Proton-Pump Inhibitors Reduce Gastrointestinal Events Regardless of Aspirin Dose in Patients Requiring Dual Antiplatelet Therapy.

BACKGROUND: The COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial) showed that proton-pump inhibitors (PPIs) safely reduced rates of gastrointestinal (GI) events in patients requiring dual antiplatelet therapy (DAPT). However, utilization of appropriate prophylactic PPI therapy remains suboptimal, especially with low-dose aspirin. OBJECTIVES: The authors investigated the safety and efficacy of PPI therapy in patients receiving DAPT in low- and high-dose aspirin subsets. METHODS: Randomized patients with available aspirin dosing information in COGENT (N = 3,752) were divided into "low-dose" (≤ 100 mg) and "high-dose" (>100 mg) aspirin groups. The primary GI and cardiovascular endpoints were composite upper GI events and major adverse cardiac events, respectively. All events were adjudicated by independent, blinded gastroenterologists and cardiologists. RESULTS: Median duration of follow-up was 110 days. Low-dose aspirin users (n = 2,480; 66.1%) were more likely to be older, female, and have higher rates of peripheral artery disease, prior stroke, and hypertension, whereas high-dose aspirin users (n = 1,272; 33.9%) had higher rates of hyperlipidemia, smoking, a history of percutaneous coronary intervention, and were more than twice as likely to be enrolled from sites within the United States (80.4% vs. 39.8%). High-dose aspirin was associated with similar 180-day Kaplan-Meier estimates of adjudicated composite GI events (1.7% vs. 2.1%; adjusted hazard ratio: 0.88; 95% confidence interval: 0.46 to 1.66) and major adverse cardiac events (4.8% vs. 5.5%; adjusted hazard ratio: 0.73; 95% confidence interval: 0.48 to 1.11) compared with low-dose aspirin. Randomization to PPI therapy reduced 180-day Kaplan-Meier estimates of the primary GI endpoint in low-dose (1.2% vs. 3.1%) and high-dose aspirin subsets (0.9% vs. 2.6%; p for interaction = 0.80), and did not adversely affect the primary cardiovascular endpoint in either group. CONCLUSIONS: Gastroprotection with PPI therapy should be utilized in appropriately selected patients with coronary artery disease requiring DAPT, even if the patients are on low-dose aspirin. (Clopidogrel and the Optimization of Gastrointestinal Events Trial [COGENT]; NCT00557921).

Prevalence of 25-hydroxyvitamin D deficiency in the acute inpatient rehabilitation population and its effect on function.

OBJECTIVES: To assess the prevalence of 25-hydroxyvitamin D (25[OH]D) insufficiency and deficiency in the acute inpatient rehabilitation setting, identify risk factors associated with low serum 25(OH)D levels, and assess whether hypovitaminosis D affects the function of rehabilitation patients. DESIGN: Retrospective cohort study. SETTING: Academic acute rehabilitation facility. PARTICIPANTS: Patients (N=101) admitted for acute inpatient rehabilitation between September 2008 and December 2008. INTERVENTIONS: Serum 25(OH)D levels drawn within 24 hours of admission. MAIN OUTCOME MEASURES: 25(OH)D level, total/motor/cognitive FIM efficiency. RESULTS: Considering patients not receiving 25(OH)D supplementation at the time of admission, 23.0% were 25(OH)D sufficient, 68.9% were insufficient, and 8.1% were deficient. Patients receiving 25(OH)D supplementation at the time of admission had significantly higher 25(OH)D levels than patients not receiving 25(OH)D supplementation (33.4±12.8 vs 23.7±11.4ng/mL; P=.001). A total of 72.2% of patients with any fracture and 80.0% of patients with fracture due to fall were not receiving supplementation at the time of admission; 72.2% of patients with any fracture and 73.3% of patients with fracture due to fall were 25(OH)D insufficient. Unadjusted total FIM efficiency scores were statistically significantly different by 25(OH)D status (2.96±1.42 vs 2.29±1.41ng/mL; P=.039). However, 25(OH)D level was not a significant predictor of total FIM efficiency score after controlling for demographic and clinical factors. CONCLUSIONS: Of acute rehabilitation patients, 77% are 25(OH)D insufficient or deficient at admission. 25(OH)D supplementation is associated with a greater 25(OH)D level in these patients; however, almost half those supplemented had 25(OH)D levels less than the reference range. Most inpatients with fracture due to fall were transferred to acute inpatient rehabilitation without 25(OH)D supplementation despite clear guidelines indicating its use in this situation.

Prevalence of 25-hydroxyvitamin D deficiency in the outpatient rehabilitation population.

OBJECTIVE: To assess the prevalence of 25-hydroxyvitamin D insufficiency and deficiency in the outpatient rehabilitation setting and to identify patient characteristics associated with low serum 25-hydroxyvitamin D levels. DESIGN: 25-Hydroxyvitamin D levels from 136 rehabilitation outpatients at an academic rehabilitation facility obtained from April 2007 to December 2008 for patient care purposes were captured via retrospective electronic medical record review. RESULTS: Considering only those subjects not receiving 25-hydroxyvitamin D supplementation at time of evaluation, 33.0% were 25-hydroxyvitamin D Sufficient while 53.2% were Insufficient and 13.8% Deficient. Those outpatient subjects receiving supplementation at time of evaluation had significantly higher 25-hydroxyvitamin D levels compared with those not receiving supplementation (34.1 ± 14.2 ng/ml vs. 25.9 ± 15.2 ng/ml; P = 0.005). Blacks had significantly lower 25-hydroxyvitamin D levels compared with whites (18.0 ± 10.6 ng/ml vs. 31.3 ± 14.3 ng/ml; P < 0.001). Subjects not on vitamin D supplementation assigned to diagnostic groups, Spinal Cord Injury, Brain Injury, and Hereditary Musculoskeletal, all had average 25-hydroxyvitamin D levels well below the lower limit of Sufficiency. CONCLUSIONS: Sixty-seven percent of rehabilitation outpatients are 25-hydroxyvitamin D Insufficient or Deficient. Supplementation significantly affects 25-hydroxyvitamin D levels in the outpatient rehabilitation population. Non-white race and history of Spinal Cord Injury, Brain Injury, or Hereditary Musculoskeletal diagnosis seem to be associated with lower 25-hydroxyvitamin D levels.

Once-weekly oral alendronate 70 mg in patients with glucocorticoid-induced bone loss: a 12-month randomized, placebo-controlled clinical trial.

OBJECTIVE: Glucocorticoid-induced osteoporosis is the most common iatrogenic form of osteoporosis. We evaluated the efficacy and safety of once-weekly bisphosphonate therapy for prevention and treatment of bone loss in patients on glucocorticoid therapy. METHODS: We conducted a 12-month, multicenter, randomized, double-blind, placebo-controlled trial with 114 and 59 patients in the treatment and placebo arms, respectively. Participants were stratified according to the duration of prior oral glucocorticoid therapy at randomization. Participants received alendronate 70 mg once weekly (ALN OW) or placebo; all received supplemental daily calcium (1000 mg) and 400 IU vitamin D. Clinical evaluations were performed at baseline, 3, 6, 9, and 12 months. RESULTS: At 12 months, there was a significant mean percentage increase from baseline in the ALN OW group for lumbar spine (2.45%), trochanter (1.27%), total hip (0.75%), and total body (1.70%) bone mineral density (BMD). Comparing ALN OW versus placebo at 12 months, a significant treatment difference for the mean percentage change from baseline was observed for lumbar spine (treatment difference of 2.92%; p

A preliminary fMRI study of analgesic treatment in chronic back pain and knee osteoarthritis.

The effects of an analgesic treatment (lidocaine patches) on brain activity in chronic low back pain (CBP) and in knee osteoarthritis (OA) were investigated using serial fMRI (contrasting fMRI between before and after two weeks of treatment). Prior to treatment brain activity was distinct between the two groups: CBP spontaneous pain was associated mainly with activity in medial prefrontal cortex, while OA painful mechanical knee stimulation was associated with bilateral activity in the thalamus, secondary somatosensory, insular, and cingulate cortices, and unilateral activity in the putamen and amygdala. After 5% lidocaine patches were applied to the painful body part for two weeks, CBP patients exhibited a significant decrease in clinical pain measures, while in OA clinical questionnaire based outcomes showed no treatment effect but stimulus evoked pain showed a borderline decrease. The lidocaine treatment resulted in significantly decreased brain activity in both patient groups with distinct brain regions responding in each group, and sub-regions within these areas were correlated with pain ratings specifically for each group (medial prefrontal cortex in CBP and thalamus in OA). We conclude that the two chronic pain conditions involve distinct brain regions, with OA pain engaging many brain regions commonly observed in acute pain. Moreover, lidocaine patch treatment modulates distinct brain circuitry in each condition, yet in OA we observe divergent results with fMRI and with questionnaire based instruments.

Osteoporosis treatment for patients with stroke.

PURPOSE: Little is known about the frequency of use of medications to maintain bone health for patients with stroke. This study was undertaken at an urban academic rehabilitation center to determine the prevalence of use of agents that could reduce bone loss in the stroke population. METHOD: A clinical database was searched for all patients 18 years old and over with stroke. The sample included 1,219 inpatients and 2,776 outpatients. Demographic information (age, gender, and race) and medications were obtained for each patient. RESULTS: Among inpatients with stroke, 7.1% were taking osteoporosis medications (bisphosphonates, calcitonin, parathyroid hormone, or hormone replacement therapy), 11.3% were taking calcium supplements, 5.9% were taking vitamin D supplements, and 45.1% were taking multivitamin supplements. Among outpatients with stroke, 5.7% were taking osteoporosis medication, 5.8% were taking calcium supplements, 2.2% were taking vitamin D supplements, and 16.0% were taking multivitamin supplements. Patients being treated with specific osteoporosis therapies tended to be older and female by calculated odds ratios. The use of multivitamins was not related to age, gender, or race. CONCLUSION: Overall, relatively few stroke patients were taking osteoporosis medications or supplements. There is a need to increase the recognition, prevention, and treatment of bone loss in this high-risk population.

Update of ACR guidelines for osteoarthritis: role of the coxibs.

The American College of Rheumatology (ACR) recently provided an update to the guidelines published in 1995 on the management of osteoarthritis (OA) of the knee and hip. Members of the Ad Hoc Committee on OA Guidelines followed an evidence-based medicine approach to revise the guidelines by reviewing an extensive literature search of the Cochrane and Medline databases and published abstracts, and discussing evidence with expert rheumatologists. The goal of the guidelines is to provide recommendations to control patients' OA pain, improve function and health-related quality of life, and avoid therapeutic toxicity. As in the original guidelines, nonpharmacologic interventions involving patient education and physical measures are recommended following initial diagnosis of OA. The pharmacologic algorithm was updated to include currently available therapeutic agents. Acetaminophen remains first-line therapy because of its cost, efficacy, and safety profiles. Cyclooxygenase-2-selective inhibitors (coxibs) have been included as an alternative to nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) in patients at risk for upper gastrointestinal adverse events. Tramadol is an available alternative for patients who have a contraindication to coxibs or nonselective NSAIDs or for those who have not responded to previous oral therapy. Intra-articular injections or topical therapy may be used as monotherapy, or as an adjunct to oral analgesia. Surgical treatment of OA remains a last resort for patients who have failed to respond to nonpharmacologic and pharmacologic treatment approaches, and have progressive limitation in their activities of daily living. Several therapies for the prevention or treatment of OA are currently under investigation, including nutritional supplements, such as glucosamine and chondroitin, disease-modifying OA drugs, and devices, such as acupuncture and electromagnetic therapy. It is anticipated that the guidelines for the management of OA will continue to evolve as new therapies become available.

Alendronate improves bone mineral density in elderly women with osteoporosis residing in long-term care facilities. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Many elderly female residents of long-term care facilities have osteoporosis and could benefit from intervention to increase bone density. OBJECTIVE: To examine the efficacy and safety of alendronate for treatment of osteoporosis in elderly female residents of long-term care facilities. DESIGN: Multicenter, randomized, double-blind, placebo-controlled 2-year study. SETTING: 25 long-term care facilities. PATIENTS: 327 elderly women with osteoporosis. INTERVENTION: Patients were randomly assigned to receive alendronate, 10 mg/d, or placebo. All patients also received vitamin D, 400 IU/d, and some patients received supplemental calcium (total intake, approximately 1500 mg/d). MEASUREMENTS: Bone mineral density (BMD) of the spine and hip and biochemical markers of bone turnover. RESULTS: Alendronate produced significantly greater increases in BMD than did placebo (24-month differences: spine, 4.4% [95% CI, 3.3% to 5.5%]; femoral neck, 3.4% [CI, 2.3% to 4.4%]). Alendronate produced greater decreases from baseline in biochemical markers of bone turnover than did placebo (P < 0.001). CONCLUSION: Alendronate increased BMD at both the spine and hip in elderly female residents of long-term care facilities.