Do Patients Taking Warfarin Experience Delays to Theatre, Longer Hospital Stay, and Poorer Survival After Hip Fracture?

BACKGROUND: Patients sustaining a fractured neck of the femur are typically of advanced age with multiple comorbidities. As a consequence, the proportion of these patients receiving warfarin therapy is approximately 10%. There are currently few studies investigating outcomes in this subset of patients. QUESTIONS/PURPOSES: The purpose of this study was to assess the association between warfarin therapy and time to surgery, length of hospital stay, and survival in patients sustaining a fractured neck of the femur. METHODS: Data for 2036 patients admitted to our center between July 2009 and July 2014 with a fractured neck of the femur were extracted from the National Hip Fracture Database. Fifty-seven patients received no surgical treatment and were excluded from analysis. Multivariable ordinary least squares regression was performed to test the association between warfarin treatment on time to surgery and length of stay, and Cox proportional hazards to test followup survival. Variables included in the regression model were age, sex, American Society of Anesthesiologists (ASA) score, admission Abbreviated Mental Test Score (AMTS), fracture type, operation type, and premorbid Work Ability Index (WAI). One hundred fifty-two of 1979 surgically treated patients (8%) were receiving warfarin therapy at the time of admission. RESULTS: After controlling for age, sex, ASA score, AMTS, fracture type, operation type, and WAI, we found that patients taking warfarin were less likely to go to surgery by 36 hours (odds ratio [OR], 0.20; 95% CI, 0.14-0.30), and less likely to go to surgery by 48 hours (OR, 0.17; 95% CI, 0.11-0.24). Patients taking warfarin had a longer length of stay (median, 15 days; interquartile range [IQR], 12-22 days) compared with patients not taking warfarin (median, 13 days; IQR, 9-20 days; p < 0.001). Survival analysis to June 2015 showed a higher mortality for patients taking warfarin (12-month survival, 66% vs 76%; hazard ratio, 1.57; 95% CI, 1.21-2.04; p < 0.001). CONCLUSIONS: After controlling for multiple prognostic factors such as age, ASA score, AMTS, and WAI, warfarin therapy at the time of injury is associated with increased time to surgery, length of stay, and decreased survival. This study highlights the need to view warfarin therapy as a 'red flag' in patients presenting with a fractured neck of the femur. Preoperatively, prompt warfarin reversal together with adequate investigation and optimization of the patient should ensure timely, safe surgery. Early involvement of the anesthesia team should ensure an appropriate level of postoperative care for these patients. LEVEL OF EVIDENCE: Level III, therapeutic study.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s11999-016-5056-

Validity of Scottish predictors of child obesity (age 12) for risk screening in mid-childhood : a secondary analysis of prospective cohort study data—with sensitivity analyses for settings without various routinely collected predictor variables

The authors acknowledge the generosity of the funders of this work, the Children’s Data Collaborative – a consortium of the Scottish Government, Data-Driven Initiative, UNICEF, and the University of Edinburgh. Additional salary support is gratefully acknowledged for LM’s/LD’S/AJW’s contributions to this work, from (respectively): LM -- School of Health Sciences, University of Dundee; LD -- School of Health in Social Science, University of Edinburgh; AJW -- School of Medicine, University of St Andrews.Objective : To analyse the Growing Up in Scotland cohort for predictors of obesity at age 12, present at school entry (age 5-6). Methods : The initial model included literature-based risk factors likely to be routinely collected in high-income countries (HICs), as well as “Adverse/Protective Childhood Experiences (ACEs/PCEs)”. Missing data were handled by Multiple Chained Equations. Variable-reduction was performed using multivariable logistic regression with backwards and forwards stepwise elimination, followed by internal validation by bootstrapping. Optimal sensitivity/specificity cut-offs for the most parsimonious and accurate models in two situations (optimum available data, and routinely available data in Scotland) were examined for their referral burden, and Positive and Negative Predictive Values. Results : Data for 2787 children with full outcome data (obesity prevalence 18.3% at age 12) were used to develop the models. The final “Optimum Data” model included six predictors of obesity: maternal body mass index, indoor smoking, equivalized income quintile, child’s sex, child’s BMI at age 5-6, and ACEs. After internal validation, the area under the receiver operating characteristic curve was 0.855 (95% CI 0.852-0.859). A cut-off based on Youden’s J statistic for the Optimum Data model yielded a specificity of 77.8% and sensitivity of 76.3%. 37.0% of screened children were “Total Screen Positives” (and thus would constitute the “referral burden”.) A “Scottish Data” model, without equivalized income quintile and ACEs as a predictor, and instead using Scottish Index of Multiple Deprivation quintile and “age at introduction of solid-foods,” was slightly less sensitive (76.2%) but slightly more specific (79.2%), leading to a smaller referral burden (30.8%). Conclusion : Universally collected, machine-readable and linkable data at age 5-6 predict reasonably well children who will be obese by age 12. However, the Scottish treatment system is unable to cope with the resultant referral burden and other criteria for screening would have to be met.Publisher PDFPeer reviewe

Size effects in ion-neutral complex-mediated alkane eliminations from ionized aliphatic ethers

AbstractThe effects of the size of the ionic and neutral partners on ion-neutral complex-mediated alkane eliminations from ionized aliphatic ethers were determined by obtaining metastable decomposition spectra and photoionization ionization efficiency curves. Increasing the size of the ionic partner decreases the competitiveness of alkane elimination with alkyl loss. This is attributed to decreasing attraction between the partners with increasing distance between the neutral partner and the center of charge in the associated ion. Increasing the size of the neutral partner lowers the threshold for alkane elimination relative to that for simple dissociation when the first threshold is above ΔHf(products). This is attributed to increasing attraction between the partners with increasing polarizability of the radical in the complex. Adding a CH2 to the radical in a complex seems to increase the attraction between the partners by about 24 kJ mol−1

A Generalized Univariate Change-of-Variable Transformation Technique

We present a generalized version of the univariate change-of-variable technique for transforming continuous random variables. Extending a theorem from Casella and Berger [1990. Statistical Inference, Wadsworth and Brooks/Cole, Inc., Pacific Grove, CA] for many-to-1 transformations, we consider more general univariate transformations. Specifically, the transformation can range from 1-to-1 to many-to-1 on various subsets of the support of the random variable of interest. We also present an implementation of the theorem in a computer algebra system that automates the technique. Some examples demonstrate the theorem\u27s application

Computing the cumulative distribution function of the Kolmogorov–Smirnov statistic

We present an algorithm for computing the cumulative distribution function of the Kolmogorov–Smirnov test statistic Dn in the all-parameters-known case. Birnbaum (1952, J. Amer. Statist. Assoc. 47, 425–441), gives an n-fold integral for the CDF of the test statistic which yields a function defined in a piecewise fashion, where each piece is a polynomial of degree n. Unfortunately, it is difficult to determine the appropriate limits of integration for computing these polynomials. Our algorithm performs the required integrations in a manner that avoids calculating the same integrals repeatedly, resulting in shorter computation time. It can be used to compute the entire CDF or just a portion of the CDF, which is more efficient for finding a critical value or a p-value associated with a hypothesis test. If the entire CDF is computed, it can be stored in memory so that various characteristics of the distribution of the test statistic (e.g., moments) can be calculated. To date, critical tables have been approximated by various techniques including asymptotic approximations, recursive formulas, and Monte Carlo simulation. Our approach yields exact critical values and significance levels. The algorithm has been implemented in a computer algebra system

Appetitive motivation predicts the neural response to facial signals of aggression

The “behavioral approach system” (BAS) (Gray, 1990) has been primarily associated with reward processing and positive affect. However, additional research has demonstrated that the BAS plays a role in aggressive behavior, heightened experience of anger, and increased attention to facial signals of aggression. Using functional magnetic resonance imaging, we show that variation in the BAS trait in healthy participants predicts activation in neural regions implicated in aggression when participants view facial signals of aggression in others. Increased BAS drive (appetitive motivation) was associated with increased amygdala activation and decreased ventral anterior cingulate and ventral striatal activation to facial signals of aggression, relative to sad and neutral expressions. In contrast, increased behavioral inhibition was associated with increased activation in the dorsal anterior cingulate, a region involved in the perception of fear and threat. Our results provide the first demonstration that appetitive motivation constitutes a significant factor governing the function of neural regions implicated in aggression, and have implications for understanding clinical disorders of aggression

Heterolysis of H−X Bonds by Pentamethylcyclopentadienyl−Aminoborole Complexes of Zirconium and Hafnium

The pentamethylcyclopentadienyl−aminoborole chloro complexes Cp*{η^5-C_4H_4BN(CHMe_2)_2}MCl·LiCl (Cp* = (η^5-C_5Me_5); M = Zr, Hf) heterolytically cleave H−X bonds to form Cp*{η^5-C_4H_4BNH(CHMe_2)_2}MCl(X) (X = OR, SR, C⋮CR). Control experiments using deuterium-labeled substrates show heterolysis occurs with no incorporation of deuterium into the 2,5 positions of the borole heterocycle. Cp*{η^5-C_4H_4BNH(CHMe_2)_2}Hf(C⋮CSiMe_3)_2 is prepared from Cp*{η^^5-C_4H_4BN(CHMe_2)_2}Hf(η^3-C_3H_5) and 2 equiv of (trimethylsilyl)acetylene. Treatment of Cp*{η^5-C_4H_4BN(CHMe_2)_2}MCl·LiCl (M = Zr, Hf) with donor ligands L yields the LiCl-free complexes Cp*{η^5-C_4H_4BN(CHMe_2)_2}MCl(L) (M = Zr, L = NMe2H; M = Hf, L = PMe_3). Cp*{η^5-C_4H_4BN(CHMe_2)_2}HfCl(PMe_3) reacts with (trimethylsilyl)acetylene with loss of HN(CHMe_2)_2 to form Cp*{η^5-C_4H_4B(C⋮CSiMe_3)}HfCl(PMe_3), resulting from formal migration of acetylide from hafnium to boron. X-ray structure determinations of Cp*{η^5-C_4H_4BNH(CHMe_2)_2}HfCl(C⋮CSiMe_3), Cp*{η^5-C_4H_4BN(CHMe_2)_2}HfCl(PMe_3), and Cp*{η^5-C_4H_4B(C⋮CSiMe_3)}HfCl(PMe_3) are reported

Unveiling Dust-enshrouded Star Formation in the Early Universe: a Sub-mm Survey of the Hubble Deep Field

The advent of sensitive sub-mm array cameras now allows a proper census of dust-enshrouded massive star-formation in very distant galaxies, previously hidden activity to which even the faintest optical images are insensitive. We present the deepest sub-mm survey of the sky to date, taken with the SCUBA camera on the James Clerk Maxwell Telescope and centred on the Hubble Deep Field. The high source density found in this image implies that the survey is confusion-limited below a flux density of 2 mJy. However, within the central 80 arcsec radius independent analyses yield 5 reproducible sources with S(850um) > 2 mJy which simulations indicate can be ascribed to individual galaxies. We give positions and flux densities for these, and furthermore show using multi-frequency photometric data that the brightest sources in our map lie at redshifts z~3. These results lead to integral source counts which are completely inconsistent with a no-evolution model, and imply that massive star-formation activity continues at redshifts > 2. The combined brightness of the 5 most secure sources in our map is sufficient to account for 30 - 50% of the previously unresolved sub-mm background, and we estimate statistically that the entire background is resolved at about the 0.3 mJy level. Finally we discuss possible optical identifications and redshift estimates for the brightest sources. One source appears to be associated with an extreme starburst galaxy at z~1, whilst the remaining four appear to lie in the redshift range 2 < z < 4. This implies a star-formation density over this redshift range that is at least five times higher than that inferred from the ultraviolet output of HDF galaxies.Comment: 19 pages, 6 figures (to appear as a Nature Article