Glucocorticoid exposure and fracture risk in patients with new-onset rheumatoid arthritis.

Retrospective claims analysis indicated that high levels of daily and cumulative doses of systemic glucocorticoids were associated with elevated fracture risk in a large cohort of new RA patients under age 65. Heightened risk began to decline within months of discontinuation. Findings were similar among patients age <50 years. INTRODUCTION: We evaluated the impact of systemic glucocorticoid exposure on fracture risk among relatively young patients with new-onset rheumatoid arthritis (RA). METHODS: Using administrative data, we identified 42,127 RA patients diagnosed January 1, 2005-December 31, 2012, age 18-64 years, with benefits coverage for ≥12 months before RA diagnosis. Follow-up extended to clinical fracture, cancer diagnosis, or December 31, 2012. Glucocorticoid users were new to therapy. Fracture incidence rates (IR) were stratified by glucocorticoid exposure expressed as prednisone equivalent doses. Cox's proportional hazards models estimated fracture risk adjusted for demographics and baseline clinical characteristics to assess dose-response relationships with current (daily) and prior (cumulative) dose, and by time since discontinuation. RESULTS: Most patients (85 %) had glucocorticoid exposure. Exposed and unexposed patients were demographically similar (74 % female; mean age 49.7 and 48.8 years); 1 % had prior fracture. Fracture IRs (95 % confidence intervals) were 5 to 9 per 1000 person-years at doses <15 mg/day, 16.0 (11.0, 22.6) at doses ≥15 mg/day, and 13.4 (10.7, 16.7) at cumulative doses ≥5400 mg. Adjusted fracture risk was approximately 2-fold higher at highest dose levels compared with 0 mg/day current daily dose and <675 mg cumulative dose, respectively. Fracture risk was 29 % lower at 60-182 days post-discontinuation compared with ongoing use and was similar to unexposed patients by 12 months. Findings were similar among patients age <50 years. CONCLUSIONS: Among younger, new-onset RA patients, fracture risk was significantly elevated at high levels of daily and cumulative dose, and was similar to unexposed patients by 12 months post-discontinuation.

Self-reported calcium use in a cohort of postmenopausal women receiving osteoporosis therapy: results from POSSIBLE US™.

UNLABELLED: Calcium use was common and remained high among women on osteoporosis therapy. Use of calcium-supplemented pharmacologic therapy increased from 65.1 to 76.0% in these women (mean follow-up, 27.5 months). Over 12 months, calcium discontinuation was fairly similar among women using calcium only (23.7%) and women supplementing pharmacologic therapy with calcium (22.5%). INTRODUCTION: Calcium has an important role in bone health. This study describes calcium use and persistence in a postmenopausal osteoporosis treatment cohort. METHODS: Subject-reported calcium use was analyzed for 3,722 participants of the Prospective Observational Scientific Study Investigating Bone Loss Experience (POSSIBLE US(TM)) who used calcium either as their sole osteoporosis treatment (calcium only) or to supplement pharmacologic osteoporosis therapy (supplementers). Descriptive analyses were conducted. Kaplan-Meier methods were used to estimate the probability of discontinuing calcium therapy, and logistic regression was used to assess associations (age-adjusted odds ratios) between healthy behaviors and calcium use. RESULTS: At entry, there were 711 calcium-only subjects and 1,960 of 3,011 subjects on pharmacologic osteoporosis therapy also supplementing with calcium (supplementers). The percentage of supplementers increased from 65.1 to 76.0% during follow-up (mean, 27.5 months). During the first 12 months on study, the probability of calcium discontinuation was 23.7% (95 % confidence interval [CI], 20.7 - 27.0) among calcium-only subjects and 22.5% (95% CI, 20.7-24.5) among supplementers. Supplementers who discontinued pharmacologic therapy were more likely to discontinue calcium than supplementers who continued pharmacologic therapy (34.9 versus 14.8%). Overall 54.2% of calcium-only subjects who discontinued calcium and 42.3% of supplementers who discontinued calcium resumed calcium use during follow-up. Regular exercise was positively correlated with calcium use at study entry. CONCLUSIONS: Calcium supplementation in pharmacologically treated subjects increased over time. Persistence with calcium was high. Discontinuation of pharmacologic osteoporosis therapy was associated with an increased likelihood of discontinuing calcium use.

Long-term persistence and switching patterns among women using osteoporosis therapies: 24- and 36-month results from POSSIBLE US™.

UNLABELLED: Persistence with postmenopausal osteoporosis (PMO) medications is not well characterized beyond 12 months. Of 3,011 postmenopausal women treated in primary care, 36.8 % continued baseline PMO medication during 36 months of follow-up. Many factors were associated with nonpersistence, including newly initiating or switching therapy, and reporting moderate to severe side effects. INTRODUCTION: Persistence with postmenopausal osteoporosis (PMO) medications is not well characterized beyond 12 months. We describe 24- and 36-month persistence using patient-reported data from women with different PMO treatment histories in the US primary care setting. METHODS: Data from 3,011 participants of the Prospective Observational Scientific Study Investigating Bone Loss Experience (POSSIBLE US™, 10/2005-12/2008) and Kaplan-Meier methods were used to estimate the probability of persisting (i.e., not discontinuing or switching PMO agents) with baseline PMO medication and hazard ratios for predictors of nonpersistence 24 and 36 months after study entry. RESULTS: The probability of persisting with the baseline medication was 46.2 % (95 % confidence interval [CI] 44.2-48.1 %) during 24 months of follow-up and 36.8 % (95 % CI 34.7-38.9 %) during 36 months of follow-up. In adjusted analyses, newly initiating therapy or switching to a new agent, reporting moderate to severe side effects, having lower disease-specific quality of life scores, smoking, and residing in the South or West USA (all measured at study entry) were independent predictors of nonpersistence in both time periods. The majority of participants who discontinued therapy and had the opportunity to reinitiate (i.e., discontinued ≥4 months before the end of follow-up) restarted therapy (24 months 69 %; 36 months 75 %). CONCLUSIONS: In this primary care cohort, a minority of women continued their baseline PMO therapy during a 24- to 36-month follow-up. Supporting patients during the initiation of a new therapy or if side effects occur may improve persistence and increase the therapeutic benefit of PMO medications.

Treatment satisfaction and persistence among postmenopausal women on osteoporosis medications: 12-month results from POSSIBLE US™.

SUMMARY: Women in POSSIBLE US™ who expressed greater treatment satisfaction at study entry were more likely to persist with osteoporosis therapy over a 1-year period. Lower satisfaction among women with moderate/severe side effects increased the risk of discontinuation/switching by 67%. Treatment satisfaction and side effect experience influence osteoporosis medication adherence. INTRODUCTION: Non-adherence is common among women using postmenopausal osteoporosis (PMO) medications. We describe the association between treatment satisfaction, measured with the Treatment Satisfaction Questionnaire for Medication (TSQM), and the risk of discontinuation/switching PMO medications using patient-reported data from a large, longitudinal cohort study. METHODS: Data from 2,405 participants in the Prospective Observational Scientific Study Investigating Bone Loss Experience (POSSIBLE US™) Study were evaluated. Cox proportional hazards regression was used to estimate hazard ratios (HR) for the association between treatment satisfaction at study entry and self-reported discontinuation/switching of pharmacologic PMO medications over a 1-year follow-up period. Logistic regression was used to evaluate relationships between treatment satisfaction, lifestyle behaviors, and compliance with bisphosphonate dosing instructions. RESULTS: Median TSQM scores were highest (indicating greatest satisfaction) for the side effects domain [n = 1,182; median = 87.5 (Q1 = 75.0, Q3 = 100.0)] and lowest for global satisfaction [n = 2,340; median = 64.0 (Q1 = 55.7, Q3 = 77.7)]. Median scores decreased for the side effects and global satisfaction domains as patient-reported side effect severity increased. Women with higher satisfaction were less likely to discontinue/switch medications than women with lower scores (adjusted HRs for convenience 0.73, 95% CI = 0.63-0.85; effectiveness 0.82, 95% CI = 0.70-0.97; and global satisfaction 0.73, 95% CI = 0.63-0.85). Lower treatment satisfaction was particularly influential among women who reported moderate/severe side effects (HR = 0.60, 95% CI = 0.37-0.97). CONCLUSIONS: Lower treatment satisfaction was associated with a 22% (1/0.82) to 67% (1/0.60) increased risk of discontinuation/switching osteoporosis medication during 1 year of follow-up.

Persistence and switching patterns among women with varied osteoporosis medication histories: 12-month results from POSSIBLE US.

UNLABELLED: During the first year of Prospective Observational Scientific Study Investigating Bone Loss Experience (POSSIBE US), many women transitioned (i.e., discontinued or switched) from their baseline osteoporosis medication. Participants not on stable therapy at entry, with side effects, and with poor physical status were at higher risk of transitioning. Understanding factors associated with persistence may lead to improved outcomes. INTRODUCTION: Postmenopausal osteoporosis (PMO) medication use patterns may differ by treatment history and drug class. We describe these patterns among patients in primary care settings using patient-reported data. METHODS: Data from 3,006 participants of the POSSIBLE US were used to estimate the probability of a baseline PMO medication transition (i.e., discontinuation or switch) and hazard ratios (HRs) for predictors of these transitions. RESULTS: One year after study entry, the probability of persisting with a baseline medication was 66% (95% CI: 64-68%). After adjusting for age and osteoporosis diagnosis, factors at entry independently associated with a higher risk of baseline medication transition were treatment status cohort, side effect severity, and OPAQ-SV physical function score. Compared to participants stable on therapy at entry, others had a higher risk, ranging from HR = 1.59 (95% CI: 1.36-1.85) for those new to therapy to HR = 2.00 (95% CI: 1.27-3.15) for those who recently augmented therapy at entry. Participants reporting moderate (HR = 1.31, 95% CI: 1.09-1.57) or severe (HR = 1.88, 95% CI: 1.49-2.39) side effects had a higher risk than those not reporting side effects. Participants reporting Osteoporosis Assessment Questionnaire-Short Version physical function scores in the lowest tertile had a higher risk (HR = 1.27, 95% CI: 1.07-1.52) than those reporting scores in the highest tertile. CONCLUSION: Baseline osteoporosis medication transitions were common in the first year of POSSIBLE US. Participants not on stable therapy at entry, or who reported severe side effects, or had poor physical health status were at higher risk for these transitions.

Respiratory syncytial virus hospitalization outcomes and costs of full-term and preterm infants.

OBJECTIVE: Infection with respiratory syncytial virus (RSV), which causes lower respiratory tract infections, is the leading cause of hospitalization among children <1 year old in the United States. Risk factors for RSV hospitalization include premature birth and younger chronologic age, along with several comorbid conditions. However, in terms of RSV hospitalization costs, premature infants are rarely studied separately from full-term infants. The objective of this study is to describe the cost and severity of RSV hospitalizations among preterm and full-term infants without chronic lung disease or other high-risk conditions. STUDY DESIGN: This analysis used Truven Health Market Scan Multi-State Medicaid and Commercial Claims and Encounters databases, which contain a combined 4 million births from 2003 to 2013. Infants with comorbid conditions associated with increased risk for RSV infection were excluded. Infants were classified as preterm (<29, 29-30, 31-32, 33-34 and 35-36 weeks' gestational age (wGA)) or full term based on diagnostic coding. Health-care claims during the first year of life were evaluated for RSV hospitalizations, defined as inpatient claims with a diagnosis code for RSV in any position. Costs of RSV hospitalizations were captured and reported in 2014 USD. Inpatient claims for RSV hospitalizations were evaluated for the presence of codes indicating admission to the intensive care unit (ICU), use of mechanical ventilation (MV) and length of stay. These three measures were used to describe hospital severity. Chronologic age at the time of RSV hospitalization was also captured. Data were summarized and no statistical comparisons were conducted. RESULTS: There were 1 683 188 infants insured through Medicaid and 1 663 832 infants insured through commercial plans born from 1 July 2003 to 30 June 2013. Of those, 10.8 and 8.8% in each database, respectively, were born prematurely. There were 29 967 Medicaid-insured infants and 16 310 commercially insured infants with an RSV hospitalization during their first year of life. Mean first-year RSV hospitalization costs were higher for preterm infants, ranging from $8324 and $10 570 for full-term infants to $15 839 and $19 931 for preterm infants 33-34 wGA, and to $39 354 and $40 813 for preterm infants <29 wGA, among Medicaid-insured and commercially insured infants, respectively. RSV hospitalizations also tended to be more severe among preterm infants, with longer lengths of stay, a higher proportion of infants admitted to the intensive care unit (ICU) and increased use of MV compared with full-term infants. Mean costs of RSV hospitalizations with a PICU admission ranged from approximately $35 000 to $89 000. In both Medicaid and commercial groups, costs were greater for infants hospitalized at <90 days of age compared with older infants. CONCLUSIONS: Infants who were born prematurely and those hospitalized at <90 days of age have more costly and more severe RSV hospitalizations during the first year of life. These findings demonstrate important differences in the costs and severity of first-year RSV hospitalizations of premature and full-term infants. These differences are likely to be obscured in combined analysis, in which full-term infants predominate. Clinical guidelines and health-care policies relating to RSV would benefit from the availability of data obtained from separate analyses of these two infant subgroups.

The effect of ocular torsional position on perception of the roll-tilt of visual stimuli.

Perceived postural orientation during whole-body roll-tilt is commonly inferred from settings of a visual line to the perceived gravitational horizontal or vertical. This inference assumes that the change in ocular torsional position (ocular counterrolling) which occurs during roll-tilt has no effect on the perceived orientation of the visual stimulus. We investigated this assumption by measuring, during whole body roll-tilt stimulation, settings of a visual line and a somatosensory bar to the perceived gravitational horizontal and comparing the difference in these settings to the objectively measured ocular torsional position for each subject. Two stimulus paradigms were used: one where the subject was given a roll-tilt stimulus and the eye torted, the other where there was eye torsion without a roll-tilt stimulus. In both paradigms there was a very close relationship in magnitude and direction between the difference in the settings of the two perceptual indicators to gravitational horizontal and the objectively measured ocular torsion. We conclude that change in ocular torsional position alone changes the perceived orientation of a visual line. The corollary is that settings of a visual line cannot be used to infer perceived postural orientation directly.

Estimating prevalence of osteoporosis: examples from industrialized countries.

UNLABELLED: In nine industrialized countries in North America, Europe, Japan, and Australia, country-specific osteoporosis prevalence (estimated from published data) at the total hip or hip/spine ranged from 9 to 38 % for women and 1 to 8 % for men. In these countries, osteoporosis affects up to 49 million individuals. PURPOSE: Standardized country-specific prevalence estimates are scarce, limiting our ability to anticipate the potential global impact of osteoporosis. This study estimated the prevalence of osteoporosis in several industrialized countries (USA, Canada, five European countries, Australia, and Japan) using the World Health Organization (WHO) bone mineral density (BMD)-based definition of osteoporosis: BMD T-score assessed by dual-energy x-ray absorptiometry ≤-2.5. METHODS: Osteoporosis prevalence was estimated for males and females aged 50 years and above using total hip BMD and then either total hip or spine BMD. We compiled published location-specific data, using the National Health and Nutrition Examination Survey (NHANES) III age and BMD reference groups, and adjusted for differences in disease definitions across sources. Relevant NHANES III ratios (e.g., male to female osteoporosis at the total hip) were applied where data were missing for countries outside the USA. Data were extrapolated from geographically similar countries as needed. Population counts for 2010 were used to estimate the number of individuals with osteoporosis in each country. RESULTS: For females, osteoporosis prevalence ranged from 9 % (UK) to 15 % (France and Germany) based on total hip BMD and from 16 % (USA) to 38 % (Japan) when spine BMD data were included. For males, prevalence ranged from 1 % (UK) to 4 % (Japan) based on total hip BMD and from 3 % (Canada) to 8 % (France, Germany, Italy, and Spain) when spine BMD data were included. CONCLUSIONS: Up to 49 million individuals met the WHO osteoporosis criteria in a number of industrialized countries in North America, Europe, Japan, and Australia.

Sex- and age-specific incidence of non-traumatic fractures in selected industrialized countries.

UNLABELLED: Various methodological approaches have estimated the incidence of osteoporosis-related fractures, making comparisons difficult. This study estimated the incidence rates of non-traumatic fractures in 12 countries using standard definitions. Applying these rates to the 2010 population figures of these countries, a total of 5.2 million non-traumatic fractures were estimated, mostly in women. PURPOSE: The purpose of this study was to estimate annual country-, sex-, and age-specific incidence of non-traumatic hip, vertebral, and other fractures for women aged ≥50 and men ≥60 years and the number of fractures expected in 12 countries based on these incidence rates. METHODS: Electronically indexed medical literature and relevant web sites were reviewed to identify studies reporting age- and sex-specific fracture incidence rates to obtain estimates of the proportion of fractures considered to be non-traumatic and to gather relevant census data. From these data, we extrapolated to estimate the number of fractures in 12 countries in North America, Europe, Japan, and Australia. RESULTS: Annual non-traumatic hip fracture incidence rates were highest for women in Sweden, Denmark, and Finland. In women, vertebral fractures were more common than hip fractures. The incidence of vertebral fractures was highest among Scandinavian and Canadian women. In men, Scandinavians had the highest incidence of hip fractures, while Australian men had the highest incidence of vertebral fractures. Hip and vertebral fracture incidence increased steeply with age for both women and men. Age appears to exert less influence on the incidence of fractures at sites other than hip and vertebrae. In 2010, 5.2 million non-traumatic fractures were expected in the 12 countries studied, of which 2.8 million were at the hip or spine. Women accounted for most of the total non-traumatic fracture burden (77 %). CONCLUSIONS: Non-traumatic fractures pose a significant burden, affecting millions of women and men in countries around the world each year.

Ocular torsion position and the perception of visual orientation.

Previous studies have shown that in patients with unilateral vestibular deafferentation (UVD) there is a close relationship between the change in ocular torsional position consequent on the UVD, and the visually perceived orientation of short dim lines in an otherwise darkened room (1). However that result may have been confounded because the UVD may have affected both ocular torsion and sensory information about head position re gravity which must be used in making the visual perceptual judgement. Therefore we have sought a means of testing the relationship between ocular torsional position and the visual perception of orientation which was not confounded by the possible effect of changes in perceived head position.

What is the minimal vestibular function required for compensation?

Living with an uncompensated, abnormal vestibular system requires oppressive modification of life style and often prevents return to work and activities of daily living. Patients with vestibular abnormalities were studied to determine the minimal residual vestibular function required to achieve compensation. Three groups of patients with (a) complete unilateral loss of vestibular function with normal horizontal canal-vestibulo-ocular (HCVOR) function in the opposite ear, (b) complete unilateral loss with abnormal HCVOR function in the opposite ear, and (c) bilateral reduction of vestibular function from aminoglycoside toxicity underwent vestibuloocular (VOR), optokinetic (OKN), visual-VOR (VVOR), and computerized dynamic posturography (CDP) tests before and after therapeutic procedures. Results suggest that a minimal VOR response amplitude must be present for compensation of VVOR function to occur. The roles of VOR and OKN phase shifts in vestibular compensation are more complicated and require further study. Compensation of vestibulospinal function does not necessarily accompany VOR or VVOR compensation. Ascending and descending vestibular compensatory mechanisms may involve different spatial sensory inputs. Results of these studies have important implications for the diagnosis and treatment of patients with vestibular disorders, including selection and monitoring of patients for therapeutic regimens such as vestibular nerve section and streptomycin therapy.

Time constant of nystagmus slow-phase velocity to yaw-axis rotation as a function of the severity of unilateral caloric paresis.

OBJECTIVE: Complete unilateral loss of vestibular function results in a phase advance (reduced time constant) of the horizontal slow-phase nystagmus response to yaw-axis rotation. The objective of this study was to determine whether partial losses of lateral semicircular canal function would result in proportional reductions in the time constant. SETTING AND STUDY DESIGN: This was a retrospective study of consecutive patients' records at two tertiary referral centers for vestibular disorders. PATIENTS: Four hundred fifty-four patients who presented for evaluation of vertigo or imbalance or both and who were found to have partial or complete unilateral canal paresis on caloric testing. MAIN OUTCOME MEASURES: In 372 patients, the gain and time constant of the horizontal nystagmus response was measured using a 5-second velocity ramp of constant yaw-axis acceleration. Caloric responses to standard bithermal irrigations at 30 degrees and 44 degrees were obtained using an open-loop irrigation system. In a second group of 82 patients, the gain and time constant of the horizontal vestibulo-ocular reflex were measured using a sum-of-sines (pseudorandom) yaw-axis acceleration. The caloric response was measured using a closed-loop system. RESULTS: In both groups, the peak gain of the nystagmus response was independent of the level of the canal paresis. However, the time constant of the response both toward and away from the lesioned side decreased proportionally with increasing canal paresis. CONCLUSION: This result supports the hypothesis that bilateral symmetrical peripheral vestibular input is a necessary condition for the mechanisms or processes underlying normal horizontal slow-phase velocity storage.

An evaluation of Duke University's LIVE FOR LIFE health promotion program on changes in worker absenteeism.

The effect of an employer-sponsored health promotion program on worker absenteeism is examined over a 4-year period in a group of 4972 Duke University hourly employees. Program participants experienced an average of 4.6 fewer absentee hours in the third year of program availability than did nonparticipants, after controlling for baseline absenteeism, gender, race, education, and age. These results suggest that employer-sponsored health promotion initiatives can have a favorable influence on absenteeism.