generalized search of MEDLINE from 1966 through April 2004 using the terms osteoporosis, fracture risk, and the specific bone biomarkers of interest was conducted to identify articles relating to these biomarkers and their relationship to prediction of fracture risk. A second MEDLINE search for the same period used the terms calcium, biological markers, and fracture risk to identify studies of calcium supplementation and bone biomarkers. In both cases, the reference lists of identified review articles were searched for additional publications. RESULTS: : Several biochemical markers of bone remodeling have been shown to be positively correlated with bone mineral density and fracture risk. Furthermore, calcium supplementation has been shown to have a significant correlation with levels of a number of these biomarkers (P < 0.05): the markers of bone formation procollagen type I carboxy and amino terminal peptides and serum bone-specific alkaline phosphatase, and the markers of bone resorption urinary hydroxyproline, urinary pyridinoline, urinary deoxypyridinoline, urinary amino terminal crosslinked telopeptide, and urinary and serum carboxy terminal crosslinked telopeptide. CONCLUSIONS: Calcium supplementation has a significant effect on a number of biomarkers of bone remodeling, an effect that is, in turn, correlated with decreased fracture risk. Most studies of the efficacy of calcium supplementation in reducing bone remodeling and influencing bone mineral density and fracture risk have involved calcium carbonate, although a few studies have found that other calcium salts may produce similar results.

The role of calcium in osteoporosis drug therapy.

Great advances have been made in the field of osteoporosis treatment and prevention in recent years that have led to the availability of powerful new drugs. These drugs are viewed by patients and physicians as a major breakthrough in the management of osteoporosis. Unfortunately, this view has led many to ignore the importance of concurrent calcium supplementation to ensure the maximum benefit from these drugs, as evidenced by the recent decline in use of calcium supplements. As the majority of patients fail to consume the minimum recommended dietary intake of calcium, it is critical to recommend calcium supplements to raise total daily calcium intake to the levels needed to ensure maximum efficacy of osteoporosis treatments. Furthermore, osteoporosis drug labeling should be strengthened to encourage proper use of these drugs in combination with calcium supplements.

The calcium connection to bone health across a woman's lifespan: a roundtable.

Adequate calcium throughout a woman's lifespan is a critical step to achieving and improving bone health. Unfortunately, there is no time across this continuum where the average intake is optimal. This paper reviews the output of a roundtable of scientific professionals who gathered to discuss approaches for turning high levels of awareness regarding the importance of adequate calcium intake into behaviors that actualize this recognition throughout the life of a woman. The critical time periods of pregnancy, lactation, perimenopause and menopause, in which adequate calcium intake is most important, are particularly highlighted. Recommended levels of calcium and vitamin D are reviewed with emphasis on diet and supplemental sources of these nutrients. Knowledge of the current shortfall in calcium intake across the life continuum coupled with health care professional education about the importance of compliance with recommendations will increase calcium awareness and utilization and improve bone health.

An update on aspirin in the primary prevention of cardiovascular disease.

BACKGROUND: In 1988, the aspirin component of the Physicians' Health Study, a randomized, double-blind, placebo-controlled trial of 22 071 apparently healthy men was terminated early, due principally to a statistically extreme (P<.00001) 44% reduction in the risk of a first myocardial infarction (MI). The Cardio-Renal Drugs Advisory Committee recommended that the US Food and Drug Administration approve professional labeling of aspirin to prevent first MI. The agency did not act on this recommendation because the only other trial, the British Doctors' Trial of 5139 men, showed no significant benefits. Since that time, 3 additional randomized trials (which included men and women) of aspirin in the primary prevention of MI have been published. METHODS: A computerized search of the English literature from 1988 to the present revealed 5 published trials: the Physicians' Health Study (22 071 participants), the British Doctors' Trial (5139), the Thrombosis Prevention Trial (5085), the Hypertension Optimal Treatment Study (18 790), and the Primary Prevention Project (4495). RESULTS: Among the 55 580 randomized participants (11 466 women), aspirin was associated with a statistically significant 32% reduction in the risk of a first MI and a significant 15% reduction in the risk of all important vascular events, but had no significant effects on nonfatal stroke or vascular death. CONCLUSIONS: The current totality of evidence provides strong support for the initial finding from the Physicians' Health Study that aspirin reduces the risk of a first MI. For apparently healthy individuals whose 10-year risk of a first coronary event is 10% or greater, according to the US Preventive Services Task Force and the American Heart Association, the benefits of long-term aspirin therapy are likely to outweigh any risks.

Critical evaluation of the safety of Cimicifuga racemosa in menopause symptom relief.

OBJECTIVE: This comprehensive review examines the safety of Cimicifuga racemosa for the treatment of menopause symptoms, particularly in populations in which conventional menopause treatment regimens, including estrogen replacement, are contraindicated. DESIGN: An extensive database of information on Cimicifuga, which included all published literature pertaining to preclinical and clinical safety of various forms of Cimicifuga, the FDA and World Health Organization adverse-event reporting systems, monographs, compendia, internal unpublished data from a major manufacturer, foreign literature, and historical anecdotal reports, was reviewed, and findings pertaining to the safety of Cimicifuga use for menopause treatment were reported. RESULTS: Uncontrolled reports, postmarketing surveillance, and human clinical trials of more than 2,800 patients demonstrate a low incidence of adverse events (5.4%). Of the reported adverse events, 97% were minor and did not result in discontinuation of therapy, and the only severe events were not attributed to Cimicifuga treatment. CONCLUSIONS: Although the effects of Cimicifuga may be dependent on the specific extract preparation, this review clearly supports the safety of specific Cimicifuga extracts, particularly isopropanolic preparations, for use in women experiencing menopausal symptoms and as a safe alternative for women in whom estrogen therapy is contraindicated.

Evaluation of the benefits and risks of low-dose aspirin in the secondary prevention of cardiovascular and cerebrovascular events.

BACKGROUND: In spite of the clear evidence of benefit of aspirin in the secondary prevention of cerebrovascular and cardiovascular thrombotic events, its use in patients at high risk due to a previous event remains suboptimal. A possible explanation for this underuse is concern regarding the relative benefit in relation to the potential risk for serious gastrointestinal events. OBJECTIVE: To compare the benefit and gastrointestinal risk of aspirin use for the secondary prevention of thromboembolic events. DESIGN: A meta-analysis was conducted using 6 trials (6300 patients) meeting the inclusion requirement of use of low-dose aspirin (< or =325 mg/d) in approved secondary prevention indications. RESULTS: Aspirin reduced all-cause mortality by 18%. In addition, aspirin use reduced the number of strokes by 20%, myocardial infarctions by 30%, and other "vascular events" by 30%. Alternately, patients who took aspirin were 2.5 times more likely than those in the placebo group to have gastrointestinal tract bleeding. The number needed to treat for aspirin to prevent 1 death from any cause of mortality was 67, while 100 needed to be treated to detect 1 nonfatal gastrointestinal tract bleeding. CONCLUSION: Aspirin use for the secondary prevention of thromboembolic events has a favorable benefit-to-risk profile and should be encouraged in those at high risk.