Markers of cerebral damage during delirium in elderly patients with hip fracture

Background  

S100B protein and Neuron Specific Enolase (NSE) can increase due to brain cell damage and/or increased permeability of the blood-brain-barrier. Elevation of these proteins has been shown after various neurological diseases with cognitive dysfunction. Delirium is characterized by temporal cognitive deficits and is an important risk factor for dementia. The aim of this study was to compare the level of S100B and NSE of patients before, during and after delirium with patients without delirium and investigate the possible associations with different subtypes of delirium.     

Cortical bone thickness can adapt locally to muscular loading while changing with age

Mechanical loading of muscle action is concentrated at muscle attachment sites; thus there may be a potential for site-specific variation in cortical bone thickness. Humeri from an early 20th-century Finnish (Helsinki) and two medieval English (Newcastle, Blackgate and York, Barbican) populations were subjected to pQCT scanning to calculate site-specific cross-sectional cortical bone area (CA) for four locations and to measure cortical thickness at muscle attachment sites and non-attachment sites. We found that CA at 80% of humerus length was significantly reduced compared to more distal cross-sections, which can be due to reduced stresses at the proximal shaft. The principal direction of loading at 80% humerus length was towards mediolateral plane, likely due to fixing the humerus close to the torso. At 35% the main direction of loading was towards anteroposterior plane, reflecting elbow flexing forces. The principal direction of loading varied between populations, sides and sexes at 50% humerus length due to preference between elbow and shoulder joint; thus this location might be useful when trying to infer differences in activity. These changes are likely due to overall shaft adaptation to forces acting at the humerus. In addition, we found a potential for site-specific variation in cortical thickness; cortical bone at muscle attachment sites was significantly thicker compared to non-attachment sites. Lastly, CA at 35% of humerus length and cortical thickness at non-attachment sites decreased with age. These results underline the importance of muscle loading for bone mass preservation as well as indicate that a site-specific variation of bone mass is possible.     

Effects of trochanteric soft tissue thickness and hip impact velocity on hip fracture in sideways fall through 3D finite element simulations

A major worldwide health problem is hip fracture due to sideways fall among the elderly population. The effects of sideways fall on the hip are required to be investigated thoroughly. The objectives of this study are to evaluate the responses to trochanteric soft tissue thickness (T) variations and hip impact velocity (V) variations during sideways fall based on a previously developed CT scan derived 3D non-linear and non-homogeneous finite element model of pelvis-femur-soft tissue complex with simplified biomechanical representation of the whole body. This study is also aimed at quantifying the effects [peak impact force (F(max)), time to F(max), acceleration and peak principal compressive strain (epsilon(max))] of these variations (T,V) on hip fracture. It was found that under constant impact energy, for 81% decrease in T (26-5mm), F(max) and epsilon(max) increased by 38% and 97%, respectively. Hence, decrease in T (as in slimmer persons) strongly correlated to risk for hip fracture (phi) and strain ratio (SR) by 0.972 and 0.988, respectively. Also under same T and body weight, for 75% decrease in V (4.79-1.2m/s), F(max) and epsilon(max) decreased by 70% and 86%, respectively. Hence, increase in V (as in taller persons) strongly correlated to phi and SR by 0.995 and 0.984, respectively. For both variations in T and V, inter-trochanteric fracture situations were well demonstrated by phi as well as by SR and strain contours, similar to clinically observed fractures. These quantifications would be helpful for effective design of person-specific hip protective devices.     

Multifaceted intervention to improve diagnosis and treatment of osteoporosis in patients with recent wrist fracture: a randomized controlled trial

Background

Older patients who experience a fragility fracture are at high risk of future fractures but are rarely tested or treated for osteoporosis. We developed a multifaceted intervention directed at older patients with wrist fractures (in the form of telephone-based education) and their physicians (in the form of guidelines endorsed by opinion leaders, supported by reminders) to improve the quality of osteoporosis care.

Methods

In a randomized controlled trial with blinded ascertainment of outcomes, we compared our intervention with usual care (provision of printed educational materials to patients). Eligible patients were those older than 50 years of age who had experienced a wrist fracture and were seen in emergency departments and fracture clinics; we excluded those who were already being treated for osteoporosis. The primary outcome was bisphosphonate treatment within 6 months after the fracture. Secondary outcomes included bone mineral density testing, “appropriate care” (consisting of bone mineral density testing with treatment if bone mass was low) and quality of life.

Results

We screened 795 patients for eligibility and randomly assigned 272 to the intervention (137 patients) or control (135 patients) group. The median age was 60 years; 210 (77%) of the subjects were women, and 130 (48%) reported a previous fracture as an adult. Six months after the fracture, 30 (22%) of the intervention patients, as compared with 10 (7%) of the control patients, were receiving bisphosphonate therapy for osteoporosis (adjusted relative risk [RR] 2.6, 95% confidence interval [CI] 1.3–5.1, p = 0.008). Intervention patients were more likely than control patients to undergo bone mineral density testing (71/137 [52%] v. 24/135 [18%]; adjusted RR 2.8, 95% CI 1.9–4.2, p < 0.001) and to receive appropriate care (52/137 [38%] v. 15/135 [11%]; adjusted RR 3.1, 95% CI 1.8–5.3, p < 0.001). There were no differences between the groups in other outcomes. One patient died, and 4 others experienced recurrent fracture.

Interpretation

A multifaceted intervention directed at high-risk patients and their physicians substantially increased rates of testing and treatment for osteoporosis. Nevertheless, more than half of the patients in the intervention group were not receiving appropriate care 6 months after their fracture, which suggests that additional strategies should be explored. (ClinicalTrials.gov trial register no. NCT00152321.)Osteoporosis is a common, chronic and costly condition affecting at least 25% of women and 12% of men over 50 years of age.^1–3 Without better prevention strategies, the incidence of and costs related to osteoporotic fractures are expected to increase by 50% over the next 2 decades.³ Case-finding and secondary prevention (e.g., by identifying patients who have experienced a fragility fracture, ensuring that their bone mineral density is tested and offering efficacious osteoporosis treatments to those with low bone mass) constitute the most cost-effective strategy for reducing future fractures.^4–6An obvious target group for case-finding consists of older patients who experience a wrist fracture. Wrist fracture is the most common symptomatic fracture related to osteoporosis; its occurrence is a powerful forecaster of future fractures, and these fractures typically occur 10–20 years before the more devastating osteoporosis-related fractures of the spine or the hip.⁷ Unfortunately, although most older patients with wrist fractures have low bone mass and are eligible for treatment,^4,7 less than about 10% to 20% are tested or treated for osteoporosis in the 6 to 12 months after a wrist fracture.^4–9We previously reported a nonrandomized study of an intervention that incorporated patient education, physician reminders and treatment guidelines endorsed by opinion leaders, to improve osteoporosis treatment in patients with wrist fractures; in that study, which involved 102 patients, the rate of treatment was 40% in the intervention group but only 10% in the group receiving usual care.⁷ Several concerns were raised about the internal and external validity of that small study, so we conducted a randomized controlled trial of the intervention, which is reported here.     

Cortical thickness and behavior abnormalities in children born preterm

Aim

To identify long-term effects of preterm birth and of periventricular leukomalacia (PVL) on cortical thickness (CTh). To study the relationship between CTh and cognitive-behavioral abnormalities.

Methods

We performed brain magnetic resonance imaging on 22 preterm children with PVL, 14 preterm children with no evidence of PVL and 22 full-term peers. T1-weighted images were analyzed with FreeSurfer software. All participants underwent cognitive and behavioral assessments by means of the Wechsler Intelligence Scales for Children-Fourth Edition (WISC-IV) and the Child Behavior Checklist (CBCL).

Results

We did not find global CTh differences between the groups. However, a thinner cortex was found in left postcentral, supramarginal, and caudal middle rostral gyri in preterm children with no evidence of PVL than in the full-term controls, while PVL preterm children showed thicker cortex in right pericalcarine and left rostral middle frontal areas than in preterm children with no evidence of PVL. In the PVL group, internalizing and externalizing scores correlated mainly with CTh in frontal areas. Attentional scores were found to be higher in PVL and correlated with CTh increments in right frontal areas.

Interpretation

The preterm group with no evidence of PVL, when compared with full-term children, showed evidence of a different pattern of regional thinning in the cortical gray matter. In turn, PVL preterm children exhibited atypical increases in CTh that may underlie their prevalent behavioral problems.     

Cortical bone mapping: An application to hand and foot bones in hominoids

Bone form reflects both the genetic profile and behavioural history of an individual. As cortical bone is able to remodel in response to mechanical stimuli, interspecific differences in cortical bone thickness may relate to loading during locomotion or manual behaviours during object manipulation. Here, we test the application of a novel method of cortical bone mapping to the third metacarpal (Mc3) and talus of Pan, Pongo, and Homo. This method of analysis allows measurement of cortical thickness throughout the bone, and as such is applicable to elements with complex morphology. In addition, it allows for registration of each specimen to a canonical surface, and identifies regions where cortical thickness differs significantly between groups. Cortical bone mapping has potential for application to palaeoanthropological studies; however, due to the complexity of correctly registering homologous regions across varied morphology, further methodological development would be advantageous.     

A new cortical thickness mapping method with application to an in vivo finite element model

Finite element modelling of musculoskeletal systems, with geometrical structures constructed from computed tomography (CT) scans, is a useful and powerful tool for biomechanical studies. The use of CT scans from living human subjects, however, is still limited. Accurate reconstruction of thin cortical bone structures from CT scans of living human subjects is especially problematic, due to low CT resolution that results from mandatory low radiation doses and/or involuntary movements of the subject. In this study, a new method for mapping cortical thickness is described. Using the method, cortical thickness measurements of a coxal (pelvis) bone obtained from CT scans of a cadaver were mapped to the coxal geometry as obtained through CT scans of a live human subject, resulting in accurate cortical thickness while maintaining geometric fidelity of the live subject. The mapping procedure includes shape-preserving parameterisation, mesh movement and interpolation of thickness using a search algorithm. The methodology is applicable to modelling of other bones where accurate cortical thickness is needed and for which such data exist.     

Serum resistin in older patients with hip fracture: Relationship with comorbidity and biochemical determinants of bone metabolism

Objectives

To determine the relationship of serum resistin concentrations to biochemical determinants of bone metabolism, comorbidity and outcomes in patients with hip fracture (HF).

Methods

In 256 consecutive patients (mean age 81.9 ± 7.8 years; 71.1% women) serum levels of resistin (determined by ELISA), biochemical parameters of bone turnover and mineral metabolism as well as routine haematological and biochemical parameters were measured. Clinical data were recorded prospectively.

Results

In multivariate analysis cervical HF (OR = 1.81; 95% CI 1.05–3.11), diabetes (OR = 2.60; 95% CI 1.23–5.51) and history of stroke (OR = 2.67; 95% CI 1.17–6.13) were significant independent predictors of higher resistin levels (?16.26 ng/ml, median value). The independent correlates of serum resistin levels in patients with cervical HF were serum osteocalcin and magnesium (both negatively associated) and in patients with trochanteric HF, serum PTH, calcium and age (all positively associated). Resistin and glomerular filtration rate were the only independent (inverse) predictors of serum osteocalcin. Resistin levels on admission did not predict short-term outcomes.

Conclusions

In older patients with HF there is a significant association of higher resistin levels with cervical fracture, type 2 diabetes and history of stroke, which is partly influenced by the reciprocal interaction between resistin and osteocalcin. However, the design of the study does not prove causality and further prospective studies are needed to clarify these relationships.     

Autosomal genome-wide linkage analysis to identify loci for gallbladder wall thickness in Mexican Americans

The significance of gallbladder wall thickness (GBWT) in regard to gallbladder disease (GBD) is not completely understood. Thickening of the gallbladder wall has been observed in patients with acute calculous and acalculous cholecystitis and chronic cholecystitis. However, various pathologic processes, such as gallbladder cancer and nonbiliary disorders such as liver cirrhosis and viral hepatitis, could also cause thickening of the gallbladder wall. To date, there is no report available on the genetic factors influencing GBWT. Therefore we sought to estimate the heritability (h2) of GBWT and to perform a genome-wide search to identify the susceptibility genes for GBWT, using data from the San Antonio Family Diabetes/Gallbladder Study (SAFDGS), a family study of Mexican Americans. GBWT was measured by ultrasound. After adjusting for the significant effects of age, sex, GBD (i.e., asymptomatic gallstones), metabolic syndrome, and duration of type 2 diabetes (T2DM), GBWT was found to be under significant and appreciable additive genetic influences (h2 +/- SE = 0.38 +/- 0.09, P < 0.0001). The strongest evidence for linkage occurred between markers D11S912 and D11S968 on chromosome 11q24-q25 (LOD = 2.7), where we have already shown suggestive evidence for linkage of GBD (LOD = 2.7) in a subset of our SAFDGS data. Potential evidence for linkage occurred at markers D1S1728 (1p31.1; LOD = 1.4) and D16S748 (16p13.1; LOD = 1.4), respectively. In conclusion, our study provides suggestive evidence for linkage of GBWT on chromosome 11q in Mexican Americans, and future tasks of mapping susceptibility gene(s) for GBD and its related traits, such as GBWT, in this chromosomal region can be fruitful.