GLOW is an observational, longitudinal, practice-based cohort study of osteoporosis in 60,393 women aged ≥ 55 years in 10 countries on three continents. In this Review, we present insights from the first 3 years of the study. Despite cost analyses being frequently based on spine and hip fractures, we found that nonvertebral, nonhip fractures were around five times more common and doubled the use of health-care resources compared with hip and spine fractures combined. Fractures not at the four so-called major sites in FRAX(®) (upper arm, forearm, hip and clinical vertebral fractures) account for > 40% of all fractures. The risk of fracture is increased by various comorbidities, such as Parkinson disease, multiple sclerosis and lung and heart disease. Obesity, although thought to be protective against all fractures, substantially increased the risk of fractures in the ankle or lower leg. Simple assessment by age plus fracture history has good predictive value for all fractures, but risk profiles differ for first and subsequent fractures. Fractures diminish quality of life as much or more than diabetes mellitus, arthritis and lung disease, yet women substantially underestimate their own fracture risk. Treatment rates in patients at high risk of fracture are below those recommended but might be too frequent in women at low risk. Comorbidities and the limits of current therapeutic regimens jeopardize the efficacy of drugs; new regimens should be explored for severe cases.
Frailty index of deficit accumulation and falls: data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) Hamilton cohort
BACKGROUND: To investigate the association between frailty index (FI) of deficit accumulation and risk of falls, fractures, death and overnight hospitalizations in women aged 55 years and older.
METHODS: The data were from the Global Longitudinal Study of Osteoporosis in Women (GLOW) Hamilton Cohort. In this 3-year longitudinal, observational cohort study, women (N=3,985) aged ≥ 55 years were enrolled between May 2008 and March 2009 in Hamilton, Canada. A FI including co-morbidities, activities of daily living, symptoms and signs, and healthcare utilization was constructed using 34 health deficits at baseline. Relationship between the FI and falls, fractures, death and overnight hospitalizations was examined.
RESULTS: The FI was significantly associated with age, with a mean rate of deficit accumulation across baseline age of 0.004 or 0.021 (on a log scale) per year. During the third year of follow-up, 1,068 (31.89%) women reported at least one fall. Each increment of 0.01 on the FI was associated with a significantly increased risk of falls during the third year of follow-up (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.02-1.03). The area under the curve (AUC) of the predictive model was 0.69 (95% CI: 0.67-0.71). Results of subgroup and sensitivity analyses indicated the relationship between the FI and risk of falls was robust, while bootstrap analysis judged its internal validation. The FI was significantly related to fractures (hazard ratio [HR]: 1.02, 95% CI: 1.01-1.03), death (OR: 1.05, 95% CI: 1.03-1.06) during the 3-year follow-up period and overnight hospitalizations (incidence rate ratio [IRR]: 1.02, 95% CI: 1.02-1.03) for an increase of 0.01 on the FI during the third year of follow-up. Measured by per standard deviation (SD) increment of the FI, the ORs were 1.21 and 1.40 for falls and death respectively, while the HR was 1.17 for fractures and the IRR was 1.18 for overnight hospitalizations respectively.
CONCLUSION: The FI of deficit accumulation increased with chronological age significantly. The FI was associated with and predicted increased risk of falls, fractures, death and overnight hospitalizations significantly.
Concern and risk perception of osteoporosis and fracture among post-menopausal Australian women: results from the Global Longitudinal Study of Osteoporosis in Women (GLOW) cohort
PURPOSE: The purpose of this study is to identify factors associated with concern and perception of risks of osteoporosis and osteoporotic fractures and determine whether bone mineral density (BMD) testing influenced concern and risk perception.
METHODS: Study subjects (n = 1,082, age 55-94 years) were female Australian participants of the Global Longitudinal Study of Osteoporosis in Women (GLOW). Self-administered questionnaires were sent annually from 2007 to 2010. Study outcomes included 'concern about osteoporosis', 'perception of getting osteoporosis' and 'perception of fracture risk' compared to similar aged women. The closest post-BMD testing or baseline questionnaires were used for women with and without BMD testing, respectively. Multinomial logistic regression was used for the analysis.
RESULTS: BMD testing, prior fracture after age 45, younger age and lower self-reported general health were significantly associated with being 'very' or 'somewhat concerned' about osteoporosis and having a 'much higher' or 'little higher' risk perception of osteoporosis and fractures. A poorer BMD result was associated with higher concern and higher risk perceptions. The presence of comorbidities, having >/=2 falls in the preceding year and maternal osteoporosis were associated with higher concern. Maternal osteoporosis, presence of comorbidities, weight loss of >/=5 kg in the preceding year and low body mass index were associated with higher perceptions of osteoporosis risk.
CONCLUSION: Women's concern and risk perception of osteoporosis and osteoporotic fractures were reasonably well founded. However, increasing age, height loss, smoking and drinking were not associated with concern and perception despite being known osteoporosis risk factors. These factors should be considered in planning for education and awareness raising programmes.
Comparison between Frailty Index of Deficit Accumulation and Phenotypic Model to Predict Risk of Falls: Data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) Hamilton Cohort
OBJECTIVES: To compare the predictive accuracy of the frailty index (FI) of deficit accumulation and the phenotypic frailty (PF) model in predicting risks of future falls, fractures and death in women aged > /=55 years.
METHODS: Based on the data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) 3-year Hamilton cohort (n = 3,985), we compared the predictive accuracy of the FI and PF in risks of falls, fractures and death using three strategies: (1) investigated the relationship with adverse health outcomes by increasing per one-fifth (i.e., 20%) of the FI and PF; (2) trichotomized the FI based on the overlap in the density distribution of the FI by the three groups (robust, pre-frail and frail) which were defined by the PF; (3) categorized the women according to a predicted probability function of falls during the third year of follow-up predicted by the FI. Logistic regression models were used for falls and death, while survival analyses were conducted for fractures.
RESULTS: The FI and PF agreed with each other at a good level of consensus (correlation coefficients > /= 0.56) in all the three strategies. Both the FI and PF approaches predicted adverse health outcomes significantly. The FI quantified the risks of future falls, fractures and death more precisely than the PF. Both the FI and PF discriminated risks of adverse outcomes in multivariable models with acceptable and comparable area under the curve (AUCs) for falls (AUCs > /= 0.68) and death (AUCs > /= 0.79), and c-indices for fractures (c-indices > /= 0.69) respectively.
CONCLUSIONS: The FI is comparable with the PF in predicting risks of adverse health outcomes. These findings may indicate the flexibility in the choice of frailty model for the elderly in the population-based settings.
Empirically based composite fracture prediction model from the Global Longitudinal Study of Osteoporosis in Postmenopausal Women (GLOW)
CONTEXT: Several fracture prediction models that combine fractures at different sites into a composite outcome are in current use. However, to the extent individual fracture sites have differing risk factor profiles, model discrimination is impaired.
OBJECTIVE: The objective of the study was to improve model discrimination by developing a 5-year composite fracture prediction model for fracture sites that display similar risk profiles.
DESIGN: This was a prospective, observational cohort study.
SETTING: The study was conducted at primary care practices in 10 countries.
PATIENTS: Women aged 55 years or older participated in the study.
INTERVENTION: Self-administered questionnaires collected data on patient characteristics, fracture risk factors, and previous fractures.
MAIN OUTCOME MEASURE: The main outcome is time to first clinical fracture of hip, pelvis, upper leg, clavicle, or spine, each of which exhibits a strong association with advanced age.
RESULTS: Of four composite fracture models considered, model discrimination (c index) is highest for an age-related fracture model (c index of 0.75, 47 066 women), and lowest for Fracture Risk Assessment Tool (FRAX) major fracture and a 10-site model (c indices of 0.67 and 0.65). The unadjusted increase in fracture risk for an additional 10 years of age ranges from 80% to 180% for the individual bones in the age-associated model. Five other fracture sites not considered for the age-associated model (upper arm/shoulder, rib, wrist, lower leg, and ankle) have age associations for an additional 10 years of age from a 10% decrease to a 60% increase.
CONCLUSIONS: After examining results for 10 different bone fracture sites, advanced age appeared the single best possibility for uniting several different sites, resulting in an empirically based composite fracture risk model.
PURPOSE: The purpose of this exploratory focus group study was to describe the perspectives of teens and their parents about self-management knowledge, behaviors (including division of labor associated with T1D management), and resources used to manage T1D. The overall goal is to use this information to develop a teen-family transition clinic.
METHODS: The self and family management behaviors framework undergirded the separate teen-parent focus groups that were conducted concurrently. Note-based qualitative content analysis was used, resulting in several important messages. RESULTS: From the teens' perspective there was variation in interest in learning more about T1D and management. Those teens who had been diagnosed at a very young age reported not knowing anything else but diabetes, while those diagnosed later developmentally embraced the active learning process. Diabetes camp and peer group support were not seen as beneficial. All the teens were interested in "helping others" with diabetes. Parents shared the common struggle with transition of self-management, with variation in parenting styles. A small group of parents reported their "job" as a parent was to make sure their child was self-sufficient in self-management, but felt pressure from the health care providers (HCPs) to physically do the care, defeating the purpose. Parents and teens reported wanting HCPs to be less focused on "numbers" (blood glucose levels) and more on the whole person. Scheduling appointment changes and long waiting times were reported as problematic by all participants.
CONCLUSIONS: Teen and parent perspectives are critical in designing future well-received adolescent-family transition clinics. Development from the ground up with family recommendations may contribute to high-quality health outcomes.
Association between chlorinated pesticides in the serum of prepubertal Russian boys and longitudinal biomarkers of metabolic function
Organochlorine pesticides (OCPs) have been linked to adult metabolic disorders; however, few studies have examined these associations in childhood. We prospectively evaluated the associations of baseline serum OCPs (hexachlorobenzene, beta-hexachlorocyclohexane, and p,p'-dichlorodiphenyldichloroethylene) in Russian boys with subsequent repeated measurements of serum glucose, insulin, lipids, leptin, and calculated homeostatic model assessment of insulin resistance (IR). During 2003-2005, we enrolled 499 boys aged 8-9 years in a prospective cohort; 318 had baseline serum OCPs and serum biomarkers measured at ages 10-13 years. Multivariable generalized estimating equation and mediation regression models were used to examine associations and direct and indirect (via body mass index (BMI) (weight (kg)/height (m)(2))) effects of prepubertal OCP tertiles and quintiles with biomarkers. In multivariable models, higher p,p'-dichlorodiphenyldichloroethylene (quintile 5 vs. quintile 1) was associated with lower leptin, with relative mean decreases of 61.8% (95% confidence interval: 48.4%, 71.7%) in models unadjusted for BMI and 22.2% (95% confidence interval: 7.1%, 34.9%) in models adjusted for BMI; the direct effect of p,p'-dichlorodiphenyldichloroethylene on leptin accounted for 27% of the total effect. IR prevalence was 6.6% at ages 12-13 years. Higher hexachlorobenzene (tertile 3 vs. tertile 1) was associated with higher odds of IR in models adjusted for BMI (odds ratio = 4.37, 95% confidence interval: 1.44, 13.28). These results suggest that childhood OCPs may be associated with IR and lower leptin.
BACKGROUND: In animal studies, organochlorine pesticide (OCP) exposure alters pubertal development; however, epidemiological data are limited and inconsistent.
OBJECTIVE: To evaluate the associations of serum OCP concentrations [hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE)] with male pubertal onset.
METHODS: In Chapaevsk, Russia, a town environmentally contaminated with OCPs, 350 8-9 year old boys with measured OCPs were enrolled during 2003-2005 and were followed annually for eight years. We evaluated three measures of pubertal onset: testicular volume (TV) > 3 mL in either testis, or stage 2 or greater for genitalia (G2+), or pubic hair (P2+). We used multivariable interval-censored models to evaluate associations of OCPs (quartiles) with physician-assessed pubertal onset. RESULTS: In adjusted models, boys with higher HCB concentrations had later mean ages of TV > 3 mL and P2+ (but not G2+). Mean age at attaining TV > 3 mL was delayed 3.6 (95% CI: -2.6, 9.7), 7.9 (95% CI: 1.7, 14.0), and 4.7 months (95% CI: -1.4, 10.9) for HCB Q2, Q3, and Q4, respectively, compared to Q1 (trend p: 0.06). Boys with higher HCB concentrations reached P2+ 0.1 months earlier (95% CI: -5.8, 5.6) for Q2, 4.7 months later (95% CI: -1.0, 10.3) for Q3 and 4.6 months later (95% CI: -1.1, 10.3) for Q4 compared to Q1 (trend p: 0.04). There were no associations of serum beta-HCH and p,p'-DDE concentrations with age of pubertal onset.
CONCLUSION: Higher prepubertal serum HCB concentrations were associated with later age of gonadarche and pubarche.
Dantrolene for cerebral vasospasm after subarachnoid haemorrhage: a randomised double blind placebo-controlled safety trial
BACKGROUND: Dantrolene is neuroprotective in animal models and may attenuate cerebral vasospasm (cVSP) in human aneurysmal subarachnoid haemorrhage (aSAH). We evaluated safety, feasibility and tolerability of intravenous dantrolene (IV-D) in patients with aSAH.
METHODS: In this single-centre, randomised, double blind, placebo-controlled trial, 31 patients with aSAH were randomised to IV-D 1.25 mg every 6 h for 7 days (n=16) or equiosmolar free water/5% mannitol (placebo; n=15). Primary safety end points were incidence of hyponatraemia (sNa≤132 mmol/L) and liver toxicity (proportion of patients alanine transaminase, aspartate aminotransferase and AlkPhos >5× upper-limit-of-normal). Secondary end points included tolerability, systemic hypotension and intracranial hypertension. Efficacy was explored for clinical/radiological cVSP, delayed cerebral ischaemia (DCI), and 3-month functional outcomes. Quantitative analyses of angiograms and daily transcranial Doppler (TCD) were performed.
RESULTS: Between IV-D versus placebo, no differences were observed in the primary outcomes (hyponatremia 44% vs 67% (p=0.29); liver toxicity 6% vs 0% (p=1.0)). Three patients in the IV-D versus two in the placebo group had severe adverse events possibly attributable to infusion and reached stop criteria: one IV-D patient developed liver toxicity; two patients in each group developed brain oedema requiring osmotherapy. The majority of adverse events were not related to infusion (17 vs 5 (RR 2.2; 95% CI 0.7 to 6.7; p=0.16) in IV-D vs placebo). No differences in any categorical cVSP outcomes, DCI, 3-month outcomes or quantitative angiogram and TCD analyses were seen in this small safety trial not powered to detect efficacy.
CONCLUSIONS: In this small trial, IV-D after aSAH was feasible, tolerable and safe.
TRIAL REGISTRATION NUMBER: http://clinicaltrials.gov NCT01024972.
OBJECTIVES: In this prospective pilot study, the feasibility of non-contrast dedicated breast computed tomography (bCT) to determine primary tumor volume and monitor its changes during neoadjuvant chemotherapy (NAC) treatment was investigated.
MATERIALS AND METHODS: Eleven women who underwent NAC were imaged with a clinical prototype dedicated bCT system at three time points - pre-, mid-, and post-treatment. The study radiologist marked the boundary of the primary tumor from which the tumor volume was quantified. An automated algorithm was developed to quantify the primary tumor volume for comparison with radiologist's segmentation. The correlation between pre-treatment tumor volumes from bCT and MRI, and the correlation and concordance in tumor size between post-treatment bCT and pathology were determined.
RESULTS: Tumor volumes from automated and radiologist's segmentations were correlated (Pearson's r = 0.935, P < 0.001) and were not different over all time points [P = 0.808, repeated measures analysis of variance (ANOVA)]. Pre-treatment tumor volumes from MRI and bCT were correlated (r = 0.905, P < 0.001). Tumor size from post-treatment bCT was correlated with pathology (r = 0.987, P = 0.002) for invasive ductal carcinoma larger than 5 mm and the maximum difference in tumor size was 0.57 cm. The presence of biopsy clip (3 mm) limited the ability to accurately measure tumors smaller than 5 mm. All study participants were pathologically assessed to be responders, with three subjects experiencing complete pathologic response for invasive cancer and the reminder experiencing partial response. Compared to pre-treatment tumor volume, there was a statistically significant (P = 0.0003, paired t-test) reduction in tumor volume at mid-treatment observed with bCT, with an average tumor volume reduction of 47%.
CONCLUSIONS: This pilot study suggests that dedicated non-contrast bCT has the potential to serve as an expedient imaging tool for monitoring tumor volume changes during NAC. Larger studies are needed in future.
Gadoxetate disodium-enhanced liver MRI: gallbladder opacification patterns during hepatobiliary phase
OBJECTIVE(S): To describe the different patterns of gallbladder lumen opacification on gadoxetate disodium-enhanced liver magnetic resonance imaging (MRI).
METHODS: One hundred eighty-seven MRI examinations were reviewed by two abdominal imaging radiologists who described the different patterns of gallbladder opacification, based on comparing the post-contrast to the pre-contrast images.
RESULTS: Four patterns of gallbladder opacification were identified, all based on the anti-dependent distribution of the excreted biliary contrast inside the gallbladder lumen. Contrast was identified at the level of the gallbladder neck, anti-dependant wall, and gallbladder fundus. One gallbladder completely filled with contrast.
CONCLUSION(S): The opacification of the gallbladder lumen follows a distinctive anti-dependent distribution.
Delayed splenic rupture following conservative management of splenic injury is an extremely rare complication. We report a case of an adult patient who presented with delayed splenic rupture necessitating splenectomy, 2 months following blunt abdominal trauma. Imaging at the initial presentation demonstrated only minimal splenic contusion and the patient was discharge following 24 hours of observation.
Target delineation for radiosurgery of a small brain arteriovenous malformation using high-resolution contrast-enhanced cone beam CT
Three years following endovascular embolization of a 3 mm ruptured arteriovenous malformation (AVM) of the left superior colliculus in a 42-year-old man, digital subtraction angiography showed continuous regrowth of the lesion. Thin-slice MRI acquired for treatment planning did not show the AVM nidus. The patient was brought back to the angiography suite for high-resolution contrast-enhanced cone beam CT (VasoCT) acquired using an angiographic c-arm system. The lesion and nidus were visualized with VasoCT. MRI, CT and VasoCT data were transferred to radiation planning software and mutually co-registered. The nidus was annotated for radiation on VasoCT data by an experienced neurointerventional radiologist and a dose/treatment plan was completed. Due to image registration, the treatment area could be directly adopted into the MRI and CT data. The AVM was completely obliterated 10 months following completion of the radiosurgery treatment.
OBJECTIVE: A noninvasive method to predict aggressiveness of high-grade meningiomas would be desirable because it would help anticipate tumor recurrence and improve tumor management and the treatment outcomes. The Ki-67 protein is a marker of tumor proliferation, and apparent diffusion coefficient (ADC) is related to tumor cellularity. Therefore, we sought to determine whether there is a statistically significant correlation between ADC and Ki-67 values in meningiomas and whether ADC values can differentiate various meningioma subtypes.
MATERIALS AND METHODS: MRI examinations and histopathology of 68 surgically treated meningiomas were retrospectively reviewed. Mean ADC values were derived from diffusion imaging. Correlation coefficients were calculated for mean ADC and Ki-67 proliferation index values using linear regression. An independent unpaired Student t test was used to compare the ADC and Ki-67 proliferation index values from low-grade and more aggressive meningiomas.
RESULTS: A statistically significant inverse correlation was found between ADC and Ki-67 proliferation index for low-grade and aggressive meningiomas (r(2) = -0.33, p = 0.0039). ADC values (+/- SD) of low-grade meningiomas (0.84 +/- 0.14 x 10(-3) mm(2)/s) and aggressive (atypical or anaplastic) meningiomas (0.75 +/- 0.03 x 10(-3) mm(2)/s) were significantly different (p = 0.0495). Using an ADC cutoff value of 0.70 x 10(-3) mm(2)/s, the sensitivity for diagnosing aggressive meningiomas was 29%, specificity was 94%, positive predictive value was 67%, and negative predictive value was 75%.
CONCLUSION: ADC values correlate inversely with Ki-67 proliferation index and help differentiate low-grade from aggressive meningiomas.
Use of intermediate guide catheters as an adjunct in extracranial embolization to avoid onyx reflux into the anastomotic vasculature. A technical note
Onyx is a non-adhesive polymer used for embolization of arteriovenous malformations and dural arteriovenous fistulas (DAVFs). The limiting factor for Onyx embolization is usually the amount of microcatheter reflux, which can be safely tolerated. The dual microcatheter technique, compliant balloon use proximally and the use of the dual lumen Scepter balloon have been described to prevent and limit proximal Onyx reflux. We describe the use the Navien 058 intermediate guide catheter to accept the Onyx reflux in its lumen and possibly also serve as a mechanical barrier to avoid reflux into the anastomotic channel connecting the occipital artery to the vertebral artery during DAVF embolization via the occipital artery. Complete embolization of the DAVF was achieved using the lumen of the Navien catheter to accept aggressive Onyx reflux. Complete cure of the DAVF was obtained with Onyx cast filling the entire venous pouch. Besides providing distal access support, intermediate guide catheters can also prevent embolic material reflux by accepting reflux into the lumen and providing a mechanical barrier.
Flow diverter stents for unruptured saccular anterior circulation perforating artery aneurysms: safety, efficacy, and short-term follow-up
BACKGROUND: Anterior circulation perforating artery aneurysms including anterior choroidal artery and lenticulostriate artery aneurysms are rare. Injury to these vessels can lead to severe debilitating symptoms.
OBJECTIVE: To present a new approach to treatment using flow diversion technology.
METHODS: Patients treated with a Pipeline embolization device (PED) for perforator artery aneurysms at our institution between June 2012 and May 2013 were identified and included in our retrospective analysis. We evaluated patient vascular risk factors; family history of aneurysms; aneurysm characteristics; National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) on admission; and angiography follow-up and patient clinical outcome at discharge, 6 months, and 1 year.
RESULTS: We included four patients with a mean age of 59.8 years. Two patients had a positive family history of aneurysms. Patient vascular risk factors included smoking, dyslipidemia, and hypertension. All patients presented with a NIHSS and mRS of 0 on admission. Aneurysms were located at the anterior choroidal (n=2) or lenticulostriate artery (n=2) and were treated with a single PED. No periprocedural or postprocedural complications occurred. The patients were discharged with no change in NHISS or mRS score. Six-month and 1-year follow-up angiography showed complete aneurysm occlusion. Mild intimal hyperplasia was seen in 2 cases at 6 months, but was resolved at the 1-year follow-up. No re-treatment was necessary. NIHSS and mRS remained 0 at follow-up time points.
CONCLUSIONS: Our preliminary results show that flow diversion technology is an effective and safe therapy for complex, hard-to-treat aneurysms in perforating arteries. Larger studies with long-term follow-up are needed to validate our promising results.
The most common cause of acute right lower quadrant (RLQ) pain requiring surgery is acute appendicitis (AA). This narrative's focus is on imaging procedures in the diagnosis of AA, with consideration of other diseases causing RLQ pain. In general, Computed Tomography (CT) is the most accurate imaging study for evaluating suspected AA and alternative etiologies of RLQ pain. Data favor intravenous contrast use for CT, but the need for enteric contrast when intravenous contrast is used is not strongly favored. Radiation exposure concerns from CT have led to increased investigation in minimizing CT radiation dose while maintaining diagnostic accuracy and in using algorithms with ultrasound as a first imaging examination followed by CT in inconclusive cases. In children, ultrasound is the preferred initial examination, as it is nearly as accurate as CT for the diagnosis of AA in this population and without ionizing radiation exposure. In pregnant women, ultrasound is preferred initially with MRI as a second imaging examination in inconclusive cases, which is the majority.The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.