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Summary: In elderly women with osteoporosis, prior fracture, low BMD, impaired physical functioning, poorer general health, and recent falls were all direct predictors of imminent (in next year) fracture risk. Prior fracture, older age, worse health, impaired cognitive functioning, and recent falls indirectly increased imminent risk by reducing physical functioning/general health. Introduction: This study was designed to examine determinants of imminent risk of osteoporotic fracture (i.e., next 1–2 years) in postmenopausal women. Methods: This retrospective cohort study used data from Caucasian women age 65 or older with osteoporosis who participated in the observational Study of Osteoporotic Fractures (SOF). We examined potential direct and indirect predictors of hip and nonvertebral fractures in 1-year follow-up intervals including anthropometric measures, bone mineral density (T-score), fracture since age 50, physical function, cognition, medical conditions, recent (past year) falls, and lifestyle factors. Clinically related variables were grouped into constructs via factor analysis. These constructs and selected individual variables were incorporated into a theoretical structural equation model to evaluate factors that influence imminent risk. Results: Among 2261 patients, 19.4% had a nonvertebral fracture and 5.5% had a hip fracture within 1 year of a study visit between 1992 and 2008. Prior fracture, lower T-scores, lower physical functioning, and recent falls all directly increased 1-year risk of nonvertebral fracture. For both nonvertebral and hip fractures, prior fracture and recent falls influenced risk indirectly through general health, while cognition influenced risk via physical functioning. Age influenced both physical functioning and general health. Conclusions: Several established risk factors for 10-year fracture risk also played a role in predicting imminent risk of fracture (e.g., T-scores, prior fracture), as did falls, cognition, physical functioning, and general health. Fracture risk assessments should also consider falls and fall risk factors as well as established bone-related risk factors in assessing imminent fracture risk. [ABSTRACT FROM AUTHOR]

Summary: Using data from the Study of Osteoporotic Fractures (SOF), several clinical characteristics predictive of near-term (1-year) risk of hip and non-vertebral fracture among elderly osteoporotic women were identified, and a subset of those for hip fracture was incorporated into a risk assessment tool. Additional research is needed to validate study findings. Introduction: While several risk factors are known to contribute to long-term fracture risk in women with osteoporosis, factors predicting fracture risk over a shorter time horizon, such as over a 1-year period, are less well-established. Methods: We utilized a repeated-observations design and data from the Study of Osteoporotic Fractures to identify factors contributing to near-term risk of hip fracture and any non-vertebral fracture, respectively, among osteoporotic women aged ≥65 years. Potential predictors of hip fracture and any non-vertebral fracture over the 1-year period subsequent to each qualifying SOF exam were examined using multivariable frailty models. Because the discriminative ability of the hip fracture model was acceptable, a corresponding risk-prediction tool was also developed. Results: Study population included 2499 women with osteoporosis, who contributed 6811 observations. Incidence of fracture in the 1-year period subsequent to each exam was 2.2% for hip fracture and 6.6% for any non-vertebral fracture. Independent predictors of hip fracture included low total hip T-score, prior fracture, and risk factors for falls (multivariable model c-statistic = 0.71 (95% CI 0.67-0.76)). Independent predictors of any non-vertebral fracture included age, total hip T-score, prior falls, prior fracture, walking speed, Parkinson's disease or stroke, and smoking (multivariable model c-statistic = 0.62 (0.59-0.65)). Conclusions: Several clinical characteristics predictive of hip and non-vertebral fracture within a 1-year follow-up period among elderly women with osteoporosis were identified, and a subset of those for hip fracture was incorporated into a risk assessment tool. Assessment of these risk factors may help guide osteoporosis treatment choices by identifying patients in whom there is urgency to treat. Additional research is needed to validate the findings of this study and the accuracy of the risk assessment tool. [ABSTRACT FROM AUTHOR]

Summary: In clinical practice, adherence with bisphosphonate therapy varies greatly among women with osteoporosis or osteopenia. Our study suggests that better adherence with bisphosphonates confers tangible benefits in terms of graded increases in bone mineral density. Interventions to improve drug adherence should be an important component of disease management. Introduction: In clinical trials, bisphosphonates have been found to increase bone mineral density (BMD) in women with osteoporosis or osteopenia. In clinical practice, where drug adherence is more variable, change in BMD with bisphosphonate therapy-overall and by level of adherence-is largely unknown. Methods: A retrospective cohort study was conducted at Henry Ford Health System (Detroit, MI, USA). Study subjects were women who had low BMD at the left total hip (T-score < −1.0), began oral bisphosphonate therapy, and had ≥1 BMD measurements at the left total hip ≥6 months following treatment initiation. Change in BMD was calculated between the most recent pretreatment scan and the first follow-up scan. Adherence (i.e., medication possession ratio (MPR)) was measured from therapy initiation to the first follow-up scan. Results: Among 644 subjects, mean age was 66 years, pretreatment BMD was 0.73 g/cm, and pretreatment T-score was −1.8. Over a mean follow-up of 27.1 months, mean MPR was 0.57 (95 % CI, 0.54 and 0.59), and mean percentage change in BMD was 1.5 % (1.1 and 1.9 %). Within the MPR strata (five consecutive equi-intervals, from low (0-0.19) to high (0.80-1.0)), mean change in BMD was −0.8 % (−1.6 and 0.1 %), 0.7 % (−0.3 and 1.7 %), 2.1 % (1.1 and 3.0 %), 2.1 % (1.4 and 2.9 %), and 2.9 % (2.3 and 3.5 %), respectively. In adjusted analyses, percentage change in BMD was higher (by 1.4-3.4 %, p < 0.05 for all) in the highest four MPR intervals, respectively, versus MPR 0-0.19. Conclusions: Among women with osteoporosis or osteopenia in clinical practice, better adherence with bisphosphonates appears to confer tangible benefits in terms of increases in BMD. [ABSTRACT FROM AUTHOR]

Rationale: Forced vital capacity (FVC) is an established measure of pulmonary function in idiopathic pulmonary fibrosis (IPF). Evidence regarding its measurement properties and minimal clinically important difference (MCID) in this population is limited. Objectives: To assess the reliability, validity, and responsiveness of FVC and estimate the MCID in patients with IPF. Methods: The study population included all 1,156 randomized patients in two clinical trials of IFN-[gamma]1b. FVC and other measures of functional status were measured at screening or baseline and 24-week intervals thereafter. Reliability was assessed based on two proximal measures of FVC, validity was assessed based on correlations between FVC and other measures of functional status, and responsiveness was assessed based on the relationship between 24-week changes in FVC and other measures of functional status. Distribution-based and anchor-based methods were used to estimate the MCID. Measurements and Main Results: Correlation of percent-predicted FVC between measurements (mean interval, 18 d) was high (r = 0.93; P < 0.001). Correlations between FVC and other parameters were generally weak, with the strongest observed correlation between FVC and carbon monoxide diffusing capacity (r = 0.38; P < 0.001). Correlations between change in FVC and changes in other parameters were slightly stronger (range, r = 0.16-0.37; P < 0.001). Importantly, 1-year risk of death was more than twofold higher (P < 0.001) in patients with a 24-week decline in FVC between 5% and 10%. The estimated MCID was 2-6%. Conclusions: FVC is a reliable, valid, and responsive measure of clinical status in patients with IPF, and a decline of 2-6%, although small, represents a clinically important difference. [ABSTRACT FROM AUTHOR]

Rationale: The 6-minute-walk test (6MWT) is a practical and clinically meaningful measure of exercise tolerance with favorable performance characteristics in various cardiac and pulmonary diseases. Performance characteristics in patients with idiopathic pulmonary fibrosis (IPF) have not been systematically evaluated. Objectives: To assess the reliability, validity, and responsiveness of the 6MWT and estimate the minimal clinically important difference (MCID) in patients with IPF. Methods: The study population included all subjects completing a 6MWT in a clinical trial evaluating interferon gamma-1b (n = 822). Six-minute walk distance (6MWD) and other parameters were measured at baseline and at 24-week intervals using a standardized protocol. Parametric and distribution-independent correlation coefficients were used to assess the strength of the relationships between 6MWD and measures of pulmonary function, dyspnea, and health-related quality of life. Both distribution-based and anchor-based methods were used to estimate the MCID. Measurements and Main Results: Comparison of two proximal measures of 6MWD (mean interval, 24 d) demonstrated good reliability (coefficient = 0.83; P < 0.001). 6MWD was weakly correlated with measures of physiologic function and health-related quality of life; however, values were consistently and significantly lower for patients with the poorest functional status, suggesting good construct validity. Importantly, change in 6MWD was highly predictive of mortality; a 24-week decline of greater than 50 m was associated with a fourfold increase in risk of death at 1 year (hazard ratio, 4.27; 95% confidence interval, 2.57- 7.10; P < 0.001). The estimated MCID was 24-45 m. Conclusions: The 6MWT is a reliable, valid, and responsive measure of disease status and a valid endpoint for clinical trials in IPF. [ABSTRACT FROM AUTHOR]

Objective: The efficacy and safety of memantine in patients with moderate-to-severe Alzheimer's disease (AD) receiving stable doses of donepezil were recently demonstrated in a phase III trial. The cost-effectiveness of such therapy is unknown.Research Design and Methods: A microsimulation model was developed to depict AD progression over time and associated clinical and economic outcomes. AD progression was measured in terms of decline in cognitive function, as assessed by the Severe Impairment Battery (SIB). At model entry, patients were assumed to have moderate-to-severe AD, to be on stable doses of donepezil, and to begin combination therapy with memantine, or continue to receive donepezil alone; duration of therapy was assumed to be 1 year. Drug efficacy was based on data from a phase III trial. Key assumptions of the model included: (1) efficacy of study drugs would extend to 1 year; (2) measures of cognitive function could be mapped to one another, as well as to global measures of disease severity; and (3) following therapy discontinuation, cognitive function would revert immediately to natural history levels. Cost-effectiveness was assessed in terms of cost (2005 US$) per quality-adjusted life-year (QALY) gained over a lifetime (3% discount rate).Results: SIB scores were estimated to improve by 3.3 over 1 year from therapy with memantine plus donepezil (vs. donepezil alone). While pharmacotherapy costs were estimated to increase by $1250 during the year of memantine treatment, costs of formal and informal services were estimated to decrease by $1240 over this period and by $1493 (discounted present value) over a lifetime. Findings were sensitive to the assumed SIB score at therapy initiation; cost-effectiveness was better for patients with higher initial SIB scores (i.e., less severe disease).Conclusion: In patients with moderate-to-severe AD already receiving donepezil, treatment with memantine results in improved clinical outcomes and reduced total costs of care. [ABSTRACT FROM AUTHOR]

In the Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial, the risk of new-onset diabetes was reported to be 23% lower among patients initiating therapy with valsartan versus amlodipine. The objective of our study was to examine whether this finding is generalizable to ‘real-world’ clinical practice. A retrospective cohort design and a large US health insurance database were employed for analyses. Study subjects included all hypertensive patients, aged 35 years, who were free from diabetes and who initiated treatment with valsartan (n=9999) or amlodipine (n=18 698) between January 1999 and March 2005. Unadjusted absolute risks of diabetes were 21.4 (95% confidence interval (CI) 18.9–24.3) and 26.3 (95% CI 24.3–28.3) per 1000 patient-years for valsartan and amlodipine, respectively; the corresponding relative risk (RR) for valsartan was 0.82 (95% CI 0.70–0.94). Multivariate analyses – controlling for age, sex, presence of hypercholesterolemia, cardiovascular disease and kidney disease, and pretreatment medical care expenditures – yielded similar results (RR=0.79, 95% CI 0.68–0.92). Our study thus corroborates the finding from VALUE that diabetes risk is lower for patients who receive valsartan versus amlodipine, and extends this finding to a ‘real-world’ setting.Journal of Human Hypertension (2007) 21, 374–380. doi:10.1038/sj.jhh.1002159; published online 22 February 2007 [ABSTRACT FROM AUTHOR]

Patient compliance with osteoporosis drug therapy is often poor in clinical practice and may be associated with higher risk of fracture. A nested case-control study was undertaken using a US health insurance claims database. The source population included all women aged ≥45 years who began drug therapy for osteoporosis. Cases consisted of those who experienced an osteoporosis-related fracture; they were matched to controls without osteoporosis-related fracture. Compliance with osteoporosis drug treatment was assessed in terms of the number of therapy-days received and medication possession ratio (MPR). Conditional logistic regression was employed to examine the relationship between compliance and fracture risk. A total of 453 women with osteoporosis-related fracture were identified and matched to 2,160 controls. Fracture risk was significantly lower for patients with >180 days of therapy [181–360 days: odds ratio (OR) = 0.70, 95% CI = 0.49–0.99; >360 days: OR = 0.65, 95% CI = 0.43–0.99) versus those with ≤30 days. Risk was also lower for patients with MPR ≥90% (OR = 0.70, 95% CI = 0.52–0.93) versus those with MPR <30%. Fracture risk decreased as compliance increased (ptrend < 0.05). Among women initiating drug therapy for osteoporosis, better compliance is associated with reduced risk of fracture. [ABSTRACT FROM AUTHOR]

Patient compliance with pharmacotherapy for osteoporosis is typically poor in clinical practice; less frequent dosing with bisphosphonates may improve compliance. Using data from 49 US health plans, we identified all women aged ≥45 years with osteoporosis who initiated therapy with a bisphosphonate, calcitonin, estrogen, or raloxifene. Compliance was examined alternatively in terms of incidence of adherence failure (medication days <80% of possible) and persistence failure (gap in therapy ≥90 days), and was compared across treatment groups using Kaplan-Meier methods and Cox proportional hazards models. The study population included 18,822 women, 48% of whom initiated weekly bisphosphonate therapy. Overall risk of adherence failure was 47% at 3 months, 70% at 1 year, and 84% at 3 years. Risk of persistence failure was 47% at 1 year, and 77% at 3 years. In multivariate analyses, risk of adherence failure was higher for calcitonin (hazard ratio=2.7 vs weekly bisphosphonate therapy, p<0.01), but comparable for all other therapies. Relative risks of persistence failure were generally similar. Approximately three-quarters of women who initiate osteoporosis drug therapy are non-adherent with treatment within 12 months, and almost 50% have discontinued such therapy by this time. Compliance with weekly bisphosphonate therapy is generally no better than that with osteoporosis medications requiring more frequent dosing. [ABSTRACT FROM AUTHOR]

Rationale: Idiopathic pulmonary fibrosis is a chronic interstitial lung disease of unknown etiology; its epidemiology in the United States has not been well characterized. Objective: To estimate the annual incidence and prevalence of idiopathic pulmonary fibrosis in the United States. Methods: Retrospective cohort design utilizing a large health care claims database spanning the period January 1996 through December 2000. Measurements and Main Results: Persons with idiopathic pulmonary fibrosis were identified based on diagnosis and procedure codes. Using broad case-finding criteria, prevalence was estimated to range from 4.0 per 100,000 persons aged 18 to 34 yr to 227.2 per 100,000 among those 75 yr or older; annual incidence was estimated to range from 1.2 to 76.4 per 100,000. Using narrow case-finding criteria, prevalence ranged from 0.8 to 64.7 per 100,000 persons; comparable figures for incidence were 0.4 to 27.1 per 100,000 persons. Extrapolating these rates to the overall United States' population, prevalence was estimated to be 42.7 per 100,000 (incidence, 16.3 per 100,000) using broad criteria; with narrow criteria, prevalence was estimated to be 14.0 per 100,000 (incidence, 6.8 per 100,000). Conclusions: Our results suggest that idiopathic pulmonary fibrosis is probably more common in the United States than previously reported. [ABSTRACT FROM AUTHOR]

This paper examines whether a physician's future claims of medical malpractice are predictable from information on the physician's recent claims history, training credentials, practice characteristics, and demographics. Data on the medical malpractice experience of 8,733 Michigan physicians between 1980 and 1989 is analyzed. We find strong evidence of repetition over time regarding who was sued and who paid claims. The worse a physician's malpractice litigation record during 1980-1984, the worse was his record during 1985-1989. Training credentials were also highly predictive of future malpractice experience. Physicians trained at lower ranked medical schools or who went through lower-ranked residency programs faced higher odds of developing adverse malpractice records, even after controlling for their previous litigation record. Growing internet access to information on these characteristics will help inform prospective patients if they wish to avoid physicians likely to be sued and likely to make payments in the future for malpractice. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about the risk of chronic kidney disease published in the August 30, 2007 issue of "Journal of human Hypertension."