Robert A. Yood

Alendronate treatment of the postmenopausal osteoporotic woman: Effect of multiple dosages on bone mass and bone remodeling

BACKGROUND The effects of the aminobisphosphonate alendronate sodium on bone mass and markers of bone remodeling were investigated. PATIENTS AND METHODS In a multicenter, randomized, double-blind, placebo-controlled, 2-year study, 188 postmenopausal women, aged 42 to 75 years, with low bone mineral density (BMD) of the lumbar spine were randomly assigned to 1 of 6 daily treatment groups: placebo for 2 years, alendronate 5 or 10 mg for 2 years, alendronate 20 or 40 mg for 1 year followed by placebo for 1 year, or alendronate 40 mg for 3 months followed by 2.5 mg for 21 months. All subjects were given 500 mg/d of elemental calcium as calcium carbonate. RESULTS At each dose, alendronate produced significant reductions in markers of bone resorption and formation, and significantly increased bone mass at the lumbar spine, hip, and total body, as compared with decreases (significant at lumbar spine) in subjects receiving placebo. In the 10-mg group, mean urinary deoxypyridinoline/creatinine had declined by 47% at 3 months, and mean serum osteocalcin by 53% at 6 months. Mean changes in BMD over 24 months with 10 mg alendronate were +7.21% +/- 0.49% for the lumbar spine, +5.27% +/- 0.70% for total hip, and +2.53% +/- 0.68% for total body (each P < 0.01) compared to changes of -1.35% +/- 0.61%, -1.20% +/- 0.64% and -0.31% +/- 0.44% at these sites, respectively, with placebo treatment. Progressive increases in BMD of both lumbar spine and total hip were observed in the second year of treatment with 10 mg alendronate (both P < 0.05). CONCLUSION Alendronate, a potent inhibitor of bone resorption, reduces markers of bone remodeling and significantly increases BMD at the lumbar spine, hip, and total body, and is well tolerated at therapeutic doses (5 or 10 mg daily) in the treatment of osteoporosis in postmenopausal women.

Efficacy and Tolerability of Pegloticase for the Treatment of Chronic Gout in Patients Refractory to Conventional Treatment: Two Randomized Controlled Trials

CONTEXT Patients with chronic disabling gout refractory to conventional urate-lowering therapy need timely treatment to control disease manifestations related to tissue urate crystal deposition. Pegloticase, monomethoxypoly(ethylene glycol)-conjugated mammalian recombinant uricase, was developed to fulfill this need. OBJECTIVE To assess the efficacy and tolerability of pegloticase in managing refractory chronic gout. DESIGN, SETTING, AND PATIENTS Two replicate, randomized, double-blind, placebo-controlled trials (C0405 and C0406) were conducted between June 2006 and October 2007 at 56 rheumatology practices in the United States, Canada, and Mexico in patients with severe gout, allopurinol intolerance or refractoriness, and serum uric acid concentration of 8.0 mg/dL or greater. A total of 225 patients participated: 109 in trial C0405 and 116 in trial C0406. INTERVENTION Twelve biweekly intravenous infusions containing either pegloticase 8 mg at each infusion (biweekly treatment group), pegloticase alternating with placebo at successive infusions (monthly treatment group), or placebo (placebo group). MAIN OUTCOME MEASURE Primary end point was plasma uric acid levels of less than 6.0 mg/dL in months 3 and 6. RESULTS In trial C0405 the primary end point was reached in 20 of 43 patients in the biweekly group (47%; 95% CI, 31%-62%), 8 of 41 patients in the monthly group (20%; 95% CI, 9%-35%), and in 0 patients treated with placebo (0/20; 95% CI, 0%-17%; P < .001 and <.04 for comparisons between biweekly and monthly groups vs placebo, respectively). Among patients treated with pegloticase in trial C0406, 16 of 42 in the biweekly group (38%; 95% CI, 24%-54%) and 21 of 43 in the monthly group (49%; 95% CI, 33%-65%) achieved the primary end point; no placebo-treated patients reached the primary end point (0/23; 95% CI, 0%-15%; P = .001 and < .001, respectively). When data in the 2 trials were pooled, the primary end point was achieved in 36 of 85 patients in the biweekly group (42%; 95% CI, 32%-54%), 29 of 84 patients in the monthly group (35%; 95% CI, 24%-46%), and 0 of 43 patients in the placebo group (0%; 95% CI, 0%-8%; P < .001 for each comparison). Seven deaths (4 in patients receiving pegloticase and 3 in the placebo group) occurred between randomization and closure of the study database (February 15, 2008). CONCLUSION Among patients with chronic gout, elevated serum uric acid level, and allopurinol intolerance or refractoriness, the use of pegloticase 8 mg either every 2 weeks or every 4 weeks for 6 months resulted in lower uric acid levels compared with placebo. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00325195.

Effects of conjugated equine estrogen on risk of fractures and BMD in postmenopausal women with hysterectomy: Results from the women's health initiative randomized trial

Further analyses from the Womens Health Initiative estrogen trial shows that CEE reduced fracture risk. The fracture reduction at the hip did not differ appreciably among risk strata. These data do not support overall benefit over risk, even in women at highest risk for fracture.

A demonstration of the impact of response bias on the results of patient satisfaction surveys

OBJECTIVES The purposes of the present study were to examine patient satisfaction survey data for evidence of response bias, and to demonstrate, using simulated data, how response bias may impact interpretation of results. DATA SOURCES Patient satisfaction ratings of primary care providers (family practitioners and general internists) practicing in the context of a group-model health maintenance organization and simulated data generated to be comparable to the actual data. STUDY DESIGN Correlational analysis of actual patient satisfaction data, followed by a simulation study where response bias was modeled, with comparison of results from biased and unbiased samples. PRINCIPAL FINDINGS A positive correlation was found between mean patient satisfaction rating and response rate in the actual patient satisfaction data. Simulation results suggest response bias could lead to overestimation of patient satisfaction overall, with this effect greatest for physicians with the lowest satisfaction scores. CONCLUSIONS Findings suggest that response bias may significantly impact the results of patient satisfaction surveys, leading to overestimation of the level of satisfaction in the patient population overall. Estimates of satisfaction may be most inflated for providers with the least satisfied patients, thereby threatening the validity of provider-level comparisons.

Increments in Bone Mineral Density of the Lumbar Spine and Hip and Suppression of Bone Turnover Are Maintained after Discontinuation of Alendronate in Postmenopausal Women

PURPOSE Previously we have reported a significant increase in bone mineral density (BMD) of the spine and the hip and reductions in biochemical indices of bone turnover in postmenopausal women with osteoporosis treated with alendronate at various doses over 1 to 2 years. We have followed BMD and biochemical parameters in these patients for 1 or 2 years after discontinuation of alendronate to determine resolution of alendronate effects. PATIENTS AND METHODS Participants received daily oral doses of placebo, 5 or 10 mg of alendronate for 2 years, or 20 or 40 mg of alendronate for 1 year followed by 1 year of placebo. No treatment was given in the third year of study. RESULTS Lumbar spine BMD changes in the 5- and 10-mg groups (-1.4 and -0.4%) were similar to those in the placebo group (-1.2%) 1 year after discontinuation of drug and lumbar spine BMD changes in the 20- and 40-mg groups (-1.2% and 0.8%) were similar to those in the placebo group (-0.9%) 2 years after discontinuation of drug. BMD of the total hip followed the same pattern of resolution. The difference in BMD between alendronate and placebo groups at the end of alendronate treatment was maintained up to 2 years. Residual reductions in the bone resorption markers urinary deoxypyridinoline (D-Pyr) and collagen type 1 cross-linked N telopeptides and the bone formation markers serum bone-specific alkaline phosphatase and osteocalcin remained for 1 year after discontinuation of 5 and 10 mg of alendronate and for 2 years after discontinuation of 20 and 40 mg of alendronate, other than return of D-Pyr to baseline 1 year after cessation of treatment with the 5- and 10-mg doses. CONCLUSIONS A residual decrease in bone turnover may be found up to 2 years after discontinuation of alendronate. Accelerated bone loss is not observed when treatment is discontinued. However, continuous therapy with alendronate is required to achieve a continuous gain in BMD.

Adherence with urate-lowering therapies for the treatment of gout.

IntroductionAdherence to urate-lowering drugs (ULDs) has not been well evaluated among those with gout. Our aim was to assess the level and determinants of non-adherence with ULDs prescribed for gout.MethodsWe identified persons using two integrated delivery systems aged 18 years or older with a diagnosis of gout who initiated use of allopurinol, probenecid or sulfinpyrazone from 1 January 2000 to 30 June 2006. Non-adherence was measured using the medication possession ratio (MPR) over the first year of therapy and defined as an MPR < 0.8. Descriptive statistics were calculated and logistic regression was used to estimate the strength of the association between patient characteristics and non-adherence.ResultsA total of 4,166 gout patients initiated ULDs; 97% received allopurinol. Median MPR for any ULD use was 0.68 (interquartile range (IQR) 0.64). Over half of the patients (56%) were non-adherent (MPR < 0.8). In adjusted analyses, predictors of poor adherence included younger age (odds ratio (OR) 2.43, 95% confidence interval (CI) 1.86 to 3.18 for ages <45 and OR 1.44, 95% CI 1.08 to 1.93 for ages 45 to 49), fewer comorbid conditions (OR 1.46, 95% CI 1.20 to 1.77), no provider visits for gout prior to urate-lowering drug initiation (OR 1.28, 95% CI 1.05 to 1.55), and use of non-steroidal anti-inflammatory drugs in the year prior to urate-lowering drug initiation (OR 1.15, 95% CI 1.00 to 1.31).ConclusionsNon-adherence amongst gout patients initiating ULDs is exceedingly common, particularly in younger patients with less comorbidity and no provider visits for gout prior to ULD initiation. Providers should be aware of the magnitude of non-adherence with ULDs.

Disclosure of Medical Errors: What Factors Influence How Patients Respond?

AbstractBACKGROUND: Disclosure of medical errors is encouraged, but research on how patients respond to specific practices is limited. OBJECTIVE: This study sought to determine whether full disclosure, an existing positive physician-patient relationship, an offer to waive associated costs, and the severity of the clinical outcome influenced patients’ responses to medical errors. PARTICIPANTS: Four hundred and seven health plan members participated in a randomized experiment in which they viewed video depictions of medical error and disclosure. DESIGN: Subjects were randomly assigned to experimental condition. Conditions varied in type of medication error, level of disclosure, reference to a prior positive physician-patient relationship, an offer to waive costs, and clinical outcome. MEASURES: Self-reported likelihood of changing physicians and of seeking legal advice; satisfaction, trust, and emotional response. RESULTS: Nondisclosure increased the likelihood of changing physicians, and reduced satisfaction and trust in both error conditions. Nondisclosure increased the likelihood of seeking legal advice and was associated with a more negative emotional response in the missed allergy error condition, but did not have a statistically significant impact on seeking legal advice or emotional response in the monitoring error condition. Neither the existence of a positive relationship nor an offer to waive costs had a statistically significant impact. CONCLUSIONS: This study provides evidence that full disclosure is likely to have a positive effect or no effect on how patients respond to medical errors. The clinical outcome also influences patients’ responses. The impact of an existing positive physician-patient relationship, or of waiving costs associated with the error remains uncertain.

Sex differences in gout epidemiology, evaluation and treatment

Background: Little is known about the characteristics, evaluation and treatment of women with gout. Objective: To examine the epidemiological differences and differences in treatment between men and women in a large patient population. Methods: The data from approximately 1.4 million people who were members of seven managed care plans in the USA for at least 1 year between 1 January 1999 and 31 December 2003 were examined. Adult members who had pharmacy benefits and at least two ambulatory claims specifying a diagnosis of gout were identified. In addition, men and women who were new users of urate-lowering drugs (ULDs) were identified to assess adherence with recommended surveillance of serum urate levels within 6 months of initiating urate-lowering treatment. Results: A total of 6133 people (4975 men and 1158 women) with two or more International Classification of Disease-9 codes for gout were identified. As compared with men with gout, women were older (mean age 70 (SD 13) v 58 (SD 14), p<0.001) and had comorbidities and received diuretics more often (77% v 40%; p<0.001). Only 37% of new users of urate-lowering treatment had appropriate surveillance of serum urate levels post-initiation of urate-lowering treatment. After controlling for age, comorbidities, gout treatments, number of ULD dispensings and health plan, women were more likely (odds ratio 1.36, 95% confidence interval 1.11 to 1.67) to receive the recommended serum urate level testing. Conclusions: Women with gout were older, had greater comorbidities and more often used diuretics and received appropriate surveillance of serum urate levels, suggesting that the factors leading to gout as well as monitoring of treatment are very different in women and men.

Patients and providers view gout differently: a qualitative study.

Objectives: We sought to examine patients’ and providers’ views on the treatment of gout to better understand why management is suboptimal. Methods: In-depth telephone interviews were conducted with gout patients (n = 26) who initiated treatment with a urate-lowering drug (ULD) in the previous 6 months and with providers who care for gout patients (n = 15). The interviews were audiotaped and transcribed verbatim. Using qualitative methods, results were analysed and themes were identified. Interviews focused on the acute management, chronic management and prevention and improvement strategies. Results: Providers viewed the majority of patients as having excellent relief with non-steroidal anti-inflammatories, colchicine and glucocorticoids, while some patients felt these medications were ineffective. Providers felt that most patients had a good understanding of the rationale for ULD therapy and that patients responded well. Some patients felt ULDs triggered, worsened or had no impact on their disease. Most providers thought medication adherence was relatively good. Some patients reported discontinuing medications. Discontinuations were largely purposeful and due to clinical or financial concerns. Most providers thought they had adequate skills to teach disease self-management behaviours. Patients requested more information and longer visit times. Conclusions: Providers view gout as easily managed, while patients report challenges and purposeful non-adherence.

Patient Decision to Initiate Therapy for Osteoporosis: The Influence of Knowledge and Beliefs

BackgroundThere are effective treatments to prevent osteoporotic fractures, but these treatments are underutilized.ObjectiveTo evaluate the influence of patient characteristics, perceptions, knowledge and beliefs about osteoporosis on the decision to initiate osteoporotic treatment.ParticipantsWe identified female members of a managed care plan who had a dual energy x-ray absorptiometry (DXA) bone density test and fulfilled World Health Organization criteria for osteoporosis. Patients were excluded if they received osteoporotic medications in the prior 6 months.MeasurementsPatients were sent a questionnaire that included items assessing satisfaction with physician–patient communication, trust in the physician, osteoporosis knowledge and beliefs, beliefs about prescription medications, and perceptions of barriers to medication use. Administrative electronic health records were used to identify prescription drug use and health care utilization.ResultsTwo hundred and thirty-six women returned surveys and research authorization forms out of 465 contacted for participation. One hundred and thirty-five (57.2%) filled a prescription for an osteoporotic drug in the first 3 months after the DXA exam. The largest differences between initiators and non-initiators were in beliefs in the benefits of medications, and distrust of medications, with initiators believing more strongly in the benefits and effectiveness of medications (p < .001), and non-initiators reporting more distrust of medications (p < .001). Osteoporosis knowledge and the belief that osteoporosis is a serious disease were also related to therapy initiation in bivariate analysis.ConclusionsOnly 57% of patients initiated osteoporotic medication within 3 months of diagnosis. The decision to start osteoporosis treatment appeared to be related to a patient’s beliefs in the effectiveness of osteoporosis medications and distrust of medications.