Treatment Persistence and Medication Switch Associated With Subsequent Fractures After Osteoporotic Fractures.

CONTEXT: Despite prevalent anti-osteoporosis medication (AOM) switching in real-world osteoporosis management, few studies have evaluated the impact of persistent AOM treatment, allowing for AOM switching, on the risk of subsequent fracture. OBJECTIVE: We examined the association between persistence in AOM and subsequent fractures, allowing for medication switching among patients with osteoporotic fractures. METHODS: This retrospective cohort study used Taiwan National Health Insurance claims data to select patients who initiated AOM between 2013 and 2016. Treatment persistence was defined as use of any AOM on a given day of interest with a 45-day grace period. Medication switch was allowed for persistence if remaining on treatment. AOMs with long-lasting inhibition of bone resorption (zoledronate and denosumab) were categorized as high-potency; others as low-potency. Multivariate Cox models were used to evaluate risk of subsequent fractures ≥3 months after initiating AOM. RESULTS: A total of 119 473 patients were included (mean [SD] follow-up 46.4 [15.6] months), and 26.8% switched from the index AOM. Within 1 year, 52% remained persistent with AOM. Compared to patients with persistent AOM, those not persistent had higher risk of subsequent hip (adjusted hazard ratio [aHR] = 1.31; 95% CI, 1.21-1.42), vertebral (aHR = 1.17; 95% CI, 1.13-1.22), and radius fractures (aHR = 1.16; 95% CI, 1.08-1.25). Patients with persistent AOM who switched from high- to low-potency AOM had higher risk of subsequent vertebral fractures than those with persistent AOM and no potency switch (aHR = 1.28; 95% CI, 1.02-1.60). CONCLUSION: Patients with non-persistent AOM had higher risk of subsequent fractures than persistent users when allowing AOM switch. Switching AOM potency may influence the risk of subsequent vertebral fractures and warrants further investigation.

Treatment patterns of long-dose-interval medication for persistent management of osteoporosis in Taiwan.

Treatment persistence was higher among the patients who initially received an anti-osteoporosis medication (AOM) with a long-dose-interval. PURPOSE: With long-dose-interval anti-osteoporosis medications (AOMs) available for osteoporosis management, it is important to evaluate persistence of any AOM as long as it is continuously used. The purpose of this study was to investigate the treatment pattern and persistence of AOMs, allowing for medication switch. METHODS: This study was an observational retrospective cohort study using Taiwan's National Health Insurance claims data. We selected patients who first initiated an AOM between January 1, 2013, and June 30, 2016. AOM therapy included alendronate, raloxifene, teriparatide, denosumab, zoledronate, and ibandronate; the latter three were categorized as long-dose-interval medications. Persistence was defined as continual prescription of any AOM at a given time point with a grace period of 45 days within which to obtain prescription refill. The competing risk model was used to examine the factors affecting patients switching their initial AOM. RESULTS: During the study period, 126,539 patients with mean age of 75 years met the inclusion criteria; 85% were female. For initial AOM, 43.3%, 25.6%, 14.6%, 9.3%, 5.3%, and 1.9% of the patients received alendronate, denosumab, raloxifene, zoledronate, ibandronate, and teriparatide, respectively. During a mean 36-month follow-up, 29.6% of the patients who received at least two AOM pharmacy claims throughout the study period have ever switched their initial medication. Long-dose-interval medications, mainly denosumab and zoledronate, were the preferred choice for medication switch. Treatment persistence was higher in patients who initiated with long-dose-interval AOMs. CONCLUSION: The real-world data reveal long-dose-interval therapy as an initial treatment or at the first switch stage may improve management of persistent AOM treatment.

Incidence of different types of subsequent fractures and related mortality in Taiwan.

Hip fracture is the most common type of fracture to occur within 2 years after an initial fracture. Mortality risk increases when a subsequent fracture occurs. The occurrence of subsequent fracture is significantly higher in patients with hip fractures than others. Prevention of subsequent fracture is of paramount important. PURPOSE: Osteoporotic fracture significantly increases risk of subsequent fracture. In this retrospective cohort study, we used the Taiwan National Health Insurance Database (NHIRD) to analyze data on fractures in a group at high risk of osteoporosis. We aimed to distinguish differences in subsequent fracture types and their relationship with mortality. METHODS: We enrolled patients aged ≥ 50 years old who were diagnosed with an initial fracture classified as hip, vertebral, upper end of the humerus, or wrist. Data from 2 years of follow-up were analyzed. Risks of subsequent fracture events and mortality were calculated by Kaplan-Meier estimation and assessed with Cox proportional hazards models. RESULTS: We included 375,836 patients from the 2011-2015 NHIRD. Patients with initial hip fracture had the highest incidence of subsequent fracture at both 1- and 2-year follow-up (7.0% and 10.9%). Subsequent fractures occurred mainly at the hip. Conversely, other patients had a higher proportion of subsequent vertebral fracture. Patients with subsequent fracture classified as hip, vertebral, and upper end of the humerus had significantly higher cumulative mortality rates than that of patients who had no subsequent fracture, with adjusted hazard ratios of 1.64 (95% CI = 1.57-1.71, p < 0.01), 1.06 (95% CI = 1.00-1.12, p = 0.04), 1.31 (95% CI = 1.17-1.46, p < 0.01), respectively. CONCLUSION: Patients who experienced an initial hip fracture are at greatest risk of subsequent fracture, most commonly the hip. Occurrence of subsequent fractures was associated with an increased mortality risk. Thus, there is a need for early intervention following initial hip fractures.

Likelihood of Neoplasia for Diagnoses Modified by Probability Terms in Canine and Feline Lymph Node Cytology: How Probable Is Probable?

Background: Descriptive probability modifiers are used often to convey the uncertainty of a pathology diagnosis, but they also contribute to ambiguity in communication between pathologists and clinicians. Objectives: Our goal was to determine the frequency and use of probability modifiers in canine and feline lymph node cytology diagnoses, and to determine the actual likelihood of neoplasia for diagnoses with and without modifiers, based on the histologic outcome. Methods: Canine and feline lymph node cytology and histology reports over an 11-year period (2001-2011; n = 367) were evaluated retrospectively. Diagnoses were categorized as neoplastic/malignant (lymphoma, metastatic) or non-neoplastic/benign. The frequency and type of modifier, and the sensitivity, specificity, and predictive values for neoplasia were determined for modified and unmodified diagnoses using histology as the gold standard. Results: Ninety-one of 367 (24.8%) cytology diagnoses were modified by probability terms, including 25/204 (12.2%) diagnoses of non-neoplastic lesions and 66/163 (40.5%) diagnoses of neoplasia. In addition, 26 unmodified diagnoses of neoplasia were followed by a probability phrase indicating specific tumor type. Based on the histologic outcome, modified diagnoses had higher sensitivity (87.3%, confidence interval [CI] 75.5, 94.7%) but lower specificity (50.0%, CI 32.9, 67.1%) for neoplasia than did unmodified diagnoses (60.6 and 100%, respectively; P < 0.0001, Chi square). Modified phrases indicating the probability of a specific tumor type were accurate in 22/26 (84.6%) cases. Positive predictive values for neoplasia were 100% (CI 96.2, 100%) for unmodified and 72.7% (CI 60.4, 83.0%) for modified diagnoses. Negative predictive values were 65.9% (CI 58.5, 72.8%) for unmodified and 72.0% (CI 60.4, 83.0%) for modified diagnoses. No significant difference was found in the likelihood of neoplasia for individual terms used to modify a cytologic diagnosis except for "cannot rule out" (P = 0.0368). Conclusions: Most modified diagnoses of cancer in canine and feline lymph node cytology have a 60-83% likelihood of neoplasia based on histologic outcome, compared with 96-100% for unmodified diagnoses. Non-neoplastic lesions, regardless of modifiers, have a 12-49% likelihood of neoplasia. A limited number of risk categories based on these likelihoods may be a more effective and accurate way to communicate the risk of malignancy in lymph node cytology.