Proton-pump inhibitors in patients requiring antiplatelet therapy: new FDA labeling.

Proton-pump inhibitors (PPIs) are recommended for patients who require antiplatelet therapy and have a history of upper gastrointestinal bleeding. Proton-pump inhibitors should also be considered for patients receiving antiplatelet therapy who have other risk factors for gastrointestinal bleeding, including use of aspirin. Thus, evidence of pharmacokinetic and pharmacodynamic interactions between PPIs and consequent impaired effectiveness of the antiplatelet agent clopidogrel has caused concern. Here, we discuss comparative studies suggesting that the extent to which a PPI reduces exposure to the active metabolite of clopidogrel and attenuates its antithrombotic effect differs among PPIs. Although a clinically meaningful effect of the interaction between PPIs and clopidogrel on cardiovascular outcomes has not been established, these studies provided the basis for recent changes in US Food and Drug Administration (FDA) labeling for several PPIs and clopidogrel. New labeling suggests that PPI use among patients taking clopidogrel be limited to pantoprazole, rabeprazole, lansoprazole, or dexlansoprazole. Because comparative studies indicate that omeprazole and esomeprazole have a greater effect on the CYP2C19-mediated conversion of clopidogrel to its active metabolite and, consequently, clopidogrel's effect on platelet reactivity, FDA labeling recommends avoiding omeprazole and esomeprazole in patients taking clopidogrel. Even a 12-hour separation of dosing does not appear to prevent drug interactions between omeprazole and clopidogrel.

Effects of consumption of pomegranate juice on carotid intima-media thickness in men and women at moderate risk for coronary heart disease.

This randomized, double-blind, parallel trial assessed the influence of pomegranate juice consumption on anterior and posterior carotid intima-media thickness (CIMT) progression rates in subjects at moderate risk for coronary heart disease. Subjects were men (45 to 74 years old) and women (55 to 74 years old) with > or =1 major coronary heart disease risk factor and baseline posterior wall CIMT 0.7 to 2.0 mm, without significant stenosis. Participants consumed 240 ml/day of pomegranate juice (n = 146) or a control beverage (n = 143) for up to 18 months. No significant difference in overall CIMT progression rate was observed between pomegranate juice and control treatments. In exploratory analyses, in subjects in the most adverse tertiles for baseline serum lipid peroxides, triglycerides (TGs), high-density lipoprotein (HDL) cholesterol, TGs/HDL cholesterol, total cholesterol/HDL cholesterol, and apolipoprotein-B100, those in the pomegranate juice group had significantly less anterior wall and/or composite CIMT progression versus control subjects. In conclusion, these results suggest that in subjects at moderate coronary heart disease risk, pomegranate juice consumption had no significant effect on overall CIMT progression rate but may have slowed CIMT progression in subjects with increased oxidative stress and disturbances in the TG-rich lipoprotein/HDL axis.

Unmet medical needs among patients with gastroesophageal reflux disease: a foundation for improving management in primary care.

Gastroesophageal reflux disease (GERD) is a common disease that has a significant impact on patients' health-related quality of life. While proton pump inhibitors have transformed GERD therapy, effective management of this disease is still a challenge. This review consolidates data from the recently published Burning Questions and Burning Desires surveys to provide a foundation for improved primary care management of GERD. First, the surveys confirm the significant troublesome impact of GERD on patients' health-related quality of life. Negative effects on sleeping and eating were identified as the leading causes for concern among such patients. Second, a lack of symptom control was identified among patients receiving physician-guided care for GERD, with many patients experiencing persistent symptoms. This was likely to be responsible for the third major finding of these surveys - the high rate of concomitant over-the-counter medication use among patients receiving prescription therapy. The surveys also uncovered a disconnect between patients and physicians in terms of GERD symptom severity, and perceptions of GERD and its treatment. Such findings outline the requirement for improved management of GERD, including the need to identify patients who may benefit from reassessment and more effective therapies. Patient-reported, questionnaire-based tools may aid physicians in this regard.

How do people with gastro-oesophageal reflux disease perceive their disease? Results of a multinational survey.

OBJECTIVE: To determine how patients with gastro-oesophageal reflux disease (GERD) perceive their condition. METHODS: Subjects with a formal diagnosis of GERD (n = 929) and those who did not have a formal diagnosis but regularly suffered from symptoms suggestive of GERD (heartburn or acid regurgitation, n = 924) were identified as part of a multinational survey. RESULTS: Symptoms had been present for a mean of 11 years in diagnosed individuals and 8 years in undiagnosed individuals. Over-the-counter (OTC) antacids were used by 78% of undiagnosed individuals. Most patients (68% of undiagnosed and 46% of diagnosed subjects) did not consider themselves to have a serious condition, while 70% of undiagnosed and 58% of diagnosed respondents believed that their condition would not have any long-term health consequences. A key perception driving the decision to seek medical care was the belief that a physician, and prescribed medication, could help. Conversely, the perception that OTC medications work effectively was the greatest barrier to visiting a physician. Diagnosed patients, who, on average, waited 2 years before seeking medical advice, indicated that prescription medication reduced the severity and frequency of their symptoms. CONCLUSIONS: There is widespread perception that GERD is a non-serious disease without long-term health consequences, and some patients find that OTC medications are a sufficiently effective treatment option. Educational initiatives should perhaps be targeted at those in greatest medical need, overcoming the barriers that dissuade many of these patients from seeking appropriate medical care.

Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer.

PURPOSE: Phytochemicals in plants may have cancer preventive benefits through antioxidation and via gene-nutrient interactions. We sought to determine the effects of pomegranate juice (a major source of antioxidants) consumption on prostate-specific antigen (PSA) progression in men with a rising PSA following primary therapy. EXPERIMENTAL DESIGN: A phase II, Simon two-stage clinical trial for men with rising PSA after surgery or radiotherapy was conducted. Eligible patients had a detectable PSA > 0.2 and < 5 ng/mL and Gleason score < or = 7. Patients were treated with 8 ounces of pomegranate juice daily (Wonderful variety, 570 mg total polyphenol gallic acid equivalents) until disease progression. Clinical end points included safety and effect on serum PSA, serum-induced proliferation and apoptosis of LNCaP cells, serum lipid peroxidation, and serum nitric oxide levels. RESULTS: The study was fully accrued after efficacy criteria were met. There were no serious adverse events reported and the treatment was well tolerated. Mean PSA doubling time significantly increased with treatment from a mean of 15 months at baseline to 54 months posttreatment (P < 0.001). In vitro assays comparing pretreatment and posttreatment patient serum on the growth of LNCaP showed a 12% decrease in cell proliferation and a 17% increase in apoptosis (P = 0.0048 and 0.0004, respectively), a 23% increase in serum nitric oxide (P = 0.0085), and significant (P < 0.02) reductions in oxidative state and sensitivity to oxidation of serum lipids after versus before pomegranate juice consumption. CONCLUSIONS: We report the first clinical trial of pomegranate juice in patients with prostate cancer. The statistically significant prolongation of PSA doubling time, coupled with corresponding laboratory effects on prostate cancer in vitro cell proliferation and apoptosis as well as oxidative stress, warrant further testing in a placebo-controlled study.

Managing gastroesophageal reflux disease in primary care: the patient perspective.

Gastroesophageal reflux disease (GERD) is a chronic disease that affects up to 20% of the population of Western countries and accounts for around 5% of a primary-care physician's workload. A better understanding of how GERD affects many aspects of patients' lives may aid the management of patients in primary care. We conducted a systematic review of the effect of GERD on health-related quality of life (HRQL) in the primary-care setting and in the community. Validated questionnaires have shown that GERD patients consulting in primary care experience substantial reductions in both physical and psychosocial aspects of HRQL, as well as work productivity. Impairments in HRQL are seen whether or not reflux esophagitis or Barrett's esophagus is present on endoscopy, and are comparable with or worse than those seen in patients with other chronic diseases such as heart disease, diabetes, and cancer. Surveys in primary care and in the community highlight disrupted sleep, reduced concentration at work, and interference with physical activities such as exercise, housework, and gardening. Psychosocial aspects of patient well-being are also impaired, including enjoyment of social gatherings, intimacy, sex, and many individuals with GERD remain worried about the underlying cause of their symptoms. In conclusion, many aspects of HRQL are impaired in GERD patients. The primary-care physician is uniquely placed to assess and address the impact of GERD on patients' lives.

Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation.

Dietary supplementation with polyphenolic antioxidants to animals was shown to be associated with inhibition of LDL oxidation and macrophage foam cell formation, and attenuation of atherosclerosis development. We investigated the effects of pomegranate juice (PJ, which contains potent tannins and anthocyanins) consumption by atherosclerotic patients with carotid artery stenosis (CAS) on the progression of carotid lesions and changes in oxidative stress and blood pressure. Ten patients were supplemented with PJ for 1 year and five of them continued for up to 3 years. Blood samples were collected before treatment and during PJ consumption. In the control group that did not consume PJ, common carotid intima-media thickness (IMT) increased by 9% during 1 year, whereas, PJ consumption resulted in a significant IMT reduction, by up to 30%, after 1 year. The patients' serum paraoxonase 1 (PON 1) activity was increased by 83%, whereas serum LDL basal oxidative state and LDL susceptibility to copper ion-induced oxidation were both significantly reduced, by 90% and 59%, respectively, after 12 months of PJ consumption, compared to values obtained before PJ consumption. Furthermore, serum levels of antibodies against oxidized LDL were decreased by 19%, and in parallel serum total antioxidant status (TAS) was increased by 130% after 1 year of PJ consumption. Systolic blood pressure was reduced after 1 year of PJ consumption by 12% [corrected] and was not further reduced along 3 years of PJ consumption. For all studied parameters, the maximal effects were observed after 1 year of PJ consumption. Further consumption of PJ, for up to 3 years, had no additional beneficial effects on IMT and serum PON1 activity, whereas serum lipid peroxidation was further reduced by up to 16% after 3 years of PJ consumption. The results of the present study thus suggest that PJ consumption by patients with CAS decreases carotid IMT and systolic blood pressure and these effects could be related to the potent antioxidant characteristics of PJ polyphenols.

Vitamin D-mediated hypercalcemia in lymphoma: evidence for hormone production by tumor-adjacent macrophages.

Nearly one-half of all hypercalcemic patients with lymphoma present with inappropriately elevated circulating concentrations of the active vitamin D metabolite 1,25-dihydroxyvitamin D (1,25(OH)2D3). However, the cellular source of the vitamin D hormone in lymphomas remains unclear. To address this, we report the case of a 75-year-old man with hypercalcemia associated with raised circulating concentrations of 1,25(OH)2D3 and suppressed parathyroid hormone (PTH) levels. Positron emission tomographic (PET) and computed tomographic (CT) imaging revealed the presence of a large lymphoma that was confined to the spleen; subsequent pathological analysis showed that this was an intermediate grade B-cell lymphoma. After surgical removal of the spleen, serum calcium and 1,25(OH)2D3 levels became normalized within 24 h. Immunolocalization of the vitamin D-activating enzyme 25-hydroxyvitamin D3-1alpha-hydroxylase (la-hydroxylase) in sections of resected spleen showed that staining was negative in the lymphoma cells but positive in neighboring macrophages. This case study indicates that the hypercalcemia associated with lymphomas may be due, in some instances, to excessive extrarenal production of 1,25(OH)2D3. Furthermore, by using immunohistochemistry to assess the distribution of la-hydroxylase, we have been able to show for the first time that tissue macrophages, rather than actual tumor cells, are the most likely ectopic source of this enzyme. Based on this case study, we propose that the abnormal synthesis of 1,25(OH)2D3 associated with some lymphomas is because of paracrine regulation of tumor-associated macrophages.