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Background: Low-dose oral vitamin K decreases the international normalized ratio (INR) in overanticoagulated patients who receive warfarin therapy. Its effects on bleeding events are uncertain.Objective: To see whether low-dose oral vitamin K reduces bleeding events over 90 days in patients with warfarin-associated coagulopathy.Design: Multicenter, randomized, placebo-controlled trial. Randomization was computer-generated, and participants were allocated to trial groups by using sequentially numbered study drug containers. Patients, caregivers, and those who assessed outcomes were blinded to treatment assignment.Setting: 14 anticoagulant therapy clinics in Canada, the United States, and Italy.Patients: Nonbleeding patients with INR values of 4.5 to 10.0.Intervention: Oral vitamin K, 1.25 mg (355 patients randomly assigned; 347 analyzed), or matching placebo (369 patients randomly assigned; 365 analyzed).Measurements: Bleeding events (primary outcome), thromboembolism, and death (secondary outcomes).Results: 56 patients (15.8%) in the vitamin K group and 60 patients (16.3%) in the placebo group had at least 1 bleeding complication (absolute difference, -0.5 percentage point [95% CI, -6.1 to 5.1 percentage points]); major bleeding events occurred in 9 patients (2.5%) in the vitamin K group and 4 patients (1.1%) in the placebo group (absolute difference, 1.5 percentage points [CI, -0.8 to 3.7 percentage points]). Thromboembolism occurred in 4 patients (1.1%) in the vitamin K group and 3 patients (0.8%) in the placebo group (absolute difference, 0.3 percentage point [CI, -1.4 to 2.0 percentage points]). Other adverse effects were not assessed. The day after treatment, the INR had decreased by a mean of 1.4 in the placebo group and 2.8 in the vitamin K group (P < 0.001).Limitation: Patients who were actively bleeding were not included, and warfarin dosing after enrollment was not mandated or followed.Conclusion: Low-dose oral vitamin K did not reduce bleeding in warfarin recipients with INRs of 4.5 to 10.0.Funding: Canadian Institutes of Health Research and Italian Ministry of Universities and Research. [ABSTRACT FROM AUTHOR]

Study Objective: This study assesses outcomes associated with the implementation of an emergency department (ED) for seniors in which a clinical pharmacy specialist, with specialized geriatric training that included medication management training, is a key member of the ED care team., Methods: This was a retrospective cohort analysis of patients aged 65 years or older who presented at an ED between November 1, 2012, and May 31, 2013. Three groups of seniors were assessed: treated by the clinical pharmacy specialist in the ED for seniors, treated in the ED for seniors but not by the clinical pharmacy specialist, and not treated in the ED for seniors. Outcomes included rates of an ED return visit, mortality and hospital admissions, and follow-up total health care costs. Multivariable regression modeling was used to adjust for any potential confounders in the associations between groups and outcomes., Results: A total of 4,103 patients were included, with 872 (21%) treated in the ED for seniors and 342 (39%) of these treated by the clinical pharmacy specialist. Groups were well matched overall in patient characteristics. Patients who received medication review and management by the clinical pharmacy specialist did not experience a reduction in ED return visits, mortality, cost of follow-up care, or hospital admissions compared with the other groups. Of the patients treated by the clinical pharmacy specialist, 154 (45.0%) were identified as having at least 1 medication-related problem., Conclusion: Although at least 1 medication-related problem was identified in almost half of patients treated by the clinical pharmacy specialist in the ED for seniors, incorporation of a clinical pharmacy specialist into the ED staff did not improve clinical outcomes., (Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Proximal interphalangeal joint (PIPJ) fractures are a treatment challenge for hand surgeons. Poor treatment options may lead to stiffness, non-union and markedly reduced range of movement (ROM). We describe our experience using the Hoffman-2 micro static external fixation device (Stryker) in a case series of ten patients with closed comminuted intra-articular PIPJ fractures. The use of this device in the management of these fractures has not previously been described. The mean total active motion (TAM) of the injured joint had recovered to 80% of normal at the six-month follow up.

Background: When interacting medications, such as doxycycline, are initiated during warfarin therapy, one method to correct for non-therapeutic international normalized ratio (INR) is adjusting the warfarin dose, if necessary. Another approach is preemptive warfarin dose adjustment. This study's objective was to evaluate the utility of preemptive warfarin dose adjustment for preventing non-therapeutic INR following doxycycline-warfarin co-administration., Methods: Patients were randomized to either a 10% to 20% preemptive warfarin dose reduction (intervention) or reactive warfarin dose adjustment (control) within 72 hours of warfarin-doxycycline co-administration. Subjects received a follow-up INR within 7 days (index INR). Primary outcome was the occurrence of index INR ≥ 1 point over the INR goal range upper limit. Secondary outcomes included INR control, purchases of prescription vitamin K, and warfarin-associated adverse events in the 30 days after doxycycline initiation., Results: Twenty and 17 patients comprised the intervention and control groups. The intervention group's warfarin dose was reduced by a median of 11%. More control patients (n=2) experienced an INR ≥ 1 point over the INR goal range upper limit compared to intervention (n=0); however, the difference (12% vs. 0%) was not statistically significant (p=0.20). A higher percentage of intervention patients had subtherapeutic index INRs compared to control (35% vs. 6%, p<0.05). One patient from each group experienced warfarin-associated bleeding. No thromboembolic complications or vitamin K use were observed., Conclusions: For warfarin patients initiating doxycycline therapy, preemptive warfarin dose reduction did not result in supratherapeutic INRs but increased the likelihood of subtherapeutic INRs compared to INR monitoring with reactive warfarin dose adjustment., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Patients presenting with distal end radius fractures may have concomitant carpal instability due to disruption of the scapholunate ligament. This study examined the incidence of static radiographic signs of carpal instability in patients with distal radial fractures before and after fracture treatment. We performed a retrospective radiographic study of 141 patients presenting to Central Middlesex Hospital, London between January 2002-May 2004 with distal end radius fractures. We used abnormal scapholunate angle as the primary indicator of possible carpal dissociation. Abnormal scapholunate angles were noted in 39% of patients at presentation and 35% of patients after treatment with no statistically significant intra-patient variability. Persistent static radiographic signs of carpal instability are high in this subset of patients. The long-term morbidity of persistent wrist instability may be avoided by early radiological diagnosis with clinical correlation to identify carpal ligament injuries and initiate treatment that addresses both the bony and ligamentous components of the injury.

Typically, the international normalized ratio (INR) is monitored and warfarin dose adjusted, if necessary, to correct non-therapeutic INR after interacting medications, like prednisone, are initiated during warfarin therapy. Preemptively adjusting the warfarin dose is another approach. To evaluate the utility of preemptive warfarin dosage adjustment for preventing non-therapeutic INR following prednisone-warfarin co-administration. Patients were randomized to either a preemptive warfarin dose reduction between 10 and 20% (intervention) or reactive warfarin dose adjustment (control) within 72 h of warfarin-prednisone co-administration. Subjects received a follow-up INR within 7 days. Primary outcome was the occurrence of follow-up INR ≥ 1 point over the INR goal range upper limit. Secondary outcomes included INR control, purchases of prescription vitamin K, and warfarin-associated adverse events in the 30 days after prednisone initiation. Twenty and 17 patients comprised the intervention and control groups. The intervention group's warfarin dose was reduced by a median of 11.8%. More control patients (n = 5) experienced an INR ≥ 1 point over the INR goal range upper limit compared to intervention (n = 2); however, the actual difference (29.4 vs.10.0%) was not statistically significant (P = 0.21). A higher percentage of intervention patients had a subtherapeutic follow-up INR compared to control (40 vs. 5.9%, P = 0.02). One patient from each group experienced warfarin-associated bleeding. No thromboembolic complications or vitamin K purchases were observed. For patients initiating prednisone therapy, preemptive warfarin dose reduction resulted in a non-significant reduction in supratherapeutic INR but increased the likelihood of subtherapeutic INR compared to INR monitoring with reactive warfarin dose adjustment.

Unanticipated elevation of the INR is common in patients receiving warfarin. We performed a prospective cohort study of 107 warfarin-treated patients with INR values of more than 10 who received a single 2.5 mg dose of oral vitamin K. During the first week, one patient experienced major bleeding, and one died. In the first 90 days after enrolment four patients had major bleeding (3.7%, 1.0% to 9.3%), eight patients (7.5%, 3.3% to 14.2%) died and two had objectively confirmed thromboembolism. Based on our low rate of observed major bleeding we conclude that 2.5 mg of oral vitamin K is a reasonable treatment for patients with INR values of more than 10 who are not actively bleeding.

Well-characterized genes that affect warfarin metabolism (cytochrome P450 (CYP) 2C9) and sensitivity (vitamin K epoxide reductase complex 1 (VKORC1)) explain one-third of the variability in therapeutic dose before the international normalized ratio (INR) is measured. To determine genotypic relevance after INR becomes available, we derived clinical and pharmacogenetic refinement algorithms on the basis of INR values (on day 4 or 5 of therapy), clinical factors, and genotype. After adjusting for INR, CYP2C9 and VKORC1 genotypes remained significant predictors (P < 0.001) of warfarin dose. The clinical algorithm had an R(2) of 48% (median absolute error (MAE): 7.0 mg/week) and the pharmacogenetic algorithm had an R(2) of 63% (MAE: 5.5 mg/week) in the derivation set (N = 969). In independent validation sets, the R(2) was 26-43% with the clinical algorithm and 42-58% when genotype was added (P = 0.002). After several days of therapy, a pharmacogenetic algorithm estimates the therapeutic warfarin dose more accurately than one using clinical factors and INR response alone.

Background and Aims: To assess the effect of warfarin anticoagulation therapy (AC) on the incidence of colon bleeding after elective colonoscopy with polypectomy and to identify independent predictors of post-polypectomy colon bleeding., Methods: This was a retrospective cohort analysis. Patients interrupting warfarin AC therapy for polypectomy (AC group) were matched on age (+/- 3 years) with up to two patients who underwent polypectomy but were not receiving AC (non-AC group). Data were extracted from electronic medical, pharmacy and laboratory claims and records and manual medical chart review. Incidence rates of colon bleeding requiring hospitalization, other gastrointestinal bleeding, thrombosis and death in the 30 days post-polypectomy were compared between groups. Multivariate regression techniques were used to identify independent predictors of post-polypectomy colon bleeding., Results: A total of 425 AC group patients were matched to 800 non-AC group patients. Post-polypectomy colon bleeding occurred more often in AC group patients (2.6% vs. 0.2%, P = 0.005). There were no differences in the rates of other outcomes (P > 0.05). Independent predictors of colon bleeding included AC group status [adjusted odds ratio (AOR) = 11.6; 95% confidence interval (CI) = 2.3-57.3], number of polyps removed (AOR = 1.2; 95% CI = 1.1-1.4) and male gender (AOR = 9.2, 95% CI = 1.1-74.9)., Conclusions: The incidence of post-polypectomy colon bleeding was higher in patients receiving AC even although warfarin was interrupted for the procedure. Independent predictors of colon bleeding were identified as: receiving AC, removal of multiple polyps and male gender. Our findings suggest that additional methods to reduce the likelihood of post-polypectomy colon bleeding in AC patients should be investigated.

Background: Warfarin is commonly prescribed for prophylaxis and treatment of thromboembolism after orthopedic surgery. During warfarin initiation, out-of-range International Normalized Ratio (INR) values and adverse events are common., Methods: In orthopedic patients beginning warfarin therapy, we developed and prospectively validated pharmacogenetic and clinical dose refinement algorithms to revise the estimated therapeutic dose after 4 days of therapy., Results: The pharmacogenetic algorithm used the cytochrome P450 (CYP) 2C9 genotype, smoking status, peri-operative blood loss, liver disease, INR values and dose history to predict the therapeutic dose. The R(2) was 82% in a derivation cohort (n = 86) and 70% when used prospectively (n = 146). The R(2) of the clinical algorithm that used INR values and dose history to predict the therapeutic dose was 57% in a derivation cohort (n = 178) and 48% in a prospective validation cohort (n = 146). In 1 month of prospective follow-up, the percent time spent in the therapeutic range was 7% higher (95% CI: 2.7-11.7) in the pharmacogenetic cohort. The risk of a laboratory or clinical adverse event was also significantly reduced in the pharmacogenetic cohort (Hazard Ratio 0.54; 95% CI: 0.30-0.97)., Conclusions: Warfarin dose adjustments that incorporate genotype and clinical variables available after four warfarin doses are accurate. In this non-randomized, prospective study, pharmacogenetic dose refinements were associated with more time spent in the therapeutic range and fewer laboratory or clinical adverse events. To facilitate gene-guided warfarin dosing we created a non-profit website, http://www.WarfarinDosing.org.

Background: Cutaneous sebaceous carcinoma (SC) is a rare malignancy derived from adnexal epithelium of sebaceous glands. Periorbital SC is approximately three times more common than extraorbital SC. To date, there are few data from an Australian source to document the prevalence or clinical outcome of this tumour., Methods: A retrospective review was undertaken of the cases from the Institute of Clinical Pathology and Medical Research using their histopathology database for patients with a diagnosis of SC. Patients were identified over a period of 34 years from 1971-2005 and their management and follow up are reported., Results: There were 25 patients in all. Seventeen were men and eight were women. Of the 25 cases, 12 were extraorbital and 13 were periorbital. Three metastases and one tumour showed extensive local invasion. There were nine cases of incomplete excisions and 13 patients were reoperated on for either incomplete excisions, to obtain a wider margin or for local recurrences. Adjuvant radiotherapy was used on five patients, three of whom had lymph node deposits., Conclusion: Sebaceous carcinoma is a rare tumour. Extraorbital SC is an aggressive and invasive malignancy. Excision margins may need to be wider than previously thought. Exposure to ultraviolet radiation (sunlight) may play a role in the aetiology. Wide excision and selective use of radiotherapy remain the treatment of choice.

An "off the shelf" vascular conduit for free flap surgery that remained patent until the flap is vascularized from the recipient bed would be useful to avoid autograft donor-site morbidity and reduce operation time. To date, no successful studies of microvascular prostheses in low-flow states exist. This study investigated the effects of L-arginine on neointimal hyperplasia and the overall patency of cold-stored femoral arterial allografts implanted into a low-flow arterial defect model in rabbits. A cutaneous island flap based on the inferior epigastric artery was raised, and the femoral artery was ligated distally. Immediately proximal to the inferior epigastric artery, the femoral artery was divided and a 1-cm long cold-stored femoral arterial allograft was inserted into the defect. Half of the animals received L-arginine as a subcutaneous injection. When harvested at 4 weeks, 9 out of 11 allografts of the L-arginine-treated group and 8 out of 14 grafts of the control group were patent. Intimal thickening and graft stenosis were significantly reduced in the L-arginine group. Our findings reveal the potential of a combined approach of an arterial allograft and the use of L-arginine as a short-term vein graft substitute.

This study reports the outcome of immediate re-repair of primary flexor tendon repairs in zones 1 and 2 of the fingers which had ruptured. Between June 1989 and May 2003, a total of 62 fingers in 61 patients presented with ruptured flexor tendon repairs within 48 hours from rupture. Immediate re-repair and rehabilitation was carried out in 44 fingers (71%) in 43 (70%) patients. Thirty-six patients completed the 8-week therapy programme after re-repair in 37 fingers. Nine (24%) had excellent, 10 (27%) good, 5 (14%) fair and 13 (35%) had poor results when assessed by the original Strickland method. Five fingers in five patients ruptured the re-repair. Poor results and second ruptures were particularly common after re-repair of ruptured tendon repairs in the little finger. In the light of these findings, a policy for dealing with ruptured primary flexor tendon repairs in the fingers is suggested.