Prospective monitoring of adverse events following vaccination with Modified vaccinia Ankara - Bavarian Nordic (MVA-BN) administered to a Canadian population at risk of Mpox: A Canadian Immunization Research Network study.

MVA-BN is an orthopoxvirus vaccine that provides protection against both smallpox and mpox. In June 2022, Canada launched a publicly-funded vaccination campaign to offer MVA-BN to at-risk populations including men who have sex with men (MSM) and sex workers. The safety of MVA-BN has not been assessed in this context. To address this, the Canadian National Vaccine Safety Network (CANVAS) conducted prospective safety surveillance during public health vaccination campaigns in Toronto, Ontario and in Vancouver, British Columbia. Vaccinated participants received a survey 7 and 30 days after each MVA-BN dose to elicit adverse health events. Unvaccinated individuals from a concurrent vaccine safety project evaluating COVID-19 vaccine safety were used as controls. Vaccinated and unvaccinated participants that reported a medically attended visit on their 7-day survey were interviewed. Vaccinated participants and unvaccinated controls were matched 1:1 based on age group, gender, sex and provincial study site. Overall, 1,173 vaccinated participants completed a 7-day survey, of whom 75 % (n = 878) also completed a 30-day survey. Mild to moderate injection site pain was reported by 60 % of vaccinated participants. Among vaccinated participants 8.4 % were HIV positive and when compared to HIV negative vaccinated individuals, local injection sites were less frequent in those with HIV (48 % vs 61 %, p = 0.021), but health events preventing work/school or requiring medical assessment were more frequent (7.1 % vs 3.1 %, p = 0.040). Health events interfering with work/school, or requiring medical assessment were less common in the vaccinated group than controls (3.3 % vs. 7.1 %, p < 0.010). No participants were hospitalized within 7 or 30 days of vaccination. No cases of severe neurological disease, skin disease, or myocarditis were identified. Our results demonstrate that the MVA-BN vaccine appears safe when used for mpox prevention, with a low frequency of severe adverse events and no hospitalizations observed.

Novice lifters exhibit a more kyphotic lifting posture than experienced lifters in straight-leg lifting.

As torso flexion and repetitive lifting are known risk factors for low back pain and injury, it is important to investigate lifting techniques that might reduce injury during repetitive lifting. By normalizing lumbar posture to a subject's range of motion (ROM), as a function of torso flexion, this research examined when subjects approached their range of motion limits during dynamic lifting tasks. For this study, it was hypothesized that experienced lifters would maintain a more neutral lumbar angle relative to their range of motion, while novice lifters would approach the limits of their lumbar ROM during the extension phase of a straight-leg lift. The results show a statistically significant difference in lifting patterns for these two groups supporting this hypothesis. The novice group maintained a much more kyphotic lumbar angle for both the flexion (74% of the lumbar angle ROM) and extension phases (86% of the lumbar angle ROM) of the lifting cycle, while the experienced group retained a more neutral curvature throughout the entire lifting cycle (37% of lumbar angle ROM in flexion and 48% of lumbar angle ROM in extension). By approaching the limits of their range of motion, the novice lifters could be at greater risk of injury by placing greater loads on the supporting soft tissues of the spine. Future research should examine whether training subjects to assume more neutral postures during lifting could indeed lower injury risks.

A systematic review of tetanus in individuals with previous tetanus toxoid immunization.

OBJECTIVES: To assess the characteristics of tetanus in previously immunized individuals. METHODS: A systematic literature search was undertaken using Ovid MEDLINE(R) and EMBASE databases for articles published between 1946 and September 3, 2013. The search strategy was developed using MESH terms for "tetanus", "immunization" and "vaccination". Inclusion criteria were articles in English or French that described at least one case of tetanus, immunization history and/or the results of anti-tetanus antibodies. Articles were reviewed for relevant references. RESULTS: 51 unique articles published from1946-2013 were included in the review. The articles described 359 cases of clinical tetanus in individuals with prior receipt of one or more doses of tetanus toxoid vaccine and/or levels of tetanus antibody titres generally considered protective. Of the 210 cases that reported patient status at discharge, 180 (85.7%) survived with only three cases reporting residual deficits. CONCLUSION: Tetanus spores are ubiquitous and this report clearly documents that tetanus cases can occur in individuals previously immunized with tetanus toxoid vaccine. Clinicians should not rule out tetanus when clinical symptoms suggest it, regardless of the vaccination history. When treated, the prognosis for tetanus is good. Further research is needed to assess the incidence of tetanus in partially- and fully-immunized populations and determine whether this is due to waning immunity of vaccine failure.

Stromal fibroblast-bone marrow-derived cell interactions: implications for myofibroblast development in the cornea.

The purpose of this study was to test the hypothesis that mouse corneal stromal fibroblast and bone marrow-derived cell interactions augment corneal myofibroblast generation and, if so, to study whether such interactions are mediated by paracrine or juxtacrine mechanisms. Mouse bone marrow-derived cells and mouse corneal stromal fibroblasts were obtained from both mice with green fluorescent protein (GFP) expressed in all cells and normal GFP- BL6 control mice. To study the interactions of the different cell types, GFP+ cells of one type were co-cultured with GFP- cells of the other type in Primaria plates (to monitor juxtacrine signaling) or Transwell System plates (to monitor paracrine effects mediated by soluble mediators). Both cell types were cultured at a cell density of 1 × 10(5) cells per ml. The percentage of alpha smooth muscle actin+ myofibroblasts was significantly higher (ANOVA, p<0.001) when bone marrow-derived cells and mouse corneal stromal fibroblasts were co-cultured compared to when bone marrow-derived cells and mouse corneal stromal fibroblasts were cultured alone (control). The in vitro studies using GFP+ corneal fibroblasts or GFP+ bone marrow-derived cells demonstrated conclusively that both cells types could transform into myofibroblasts. However, the percentage of alpha smooth muscle actinassds+ myofibroblasts generated from either cell type precursor was higher when both cells were co-cultured together (juxtacrine) as compared to when bone marrow-derived cells and mouse corneal stromal fibroblasts were co-culture in different compartments of Transwell System (paracrine). Thus, more alpha smooth muscle actin+ GFP+ myofibroblasts were generated from GFP+ corneal stromal fibroblasts when GFP- bone marrow-derived cells were present and more alpha smooth muscle actin+ GFP+ myofibroblasts were generated from GFP+ bone marrow-derived cells when GFP- corneal stromal fibroblasts were present. Polyclonal anti-human latency associated peptide (LAP) (transforming growth factor-ß1) neutralizing antibody (a-LAP) and/or transforming growth factor-ß type I receptor kinase inhibitor (LY-364947) inhibited the generation of alpha smooth muscle actin+ myofibroblasts from either precursor cell in Transwell System co-culture experiments. These data suggest that TGFß is a paracrine modulator that regulates the generation of myofibroblasts from either corneal fibroblasts or bone marrow-derived cell precursors.

Interleukin-1 receptor role in the viability of corneal myofibroblasts.

The purpose of this study was to investigate the role of interleukin-1 (IL-1) in modulating myofibroblast viability in mouse corneas with stromal opacity. Twenty-four female B6; 129S1-Il1r1tm1Roml/J homozygous IL-1RI knockout mice and 24 control B6129SF2/J mice were included in this study. Each mouse had opacity-generating irregular phototherapeutic keratectomy (PTK) performed with an excimer laser in one eye. Groups of 8 mice from each group were euthanized at one month, three months and six months after surgery and the eyes cryo-preserved. The contralateral eye served as unwounded control. Immunohistochemistry was performed for α-smooth muscle actin (SMA) in central sections of all corneas. The TUNEL assay for apoptosis was performed on 8 sections of four eyes from each group. No SMA+ cells were detected in the stroma of unwounded control or knockout corneas. SMA+ myofibroblast density was significantly higher (p < 0.001) in the IL-1RI knockout group than in the control group at one month, three and six months after irregular PTK. Mean TUNEL+ stromal cells in the anterior 50 µm of stroma was significantly lower in the IL-1RI knockout group compared to the control group at six months after irregular PTK (p = 0.04). These results corroborate the findings of recent in vitro work that demonstrated an antagonistic effect of TGFß and IL-1 on myofibroblast viability, and found that IL-1-triggered myofibroblast apoptosis was suppressed by TGFß. Thus, IL-1 is an important modulator of myofibroblast viability during corneal wound healing.

Effect of TGFß and PDGF-B blockade on corneal myofibroblast development in mice.

The purpose of this study was to investigate the role of transforming growth factor beta (TGFß) and/or platelet-derived growth factor-B (PDGF-B) blockade on the differentiation of vimentin and alpha-smooth muscle actin (αSMA)-expressing myofibroblasts associated with haze in mice. Mouse corneas had haze-generating irregular PTK (phototherapeutic keratectomy) and topical treatment with the vectors. Six study groups of PTK treated corneas, with four corneas per group in each experiment, were Group 1) treated with TGFß-KDEL vector interfering with TGFß signaling through anomalous sorting of cytokine bound to the expressed altered receptor; Group 2) treated with PDGF-B-KDEL vector interfering with PDGF signaling through anomalous sorting of cytokine bound to the expressed altered receptor; Group 3) treated with both TGFß-KDEL vector and PDGF-B-KDEL vector to interfere with signaling of both cytokines; Group 4) empty pGFPC1 vector; Group 5) empty pCMV vector; and Group 6) no vector treatment control. At one month after surgery, the corneas were analyzed by immunocytochemistry (IHC) for central stromal cells expressing myofibroblast markers vimentin and αSMA. The stroma of corneas treated with the TGFß-KDEL vector alone (p < 0.05) or both the TGFß-KDEL and PDGF-B-KDEL vectors (P < 0.05) had significantly lower density of vimentin-positive cells compared to the corresponding control group. The central stroma of corneas treated with the TGFß-KDEL vector (p < 0.05) or the PDGF-B-KDEL vector (p < 0.05) had lower density of αSMA-positive cells compared to the corresponding control group. The density of αSMA-positive stromal cells was also significantly lower (p < 0.05) when both the TGFß-KDEL and PDGF-B-KDEL and vectors were applied together compared to the corresponding control groups. This study provides in situ evidence that TGFß and PDGF-B have important roles in modulating myofibroblast generation in the mouse cornea after haze-associated injury.

Monocyte development inhibitor PRM-151 decreases corneal myofibroblast generation in rabbits.

This study investigated whether PRM-151 (Promedior, Inc., Malvern, PA), a recombinant form of human pentraxin-2 (PTX-2, also referred to as serum amyloid P, hSAP), that inhibits differentiation of circulating monocytes into fibrocytes and profibrotic macrophages, could modulate generation of myofibroblasts after opacity-producing corneal injury in rabbits, and, therefore, have potential to reduce or prevent haze after PRK. Nine diopter PRK for myopia was performed with the VISX S4 IR laser. Four groups of 6 animals were treated in masked fashion: Group 1: 30 µl of topical PRM-151 (20 mg/ml) 6 times a day for 5 days; Group 2: 30 µl topical vehicle 6 times a day for 5 days; Group 3: 200 µl sub-conjunctival PRM-151 (total injection of 4 mg) immediately after surgery and every other day until day 8; Group 4: 200 µl sub-conjunctival injections of vehicle according to the same schedule as group 3. At one month after PRK, the animals were euthanized and immunohistochemistry was performed for the myofibroblast marker α-smooth muscle actin (SMA). The density of SMA+ cells/400× field in the central stroma was determined in each cornea. Myofibroblast density at one month after surgery was significantly lower (p = 0.006) after sub-conjunctival PRM-151 treatment (5.8 ± 2.8 cells/400× stromal field) compared to sub-conjunctival vehicle treatment (15.3 ± 2.9 cells/400× stromal field). There was no significant (p = 0.27) decrease in stromal myofibroblasts triggered by topical PRM-151 treatment (11.8 ± 6.6 cells/400× stromal field) compared to the topical vehicle treatment (14.2.8 ± 6.2 cells/400× stromal field). PRM-151 inhibits myofibroblast generation when administered by sub-conjunctival injection, but not when administered topically, after opacity-producing corneal injury. This study provides additional confirmation that bone marrow-derived cells contribute to corneal myofibroblast generation.

Stromal interleukin-1 expression in the cornea after haze-associated injury.

The purpose of this study was to determine whether myofibroblasts or other cells in the stroma in the cornea produce interleukin (IL)-1alpha or IL-1beta that could modulate myofibroblast viability in corneas with haze after photorefractive keratectomy (PRK). Twenty-four female rabbits had haze-generating PRK for 9 diopters of myopia and were sacrificed at 1 week, 2 weeks, 3 weeks or 4 weeks after surgery. Corneal rims were removed, frozen in OCT at -80 degrees C, and analyzed by immunocytochemistry using primary antibodies to IL-1alpha, IL-1beta and alpha smooth muscle actin (SMA). Double immunostaining was performed for the co-localization of SMA with IL-1alpha or IL-1beta. Central dense haze and peripheral slight haze regions of each cornea were analyzed. SMA+ cells that expressed IL-1alpha protein were detected in both regions of the corneas at most time points following PRK. However, in the haze region at the 1, 3 and 4 week time points, significantly more (p<0.01) SMA+ cells did not express IL-1alpha. Also, in the haze region at all three time points, significantly more (p<0.01) SMA- cells than SMA+ cells expressed interleukin-1alpha protein. IL-1beta expression patterns in SMA+ and SMA- stromal cells was similar to that of IL-1alpha after PRK. Previous studies have demonstrated that IL-1alpha or IL-1beta triggers myofibroblast apoptosis in vitro, depending on the available concentration of apoptosis-suppressive TGFbeta. This study demonstrates that SMA- cells such as corneal fibroblasts, keratocytes, or inflammatory cells may produce IL-1alpha and/or IL-1beta that could act in paracrine fashion to regulate myofibroblast apoptosis--especially in the region where there is haze in the cornea after PRK was performed and SMA+ myofibroblasts are present at higher density. However, some SMA+ myofibroblasts themselves produce IL-1alpha and/or IL-1beta, suggesting that myofibroblast viability could also be regulated via autocrine mechanisms.

Lumbar position sense with extreme lumbar angle.

Tasks involving flexed torso postures have a high incidence of low back injuries. Changes in the ability to sense and adequately control low back motion may play a role in these injuries. Previous studies examining position sense errors of the lumbar spine with torso flexion found significant increases in error with flexion. However, there has been little research on the effect of lumbar angle. In this study, the aim of the study was to examine how position sense errors would change with torso flexion as a function of the target lumbar angle. Fifteen healthy volunteers were asked to assume three different lumbar angles (maximum, minimum and mid-range) at three different torso flexion angles. A reposition sense protocol was used to determine a subject's ability to reproduce the target lumbar angles. Reposition sense error was found to increase 69% with increased torso flexion for mid-range target curvatures. With increasing torso flexion, the increase in reposition sense errors suggests a reduction in sensation and control in the lumbar spine that may increase risk of injury. However, the reposition error was smaller at high torso flexion angles in the extreme target curvatures. Higher sensory feedback at extreme lumbar angles would be important in preventing over-extension or over-flexion. These results suggest that proprioceptive elements in structures engaged at limits (such as the ligaments and facet joints), may provide a role in sensing position at extreme lumbar angles. Sensory elements in the muscles crossing the joint may also provide increased feedback at the edges of the range of motion.

Microbial sealing: a new approach to reducing contamination.

Most surgical site infections (SSIs) are caused by the patient's endogenous flora, and hence strategies to prevent bacterial contamination of the surgical incision have a central role in the prevention of such infections. However, even with optimal skin preparation, true sterilisation of the skin is not possible. A recently available method of preventing infection is a cyanoacrylate-based microbial sealant (marketed as InteguSeal(*) Microbial Sealant), which mechanically blocks migration of pathogens to the surgical wound. In in-vitro studies, this preoperative preparation reduced the recovery of pathogens commonly implicated in SSIs by up to 99.9%. Similarly, the incidence of wound contamination was lower with the microbial sealant than with antimicrobial surgical drapes in in-vivo studies. Other studies have shown that this microbial sealant significantly improves the effect of povidone iodine by fixing it on the skin and avoiding wash off, and does not affect normal skin transpiration. In a clinical study in 177 patients, the incidence of wound contamination was 53.0% with the sealant, compared with 68.7% using povidone iodine. The conclusion of this clinical study is that InteguSeal(*) Microbial Sealant significantly reduces surgical wound bacterial contamination when used in conjunction with 10% povidone iodine skin preparation, as compared to povidone iodine alone. The clinical experience to date is that this sealant is easy to apply and can be used with a variety of skin preparation solutions and with most wound closure techniques. It also has a good safety profile. This preparation may therefore form a valuable part of strategies to reduce bacterial contamination of surgical incisions, thereby potentially decreasing the risk of SSIs.

Paraspinal muscle vibration alters dynamic motion of the trunk.

Loss in dynamic stability of the low back has been identified as a potential factor in the etiology of low back injuries. A number of factors are important in the ability of a person to maintain an upright trunk posture including the preparatory stiffness of the trunk and the magnitude and timing of the neuromotor response. A neuromotor response requires appropriate sensing of joint motion. In this research, the role of this sensory ability in dynamic performance of the trunk was examined using a simple pendulum model of the trunk with neuromotor feedback. An increased sensory threshold was found to lead to increased torso flexion and increased delay in neuromotor response. This was confirmed experimentally using paraspinal muscle vibration which is known to alter proprioception of the muscle spindle organs. Before, during and after exposure to bilateral, paraspinal muscle vibration for 20 minutes, the dynamic response of subjects to an unexpected torso flexion load was examined. Subjects were found to have a 19.5% slower time to peak muscle activity and a 16.1% greater torso flexion during exposure to paraspinal muscle vibration. Torso flexion remained significantly increased after vibration exposure relative to before exposure. These results suggest that the neuromotor response plays an important role in trunk dynamics. Loss in sensitivity of the sensory system can have a detrimental effect on trunk dynamics, increasing delays in neuromotor response and increasing the motion of the trunk in response to an unexpected load.

Lumbar-pelvic range and coordination during lifting tasks.

Spine motion has been described to have two regions, a neutral zone where lumbar rotation can occur with little resistance and an elastic zone where structures such as ligaments, facet joints and intervertebral disks resist rotation. In vivo, the passive musculature can contribute to further limiting the functional neutral range of lumbar motion. Movement out of this functional neutral range could potentially put greater loads on these structures. In this study, the range of lumbar curvature rotation was examined in twelve healthy, untrained volunteers at four torso inclination angles. The lumbar curvature during straight-leg lifting tasks was then defined as a percentage of this range of possible lumbar curvatures. Subjects were found to remain neutrally oriented during the flexion phase of a lifting task. During the extension phase of the lifting task, however, subjects were found to assume a more kyphotic posture, approaching the edge of the functional range of motion. This was found to be most pronounced for heavy lifting tasks. By allowing the lumbar curvature to go into a highly kyphotic posture, subjects may be taking advantage of stretch-shortening behavior in extensor musculature and associated tendons to reduce the energy required to raise the torso. Such a kyphotic posture during extension, however, may put excessive loading on the elastic structures of the spine and torso musculature increasing the risk of injury.

Functional patency of autogenous AV fistulas for hemodialysis.

BACKGROUND: Although AV fistulas are the preferred access for hemodialysis and have low complication rates, failure to function remains high and time to first dialysis may be several months. METHODS: Data from a Computerized Patient Record System of patients undergoing AV fistula from October 2000 to March 2006 were reviewed for type of fistula, interval from AV fistula construction to first hemodialysis, patency period, and complication rate. RESULTS: 129 patients were identified who underwent 155 autogenous AV fistula constructions. The average age was 62.1 (range 40-84) years old. 114 radiocephalic and 41 brachiocephalic fistulas were performed. 57 (50%) radiocephalic fistulas allowed successful hemodialysis after an average length of 13+/-5 weeks with a primary patency of 13+/-4 months. 24 (42%) fistulas subsequently thrombosed, 7 (12%) developed fistula stenosis, and 2 (4%) developed steal syndrome. 28 (68%) brachiocephalic fistulas reached successful hemodialysis after 6+/-2 weeks with a primary patency of 16+/-7 months. Eleven (42%) of the brachiocephalic fistulas that reached hemodialysis remained patent while four (15%) thrombosed. Two (8%) brachiocephalic fistulas thrombosed before reaching hemodialysis. There were two incidences (5%) of steal syndrome in the brachiocephalic group with one case being severe leading to tissue loss in the hand. CONCLUSION: Brachiocephalic fistulas were superior to radiocephalic in both time to maturity, primary patency, and functional primary patency. Brachiocephalic fistulas had a higher maturation rate and were less likely to fail once hemodialysis began. Vascular surgeons should develop better patient selection to predict which fistulas will function successfully rather than risk complications of prolonged central catheters.

Laparoscopic esophagectomy.

Minimally invasive esophagectomy is emerging as an alternative option to open esophagectomy for benign and malignant esophageal diseases. This article provides a detailed review of the history of minimally invasive esophagectomy and an update on the currently accepted techniques for minimally invasive esophagectomy and its outcomes.

Active stiffness of the ankle in response to inertial and elastic loads.

Effective stiffness of the musculoskeletal system was examined as a function of the characteristics of an external load. Thirteen healthy subjects provided active contraction of the ankle plantarflexion musculature in a neutral ankle posture to support an external load. Musculoskeletal stiffness was computed from kinetic data recorded in response to dorsiflexion/plantarflexion perturbations. Ankle dynamics were recorded while supporting external loads of 19 and 38 kg with and without antagonistic co-contraction. External loads were applied using pure gravitational mass. In separate trials external loads were applied from stretch of steel springs in parallel with the plantarflexion musculature that also provided added parallel stiffness to the system. Adding external stiffness of 4.9 and 8.1 kN/m surprisingly failed to significantly change the stiffness of the ankle-plus-spring system. This suggests contributions from intrinsic muscle stiffness and reflex stiffness declined in response to added external stiffness. This could not be explained by load magnitudes, ankle postures, or co-activation as these were similar between the inertial and elastic loading conditions. However, non-linear parametric analyses suggest mean intrinsic stiffness of 35.5 kN/m and reflex gain of 11.6 kN/m with a constant reflex delay of 70 ms accurately described the empirical results. The phase response between the mechanical dynamics of the musculoskeletal system and delayed neuromotor feedback combine to provide robust control of system behavior.

Gender differences in active musculoskeletal stiffness. Part II. Quantification of leg stiffness during functional hopping tasks.

Leg stiffness was compared between age-matched males and females during hopping at preferred and controlled frequencies. Stiffness was defined as the linear regression slope between the vertical center of mass (COM) displacement and ground-reaction forces recorded from a force plate during the stance phase of the hopping task. Results demonstrate that subjects modulated the vertical displacement of the COM during ground contact in relation to the square of hopping frequency. This supports the accuracy of the spring-mass oscillator as a representative model of hopping. It also maintained peak vertical ground-reaction load at approximately three times body weight. Leg stiffness values in males (33.9+/-8.7 kN/m) were significantly (p<0.01) greater than in females (26.3+/-6.5 kN/m) at each of three hopping frequencies, 3.0, 2.5 Hz, and a preferred hopping rate. In the spring-mass oscillator model leg stiffness and body mass are related to the frequency of motion. Thus male subjects necessarily recruited greater leg stiffness to drive their heavier body mass at the same frequency as the lighter female subjects during the controlled frequency trials. However, in the preferred hopping condition the stiffness was not constrained by the task because frequency was self-selected. Nonetheless, both male and female subjects hopped at statistically similar preferred frequencies (2.34+/-0.22 Hz), therefore, the females continued to demonstrate less leg stiffness. Recognizing the active muscle stiffness contributes to biomechanical stability as well as leg stiffness, these results may provide insight into the gender bias in risk of musculoskeletal knee injury.

Treatment of warfarin-associated coagulopathy: a physician survey.

STUDY OBJECTIVES: (1) To determine physician preferences in the management of warfarin-induced excessive anticoagulation (AC); and (2) to assess compliance with the American College of Chest Physicians (ACCP) guidelines for the reversal of excessive AC. DESIGN: Cross-sectional physician survey. PARTICIPANTS: Members of the Canadian Society of Internal Medicine practicing in Ontario, Canada. MEASUREMENTS AND RESULTS: Physicians were asked to provide management preferences in six clinical scenarios describing warfarin-induced excessive AC. The scenarios represent various combinations of international normalized ratio (INR) value, treatment setting, and presence and severity of bleeding. In scenarios with INRs < 5.2 without bleeding, conservative approaches complying with the ACCP guidelines, such as withholding warfarin or reducing its dose, were most common. In scenarios with high INRs (ie, > 7.1) and/or bleeding, the selection of vitamin K in any form ranged between 71% and 82%. However, compliance with the ACCP-recommended doses and the routes of vitamin K administration ranged from 1 to 10%. In five of the six scenarios, subcutaneous injection, a route not recommended by the ACCP, was the most common method of vitamin K delivery. CONCLUSIONS: Physician preferences for the reversal of warfarin-induced excessive AC were highly variable and, in most cases, did not follow the recommendations of the ACCP consensus guidelines. Furthermore, the widespread reported use of subcutaneous vitamin K is concerning because this route of vitamin K administration has been demonstrated to be less effective than IV administration of vitamin K. These findings highlight the need for randomized controlled trials to compare the efficacy of different routes of administration of vitamin K for warfarin-associated coagulopathy.