Acute ischemic stroke on anti-Xa inhibitors: Pharmacokinetics and outcomes.

BACKGROUND AND PURPOSE: Direct oral anticoagulant (DOAC) ingestion within 48 h is an exclusion for thrombolysis in acute ischemic stroke (AIS) patients. We aim to shed light on pharmacokinetic correlates and outcomes in patients with AIS excluded from thrombolysis due to DOAC use. METHODS: This is a single center retrospective study of consecutive patients with AIS within 4.5 h from last known normal and excluded from thrombolytic therapy due to confirmed Xa inhibitor DOAC (DOACXa) intake within the prior 48 h. We used linear regression to test the correlation between time from last DOACXa ingestion and anti-Xa level. RESULTS: Over a period of 2.5 years, we identified 44 patients who did not receive thrombolysis because of presumed DOAC intake within 48 h. In adjusted linear regression, there was an association between time from last DOAC ingestion and Xa level (beta = -0.69, p < 0.001). Among the 37 patients with known atrial fibrillation not receiving alteplase due to DOAC use, the 90-day mortality was 35.1% (13/37) and 77% (10/13) of deaths were stroke related. CONCLUSIONS: Patients with AIS on DOAC therapy face a heightened risk of mortality. Studies are needed to investigate the safety and efficacy of thrombolysis in such patients based on time of last DOAC ingestion and/or anti-Xa/drug level.

Ultrasound therapy for treatment of lower extremity intermittent claudication.

BACKGROUND: While often thought of as a diagnostic tool, ultrasound (US) can also potentially be used as a therapeutic modality. US applies mechanical stress on endothelial cells and induces nitric oxide synthase, which regulates the secretion of nitric oxide, a potent vasodilator. In animal ischemic models, US has been shown to improve hindlimb, myocardial, and cerebral perfusion. We performed a pilot trial of US therapy in the lower extremities of human subjects with intermittent claudication. METHODS: 10 subjects (5 male, 5 female, mean age 69.7 ± 10.3) with intermittent claudication were recruited. Both legs were placed in a specially designed boot with a water interface between US transducers and the legs. Subjects underwent pulsed US therapy at 250 kHz frequency for 30 min for three treatments a week for six weeks. Pre and post treatment ankle:brachial index (ABI), 6-min walk (6 MW), Walking Impairment Questionnaire (WIQ), and Short Form 36 (SF36) were performed. Pre and post-treatment results were compared with paired t-test. RESULTS: Six minute walking distance at baseline was 352 ± 70 m, after one treatment session 353 ± 70 m (p = 0.99), and at completion 372 ± 71 m (p = 0.015). There was a trend toward improved ABI after 6 weeks of treatment (0.53 ± 0.17 vs 0.64 ± 0.12, p = 0.083). After six weeks, significant improvements were noted in overall WIQ score (2.00 ± 1.48 vs 2.63 ± 1.38, p = 0.0001), WIQ (distance) 2.07 ± 1.54 vs 2.73 ± 1.42 (p = 0.036), and WIQ (stair) 2.00 ± 1.67 vs 2.62 ± 1.24, p = 0.034, with a trend in WIQ (speed), 1.89 ± 1.26 vs 2.46 ± 1.43, p = 0.069. In the SF-36, significant improvements were noted in the domains of physical functioning (44.0 ± 41.6 vs 50.5 ± 41.1, p = 0.009) and role limitations - physical (35.0 ± 48.3 vs 60.0 ± 49.6, p = 0.006) after six weeks. CONCLUSIONS: Therapeutic US is a potential noninvasive treatment for intermittent claudication. Pilot study patients noted significant improvements in 6 MW and WIQ results after 6 weeks of treatment. A nonsignificant improvement in ABI was noted. Further research will be needed to clarify optimal treatment frequency and duration.

Immediate effects of hemodialysis on upper extremity and cognitive function.

BACKGROUND: Subjects undergoing hemodialysis often describe feeling "weak" and "fatigued" after dialysis. This has not previously been quantified. We sought to evaluate upper extremity and cognitive function before and after hemodialysis to see if differences existed and how long recovery takes. METHODS: Subjects undergoing hemodialysis in an inpatient hospital dialysis unit were recruited. Subjects underwent assessment of upper extremity strength (grip (GS) and pinch (PS)), dexterity (pegboard assembly (PA)), finger sensation (monofilaments), and cognitive function (mini-mental status exam (MMS)) immediately pre- and post-dialysis, 3 h post-dialysis, and the following morning. Both the dialysis (index) and non-dialysis extremities were evaluated. Results were also stratified for fistulas vs. central venous catheters. Patients were dialyzed at the same flow rate and duration. RESULTS: 21 subjects were evaluated, 13 (62%), male, mean age 56 ± 17 years, 15 (71%) diabetic, 15 (71%) fistulas, 6 (29%) central venous catheters. Overall, there were no significant changes in GS, PS, PA, immediately or 3 h after dialysis. MMS was non-significantly reduced 3 h after dialysis (22.8 ± 10.3 vs 27.0 ± 3.5, p = 0.06). PA was significantly improved the following morning (6.4 ± 4.8 assembled units vs 7.5 ± 5.1, p = 0.049). Patients dialyzing through catheters had reduced grip strength 3 h after dialysis compared to fistulas (-4.6 ± 2.7 N from baseline vs 1.4 ± 4.3 N from baseline, p = 0.018) that was resolved by the next day. CONCLUSIONS: Hemodialysis in hospitalized inpatients does not cause acute objective deficits in upper extremity or cognitive function, with a significant improvement in hand dexterity the day after dialysis.