Prefracture functional level evaluated by the New Mobility Score predicts in-hospital outcome after hip fracture surgery

BACKGROUND AND PURPOSE: Clinicians need valid and easily applicable predictors of outcome in patients with hip fracture. Adjusting for previously established predictors, we determined the predictive value of the New Mobility score (NMS) for in-hospital outcome in patients with hip fracture. PATIENTS AND METHODS: We studied 280 patients with a median age of 81 (interquartile range 72-86) years who were admitted from their own homes to a special hip fracture unit. Main outcome was the regain of independence in basic mobility, defined as. independence in getting in and out of bed, sitting down and standing up from a chair, and walking with an appropriate walking aid. The Cumulated Ambulation score was used to evaluate basic mobility. Predictor variables were NMS functional level before fracture, age, sex, fracture type, and mental and health status. RESULTS: Except for sex, all predictor variables were statistically significant in univariate testing. In multiple logistic regression analysis, only age, NMS functional level before fracture, and fracture type were significant. Thus, patients with a low prefracture NMS and/or an intertrochanteric fracture would be 18 and 4 times more likely not to regain independence in basic mobility during the hospital stay, respectively, than patients with a high prefracture level and a cervical fracture, respectively. The model was statistically stable and correctly classified 84% of cases. INTERPRETATION: The NMS functional level before fracture, age, and fracture type facilitate prediction of the in-hospital rehabilitation potential after hip fracture surgery

Validity of Thermal Ramping Assays Used to Assess Thermal Tolerance in Arthropods

Proper assessment of environmental resistance of animals is critical for the ability of researchers to understand how variation in environmental conditions influence population and species abundance. This is also the case for studies of upper thermal limits in insects, where researchers studying animals under laboratory conditions must select appropriate methodology on which conclusions can be drawn. Ideally these methods should precisely estimate the trait of interest and also be biological meaningful. In an attempt to develop such tests it has been proposed that thermal ramping assays are useful assays for small insects because they incorporate an ecologically relevant gradual temperature change. However, recent model-based papers have suggested that estimates of thermal resistance may be strongly confounded by simultaneous starvation and dehydration stress. In the present study we empirically test these model predictions using two sets of independent experiments. We clearly demonstrate that results from ramping assays of small insects (Drosophila melanogaster) are not compromised by starvation- or dehydration-stress. Firstly we show that the mild disturbance of water and energy balance of D. melanogaster experienced during the ramping tests does not confound heat tolerance estimates. Secondly we show that flies pre-exposed to starvation and dehydration have “normal” heat tolerance and that resistance to heat stress is independent of the energetic and water status of the flies. On the basis of our results we discuss the assumptions used in recent model papers and present arguments as to why the ramping assay is both a valid and ecologically relevant way to measure thermal resistance in insects

Contribution of respiratory tract infections to child deaths: a data linkage study

Background: Respiratory tract infections (RTIs) are an important cause of death in children, and often contribute to the terminal decline in children with chronic conditions. RTIs are often underrecorded as the underlying cause of death; therefore the overall contribution of RTIs to child deaths and the potential preventability of RTI-related deaths have not been adequately quantified. Methods: We analysed deaths in children resident in England who died of non-injury causes aged 28 days to 18 years between 2001 and 2010 using death certificates linked to a longitudinal hospital admission database. We defined deaths as RTI-related if RTIs or other respiratory conditions were recorded on death certificates or linked hospital records up to 30 days before death. We examined trends in mortality by age group, year and season (winter or summer) and determined the winter excess of RTI-related deaths using rate differencing techniques. We estimated the proportion of RTI-related deaths in children with chronic conditions. Results: 22.4% (5039/22509) of child deaths were RTI-related. RTI-related deaths declined by 2.3% per year in infants aged 28 to 364 days between 2001 and 2010. No decline was observed for older children. On average there were 161 winter excess RTI-related deaths annually, accounting for 32% of all RTI-related deaths. 89.0% of children with RTI-related deaths had at least one chronic condition; neurological conditions were the most prevalent. Conclusions: RTI-related deaths have not declined in the last decade except in infants. Targeted strategies to prevent the winter excess of RTIs and to treat RTIs in children, particularly children with chronic conditions, may reduce RTI-related deaths

Predicting discharge location of hip fracture patients; the new discharge of hip fracture patients score

Purpose This paper reports on the development and validity of a new instrument, called the discharge of hip fracture patients score (DHP), that predicts at admission the discharge location in patients living in their own home prior to hip fracture surgery. Methods A total of 310 patients aged 50 years and above were included. Risk factors for discharge to an alternative location (DAL) were analysed with a multivariable regression analysis taking the admission variables into account with different weights based on the estimates. The score ranged from 0-100 points. The cut-off point for DAL was calculated using a ROC analysis. Reliability of the DHP was evaluated. Results Risk factors for DAL were higher age, female gender, dementia, absence of a partner and a limited level of mobility. The cut-off point was set at 30 points, with a sensitivity of 83.8%, a specificity of 64.7% and positive predictive value of 79.2%. Conclusion The DHP is a valid, simple and short instrument to be used at admission to predict discharge location of hip fracture patients

Eggshell membrane in the treatment of pain and stiffness from osteoarthritis of the knee: a randomized, multicenter, double-blind, placebo-controlled clinical study

Natural Eggshell Membrane (NEM®) is a new novel dietary supplement that contains naturally occurring glycosaminoglycans and proteins essential for maintaining healthy articular cartilage and the surrounding synovium. The randomized, multicenter, double-blind, placebo-controlled Osteoarthritis Pain Treatment Incorporating NEM® clinical study was conducted to evaluate the efficacy and safety of NEM® as a treatment for pain and stiffness associated with osteoarthritis of the knee. Sixty-seven patients were randomly assigned to receive either oral NEM® 500 mg (n = 34) or placebo (n = 33) daily for 8 weeks. The primary endpoint was the change in overall Western Ontario and McMasters Universities (WOMAC) Osteoarthritis Index as well as pain, stiffness, and function WOMAC subscales measured at 10, 30, and 60 days. The clinical assessment was performed on the intent-to-treat population. Supplementation with NEM® produced an absolute rate of response that was statistically significant (up to 26.6%) versus placebo at all time points for both pain and stiffness, but was not significantly improved for function and overall WOMAC scores, although trending toward improvement. Rapid responses were seen for mean pain subscores (15.9% reduction, P = 0.036) and mean stiffness subscores (12.8% reduction, P = 0.024) occurring after only 10 days of supplementation. There were no serious adverse events reported during the study and the treatment was reported to be well tolerated by study participants. Natural Eggshell Membrane (NEM®) is an effective and safe option for the treatment of pain and stiffness associated with knee osteoarthritis. Supplementation with NEM®, 500 mg taken once daily, significantly reduced both joint pain and stiffness compared to placebo at 10, 30, and 60 days. The Clinical Trial Registration number for this study is NCT00750477

High sensitivity assays for docetaxel and paclitaxel in plasma using solid-phase extraction and high-performance liquid chromatography with UV detection

BACKGROUND: The taxanes paclitaxel and docetaxel have traditionally been used in high doses every third week in the treatment of cancer. Lately there has been a trend towards giving weekly low doses to improve the therapeutic index. This article describes the development of high performance liquid chromatographic (HPLC) methods suitable for monitoring taxane levels in patients, focusing on patients receiving low-dose therapy. METHODS: Paclitaxel and docetaxel were extracted from human plasma by solid phase extraction, and detected by absorbance at 227 nm after separation by reversed phase high performance liquid chromatography. The methods were validated and their performance were tested using samples from patients receiving paclitaxel or docetaxel. RESULTS: The limits of quantitation were 1 nM for docetaxel and 1.2 nM for paclitaxel. For both compounds linearity was confirmed from the limit of quantitation up to 1000 nM in plasma. The recoveries ranged between 92% and 118% for docetaxel and between 76% and 104% for paclitaxel. Accuracy and precision were within international acceptance criteria, that is within ± 15%, except at the limit of quantitation where values within ± 20% are acceptable. Low-dose patients included in an on going clinical trial had a median docetaxel concentration of 2.8 nM at 72 hours post infusion. Patients receiving 100 mg/m(2 )of paclitaxel had a mean paclitaxel concentration of 21 nM 48 hours after the end of infusion. CONCLUSION: We have developed an HPLC method using UV detection capable of quantifying 1 nM of docetaxel in plasma samples. The method should be useful for pharmacokinetic determinations at all relevant doses of docetaxel. Using a similar methodology paclitaxel can be quantified down to a concentration of 1.2 nM in plasma with acceptable accuracy and precision. We further demonstrate that the previously reported negative influence of Cremophor EL on assay performance may be overcome by degradation of the detergent by incubation with lipase

Ge/Si nanowire mesoscopic Josephson junctions

The controlled growth of nanowires (NWs) with dimensions comparable to the Fermi wavelengths of the charge carriers allows fundamental investigations of quantum confinement phenomena. Here, we present studies of proximity-induced superconductivity in undoped Ge/Si core/shell NW heterostructures contacted by superconducting leads. By using a top gate electrode to modulate the carrier density in the NW, the critical supercurrent can be tuned from zero to greater than 100 nA. Furthermore, discrete sub-bands form in the NW due to confinement in the radial direction, which results in stepwise increases in the critical current as a function of gate voltage. Transport measurements on these superconductor-NW-superconductor devices reveal high-order (n = 25) resonant multiple Andreev reflections, indicating that the NW channel is smooth and the charge transport is highly coherent. The ability to create and control coherent superconducting ordered states in semiconductor-superconductor hybrid nanostructures allows for new opportunities in the study of fundamental low-dimensional superconductivity

Consensus guidelines for the diagnosis and management of pyridoxine-dependent epilepsy due to α-aminoadipic semialdehyde dehydrogenase deficiency

Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is an autosomal recessive condition due to a deficiency of α-aminoadipic semialdehyde dehydrogenase, which is a key enzyme in lysine oxidation. PDE-ALDH7A1 is a developmental and epileptic encephalopathy that was historically and empirically treated with pharmacologic doses of pyridoxine. Despite adequate seizure control, most patients with PDE-ALDH7A1 were reported to have developmental delay and intellectual disability. To improve outcome, a lysine-restricted diet and competitive inhibition of lysine transport through the use of pharmacologic doses of arginine have been recommended as an adjunct therapy. These lysine-reduction therapies have resulted in improved biochemical parameters and cognitive development in many but not all patients. The goal of these consensus guidelines is to re-evaluate and update the two previously published recommendations for diagnosis, treatment, and follow-up of patients with PDE-ALDH7A1. Members of the International PDE Consortium initiated evidence and consensus-based process to review previous recommendations, new research findings, and relevant clinical aspects of PDE-ALDH7A1. The guideline development group included pediatric neurologists, biochemical geneticists, clinical geneticists, laboratory scientists, and metabolic dieticians representing 29 institutions from 16 countries. Consensus guidelines for the diagnosis and management of patients with PDE-ALDH7A1 are provided. This article is protected by copyright. All rights reserved