Understanding the relationship between type 2 diabetes and depression: lessons from genetically informative study designs.

AIMS: To conduct a systematic review in order to comprehensively synthesize the findings from a diverse range of genetically informative studies on comorbid depression and type 2 diabetes. METHODS: Database searches (1 January 2008 to 1 June 2020) in PubMed and EMBASE were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Eligible reports employed any type of genetically informed design, including twin modelling, Mendelian randomization, genome-wide association studies, polygenetic risk scores, or linkage disequilibrium score regression. Searches generated 451 unique citations, and 16 manuscripts met the inclusion criteria. RESULTS: The included studies addressed three aetiological models of the depression-diabetes relationship: uni- or bi-directional phenotypic causation; shared genetic liability; or gene-environment interaction. From these studies, there is modest evidence that type 2 diabetes is causally related to risk of developing depression, but much more limited evidence that depression is causally related to risk of diabetes. There is little evidence of shared genetic liability between depression and diabetes or of gene-environment interaction. CONCLUSIONS: Findings from genetically informed studies are mixed but provide some support for the uni- or bi-directional phenotypic model of depression and type 2 diabetes. Future studies should also explore the hypothesis that this relationship may be influenced by shared environmental risk factors. Findings can inform multifaceted approaches to diabetes prevention and care that reflect how psychosocial factors contribute to type 2 diabetes risk and outcomes.

Development of a core outcome domain set for clinical research on capillary malformations (the COSCAM project).

BACKGROUND: Due to a large variety in treatment outcomes reported in therapeutic trials and lacking patient-relevant outcomes, it is hard to adequately compare and improve current therapies for patients with capillary malformations (CMs). The Core Outcome Set for Capillary Malformations (COSCAM) project aims to develop a core outcome set (COS) for use in future CM trials, in which we will first develop a core outcome (sub)domain set (CDS). Here, we describe the methods for the development of a CDS and present the results of the first development stage. METHODS: The COSCAM project is carried out according to the recommendations of the Cochrane Skin Core OUtcomes Set INitiative (CS-COUSIN) and the Core Outcome Measures in Effectiveness Trials (COMET) initiative. During the first stage, we identified all potentially relevant outcome subdomains based on a systematic review, two focus group sessions and input from patient representatives of Dutch patient organizations and the COSCAM-founding group. In stage two, we will present the subdomains in a three-round e-Delphi study and online consensus meeting, in which CM patients, parents/caregivers and CM experts worldwide rate the importance of the proposed subdomains, hereby finalizing the core outcome (sub)domains of the CDS. RESULTS: A total of 67 potential outcome subdomains were included; sixteen were previously used in the literature, 20 were proposed by Dutch patients and their parents/caregivers (n = 13) in focus group sessions and 38 were suggested by the experts of the COSCAM-founding group. Seven were excluded because of overlap. CONCLUSION: The final CDS may serve as a minimum standard in future CM trials, thereby facilitating adequate comparison of treatment outcomes. After this CDS development, we will select appropriate outcome measurement instruments to measure the core outcome subdomains.

The Association of Airflow Obstruction with Occupational Exposures in a Sample of Rural Adults in Iowa.

A recent article reported that occupational exposure to vapor-gas, dust, and fumes (VGDF) was more common in a sample of rural adults than in a sample of adults in urban settings. In another study of the same urban adults, airflow obstruction (AO) was associated with occupational VGDF and the combination of smoking and occupational exposure. The goal of the current study was to determine if similar associations were evident in the sample of rural adults. We analyzed enrollment data from the Keokuk County Rural Health Study (KCRHS), which investigated the health of rural residents in Iowa. We used the same methods as the study of urban adults. A job-exposure matrix (JEM) assigned an occupational VGDF exposure level based on each participants' last reported job. The health outcome was AO, defined as both the forced expiratory volume in one second (FEV1) and the FEV1/forced vital capacity (FVC) ratio < lower limit of normal. Of the 1699 KCRHS participants, 436 (25.7%) had high total VGDF occupational exposure, 661 (38.9%) had ever smoked cigarettes, and 110 (6.5%) had AO. The crude frequency of AO increased across the joint categories of smoking (never, ever) and high exposure (no, yes) (p < 0.05 for linear trend). After adjusting for potential confounders, AO was associated with high total occupational VGDF exposure only among smokers (OR = 1.81, 95% CI 1.002 to 3.26). In conclusion, the association of AO with occupational exposure in the current study of rural adults was similar to what was previously observed among urban adults.

Effectiveness of antibacterial prophylaxis during induction chemotherapy in children with acute lymphoblastic leukemia.

BACKGROUND: Pediatric patients receiving induction chemotherapy for newly diagnosed acute lymphoblastic leukemia (ALL) are at high risk of developing life-threatening infections. We investigated whether uniform antibacterial guidelines, including mandatory antibacterial prophylaxis in afebrile patients during induction, decreases the incidence of microbiologically documented bacteremia. METHODS: Between 2012 and 2015, 230 patients with newly diagnosed ALL (aged 1-21) were enrolled on Dana-Farber Cancer Institute ALL Consortium Protocol 11-001 (DFCI 11-001). Induction therapy, regardless of risk group, included vincristine, prednisone, doxorubicin, methotrexate, and PEG-asparaginase. Afebrile patients received fluoroquinolone prophylaxis at the initiation of induction and those presenting with fever received broad-spectrum antibiotics; antibiotics were continued until blood count recovery. Rates of documented bacteremias and fungal infections on DFCI 11-001 were compared to those on the predecessor protocol (DFCI 05-001), which included the same induction phase without antibiotic prophylaxis guidelines. RESULTS: Sixty-six (28.7%) patients received fluoroquinolone prophylaxis, the remaining patients received broad-spectrum antibiotics. Twenty-four (36.4%) patients on prophylaxis developed fever and seven (10.6%) developed bacteremia. The overall rate of infection during induction on DFCI 11-001 was lower than on DFCl 05-001 (14.3% vs. 26.3%, P < 0.0001) due to a decreased rate of bacteremia (10.9% vs. 24.4%, P < 0.0001). The rate of fungal infections (4.8% vs. 3.6%) and induction death (0.9% vs. 2%) was not significantly different. CONCLUSION: For children with newly diagnosed ALL, uniform antibiotic administration until blood count recovery, including fluoroquinolone prophylaxis for afebrile patients, reduced the incidence of bacteremia during the induction phase. Larger, randomized studies should be performed to confirm these findings.

Efficacy and safety of fulranumab as monotherapy in patients with moderate to severe, chronic knee pain of primary osteoarthritis: a randomised, placebo- and active-controlled trial.

AIMS: The efficacy and safety of monotherapy with fulranumab, a monoclonal antibody that neutralises human nerve growth factor (NGF), was evaluated compared with placebo and an active comparator, controlled-release (CR) oxycodone, in patients with moderate to severe chronic knee pain of primary osteoarthritis (OA). METHODS: In this phase-2, double-blind (DB), double-dummy, placebo- and active-controlled study, patients (40-80 years) were randomised (1:1:1:1) to placebo, fulranumab 3 or 9mg every 4 weeks (Q4 wk), or oxycodone CR twice-daily. Primary efficacy end-point: responder rates based on percent improvement in average osteoarthritis-related pain intensity (OAPI) scores from baseline to week-12 or when Food and Drug Administration (FDA) put a clinical hold on all anti-NGF trials, whichever was earlier. Secondary efficacy end-points: average OAPI score (week-16), Western Ontario and McMaster Osteoarthritis Index Global Score and subscales (pain, physical function, stiffness), and Patient Global Assessment. RESULTS: As of an FDA clinical hold on all anti-NGF trials, only 196/300 patients were randomised and 33% (65/196) had completed 12 weeks of the 16-week DB phase. Responders were patients who did not withdraw and whose pain improved. Responder rates were not significantly different between fulranumab treatment groups (3mgQ4wk: 71%, p = 0.739; 9mgQ4wk: 80%, p = 0.843) and placebo (77%), whereas, oxycodone CR (56%) had significantly lower responder rates in comparison to both fulranumab (3mgQ4wk: p = 0.008; 9mgQ4wk: p = 0.012) and placebo (p = 0.0021). Secondary efficacy results were consistent with primary. None of the joint replacements (four in three patients) were adjudicated as rapidly progressing OA/osteonecrosis. CONCLUSION: Low sample size because of early termination make interpretation of this study difficult, but fulranumab monotherapy resulted in significantly better pain relief and function compared with oxycodone CR (but not against placebo) and was generally well-tolerated. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01094262.

A comparison of microvascular responses to visible and near-infrared lasers.

BACKGROUND AND OBJECTIVE: Pulsed dye laser (PDL) is a commonly used treatment for Port Wine Stain birthmarks (PWS). However, deeper components of PWS are often resistant to PDL. Deeper penetrating lasers, including the long pulsed Neodymium:Yttrium Aluminum Garnet (Nd:YAG) laser have been used, but carry greater risk. This study evaluates the distinct blood vessel thermal responses to visible (595 nm) and near infrared (1,064 nm) lasers using animal and numerical models. STUDY DESIGN/MATERIALS AND METHODS: Blood vessels in the rodent dorsal skin chamber (DSC) were irradiated by a 595 nm PDL and a long-pulsed 1,064 nm Nd:YAG laser. Laser-induced immediate and 1-hour post-structural and functional changes in the vessels were documented. Numerical simulations were conducted using a 1,000 µm depth SD mouse skin fold to simulate experimental conditions. RESULTS: PDL irradiation produced immediate blood vessel hemorrhage. Modeling indicated this occurs due to preferential heating of the superior parts of large blood vessels. Nd:YAG irradiation resulted in blood vessel constriction; modeling indicated more uniform heating of vessel walls. CONCLUSION: PDL and Nd:YAG lasers result in distinct tissue responses. This supports different observable clinical treatment end points when using these devices. Vessel constriction associated with the Nd:YAG may be more difficult to observe and is one reason this device may carry greater risk.

A light emitting diode (LED) based spatial frequency domain imaging system for optimization of photodynamic therapy of nonmelanoma skin cancer: quantitative reflectance imaging.

BACKGROUND: Photodynamic therapy (PDT) offers the potential for enhanced treatment of nonmelanoma skin cancer (NMSC) with minimal scarring. Yet, PDT has not achieved consistent long term effectiveness to gain widespread clinical acceptance for treatment of skin cancer. Therapeutic response varies between practitioners, patients and lesions. One important contributing factor is the absence of quantitative tools to perform in vivo dosimetry. To this end, we have developed a new quantitative imaging device that can be used to investigate parameters related to optimizing dosimetry. METHODS: We present a spatial frequency domain imaging (SFDI) based device designed to: (1) determine the optical properties at the therapeutic wavelength, which can inform variations in light penetration depth and (2) measure the spatially resolved oxygen saturation of the skin cancer lesions and surrounding tissue. We have applied this system to a preliminary clinical study of nine skin cancer lesions. RESULTS: Optical properties vary greatly both spatially [101%, 48% for absorption and reduced scattering, respectively] and across patients [102%, 57%]. Blood volume maps determined using visible wavelengths (460, 525, and 630 nm) represent tissue volumes within ∼1 mm in tissue (1.17 ± 0.3 mm). Here the average total hemoglobin concentration is approximately three times greater in the lesion than that detected in normal tissue, reflecting increased vasculature typically associated with tumors. Data acquired at near infrared wavelengths (730 and 850 nm) reports tissue blood concentrations and oxygenations from the underlying dermal microvasculature (volumes reaching 4.36 ± 1.32 mm into tissue). CONCLUSIONS: SFDI can be used to quantitatively characterize in vivo tissue optical properties that could be useful for better informing PDT treatment parameters. Specifically, this information provides spatially resolved insight into light delivery into tissue and local tissue oxygenation, thereby providing more quantitative and controlled dosimetry specific to the lesion. Ultimately, by optimizing the execution of PDT, this instrument has the potential to positively improve treatment outcomes.

A two-temperature model for selective photothermolysis laser treatment of port wine stains.

Selective photothermolysis is the basic principle for laser treatment of vascular malformations such as port wine stain birthmarks (PWS). During cutaneous laser surgery, blood inside blood vessels is heated due to selective absorption of laser energy, while the surrounding normal tissue is spared. As a result, the blood and the surrounding tissue experience a local thermodynamic non-equilibrium condition. Traditionally, the PWS laser treatment process was simulated by a discrete-blood-vessel model that simplifies blood vessels into parallel cylinders buried in a multi-layer skin model. In this paper, PWS skin is treated as a porous medium made of tissue matrix and blood in the dermis. A two-temperature model is constructed following the local thermal non-equilibrium theory of porous media. Both transient and steady heat conduction problems are solved in a unit cell for the interfacial heat transfer between blood vessels and the surrounding tissue to close the present two-temperature model. The present two-temperature model is validated by good agreement with those from the discrete-blood-vessel model. The characteristics of the present two-temperature model are further illustrated through a comparison with the previously-used homogenous model, in which a local thermodynamic equilibrium assumption between the blood and the surrounding tissue is employed.

Title: Obesogenic microbial signatures and the development of obesity in childhood acute lymphoblastic leukemia.

Childhood acute lymphoblastic leukemia (ALL) is the most common childhood cancer with survival exceeding 90% for standard-risk groups. A debilitating side-effect of treatment is the development of overweight/obesity (OW/OB), which develops in approximately 40% of children by the end of treatment. The microbiome has been associated with the development of OW/OB. We examined fluctuations in the microbiome with the development of OW/OB during the first six months of treatment at diagnosis, and two subsequent timepoints (N = 62). Shotgun metagenomic sequencing was performed on Illumina Nextseq system, and taxa and functional pathways were extracted from sequences using kraken2 and humann2, respectively. An association of increased presence of several species (e.g., Klebsiella pneumoniae, Escherichia coli) was observed in children with OW/OB, while lean-promoting species (Veillonella, Haemophilus, and Akkermansia) were increased in children who maintained a normal weight. Pathway analysis revealed purine nucleotide biosynthesis, sugar nucleotide biosynthesis, and enzyme cofactor biosynthesis were positively correlated with Bacteroides spp. among children with OW/OB. We identified several taxa and functional pathways that may confer increased risk for the development of OW/OB. The associations observed in this pilot are preliminary and warrant further research in the microbiome and the development of OW/OB in childhood ALL.

Noninvasive clinical assessment of port-wine stain birthmarks using current and future optical imaging technology: a review.

Port-wine stain (PWS) birthmarks are one class of benign congenital vascular malformation. Laser therapy is the most successful treatment modality of PWS. Unfortunately, this approach has limited efficacy, with only 10% of patients experiencing complete blanching of the PWS. To address this problem, several research groups have developed technologies and methods designed to study treatment outcome and improve treatment efficacy. This article reviews seven optical imaging techniques currently in use or under development to assess treatment efficacy, focusing on: reflectance spectrophotometers/tristimulus colorimeters; laser Doppler flowmetry and laser Doppler imaging; cross-polarized diffuse reflectance colour imaging system; reflectance confocal microscopy; optical coherence tomography; spatial frequency domain imaging; and laser speckle imaging.

Topical Yunnan Baiyao administration as an adjunctive therapy for bleeding complications in adolescents with advanced cancer.

PURPOSE: Yunnan Baiyao (White Medicine from Yunnan, YNB) is a Chinese herbal medicinal powder used to stop bleeding and improve circulation in traumatic injuries. We describe the use of YNB in adolescents with cancer as an adjunct to uncontrolled bleeding in the palliative care setting. METHODS: Through a retrospective chart review of all patients receiving integrative medicine consultations at the Integrative Therapies Program at Columbia University from January 1, 2007 to January 31, 2012, we describe the outcome of patients treated with YNB for management of uncontrolled bleeding. RESULTS: Four patients were identified who received topical YNB for uncontrolled bleeding; patients included two males and two females with diagnoses of solid tumors (n = 3) and Burkitt's lymphoma (n = 1). Mean age was 15.5 years (range 15-17). Fifty percent had life-threatening bleeding from the tumor site and 50 % experienced uncontrollable epistaxis. All patients received preceding therapy with packed red blood cells and platelet transfusions, topical thrombin, and oral aminocaproic acid. Two patients used YNB in the inpatient setting, and all four patients used YNB as outpatients. In all patients, bleeding control improved with the addition of YNB to conventional hemostatic interventions. Two patients using YNB in their home reported control of bleeding episodes. There were no adverse events reported. CONCLUSIONS: YNB may be an efficacious agent for uncontrolled bleeding in conjunction with conventional hemostatic agents in adolescents with advanced cancer. It is well accepted by patients. YNB may be especially valuable in the outpatient setting to prevent the recurrence of hemorrhage.

Clinicopathological Features of Cardiac Glycolipid Storage Disease in an Adult Pug.

A 12-year-old neutered male pug suffered cardiac arrest and died under general anaesthesia during diagnostic imaging for evaluation of exercise intolerance and respiratory crisis. Histopathological evaluation revealed two types of storage material, glycolipid and lipopigment, having differential distributions in multiple organs. The heart was most strikingly affected and other less affected tissues included the liver, brain, kidneys and skin. Cardiomyocytes were swollen with extensive sarcoplasmic vacuolation together with coalescing areas of myocardial fibrosis. Transmission electron microscopy revealed irregular myelin-like structures and complex concentric lamellar bodies dominating the sarcoplasm and displacing myofibrils. These findings were consistent with a lysosomal storage disease (LSD) as the cause of cardiac disease and death. The unique clinical presentation, histomorphology and ultrastructural features of the material suggested a glycolipid storage disease most closely resembling Anderson-Fabry (Fabry) disease in man. Fabry disease is a LSD that can present in later life and is characterized by loss of α-galactosidase A function and, often, accumulation of glycosphingolipids in tissues including the heart, kidneys, vascular endothelium and smooth muscle.

The neurobiology of aging.

Basic principles of the neurobiology of aging were reviewed within selected topic areas chosen for their potential relevance to epileptogenesis in the aging brain. The availability of National Institute on Aging-supported aged mouse and rat strains and other biological resources for studies of aging and age-associated diseases was presented, and general principles of animal use in gerontological research were discussed. Neurobiological changes during normal brain aging were compared and contrasted with neuropathological events of Alzheimer's disease (AD) and age-associated memory impairment (AAMI). Major themes addressed were the loss of synaptic connections as vulnerable neurons die and circuits deteriorate in AD, the absence of significant neuron loss but potential synaptic alteration in the same circuits in AAMI, and the effects of decreased estrogen on normal aging. The "calcium hypothesis of brain aging" was examined by a review of calcium dyshomeostasis and synaptic communication in aged hippocampus, with particular emphasis on the role of L-type voltage-gated calcium channels during normal aging. Established and potential mechanisms of hippocampal plasticity during aging were discussed, including long-term potentiation, changes in functional connectivity, and increased gap junctions, the latter possibly being related to enhanced network excitability. Lastly, application of microarray gene chip technology to aging brain studies was presented and use of the hippocampal "zipper slice" preparation to study aged neurons was described.

Common and variant gene fusions predict distinct clinical phenotypes in rhabdomyosarcoma.

PURPOSE: We evaluated the clinical features of the common PAX3-FKHR and variant PAX7-FKHR gene fusions observed in rhabdomyosarcoma. PATIENTS AND METHODS: Reverse-transcriptase polymerase chain reaction (RT-PCR) assays were used to detect the gene fusions in 34 cases of rhabdomyosarcoma. Clinical data were obtained retrospectively and compared with the molecular results. RESULTS: The PAX3-FKHR and PAX7-FKHR gene fusions were present in tumors from 18 and 16 patients, respectively. The group with a PAX7-FKHR fusion was younger (P = .01) and presented more often with an extremity lesion (82% v 22%; P = .001). PAX7-FKHR tumors were more often localized than PAX3-FKHR tumors (P = .03). In patients with metastatic disease at diagnosis, the patterns were different: PAX7-FKHR patients had metastatic disease that involved only bone (n = 2) and distant nodes (n = 2), while the PAX3-FKHR group had multiple sites involved, including bone (n = 7), marrow (n = 7), lungs (n = 3), distant nodes (n = 2), skin (n = 1), and brain (n = 1). No significant difference in relapse rate was observed. A trend toward improved overall survival in the PAX7-FKHR group was noted (P = .09). Event-free survival for this PAX7-FKHR group was significantly longer (P = .04). CONCLUSION: Our results suggest that the common PAX3-FKHR and the variant PAX7-FKHR fusions are associated with distinct clinical phenotypes. Identification of fusion gene status may be a useful diagnostic tool in rhabdomyosarcoma.

Multivessel coronary angioplasty early after acute myocardial infarction.

Coronary angioplasty has been applied in patients with recent myocardial infarction, but results of angioplasty of multiple vessels early after myocardial infarction in patients with severe multivessel disease have not been reported. Coronary angioplasty of multiple vessels was performed in 105 patients 0 to 15 days (mean 5 +/- 4) after recent myocardial infarction. There were 77 men (73%) and 28 women (27%), with a mean age of 57 years. All patients had severe multivessel disease, 68% with two vessel and 32% with three vessel disease. Twenty-eight patients (27%) had successful thrombolysis before angioplasty and 70 (67%) had postinfarction angina. Mean left ventricular ejection fraction was 58 +/- 10% and was less than 45% in 13 patients (12%). Angioplasty was attempted in 319 lesions (mean 3 lesions per patient, range 2 to 9) and 252 vessels (mean 2.4 vessels per patient, range 2 to 4), with success in 302 lesions (95%) and 237 vessels (94%); angioplasty was done in two stages in 59 patients (56%). Clinical success was achieved in 102 patients (97%). Complications included myocardial infarction in six patients (5.7%) (one Q wave, five non-Q wave), urgent bypass surgery in two (1.9%) and death in one (0.9%); overall, seven patients (7%) had a major complication. All patients had a follow-up duration greater than 1 year (mean 31 months, range 12 to 73). Clinical recurrence developed in 24 patients (23%), of whom 21 had repeat angioplasty, 1 had bypass surgery and 2 were managed medically. Ten patients (9.8%) had a late infarction and 5 (4.9%) died of cardiac death during the follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS)

Triple vessel coronary angioplasty: acute outcome and long-term results.

Triple vessel coronary angioplasty, defined as angioplasty of one or more lesions in each of the three major coronary arteries (left anterior descending, left circumflex, right coronary artery) was performed in 50 (11%) of 469 patients who had angioplasty of multiple vessels. There were 32 men and 18 women with a mean age of 56 years. All 50 patients had severe three vessel coronary disease and represent approximately 5% of patients with three vessel disease who had revascularization in this institution; 8 (16%) had previous coronary bypass surgery, and 23 (46%) had previous myocardial infarction. Unstable angina was present in 33 patients (66%) and 96% had Canadian Heart Association class III or IV angina; mean left ventricular ejection fraction was 57 +/- 11%. Angioplasty was performed in 176 vessels (3.5 vessels per patient, range 3 to 6) and in 250 lesions (5 lesions per patient, range 3 to 9); angiographic success was achieved in 240 lesions (96%) and 166 vessels (94%). Success in all vessels attempted was achieved in 40 (80%) of the 50 patients. Clinical success (angiographic success associated with clinical improvement) was obtained in all 50 patients in whom triple vessel angioplasty was performed; none of them required urgent bypass surgery and 5 patients (10%) had a non-Q wave myocardial infarction. In four other patients triple vessel angioplasty was planned but not performed because of failure to dilate the primary vessel; urgent bypass surgery was required in one of these, who developed a Q wave infarction. Thus, overall clinical success in 54 patients was 93%; the incidence rate of myocardial infarction was 11%, and that of urgent surgery 1.8%.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for beta corticomuscular coherence during human standing balance: Effects of stance width, vision, and support surface.

The role of the cerebral cortex in maintaining human standing balance remains unclear. Beta corticomuscular coherence (CMC) provides a measure of communication between the sensory-motor cortex and muscle, but past literature has not demonstrated significant beta CMC during human stance. This study evaluated the effects of stance width, vision, and surface compliance on beta CMC during human stance using methods to enhance sensitivity to CMC. Ten healthy, young adults stood for three 60-s trials in each of a wide or narrow stance width while on a firm surface and in narrow stance on a foam surface, each with eyes open or closed. Beta CMC was calculated between contralateral electroencephalographic and electromyographic recordings. Electromyography was recorded from bilateral tibialis anterior and gastrocnemius lateralis muscles. CMC magnitude was defined as the average integrated area of coherence spectrum above a significance threshold. Measures of center-of-pressure (COP) sway were derived from force plates under the subjects' feet. Results of CMC from four muscles across six stance conditions (a total of 24 combinations) demonstrated significant average CMC magnitude from every subject in 20 combinations and significant average CMC magnitude in nine of 10 subjects in the remaining four combinations. The CMC magnitude was significantly larger in the wide-stance condition than in the narrow-stance condition with eyes open. No significant differences were detected when comparing eyes-open to eyes-closed conditions or when comparing firm- to foam-surface conditions. Correlations between CMC magnitude and COP sway elicited some significant relationships, but there was no consistent direction or pattern of correlation based on muscle or stance condition. Results demonstrate that significant beta CMC is evident during human standing balance, and that beta CMC is responsive to changes in mechanical, but not visual or surface, conditions.

Safety of venous thromboembolism prophylaxis with fondaparinux in ischemic stroke.

INTRODUCTION: Unfractionated heparin (UFH), low molecular weight heparin or fondaparinux are recommended for venous thromboembolism (VTE) prophylaxis in acutely ill medical patients. There are limited data on the safety of fondaparinux for VTE prophylaxis in ischemic stroke. We examined adverse event frequency in hospitalized patients with ischemic stroke who received VTE prophylaxis with fondaparinux versus UFH. MATERIALS AND METHODS: We performed a propensity score matched analysis on a retrospective cohort of 644 consecutive patients with acute ischemic stroke receiving fondaparinux (n=322) or UFH (n=322) for VTE prophylaxis. Patients who received intravenous tPA and continuous intravenous infusions of UFH were excluded. The primary outcome was major hemorrhage (intracranial or extracranial) and the secondary outcome was total hemorrhage (major and minor hemorrhage) during hospitalization. We also examined the rate of symptomatic VTE. RESULTS: Mean age of the matched cohort was 71.3±14.1 years, median NIHSS score was 4 (IQR 1-11), median duration of anticoagulant exposure was 5 (IQR 3-8) days, and 98.1% received antiplatelet medications. In the matched cohort, there were less observed major hemorrhages in the fondaparinux group 1.2% (4/322) compared to UFH 3.7% (12/322), but this difference was not significant (OR=0.33, 95% CI 0.08-1.10, p=0.08). There were also no significant differences in total hemorrhage (p=0.15), intracranial hemorrhage (p=0.48), major extracranial hemorrhage (p=0.18) and symptomatic VTE (p=1.00) between the groups. CONCLUSIONS: Fondaparinux is not associated with increased hemorrhagic complications compared with UFH in patients with ischemic stroke. There were low rates of symptomatic VTE in both groups.