Zoledronic Acid in Reducing Clinical Fracture and Mortality after Hip Fracture.

BACKGROUND: Mortality is increased after a hip fracture, and strategies that improve outcomes are needed. METHODS: In this randomized, double-blind, placebo-controlled trial, 1065 patients were assigned to receive yearly intravenous zoledronic acid (at a dose of 5 mg), and 1062 patients were assigned to receive placebo. The infusions were first administered within 90 days after surgical repair of a hip fracture. All patients received supplemental vitamin D and calcium. The median follow-up was 1.9 years. The primary end point was a new clinical fracture. RESULTS: The rates of any new clinical fracture were 8.6% in the zoledronic acid group and 13.9% in the placebo group, a 35% risk reduction (P = 0.001); the respective rates of a new clinical vertebral fracture were 1.7% and 3.8% (P = 0.02), and the respective rates of new nonvertebral fractures were 7.6% and 10.7% (P = 0.03). In the safety analysis, 101 of 1054 patients in the zoledronic acid group (9.6%) and 141 of 1057 patients in the placebo group (13.3%) died, a reduction of 28% in deaths from any cause in the zoledronic-acid group (P = 0.01). The most frequent adverse events in patients receiving zoledronic acid were pyrexia, myalgia, and bone and musculoskeletal pain. No cases of osteonecrosis of the jaw were reported, and no adverse effects on the healing of fractures were noted. The rates of renal and cardiovascular adverse events, including atrial fibrillation and stroke, were similar in the two groups. CONCLUSIONS: An annual infusion of zoledronic acid within 90 days after repair of a low-trauma hip fracture was associated with a reduction in the rate of new clinical fractures and improved survival. (ClinicalTrials.gov number, NCT00046254.).

Potential impact of single-risk-factor versus total risk management for the prevention of cardiovascular events in Seychelles.

OBJECTIVE: To assess the prevalence of cardiovascular (CV) risk factors in Seychelles, a middle-income African country, and compare the cost-effectiveness of single-risk-factor management (treating individuals with arterial blood pressure >/= 140/90 mmHg and/or total serum cholesterol >/= 6.2 mmol/l) with that of management based on total CV risk (treating individuals with a total CV risk >/= 10% or >/= 20%).METHODS: CV risk factor prevalence and a CV risk prediction chart for Africa were used to estimate the 10-year risk of suffering a fatal or non-fatal CV event among individuals aged 40-64 years. These figures were used to compare single-risk-factor management with total risk management in terms of the number of people requiring treatment to avert one CV event and the number of events potentially averted over 10 years. Treatment for patients with high total CV risk (>/= 20%) was assumed to consist of a fixed-dose combination of several drugs (polypill). Cost analyses were limited to medication.FINDINGS: A total CV risk of >/= 10% and >/= 20% was found among 10.8% and 5.1% of individuals, respectively. With single-risk-factor management, 60% of adults would need to be treated and 157 cardiovascular events per 100 000 population would be averted per year, as opposed to 5% of adults and 92 events with total CV risk management. Management based on high total CV risk optimizes the balance between the number requiring treatment and the number of CV events averted.CONCLUSION: Total CV risk management is much more cost-effective than single-risk-factor management. These findings are relevant for all countries, but especially for those economically and demographically similar to Seychelles.

Stereologic estimates of total spinophilin-immunoreactive spine number in area 9 and the CA1 field: Relationship with the progression of Alzheimer's disease

The loss of presynaptic markers is thought to represent a strong pathologic correlate of cognitive decline in Alzheimer's disease (AD). Spinophilin is a postsynaptic marker mainly located to the heads of dendritic spines. We assessed total numbers of spinophilin-immunoreactive puncta. in the CA I and CA3 fields of hippocampus and area 9 in 18 elderly individuals with various degrees of cognitive decline. The decrease in spinophilin-immunoreactivity was significantly related to both Braak neurofibrillary tangle (NFT) staging and clinical severity but not A beta deposition staging. The total number of spinophilin-immunoreactive puncta in CA I field and area 9 were significantly related to MMSE scores and predicted 23.5 and 61.9% of its variability. The relationship between total number of spinophilin-immunoreactive puncta in CA I field and MMSE scores did not persist when adjusting for Braak NFT staging. In contrast, the total number of spinophilin-immunoreactive puncta in area 9 was still significantly related to the cognitive outcome explaining an extra 9.6% of MMSE and 25.6% of the Clinical Dementia Rating scores variability. Our data suggest that neocortical dendritic spine loss is an independent parameter to consider in AD clinicopathologic correlations.

Immediate hip spica is as effective as, but more efficient than, flexible intramedullary nailing for femoral shaft fractures in pre-school children.

Flexible intramedullary nailing (FIN) is the gold standard treatment for femur fracture in school-aged children. It has been performed successfully in younger children, although Spica cast immobilisation (SCI) has been the most widely used strategy to date. METHOD: A retrospective analysis was performed between two comparable groups of children aged 1-4 years with a femoral shaft fracture. Two University hospitals, each using specific treatment guidelines, participated in the study: SCI in Group I (Basel, Switzerland) and FIN in Group II (Lausanne, Switzerland). RESULTS: Group I included 19 children with a median age of 26 months (range 12-46 months). Median hospital stay was 1 day (range 0-5 days) and casts were retained for a median duration of 21 days (range 12-29 days). General anaesthesia was used in six children and sedation in four. Skin breakdown secondary to cast irritation occurred in two children (10.5%). The median follow-up was 114 months (range 37-171 months). No significant malunion was noted. Group II included 27 children with a median age of 38.4 months (range 18.7-46.7 months). Median hospital stay was 4 days (range 1-13 days). All children required general anaesthesia for insertion and removal of the nails. Free mobilisation and full weight bearing were allowed at a median of 2 days (range 1-10 days) and 7 days (range 1-30 days), respectively, postoperatively. Nail exteriorisation was noted in three children (11%). The median follow-up was 16.5 months (range 8-172 months). No significant malunion was reported. CONCLUSIONS: Young children with a femoral shaft fracture treated by SCI or FIN had similarly favourable outcomes and complication rates. FIN allowed earlier mobilisation and full weight bearing. Compared to SCI, a greater number of children required general anaesthesia. In a pre-school child with a femoral shaft fracture, immediate SCI applied by a paediatric orthopaedic team following specific guidelines allowed early discharge from hospital with few complications.

Prothèses totales de genoux. Analyse clinique et numérique des micromouvements de l'implant tibial [Total knee prosthesis. Clinical and numerical study of micromovements of the tibial implant].

INTRODUCTION: The importance of the micromovements in the mechanism of aseptic loosening is clinically difficult to evaluate. To complete the analysis of a series of total knee arthroplasties (TKA), we used a tridimensional numerical model to study the micromovements of the tibial implant. MATERIAL AND METHODS: Fifty one patients (with 57 cemented Porous Coated Anatomic TKAs) were reviewed (mean follow-up 4.5 year). Radiolucency at the tibial bone-cement interface was sought on the AP radiographs and divided in 7 areas. The distribution of the radiolucency was then correlated with the axis of the lower limb as measured on the orthoradiograms. The tridimensional numerical model is based on the finite element method. It allowed the measurement of the cemented prosthetic tibial implant's displacements and the micromovements generated at bone-ciment interface. A total load (2000 Newton) was applied at first vertically and asymetrically on the tibial plateau, thereby simulating an axial deviation of the lower limbs. The vector's posterior inclination then permitted the addition of a tangential component to the axial load. This type of effort is generated by complex biomechanical phenomena such as knee flexion. RESULTS: 81 per cent of the 57 knees had a radiolucent line of at least 1 mm, at one or more of the tibial cement-epiphysis jonctional areas. The distribution of these lucent lines showed that they came out more frequently at the periphery of the implant. The lucent lines appeared most often under the unloaded margin of the tibial plateau, when axial deviation of lower limbs was present. Numerical simulations showed that asymetrical loading on the tibial plateau induced a subsidence of the loaded margin (0-100 microns) and lifting off at the opposite border (0-70 microns). The postero-anterior tangential component induced an anterior displacement of the tibial implant (160-220 microns), and horizontal micromovements with non homogenous distribution at the bone-ciment interface (28-54 microns). DISCUSSION: Comparison of clinical and numerical results showed a relation between the development of radiolucent lines and the unloading of the tibial implant's margin. The deleterious effect of lower limbs' axial deviation is thereby proven. The irregular distribution of lucent lines under the tibial plateau was similar of the micromovements' repartition at the bone-cement interface when tangential forces were present. A causative relation between the two phenomenaes could not however be established. Numerical simulation is a truly useful method of study; it permits to calculate micromovements which are relative, non homogenous and of very low amplitude. However, comparative clinical studies remain as essential to ensure the credibility of results.

MDCT arthrography of the hip: value of the adaptive statistical iterative reconstruction technique and potential for radiation dose reduction.

OBJECTIVE: The purpose of this article is to assess the effect of the adaptive statistical iterative reconstruction (ASIR) technique on image quality in hip MDCT arthrography and to evaluate its potential for reducing radiation dose. SUBJECTS AND METHODS: Thirty-seven patients examined with hip MDCT arthrography were prospectively randomized into three different protocols: one with a regular dose (volume CT dose index [CTDIvol], 38.4 mGy) and two with a reduced dose (CTDIvol, 24.6 or 15.4 mGy). Images were reconstructed using filtered back projection (FBP) and four increasing percentages of ASIR (30%, 50%, 70%, and 90%). Image noise and contrast-to-noise ratio (CNR) were measured. Two musculoskeletal radiologists independently evaluated several anatomic structures and image quality parameters using a 4-point scale. They also jointly assessed acetabular labrum tears and articular cartilage lesions. RESULTS: With decreasing radiation dose level, image noise statistically significantly increased (p=0.0009) and CNR statistically significantly decreased (p=0.001). We also found a statistically significant reduction in noise (p=0.0001) and increase in CNR (p≤0.003) with increasing percentage of ASIR; in addition, we noted statistically significant increases in image quality scores for the labrum and cartilage, subchondral bone, overall diagnostic quality (up to 50% ASIR), and subjective noise (p≤0.04), and statistically significant reductions for the trabecular bone and muscles (p≤0.03). Regardless of the radiation dose level, there were no statistically significant differences in the detection and characterization of labral tears (n=24; p=1) and cartilage lesions (n=40; p≥0.89) depending on the ASIR percentage. CONCLUSION: The use of up to 50% ASIR in hip MDCT arthrography helps to reduce radiation dose by approximately 35-60%, while maintaining diagnostic image quality comparable to that of a regular-dose protocol using FBP.

Multiple QTLs influencing triglyceride and HDL and total cholesterol levels identified in families with atherogenic dyslipidemia.

We conducted a genome-wide scan using variance components linkage analysis to localize quantitative-trait loci (QTLs) influencing triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol, and total cholesterol (TC) levels in 3,071 subjects from 459 families with atherogenic dyslipidemia. The most significant evidence for linkage to TG levels was found in a subset of Turkish families at 11q22 [logarithm of the odds ratio (LOD)=3.34] and at 17q12 (LOD=3.44). We performed sequential oligogenic linkage analysis to examine whether multiple QTLs jointly influence TG levels in the Turkish families. These analyses revealed loci at 20q13 that showed strong epistatic effects with 11q22 (conditional LOD=3.15) and at 7q36 that showed strong epistatic effects with 17q12 (conditional LOD=3.21). We also found linkage on the 8p21 region for TG in the entire group of families (LOD=3.08). For HDL-C levels, evidence of linkage was identified on chromosome 15 in the Turkish families (LOD=3.05) and on chromosome 5 in the entire group of families (LOD=2.83). Linkage to QTLs for TC was found at 8p23 in the entire group of families (LOD=4.05) and at 5q13 in a subset of Turkish and Mediterranean families (LOD=3.72). These QTLs provide important clues for the further investigation of genes responsible for these complex lipid phenotypes. These data also indicate that a large proportion of the variance of TG levels in the Turkish population is explained by the interaction of multiple genetic loci.

Changes in volume, surface estimate, three-dimensional shape and total number of neurons of the human primary visual cortex from midgestation until old age.

Macroscopic features such as volume, surface estimate, thickness and caudorostral length of the human primary visual cortex (Brodman's area 17) of 46 human brains between midgestation and 93 years were studied by means of camera lucida drawings from serial frontal sections. Individual values were best fitted by a logistic function from midgestation to adulthood and by a regression line between adulthood and old age. Allometric functions were calculated to study developmental relationships between all the features. The three-dimensional shape of area 17 was also reconstructed from the serial sections in 15 cases and correlated with the sequence of morphological events. The sulcal pattern of area 17 begins to develop around 21 weeks of gestation but remains rather simple until birth, while it becomes more convoluted, particularly in the caudal part, during the postnatal period. Until birth, a large increase in cortical thickness (about 83% of its mean adult value) and caudorostral length (69%) produces a moderate increase in cortical volume (31%) and surface estimate (40%) of area 17. After birth, the cortical volume and surface undergo their maximum growth rate, in spite of a rather small increase in cortical thickness and caudorostral length. This is due to the development of the pattern of gyrification within and around the calcarine fissure. All macroscopic features have reached the mean adult value by the end of the first postnatal year. With aging, the only features to undergo significant regression are the cortical surface estimate and the caudorostral length. The total number of neurons in area 17 shows great interindividual variability at all ages. No decrease in the postnatal period or in aging could be demonstrated.

Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.

Body fat distribution, particularly centralized obesity, is associated with metabolic risk above and beyond total adiposity. We performed genome-wide association of abdominal adipose depots quantified using computed tomography (CT) to uncover novel loci for body fat distribution among participants of European ancestry. Subcutaneous and visceral fat were quantified in 5,560 women and 4,997 men from 4 population-based studies. Genome-wide genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), VAT adjusted for body mass index, and VAT/SAT ratio (a metric of the propensity to store fat viscerally as compared to subcutaneously) in the overall sample and in women and men separately. A weighted z-score meta-analysis was conducted. For the VAT/SAT ratio, our most significant p-value was rs11118316 at LYPLAL1 gene (p = 3.1 × 10E-09), previously identified in association with waist-hip ratio. For SAT, the most significant SNP was in the FTO gene (p = 5.9 × 10E-08). Given the known gender differences in body fat distribution, we performed sex-specific analyses. Our most significant finding was for VAT in women, rs1659258 near THNSL2 (p = 1.6 × 10-08), but not men (p = 0.75). Validation of this SNP in the GIANT consortium data demonstrated a similar sex-specific pattern, with observed significance in women (p = 0.006) but not men (p = 0.24) for BMI and waist circumference (p = 0.04 [women], p = 0.49 [men]). Finally, we interrogated our data for the 14 recently published loci for body fat distribution (measured by waist-hip ratio adjusted for BMI); associations were observed at 7 of these loci. In contrast, we observed associations at only 7/32 loci previously identified in association with BMI; the majority of overlap was observed with SAT. Genome-wide association for visceral and subcutaneous fat revealed a SNP for VAT in women. More refined phenotypes for body composition and fat distribution can detect new loci not previously uncovered in large-scale GWAS of anthropometric traits.

Smart instrumentation for determination of ligament stiffness and ligament balance in total knee arthroplasty.

Ligament balance is an important and subjective task performed during total knee arthroplasty (TKA) procedure. For this reason, it is desirable to develop instruments to quantitatively assess the soft-tissue balance since excessive imbalance can accelerate prosthesis wear and lead to early surgical revision. The instrumented distractor proposed in this study can assist surgeons on performing ligament balance by measuring the distraction gap and applied load. Also the device allows the determination of the ligament stiffness which can contribute a better understanding of the intrinsic mechanical behavior of the knee joint. Instrumentation of the device involved the use of hall-sensors for measuring the distractor displacement and strain gauges to transduce the force. The sensors were calibrated and tested to demonstrate their suitability for surgical use. Results show the distraction gap can be measured reliably with 0.1mm accuracy and the distractive loads could be assessed with an accuracy in the range of 4N. These characteristics are consistent with those have been proposed, in this work, for a device that could assist on performing ligament balance while permitting surgeons evaluation based on his experience. Preliminary results from in vitro tests were in accordance with expected stiffness values for medial collateral ligament (MCL) and lateral collateral ligament (LCL).

Radiographic total disc replacement angle measurement accuracy using the Oxford Cobbometer: precision and bias.

Total disc replacement (TDR) clinical success has been reported to be related to the residual motion of the operated level. Thus, accurate measurement of TDR range of motion (ROM) is of utmost importance. One commonly used tool in measuring ROM is the Oxford Cobbometer. Little is known however on its accuracy (precision and bias) in measuring TDR angles. The aim of this study was to assess the ability of the Cobbometer to accurately measure radiographic TDR angles. An anatomically accurate synthetic L4-L5 motion segment was instrumented with a CHARITE artificial disc. The TDR angle and anatomical position between L4 and L5 was fixed to prohibit motion while the motion segment was radiographically imaged in various degrees of rotation and elevation, representing a sample of possible patient placement positions. An experienced observer made ten readings of the TDR angle using the Cobbometer at each different position. The Cobbometer readings were analyzed to determine measurement accuracy at each position. Furthermore, analysis of variance was used to study rotation and elevation of the motion segment as treatment factors. Cobbometer TDR angle measurements were most accurate (highest precision and lowest bias) at the centered position (95.5%), which placed the TDR directly inline with the x-ray beam source without any rotation. In contrast, the lowest accuracy (75.2%) was observed in the most rotated and off-centered view. A difference as high as 4 degrees between readings at any individual position, and as high as 6 degrees between all the positions was observed. Furthermore, the Cobbometer was unable to detect the expected trend in TDR angle projection with changing position. Although the Cobbometer has been reported to be reliable in different clinical applications, it lacks the needed accuracy to measure TDR angles and ROM. More accurate ROM measurement methods need to be developed to help surgeons and researchers assess radiological success of TDRs.