Oral bisphosphonates and upper gastrointestinal toxicity: a study of cancer and early signals of esophageal injury.

SUMMARY: We evaluated the association between bisphosphonate use and (1) upper gastrointestinal cancer, (2) upper endoscopy, (3) incident Barrett's esophagus, and (4) prescription antacid initiation among Medicare beneficiaries. We found no bisphosphonate-cancer association and negative bisphosphonate-Barrett's association. INTRODUCTION: Bisphosphonates can irritate the esophagus; a cancer association has been suggested. Widespread bisphosphonates use compels continued investigation of upper gastrointestinal toxicity. METHODS: Using a 40% Medicare random sample denominator, inpatient, outpatient (2003-2011), and prescription (2006-2011) claims, we studied patients age 68 and older with osteoporosis and/or oral bisphosphonate use. Inverse propensity weighting estimated marginal structural models for the effect of bisphosphonate intensity (pills per month) and cumulative bisphosphonate pills received on upper gastrointestinal cancer risk. Secondary analyses of sub-cohorts without past bisphosphonates or upper endoscopy assessed bisphosphonate initiation and risk of (1) upper endoscopy, (2) incident Barrett's esophagus, and (3) prescription antacid initiation. RESULTS: The cohort included 1.64 million beneficiaries: 87.9% women, mean age, 76.8 (standard deviation (SD) 9.3); mean follow-up, 39.6 months; 38.1% received oral bisphosphonates. Cumulative bisphosphonate receipt, among users, ranged from 4 to 252 pills (5th to 95th percentile). We identified 2,308 upper gastrointestinal cancers (0.43/1000 person years). We found no association between cumulative bisphosphonate pills and cancer, odds ratio (OR) for each additional pill 1.00 (95% confidence interval (CI) 1.00, 1.00). In sub-cohorts, compared to none, lowest cumulative bisphosphonate use (one to nine pills) was associated with higher risk of endoscopy (OR 1.11, 95% CI 1.08-1.14) and antacid initiation (OR 1.13, 95% CI 1.10-1.16); higher intensity conferred no increased risk. Higher intensity and higher cumulative bisphosphonate category were associated with lower Barrett's risk. CONCLUSIONS: We found no bisphosphonate-cancer association and negative bisphosphonate-Barrett's association. Bisphosphonate initiation appears to identify patients susceptible to early irritating effects; clinicians might offer alternatives and delay endoscopy or antacids.

Overuse of short-interval bone densitometry: assessing rates of low-value care.

UNLABELLED: We evaluated the prevalence and geographic variation of short-interval (repeated in under 2 years) dual-energy X-ray absorptiometry tests (DXAs) among Medicare beneficiaries. Short-interval DXA use varied across regions (coefficient of variation = 0.64), and unlike other DXAs, rates decreased with payment cuts. INTRODUCTION: The American College of Rheumatology, through the Choosing Wisely initiative, identified measuring bone density more often than every 2 years as care "physicians and patients should question." We measured the prevalence and described the geographic variation of short-interval (repeated in under 2 years) DXAs among Medicare beneficiaries and estimated the cost of this testing and its responsiveness to payment change. METHODS: Using 100 % Medicare claims data, 2006-2011, we identified DXAs and short-interval DXAs for female Medicare beneficiaries over age 66. We determined the population rate of DXAs and short-interval DXAs, as well as Medicare spending on short-interval DXAs, nationally and by hospital referral region (HRR). RESULTS: DXA use was stable 2008-2011 (12.4 to 11.5 DXAs per 100 women). DXA use varied across HRRs: in 2011, overall DXA use ranged from 6.3 to 23.0 per 100 women (coefficient of variation = 0.18), and short-interval DXAs ranged from 0.3 to 8.0 per 100 women (coefficient of variation = 0.64). Short-interval DXA use fluctuated substantially with payment changes; other DXAs did not. Short-interval DXAs, which represented 10.1 % of all DXAs, cost Medicare approximately US$16 million in 2011. CONCLUSIONS: One out of ten DXAs was administered in a time frame shorter than recommended and at a substantial cost to Medicare. DXA use varied across regions. Short-interval DXA use was responsive to reimbursement changes, suggesting carefully designed policy and payment reform may reduce this care identified by rheumatologists as low value.

Skeletal health in men with chronic lung disease: rates of testing, treatment, and fractures.

UNLABELLED: To advance our understanding of the burden of fractures among men, we studied a group of men at high risk for low bone strength due to lung disease. We found high rates of fractures but low rates of bone density testing that could predict fracture before it occurs. INTRODUCTION: To advance understanding of the burden of fragility fractures and attention to bone health among men with chronic obstructive lung disease (COPD), we quantified rates of fragility fracture, bone density testing, and anti-resorptive treatment and calculated the number needed to screen (NNS) to prevent one hip fracture in a cohort of men with COPD. METHODS: Veterans Administration (VA) and VA-Medicare administrative data permitted a retrospective cohort study of 87,360 men aged 50 and older, newly diagnosed with COPD between 1999 and 2003. Logistic regression models including patient characteristics, morbidities, and medication use assessed the effect of covariates on fracture and probability of testing or treatment. RESULTS: Mean age was 66.8. Hip and wrist fracture rates were 3.99 and 1.31 per 1,000 person years, respectively. Mean follow-up was 2.67 years; 4.4% underwent bone densitometry; 2.8% filled anti-resorptive prescriptions. Age, white race/ethnicity, more COPD exacerbations, barbiturate use, and anti-Parkinson's drug use were significantly associated with fracture. Age, and systemic corticosteroids were most significantly associated with testing or treatment. Based on published adherence and treatment effects, the cohort's calculated NNS to prevent one hip fracture is 432. CONCLUSIONS: Fracture rate was high and testing and treatment uncommon. The NNS of 432 to prevent one hip fracture is smaller than 731, the NNS for women aged 65-69 for whom universal screening is recommended. Attention to the bone health of this population is warranted. Future research must determine how testing and treatment impact overall quality of life and mortality of men with COPD.

Medical management of obesity.

Obesity is one of the most common medical problems in the United States and a risk factor for illnesses such as hypertension, diabetes, degenerative arthritis and myocardial infarction. It is a cause of significant morbidity and mortality and generates great social and financial costs. Obesity is defined as a body mass index greater than 30. Many patients accomplish weight loss with diet, exercise and lifestyle modification. Others require more aggressive therapy. Weight loss medications may be appropriate for use in selected patients who meet the definition of obesity or who are overweight with comorbid conditions. Medications are formulated to reduce energy intake, increase energy output or decrease the absorption of nutrients. Drugs cannot replace diet, exercise and lifestyle modification, which remain the cornerstones of obesity treatment. Two new agents, sibutramine and orlistat, exhibit novel mechanisms of action and avoid some of the side effects that occurred with earlier drugs. Sibutramine acts to block uptake of serotonin, norepinephrine and dopamine, while orlistat decreases fat absorption in the intestines.

Topical fluoroquinolones for eye and ear.

Topical fluoroquinolones are now available for use in the eye and ear. Their broad spectrum of activity includes the common eye and ear pathogens Staphylococcus aureus and Pseudomonas aeruginosa. For the treatment of acute otitis externa, these agents are as effective as previously available otic preparations. For the treatment of otitis media with tympanic membrane perforation, topical fluoroquinolones are effective and safe. These preparations are approved for use in children, and lack of ototoxicity permits prolonged administration when necessary. Topical fluoroquinolones are not appropriate for the treatment of uncomplicated conjunctivitis where narrower spectrum agents suffice; they represent a simplified regimen for the treatment of bacterial keratitis (corneal ulcers). When administered topically, fluoroquinolones are well tolerated and offer convenient dosing schedules. Currently, bacterial resistance appears limited.