Magnitude and consequences of misclassification of incident hip fractures in large cohort studies: the Study of Osteoporotic Fractures and Medicare claims data

Summary

In the Study of Osteoporotic Fractures (SOF), 18.5 % of incident hip fractures identified in Medicare Fee-for-Service claims data were not reported to or confirmed by the cohort. Cognitive impairment was a modest risk factor for false-negative hip fracture ascertainment via self-report.

Introduction

Prospective cohort studies of fractures that rely on participant self-report to be the initial signal of an incident fracture could be prone to bias if a significant proportion of fractures are not self-reported.

Methods

We used data from the SOF merged with Medicare Fee-for-Service claims data to estimate the proportion of participants who had an incident hip fracture identified in Medicare claims that was either not self-reported or confirmed (by review of radiographic reports) in SOF.

Results

Between 1/1/1991 and 12/31/2007, 647 SOF participants had a hip fracture identified in Medicare claims, but 120 (18.5 %) were either not reported to or confirmed by the cohort. False-negative hip fracture ascertainment was associated with a reduced modified Mini-Mental State Exam (MMSE) score (odds ratio 1.31 per SD decrease, 95 % C.I. 1.06–1.63). Point estimates of associations of predictors of incident hip fracture were changed minimally when the misclassification of incident hip fracture status was corrected with use of claims data.

Conclusions

A substantial minority of incident hip fractures were not reported to or confirmed in the SOF. Cognitive impairment was modestly associated with false-negative hip fracture ascertainment. While there was no evidence to suggest that misclassification of incident hip fracture status resulted in biased associations of potential predictors with hip fracture in this study, false-negative incident fracture ascertainment in smaller cohort studies with limited power may increase the risk of type 2 error (not finding significant associations of predictors with incident fractures).     

Associations of total and free 25OHD and 1,25(OH)<Subscript>2</Subscript>D with serum markers of inflammation in older men

Summary

Vitamin D is hypothesized to suppress inflammation. We tested total and free vitamin D metabolites and their association with inflammatory markers. Interleukin-6 levels were lower with higher 25-hydroxyvitamin D. 1,25-dihydroxyvitamin D and free 25OHD associations mirrored those of 25OHD. However, associations for the two metabolites diverged for tumor necrosis factor alpha (TNF-α) soluble receptors.

Introduction

Vitamin D is hypothesized to suppress inflammation, and circulating 25-hydroxyvitamin D (25OHD) and inflammatory markers are inversely correlated. However, total serum 25OHD may not be the best indicator of biologically active vitamin D.

Methods

We tested serum total 25OHD, total 1,25(OH)₂D, vitamin D binding protein (DBP), and estimated free 25OHD and free 1,25(OH)₂D associations with inflammatory markers serum interleukin-6 (IL-6), TNF-α and their soluble receptors, interleukin-10 (IL-10), and C-reactive protein (CRP) as continuous outcomes and the presence of ≥2 inflammatory markers in the highest quartile as a dichotomous outcome, in a random subcohort of 679 men in the Osteoporotic Fractures in Men (MrOS) study.

Results

IL-6 was lower in men with higher 25OHD (?0.23 μg/mL per standard deviation (SD) increase in 25OHD, 95 % confidence intervals (CI) ?0.07 to ?0.38 μg/mL) and with higher 1,25(OH)₂D (?0.20 μg/mL, 95 % CI ?0.0004 to ?0.39 μg/mL); free D associations were slightly stronger. 25OHD and DBP, but not 1,25(OH)₂D, were independently associated with IL-6. TNF-α soluble receptors were inversely associated with 1,25(OH)₂D but positively associated with 25OHD, and each had independent effects. The strongest association with ≥2 inflammatory markers in the highest quartile was for free 1,25(OH)₂D (odds ratios (OR) 0.70, 95 % CI 0.54 to 0.89 per SD increase in free 1,25(OH)₂D).

Conclusions

Associations of 1,25(OH)₂D and free 25OHD with IL-6 mirrored those of 25OHD, suggesting that 1,25(OH)₂D and free D do not improve upon 25OHD in population-based IL-6 studies. However, associations for the two metabolites diverged for TNF-α soluble receptor, warranting examination of both metabolites in studies of TNF-α and its antagonists.

     

Secular Trends in Hip Fractures Worldwide: Opposing Trends East Versus West

Despite wide variations in hip rates fractures worldwide, reasons for such differences are not clear. Furthermore, secular trends in the age‐specific hip fracture rates are changing the world map of this devastating disease, with the highest rise projected to occur in developing countries. The aim of our investigation is to systematically characterize secular trends in hip fractures worldwide, examine new data for various ethnic groups in the United States, evidence for divergent temporal patterns, and investigate potential contributing factors for the observed change in their epidemiology. All studies retrieved through a complex Medline Ovid search between 1966 and 2013 were examined. For each selected study, we calculated the percent annual change in age‐standardized hip fracture rates de‐novo. Although occurring at different time points, trend breaks in hip fracture incidence occurred in most Western countries and Oceania. After a steep rise in age‐adjusted rates in these regions, a decrease became evident sometimes between the mid‐seventies and nineties, depending on the country. Conversely, the data is scarce in Asia and South America, with evidence for a continuous rise in hip fracture rates, with the exception of Hong‐Kong and Taiwan that seem to follow Western trends. The etiologies of these secular patterns in both the developed and the developing countries have not been fully elucidated, but the impact of urbanization is at least one plausible explanation. Data presented here show close parallels between rising rates of urbanization and hip fractures across disparate geographic locations and cultures. Once the proportion of the urban population stabilized, hip fracture rates also stabilize or begin to decrease perhaps due to the influence of other factors such as birth cohort effects, changes in bone mineral density and BMI, osteoporosis medication use and/or lifestyle interventions such as smoking cessation, improvement in nutritional status and fall prevention. © 2014 American Society for Bone and Mineral Research.     

Multimorbidity in women with and without osteoporosis: results from a large US retrospective cohort study 2004–2009

Summary

To determine the incidence of comorbidities in women with and without osteoporosis, incidence rates per 1,000 person-years were calculated using electronic health records from an integrated healthcare system. The overall comorbidity burden and health service utilization were greater in women with osteoporosis than in the controls.

Introduction

This retrospective cohort study describes the incidence of an array of comorbidities in women with and without osteoporosis (OP).

Methods

Using electronic health records from an integrated healthcare system, we identified 22,414 women aged 55–89 years with OP and 22,414 age-matched controls without OP. Incidence rates (IRs) per 1,000 person-years (P-Y) were calculated and 95 % confidence intervals (CI) were estimated.

Results

Women with OP had significantly more comorbidities, medications, hospitalizations, and outpatient visits than the controls. Most cardiac comorbidity rates were 20–25 % lower in the OP cohort than in the control cohort. Hypertension had the largest rate difference; the IR was 42.0 per 1,000 P-Y (95 % CI 40.2–44.0) in the OP cohort compared to 94.0 (95 % CI 90.7–97.4) in the control cohort. Rates for cerebrovascular disease were similar for both cohorts at 26 per 1,000 P-Y. Bronchitis, sinusitis, and cystitis were each 55 per 1,000 P-Y in the OP cohort, whereas they ranged from 28 to 34 per 1,000 P-Y in the controls. The OP cohort had decreased incidence of ovarian, uterine, colorectal, and liver cancers and increased incidence of lung cancer, breast cancer, and multiple myeloma, compared to the non-OP cohort. Falls, depression, vision, and musculoskeletal issues were higher for the OP cohort than the controls.

Conclusions

This study demonstrates the high disease burden in women with OP. This knowledge may help guide the clinical management of this population and may aid in the interpretation of adverse events in randomized clinical trials of OP therapies.     

Association of stressful life events with accelerated bone loss in older men: the osteoporotic fractures in men (MrOS) study

Summary

Prior studies suggest an association between stressful life events and fractures that may be mediated by BMD. In the current study, risk of accelerated hip BMD loss was higher in older men with any type of stressful life event and increased with the number of types of stressful life events.

Introduction

Prior studies suggest that stressful life events may increase adverse health outcomes, including falls and possibly fractures. The current study builds on these findings and examines whether stressful life events are associated with increased bone loss.

Methods

Four thousand three hundred eighty-eight men aged ≥65 years in the Osteoporotic Fractures in Men study completed total hip bone mineral density (BMD) measures at baseline and visit 2, approximately 4.6 years later, and self-reported stressful life events data mid-way between baseline and visit 2, and at visit 2. We used linear regression to model the association of stressful life events with concurrent annualized total hip BMD loss, and log binomial regression or Poisson regression to model risk of concurrent accelerated BMD loss (>1 SD more than mean annualized change).

Results

Men (75.3 %) reported ≥1 type of stressful life event, including 43.3 % with ≥2 types of stressful life events. Mean annualized BMD loss was ?0.36 % (SD 0.88), and 13.9 % of men were categorized with accelerated BMD loss (about 5.7 % or more total loss). Rate of annualized BMD loss increased with the number of types of stressful life events after adjustment for age (p?p?=?0.07). Multivariable-adjusted risk of accelerated BMD loss increased with the number of types of stressful life events (RR, 1.10 [95 % confidence interval (CI), 1.04–1.16]) per increase of one type of stressful life event). Fracture risk was not significantly different between stressful life event-accelerated bone loss subgroups (p?=?0.08).

Conclusions

In these older men, stressful life events were associated with a small, dose-related increase in risk of concurrent accelerated hip bone loss. Low frequency of fractures limited assessment of whether rapid bone loss mediates any association of stressful life events with incident fractures. Future studies are needed to confirm these findings and to investigate the mechanism that may underlie this association.     

Apparent diffusion coefficient histogram analysis of neonatal hypoxic–ischemic encephalopathy

Background

Diffusion-weighted imaging is a valuable tool in the assessment of the neonatal brain, and changes in diffusion are seen in normal development as well as in pathological states such as hypoxic–ischemic encephalopathy (HIE). Various methods of quantitative assessment of diffusion values have been reported. Global ischemic injury occurring during the time of rapid developmental changes in brain myelination can complicate the imaging diagnosis of neonatal HIE.

Objective

To compare a quantitative method of histographic analysis of brain apparent coefficient (ADC) maps to the qualitative interpretation of routine brain MR imaging studies. We correlate changes in diffusion values with gestational age in radiographically normal neonates, and we investigate the sensitivity of the method as a quantitative measure of hypoxic–ischemic encephalopathy.

Materials and methods

We reviewed all brain MRI studies from the neonatal intensive care unit (NICU) at our university medical center over a 4-year period to identify cases that were radiographically normal (23 cases) and those with diffuse, global hypoxic–ischemic encephalopathy (12 cases). We histographically displayed ADC values of a single brain slice at the level of the basal ganglia and correlated peak (s-sD_av) and lowest histogram values (s-sD_lowest) with gestational age.

Results

Normative s-sD_av values correlated significantly with gestational age and declined linearly through the neonatal period (r ²?=?0.477, P?<?0.01). Six of 12 cases of known HIE demonstrated significantly lower s-sD_av and s-sD_lowest ADC values than were reflected in the normative distribution; several cases of HIE fell within a 95% confidence interval for normative studies, and one case demonstrated higher-than-normal s-sD_av.

Conclusion

Single-slice histographic display of ADC values is a rapid and clinically feasible method of quantitative analysis of diffusion. In this study normative values derived from consecutive neonates without radiographic evidence of ischemic injury are correlated with gestational age, declining linearly throughout the perinatal period. This method does identify cases of HIE, though the overall sensitivity of the method is low.     

河北省儿童医院住院患儿EB病毒感染流行病学特征

目的了解河北省儿童医院住院患儿EB病毒(EBV)感染的流行病学特征,为儿童EBV感染的诊断和预防提供科学依据。方法收集2017年1—12月河北省儿童医院0~14岁EBV感染住院患儿的全血样本,采用酶联免疫吸附试验(ELISA)检测其EBV衣壳抗原(VCA)IgG及IgM抗体,抗早期抗原(EA)IgG抗体和抗核抗原1(NA1)IgG抗体,以检测结果为研究样本的抗体谱。根据4种EBV抗体的检测结果分为现症感染(抗VCA-IgM抗体阳性,抗NA1-IgG抗体阴性、抗VCA-IgG抗体、抗EA-IgG抗体阳性或阴性)、亚急性感染(抗VCA-IgG抗体阳性,抗VCA-IgM抗体、抗NA1-IgG抗体、抗EA-IgG抗体阳性或阴性)、既往感染(抗NA1-IgG抗体阳性,抗VCA-IgG抗体阳性或阴性,其他抗体均为阴性)和未感染(4种抗体均阴性)。按照患儿年龄、检出月份和性别分析各组的阳性率。结果共纳入符合要求的样本4 451例,其中3 257例(73.17%)抗体谱提示EBV感染,包括现症感染380例(8.54%)、亚急性感染616例(13.84%)、既往感染2 261例(50.80%)。不同年龄组原发阳性检出率差异有统计学意义(P<0.05),其中学龄前(>3岁)组的阳性检出率最高(P<0.05);不同检出月份组阳性检出率差异有统计学意义(P<0.05),7月份阳性检出率高于其他月份(P<0.05);男性患儿与女性患儿EBV感染率差异无统计学意义(P>0.05)。380例现症感染患儿的疾病谱以血液系统疾病[传染性单核细胞增多症、急性粒细胞缺乏症、血小板减少性紫癜、EBV相关嗜血细胞综合征]为主,其中传染性单核细胞增多症为临床常见疾病;其次是呼吸系统疾病(急性支气管炎、疱疹性咽峡炎、急性扁桃体炎);其他疾病谱包括神经系统疾病及血流感染、肾病综合征、川崎病。结论河北省儿童医院住院患儿EBV阳性检出率有年龄和检出月份差异,现症感染以血液系统疾病患儿为主,医院应根据流学病学特征制定相应预防措施。