Effect of Rivaroxaban and Aspirin in Patients With Peripheral Artery Disease Undergoing Surgical Revascularization: Insights From the VOYAGER PAD Trial.

BACKGROUND: Patients with peripheral artery disease requiring lower extremity revascularization (LER) are at high risk of adverse limb and cardiovascular events. The VOYAGER PAD trial (Vascular Outcomes Study of ASA [Acetylsalicylic Acid] Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) demonstrated that rivaroxaban significantly reduced this risk. The efficacy and safety of rivaroxaban has not been described in patients who underwent surgical LER. METHODS: The VOYAGER PAD trial randomized patients with peripheral artery disease after surgical and endovascular LER to rivaroxaban 2.5 mg twice daily plus aspirin or matching placebo plus aspirin and followed for a median of 28 months. The primary end point was a composite of acute limb ischemia, major vascular amputation, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was Thrombolysis in Myocardial Infarction major bleeding. International Society on Thrombosis and Haemostasis bleeding was a secondary safety outcome. All efficacy and safety outcomes were adjudicated by a blinded independent committee. RESULTS: Of the 6564 randomized, 2185 (33%) underwent surgical LER and 4379 (67%) endovascular. Compared with placebo, rivaroxaban reduced the primary end point consistently regardless of LER method (P-interaction, 0.43). After surgical LER, the primary efficacy outcome occurred in 199 (18.4%) patients in the rivaroxaban group and 242 (22.0%) patients in the placebo group with a cumulative incidence at 3 years of 19.7% and 23.9%, respectively (hazard ratio, 0.81 [95% CI, 0.67-0.98]; P=0.026). In the overall trial, Thrombolysis in Myocardial Infarction major bleeding and International Society on Thrombosis and Haemostasis major bleeding were increased with rivaroxaban. There was no heterogeneity for Thrombolysis in Myocardial Infarction major bleeding (P-interaction, 0.17) or International Society on Thrombosis and Haemostasis major bleeding (P-interaction, 0.73) on the basis of the LER approach. After surgical LER, the principal safety outcome occurred in 11 (1.0%) patients in the rivaroxaban group and 13 (1.2%) patients in the placebo group; 3-year cumulative incidence was 1.3% and 1.4%, respectively (hazard ratio, 0.88 [95% CI, 0.39-1.95]; P=0.75) Among surgical patients, the composite of fatal bleeding or intracranial hemorrhage (P=0.95) and postprocedural bleeding requiring intervention (P=0.93) was not significantly increased. CONCLUSIONS: The efficacy of rivaroxaban is associated with a benefit in patients who underwent surgical LER. Although bleeding was increased with rivaroxaban plus aspirin, the incidence was low, with no significant increase in fatal bleeding, intracranial hemorrhage, or postprocedural bleeds requiring intervention. Registration: URL: http://www.clinicaltrials.gov; Unique Identifier: NCT02504216.

Engaging patients and caregivers to establish priorities for the management of diabetic foot ulcers.

OBJECTIVE: Effective diabetic foot ulcer (DFU) care has been stymied by a lack of input from patients and caregivers, reducing treatment adherence and overall quality of care. Our objectives were to capture the patient and caregiver perspectives on experiencing a DFU and to improve prioritization of patient-centered outcomes. METHODS: A DFU-related stakeholder group was formed at an urban tertiary care center. Seven group meetings were held across 4 months, each lasting ∼1 hour. The meeting facilitator used semistructured questions to guide each discussion. The topics assessed the challenges of the current DFU care system and identified the outcomes most important to stakeholders. The meetings were audio recorded and transcribed. Directed and conventional content analyses were used to identify key themes. RESULTS: Six patients with diabetes (five with an active DFU), 3 family caregivers, and 1 Wound Clinic staff member participated in the stakeholder group meetings. The mean patient age was 61 years, four (67%) were women, five (83%) were either African American or Hispanic, and the mean hemoglobin A1c was 8.3%. Of the five patients with a DFU, three had previously required lower extremity endovascular treatment and four had undergone at least one minor foot amputation. Overall, stakeholders described how poor communication between medical personnel and patients made the DFU experience difficult. They felt overwhelmed by the complexity of DFU care and were persistently frustrated by inconsistent medical recommendations. Limited resources further exacerbated their frustrations and barriers to care. To improve DFU management, the stakeholders suggested a centralized healthcare delivery pathway with timely access to a coordinated, multidisciplinary DFU team. The clinical outcomes most valued by stakeholders were (1) avoiding amputation and (2) maintaining or improving health-related quality of life, which included independent mobility, pain control, and mental health. From these themes, we developed a conceptual model to inform DFU care pathways. CONCLUSIONS: Current DFU management lacks adequate care coordination. Multidisciplinary approaches tailored to the self-identified needs of patients and caregivers could improve adherence. Future DFU-related comparative effectiveness studies will benefit from direct stakeholder engagement and are required to evaluate the efficacy of incorporating patient-centered goals into the design of a multidisciplinary DFU care delivery system.

Leaf and root bark extracts of Ziziphus abyssinica Hochst ex. A. Rich (Rhamnaceae) ameliorate hepatic, renal and splenic injuries induced by phenylhydrazine in rats.

Objectives Ziziphus abyssinica (ZA) is employed in managing several ailments in Traditional African Medicine. Scientific evaluations are necessary to ascertain the medicinal potential of ZA as a source of new drug molecules. This study investigated the possible therapeutic benefit of ZA leaf (ZAL) and root bark (ZARB) extracts in an experimental model of multi-organ injuries induced by phenylhydrazine (PHZ). Methods Hyperbilirubinaemia, hepatotoxicity, nephrotoxicity and splenic injuries were induced by pretreating albino rats with PHZ (40 mg/kg, p.o.) for two alternate days. Afterward, six out of the eight groups of rats (n = 5) used were treated with either ZAL or ZARB (30, 100 and 300 mg/kg/day, p.o.) for seven days. Naïve control rats received saline without PHZ whereas negative control group received saline after PHZ. After one week of treatment, rats were sacrificed and blood collected for assessment of haematological and biochemical parameters. Liver, kidney and spleen sections were processed for histology and examined under light microscope. Results Data indicate that PHZ significantly (p < 0.05) increased total bilirubin, serum alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen (BUN), creatinine and BUN/creatinine ratio whereas red blood cell count was significantly reduced. These anomalies were significantly reversed in rats treated with ZAL or ZARB. The therapeutic effect of the extracts was supported by photomicrographs of the liver, kidney, and spleen of rats which revealed recovery from PHZ-mediated pyknosis, glomerular degeneration and multiple splenic necrosis respectively. Conclusions Overall, data from this study suggest that ZA may be useful in multiple organ injuries associated with PHZ-like xenobiotic toxicity.

Pilot study evaluating the efficacy of exergaming for the prevention of deep venous thrombosis.

OBJECTIVE: Current prophylactic protocols fail to prevent deep venous thrombosis (DVT) in a significant minority of patients, and it remains one of the leading causes of preventable death. We therefore quantified the efficacy of novel game-based exercises (exergaming) to augment femoral venous parameters relative to ankle movement and muscle flexion. METHODS: Healthy volunteers were recruited to perform a series of ankle and foot exercises using a wireless foot sensor (LEGSys; BioSensics LLC, Watertown, Mass) to navigate a computer cursor sequentially on a screen to the center of 200 circular targets. A single ultrasound technician (W.A.M.) measured each patient's mean flow volume, peak flow velocity, mean flow velocity, and cross-sectional area of the right femoral vein at baseline and obtained immediate postexercise (PEX), 5-minute PEX, and 15-minute PEX measurements. Electromyography (EMG) was performed at baseline and during the exercise. Baseline demographics and medical and surgical comorbidities were also recorded. The primary end point was the difference between baseline and immediate PEX mean flow volume estimates. We secondarily explored the association of baseline characteristics and EMG measurements with femoral vein parameters. RESULTS: Fifteen healthy subjects (53% male; 28.1 ± 4.6 years) completed the exergaming task within a mean of 4 minutes, 2 ± 21 seconds. Immediately after exercise, the femoral vein mean flow volume, mean velocity, and peak systolic velocity increased by 49%, 53%, and 48%, respectively (P < .02 for each). Mean flow volume and velocity remained significantly elevated 5 minutes after exercise (P < .04 for each). Plantar flexion and dorsiflexion velocities and EMG frequency and intensity were not significantly correlated with PEX mean flow volume estimates (P > .05). Subgroup analysis revealed that women (P < .01) and Hispanics (P < .01) exhibited significantly slower PEX responses. Subjects with the largest improvements in mean flow volume had lower peak plantar flexion velocities (P < .01). CONCLUSIONS: Exergaming increases mean flow volume, mean flow velocity, and peak systolic velocity within the femoral vein by approximately 50% above baseline. Exergaming represents a novel and potentially attractive method of DVT prevention by augmenting femoral vein mean volume flow and capitalizing on biofeedback. Less forceful but more uniform contractions were found to be most effective at augmenting venous blood flow. Exergaming will require further validation in larger study bases, among patients at higher risk of DVT.

Open bypass and endoluminal therapy: complementary techniques for revascularization in diabetic patients with critical limb ischaemia.

The use of endovascular therapy (EVT) for lower extremity atherosclerosis is markedly increasing while open surgical bypass is in decline. The results of EVT for critical limb ischaemia (CLI) are difficult to evaluate, especially for patients with diabetes. To date, only one randomized, prospective trial has been published comparing EVT with open bypass for CLI. Although early costs and outcomes were equivalent or superior for EVT, after 2 years, surgery was associated with a significantly reduced risk of future amputation and death.Approximately, 40-50% of diabetic patients with CLI can be initially treated with EVT. Patients with Trans-Atlantic Inter-Society Consensus (TASC) A and B lesions should be treated endoluminally. EVT should be used with caution in patients with TASC C and D lesions; however, in selected patients, particularly if vein conduit is lacking and life expectancy is short, EVT is not unreasonable. For low-to-moderate risk patients with TASC C or D lesions, extensive tibial disease, and suitable vein conduit, surgical bypass remains the best limb preservation option. The primary therapeutic goals are relief of rest pain, healing of ischaemic lesions, and maintenance of functional status. Haemodynamic assessment is critical following both open and EVT for CLI and aids in determining the need for further revascularization; additional interventions are required in 20-30% of CLI patients depending on the degree of ischaemia, anatomical disease extent, and mode of initial therapy. At the University of Arizona, we currently recommend that TASC A and B CLI patients undergo EVT first. TASC C and D patients should undergo bypass unless available conduit is poor, surgical risk is prohibitive, or life expectancy is limited. CLI is a serious end-of-life condition given the sobering realization that only 50-55% of CLI patients are alive with an intact limb 5 years after initial presentation.