Comorbid Profile Rather than Age Determines Hip Fracture Mortality in a Nonagenarian Population

Background

In light of poor outcomes with nonoperative management of hip fractures, orthopedic surgeons are faced with difficult decisions about which patients are too ill or too old for surgical treatment.

Questions/Purposes

This study sought to investigate if patients over 90 years had different preoperative laboratory, clinical, and injury characteristics than younger patients with the same injury. We compared our cohort with previously published data. We wished to identify if there were pre-injury risk factors associated with 30-day mortality, which could be modified to enhance postoperative outcomes.

Methods

This is a retrospective review of 198 operatively managed hip fractures in patients 75 years or older. We collected data on demographics, select preoperative laboratory values, injury type, comorbidities, and 30-day mortality.

Results

Eleven (5.6%) of the cohort died within 30 days of surgery, 6.3% in the younger group, and 3.7% in the older group; the difference was not statistically significant. For baseline characteristics, there was no difference between the age groups for pre-injury comorbidities, hemoglobin, serum albumin, BUN, prevalence of UTI, or fracture type. A total of 67 (35.8%) patients had evidence of UTI on admission.

Conclusions

These findings reveal that in our dichotomized cohort, pre-injury characteristics were similar and age alone was not an independent predictor of mortality. These data may inform decision-making for orthopedic surgeons and the medical providers who consult to optimize these patients for surgery. We identified high rates of UTI in both age groups, a potentially remediable factor to optimize outcomes in hip fracture surgery in elderly patients.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-015-9435-y) contains supplementary material, which is available to authorized users.     

Effect of tetanus toxin on the accumulation of the permeant lipophilic cation tetraphenylphosphonium by guinea pig brain synaptosomes

Accumulation of the permeant lipophilic cation [(3)H]tetraphenylphosphonium (TPP(+)) by synaptosome preparations from guinea pig brain cerebral cortex is inhibited 1:10 by medium containing 193 mM K(+) and by veratridine. A further 1:10 to 1:15 decrease in TPP(+) uptake occurs under nitrogen and in the presence of mitochondrial inhibitors such as oligomycin, whereas starvation and succinate supplementation have no effect. These data indicate that, in analogy to intact neurons, there is an electrical potential (DeltaPsi, interior negative) of -60 to -80 mV across the synaptosomal membrane that is due primarily to a K(+) diffusion gradient (K(+) (in)-->K(+) (out)). The data also indicate that mitochondria entrapped within the synaptosome but not free mitochondria make a large contribution to the TPP(+) concentration gradients observed.Conditions are defined in which tetanus toxin binds specifically and immediately to synaptosomes in media used to measure TPP(+) uptake. Under these conditions tetanus toxin induces dose-dependent changes in TPP(+) uptake that are blocked by antitoxin and not mimicked by biologically inactivated toxin preparations. The effect of tetanus toxin on TPP(+) uptake is not evident in the presence of 193 mM K(+) or veratridine but remains under conditions known to abolish the mitochondrial DeltaPsi. Moreover, tetanus toxin has no effect on TPP(+) uptake by isolated synaptosomal mitochondria. The results thus define an in vitro action of tetanus toxin on the synaptosomal membrane that can be correlated with biological potency in vivo and is consistent with the in vivo effects of tetanus toxin on neuronal transmission.     

Stratification of the Impact of Inappropriate Empirical Antimicrobial Therapy for Gram-Negative Bloodstream Infections by Predicted Prognosis

The bloodstream infection mortality risk score (BSIMRS) predicts the outcome of patients with Gram-negative bloodstream infections (BSI) with high discrimination. This retrospective cohort study examined the impact of inappropriate antimicrobial therapy on mortality in adult patients with Gram-negative BSI admitted to Palmetto Health Hospitals in Columbia, SC, USA, from 1 January 2011 to 31 December 2012 after stratification by predicted prognosis at initial presentation using BSIMRS. A multivariate Cox regression model was used to identify independent risk factors for 28-day mortality overall and within each predefined BSIMRS category (<5, 5 to 9, and ≥10). Relative risk reduction (RRR), absolute risk reduction (ARR), and number needed to treat (NNT) were calculated from a predictive logistic regression model of mortality. Overall, 390 unique patients with first episodes of Gram-negative BSI were identified. The median age was 66 years, and 229 (59%) were women. There was significant association between inappropriate antimicrobial therapy and mortality in patients with BSIMRS of 5 to 9 (adjusted hazard ratio [aHR], 3.55; 95% confidence intervals [CI], 1.22 to 8.31; P = 0.02) and BSIMRS of ≥10 (aHR, 4.99; 95% CI, 1.09 to 22.87; P = 0.04) but not in those with BSIMRS of <5 (aHR, 3.34; 95% CI, 0.17 to 22.77; P = 0.34). RRR, ARR, and NNT were 0.25, 0.02, and 63 for BSIMRS of <5; 0.56, 0.32, and 3 for BSIMRS of 5 to 9; and 0.39, 0.39, and 3 for BSIMRS of ≥10, respectively. There is a significant benefit from appropriate antimicrobial therapy in patients with Gram-negative BSI with guarded (BSIMRS of 5 to 9) and poor (BSIMRS of ≥10) predicted prognosis. Survival difference remains unclear among those with good predicted prognosis (BSIMRS of <5) at initial presentation.     

Meta-Analysis to Assess the Quality of International Normalized Ratio Control and Associated Outcomes in Venous Thromboembolism Patients

Introduction

Patients with venous thromboembolism (VTE) frequently require vitamin K antagonists (VKAs) to prevent recurrent events, but their use increases hemorrhage risk. We performed a meta-analysis to assess the quality of international normalized ratio (INR) control, identify study-level predictors of poor control and to examine the relationship between INR control and adverse outcomes in VTE patients.

Materials and Methods

We searched bibliographic databases (1990-June 2013) for studies of VTE patients receiving adjusted-dose VKAs that reported time in range (2.0-3.0) or proportion of INRs in range and/or reported INR measurements coinciding with thromboembolic or hemorrhagic events. Meta-analysis and meta-regression analysis was performed.

Results

Upon meta-analysis, studies found 59% (95%CI: 54-64%) of INRs measured and 61% (95%CI: 59-63%) of the time patients were treated were spent outside the target range of 2.0-3.0; with a tendency for under- versus over-anticoagulation. Moreover, this poor INR control resulted in a greater chance of recurrent VTE (beta-coefficient = -0.46, p = 0.01) and major bleeding (beta-coefficient = -0.30, p = 0.02). Patients with an INR < 2.0 made up 58% (95%CI: 39-77%) of VTE cases, while those with an INR > 3.0 made up 48% (95%CI: 34-61%) of major hemorrhage cases. Upon meta-regression, being VKA-naïve (-14%, p = 0.04) and treated in the community (-7%, p < 0.001) were associated with less time in range, while being treated in Europe/United Kingdom (compared to North America) was associated with (11%, p = 0.003) greater time.

Conclusions

Strategies to improve INR control or alternative anticoagulants, including the newer oral agents, should be widely implemented in VTE patients to reduce the rate of recurrent events and bleeding.     

How to manage IBD in patients with infections or malignancies?

Infections and malignancies are a major issue for clinicians in the management of patients with IBD because of concerns about the safety of drugs currently used in treatment, including immunosuppressive agents, steroids and tumor necrosis factor (TNF) antagonists. Infections are strongly associated with IBD both in their etiopathogenesis and in their clinical course. A number of viral infections, tuberculosis and other therapy-related infections create challenges for the successful management of intestinal disease with immunosuppressive agents or TNF antagonists. Recently published guidelines offer a strong support to deal with these issues. Major concern about IBD patients with malignancies is related to the consequences of chemotherapy on the intestinal disease, the risk of maintaining immunosuppressant or anti-TNF therapy after the diagnosis of malignancy and the management of a clinical relapse of IBD in patients with a recent diagnosis of malignancy. Further research is required to optimize strategies for IBD patients with malignancies. At the moment, all therapeutic choice is made on an individual basis, with an integrative multidisciplinary approach.     

Discovery of Lacosamide Affinity Bait Agents That Exhibit Potent Voltage-Gated Sodium Channel Blocking Properties

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The nature of the phonemic string deficit in conduction aphasia

Abstract

A case of conduction aphasia (CM) is presented to further explore the notion that such aphasics possess a phonological output disorder in constructing phonemic strings. Most studies on this topic have been restricted to the oral production of single words. This study sought to increase understanding of this phonological deficit by examining its interference with orthographic production and its manifestation in running speech. The latter was particularly important, because the diagnosis of a phonemic string deficit in conduction aphasia has been based on a model that was developed to explain segmental errors in normal running speech (cf. Shattuck-Hufnagel 1979). Results indicated that the phonemic string deficit in CM does interfere with orthographic processing, and that while both normal adults and CM exhibit disruption in constructing phonemic strings, the manner of breakdown, as characterized by Shattuck-Hufnagel, is different. The between-word errors of normal speakers typically involve the mislocation of word-initial consonants, an error pattern that has been attributed to a momentary disruption in ordering segments within phonemic strings (Shattuck-Hufnagel 1987). By contrast, the between-word errors of CM typically involved the perseveration of segments within the rhymes of syllables (or words). The distribution of these segmental errors is attributed to difficulty in clearing a phonemic output buffer.     

Genetic counseling for men with recurrent pregnancy loss or recurrent implantation failure due to abnormal sperm chromosomal aneuploidy

Purpose

The purpose of this study is to review recurrent pregnancy loss (RPL) due to sperm chromosomal abnormalities and discuss the genetic counseling that is required for men with sperm chromosomal abnormalities.

Method

The literature was reviewed, and a genetic counselor lends her expertise as to how couples with RPL and sperm chromosomal abnormalities ought to be counseled. The review of the literature was performed using MEDLINE.

Results

Sperm fluorescence in situ hybridization (FISH) can be used to determine if disomy or unbalanced chromosomal translocations are present. In men with aneuploidy in sperm or who carry a chromosomal translocation, pre-implantation genetic screening (PGS) combined with in vitro fertilization (IVF) and intra-cytoplasmic sperm injection (ICSI) can increase chances of live birth. In men with abnormal sperm FISH results, the degree of increased risk of abnormal pregnancy remains unclear. Genetic counselors can provide information to couples about the risk for potential trisomies and sex chromosome aneuploidies and discuss their reproductive and testing options such as PGS, use of donor sperm, and adoption. The provision of genetic counseling also allows a couple to be educated about recommended prenatal testing since pregnancies conceived with a partner who has had abnormal sperm FISH are considered to be at increased risk for aneuploidy.

Conclusion

We review the literature and discuss genetic counseling for couples with RPL or recurrent implantation failure due to increased sperm aneuploidy.